The coronary circulation of the pig heart: comparison with …eurjanat.com/data/pdf/eja.05020067.pdf · The coronary circulation of the pig heart: comparison with the human heart

SUMMARY

Over the last decades, the pig has been chosenas a feasible animal organ donor for the humanspecies, namely regarding heart transplanta-tion. This has led to the development of trans-genic pigs with the goal of avoiding the rejec-tion caused by xenotransplantation. It istherefore pertinent to characterize in detail thevascular anatomy of the pig heart and compareit with that of humans. In this study, 23 heartsfrom domestic pigs were subjected to two dif-ferent anatomical techniques (resin vascularcasting and injection/dissection with contrastsuspension) in order to visualize their coronarycirculation. After defining the arterial distribu-tion and anastomoses of the branches of thecoronary arteries of the pig, these features werecompared with well-established descriptions ofthe coronary circulation in human hearts. Themain contributions of this work are: (i) newfeatures of the coronary vessels of the pig heartare documented; (ii) there is close resemblancein the architecture of the coronary arteries bet-ween the pig and humans; (iii) the frequencyof anatomical variation in the arrangement ofthe coronary arteries is lower in the pig than inhumans.

Key words: Angiology – Corrosion casts – Elec-tron microscopy – Xenotransplantation

INTRODUCTION

Human Transplantation: Scarcity of donororgans

The current need of human organs for trans-plantation is not met by the availability of donors(Samstein and Platt, 2001). For instance, duringthe last decade, there was a 3-fold increase inthe number of US patients waiting for organtransplantation (from around 22.000 to 72.000),while the number of transplant surgeries, usingcadaveric or donor organs, underwent an incre-ase of less than fifty percent (from 15.000 to21.000). In the year 2000, while 60 patients recei-ved an organ each day, 17 patients on the wai-ting list died (Cooper et al., 2002).

Xenotransplantation: Non-limited availability ofdonor organs

Because of these limitations of allotransplan-tation in humans, xenotransplantation has longbeen envisioned as an alternative. If problemsregarding graft rejection can be solved in thefuture, xenotransplantation will offer severaladvantages: i) non-limited availability of tissuesand organs for transplants; ii) planning of allprocedures, thus reducing some of the factorsfor graft rejection by the recipient; iii) control ofdonor organs to prevent transmission of infec-tious agents (Hammer, 2001; Samstein and Platt,2001).

The first clinical experiments in xenotrans-plantation were performed as early as the seven-teenth century, consisting mainly in blood trans-fusions from animals into humans. In the

Eur J Anat, 9 (2): 67-87 (2005)

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The coronary circulation of the pig heart: comparison with the human heart

M. Rodrigues, A.C. Silva, A.P. Águas and N.R. GrandeDepartment of Anatomy, ICBAS (Abel Salazar Institute for Biomedical Science) and UMIB (Unit for Multidisciplinary for Biomedical Research), University of Porto, Portugal

Correspondence to:Prof. Nuno Rodrigues Grande. Department of Anatomy, ICBAS/UP, Largo Prof. Abel Salazar2, 4099-003 Porto, Portugal. Phone: (351) 222 062 204; Fax: (351) 222 062 232 E-mail: [email protected]

Submitted: February 15, 2005Accepted: May 26, 2005

nineteenth century, some tissue xenotransplantswere attempted (reviewed in Cooper et al.,2002). Since 1960, vital organs such as the heart,liver and kidney have been thoroughly studiedand tested in different experimental modelsaimed at xenotransplantation (Cooper, 1996).From 1964 to 2001, 10 attempts of heart trans-plantation from animals to humans were docu-mented. Patients receiving organs from primatessurvived longer than those receiving non-prima-te organs (only a few hours) (Appel et al., 2001).The use of primates as organ donors is thuslikely to be the most promising approach inxenotransplantation. However, the use of prima-te donors bears some disadvantages: the highcost of acquisition and maintenance of primates;most primates belong to endangered species;primate breeding is difficult and rare (one peryear); increased risk of transmission of infectiousdiseases to humans, and, finally, genetic mani-pulation of primates is not yet possible (Igaz,2001).

The Pig as an organ donorAs an alternative to primates, other animal

species have been considered with the goal ofobtaining organs for xenotransplantation.Among these, the pig seems to be the organdonor of choice for our species, because it iseasy to breed, it has large litters, and is easilymaintained in aseptic conditions. In addition,several studies have shown that the pig can begenetically modified, and also that the risk ofporcine zoonoses affecting humans is muchlower than in the case of primates. Anotheradvantage is that the size of the organs of the pigcorresponds to those of human adults. This isnot the case in primates, since their organs aresimilar in size only to those of children (Igaz,2001; Zhang et al., 2000). On the other hand,pigs belong to a species that is phylogeneticallydistant from humans, thus having greater immu-nologic and biochemical differences withhumans (Platt et al., 2002; Hammer, 2001; Coo-per et al., 2000).

Pig Anatomy: more Information is requiredAccording to Hammer (1998), the anatomy of

the pig as well as its physiology have not beensufficiently defined. Regarding cardiac anatomy,for example, there are only a few publicationsand, although it is a common saying that thepig’s heart is similar to that of humans, there is alack of comparative anatomy between the heartsin these two species.

Both Crick et al. (1998) and Hammer (1998)suggested that at a time when transgenic pigs arebeing produced there is a need to look back atthe fundamental anatomical features of the pig.Crick et al (1998) examined the hearts of pigsand humans and reported several anatomical dif-

ferences, namely regarding the cardiac orienta-tion, the morphology of the atria, the position ofthe openings of the caval veins, and the numberof pulmonary veins. These authors also descri-bed differences in internal features, such as inthe thickness of the left ventricular wall, in thedisposition of the interventricular septum, in theprominence of the supraventricular crista, in theposition and thickness of the trabecula septo-marginalis, and in the shape of the trabeculaecarneae.

A look at the vascular anatomy of the pig heartIn this study, we have investigated the ana-

tomy of the arterial blood supply of the pigheart. Using vascular injection techniques, whichare adequate for detailed anatomical characteri-zations, we define here the detailed architecturalarrangement of the coronary circulation of thedomestic pig (Sus scrofa domestica). This animalspecies has several peculiar features in its coro-nary circulation, which this work documents andwhich will be discussed in a comparative man-ner with the heart of humans.

MATERIAL AND METHODS

Twenty-three hearts of adult pigs (Sus scrofadomestica) were collected at a local slaughter-house. The thorax was opened by sternotomyimmediately after the sacrifice of the animals andthe heart was removed together with the peri-cardium and large vessels.

The coronary arteries of the heart sampleswere cannulated separately through their ostia.The cannulas were secured with ligatures and,after a thorough wash with warm saline solution(NaCl 0.9% at 37ºC), the coronary arteries wereperfused with different substances.

1. Vascular resin castingThe right and left coronary arteries of 20

hearts were injected with methyl methacrylate(Tensol nr 70‚) mixed with either a red (Ciba-Geigy, Rouge Irgalithe 108) or a green (Bayer,Green Moltopren 768) pigment. These pigmen-ted resins were injected into the left and rightcoronary arteries, respectively. The injectionswere done simultaneously through both cannu-las, and at the same pressure. During the wholeprocedure, the hearts were immersed in a warmsaline bath (about 30ºC).

After vascular injection, the cannulas werewithdrawn and the aortic root was filled up withpolymer to complete the cast. When resin poly-merization was finished (approximately 10 hourslater), the hearts were immersed in a 33%hydrochloric acid bath for 2 or 3 days for diges-tion of the cardiac tissue. The vascular casts werewashed in water and dried.

M. Rodrigues, A.C. Silva, A.P. Águas and N.R. Grande

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These samples allowed the analysis of the dis-tribution of each coronary artery, of vascularterritories and of branches, including the deepestones. It also enabled the identification of inter-arterial anastomoses.

2. Injection/dissection with contrast suspension A contrast mixture (barium sulphate + jelly +

saline solution) was injected in the coronaryarteries of 3 of the hearts. The mixture injectedin the right coronary artery also contained greypigment (“Pelikan” Drawing Ink‚), to facilitaterecognition of its branches.

During this procedure, the hearts were keptin a warm bath (about 30ºC). Immediately afterthe injection, the samples were cooled down to0-4ºC, for polymerization of the contrast mixture.The hearts were then fixed by immersion in a10% formaldehyde solution.

Two weeks later, the hearts were studied by X-ray, followed by dissection and were photograp-hed. The dissection was performed after carefulremoval of the epicardium and adipose tissue.

Using this technique, it was possible to gain aradiographic view of the vascular casts of the coro-nary arteries and, at the same time, to study thesuperficial distribution of each of the coronaryarteries. Because in these preparations the tissueswere not corroded, the walls of the heart cham-bers and the large vessels at the base of the heartwere visible, allowing the topography of the arte-rial branches to be defined and also serving as acomparative model to the corrosion vascular casts.

3. Scanning electron microscopy (SEM)For this, 3 inter-arterial anastomoses were

selected from the corrosion casts for observationunder SEM. Using a magnifying glass (Zeiss), thesmall anastomoses were cut and applied on car-bon surfaces over brass supports. For better sta-bilization, their ends were fixed using conducti-ve carbon cement (Leit-C‚, Neubauer ChemikAlien). The anastomoses were further coveredwith a thin layer of gold (JEOL-Fine Coat IonSputter-JFC-1100). The SEM equipment usedhere was model JSM-6301F from JEOL.

SEM was used to study the three-dimensionalarrangement of small arterial branches and alsofor the analysis of the endothelial surface ofanastomotic branches.

RESULTS

The data obtained by observations of vascularcasts and of angiograms of the coronary arteriesof the pig can be organized into three parame-ters: 1) territorial distribution of each coronaryartery; 2) description of the vascular course andnumber of branches, and 3) localization of thearterial anastomoses.

Vascular territories of the left (LCA) and rightcoronary arteries (RCA)

LCAComprehensive scrutiny of the samples sug-

gested that each of the coronary arteries partici-pated almost equally in the blood supply to theheart surface, to the large vessels at the base ofthe heart, and to the septa that divide the cardiacchambers. However, considering that the volumeof the wall of the left ventricle is greater than thatof the right ventricle, it may be concluded thatthe LCA supplied blood to a larger volume ofmyocardium than the RCA. The LCA suppliedmost of the left atrium and ventricle, a small por-tion of the right ventricle (adjacent to the inter-ventricular paraconal groove), and the apex ofthe heart (Figure 1A, B and C). It also suppliedthe left half of the interventricular septum and itsmost central and dorsal portion. It also contribu-ted to the supply to the atrial septum. The bran-ches of the LCA spread to the caudal wall of theaorta and to the pulmonary veins, and also to thecaudal vena cava and arterial conus. The bloodsupply to the trabecula septomarginalis was ori-ginated mainly from branches of the LCA, asoccurred with the subauricular and subatrialpapillary muscles.

RCAThis artery supplied the right atrium and ven-

tricle, the peripheral right part of the interventri-cular septum and the left ventricular wall adja-cent to the interventricular subsinuosal groove.The interatrial septum, the arterial conus, thecranial and right walls of the aorta and the wallsof both vena cava were supplied by branches ofthe RCA (Figure 1A, C and D). The major papi-llary muscle, when identified, was supplied bybranches arising from the RCA. In two samples,these branches also reached the trabecula septo-marginalis. In a few cases, the RCA participatedin the blood supply to the subatrial papillarymuscle.

2. Origin, main courses and branches of thecoronary arteries

2.1. Left coronary artery (LCA)The LCA arose from the left sinus at the aor-

tic bulbus, above the left semilunar valve. Onaverage, it measured 4 mm in diameter and wasusually wider than the RCA (Table 1).

The LCA ran under the left auricle, betweenthe left atrium and the pulmonary trunk.Having reached the coronary groove, the LCAdivided into two strong vessels: the interventri-cular paraconal branch (which followed thegroove of the same name) and the left circum-flex branch (running in the left part of thecoronary groove) (Figure 2A). In most samples,the first branch was slightly wider than the lat-ter. They had the same diameter in only 4 out


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Fig. 1.- Pig heart injected with contrast suspension. The left coronary artery is in white and the right coronary artery is in grey. A- Auricularsurface; B- Caudal border; C- Atrial surface; D- Cranial border.Ao- Aorta; PT- Pulmonary Trunk; rA- Right Auricle; lA- Left Auricle; RA- Right Atrium; LA-Left Atrium; RV- Right Ventricle; LV- LeftVentricle.

of 23 hearts. The ventricular and atrial bran-ches ran first under the epicardium, and laterpenetrated the myocardium (Figure 2B). Allthese epicardial vessels gave off smaller myo-

cardial branches, usually at right angles, whichbranched extensively into a dense three-dimensional capillary network. We now focus

our observations mainly on the epicardial bran-ches (Diagram 1).

2.1.1. Interventricular paraconal branchThis is a wide vessel with a wavy course

along the whole of the paraconal groove. Inmost of the samples (20 out of 23 hearts), it rea-ched the apex and then changed its course obli-quely to the other surface (atrial) of the heart.Along its course, it gave off 3 collateral branches– right ventricular, left ventricular and left septal,as seen in Table 2 (Figure 3).

The right ventricular branches were the thin-nest and shortest of these branches; they spreadover the right ventricular wall adjacent to theparaconal groove. The first right ventricularbranch is called the left branch of the arterialconus, but it infrequently reached this structureand was only observed in 3 out of 23 hearts. Theleft ventricular branches were thick and long and


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Fig. 2.- Corrosion casts of coronary arteries in the pig. A- Base of the heart; B- Auricular surface.LCA- Left Coronary Artery; IVP- Interventricular Paraconal branch; LC- Left Circumflex branch; RCA- Right Coronary Artery; RV- RightVentricular branch; LV- Left Ventricular branch; A- Atrial branch; V- Ventricular branch.

Table 1.- Differences in diameter observed between left and rightcoronary arteries.LCA- Left Coronary Artery; RCA- Right Coronary Artery.

ran obliquely, parallel to the muscle fibers,towards the left ventricular border. A diagonalbranch was seldom observed. The left septalbranches were numerous, uniform and short. Intheir transversal or oblique course to the inter-ventricular septum, they ramified extensively,making them broader than the right ventricularbranches.

The first left septal branch was larger andmuch longer than all the others. It was calledthe interventricular septal branch, and it aroseclose to the end of the LCA. It followed on obli-quely towards the apex of the heart, supplyingthe most dorsal and central part of the interven-tricular septum, while the other left septal bran-ches supplied its left peripheral portion, close tothe paraconal groove (Figure 4). In 3 out of 20hearts, the interventricular septal branch wasnot identified, so that part of the interventricularseptum was supplied instead by the atrioventri-cular branch (coming from the RCA). In onesample, two interventricular septal brancheswere identified.

Besides spreading to the interventricular sep-tum, the interventricular septal branch gave off atrabecular branch that followed the trabeculaseptomarginalis (Figure 5). This branch was thinand was identified in 13 out of 20 hearts. In 2hearts, there was a contribution from the bran-ches of the RCA to the blood supply of the tra-becula septomarginalis.


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Diagram 1.- Branches of the Left Coronary Artery. IV- Interventricular; RV- Right Ventricular; LS- Left Septal;LV- Left Ventricular; LA- Left Atrium; LV- Left Ventricle;Prox.- Proximal; Interm.- Intermediate.

Fig. 3.- Auricular surface of corrosion cast of coronary arteries inthe pig.IVP- Interventricular Paraconal branch; RV- Right Ventri-cular branch; LV- Left Ventricular branch.

Fig. 4.- Cranial border of corrosion cast of coronary arteries inthe pig.

Fig. 4.- IVP- Interventricular Paraconal branch; IVS- InterventricularSeptal branch; LS- Left Septal branch.

Fig. 5.- Corrosion cast of coronary arteries in the pig.Fig. 5.- IVP- Interventricular Paraconal branch; IVS- Interventricular

Septal branch; T- Trabecular branch.

Table 2.- Variations in number of branches emerging from theInterventricular Paraconal Branch.

2.1.2. Left circumflex branchThis artery was quite long, although slightly

shorter than the interventricular paraconalbranch. Initially covered by the left auricle, theleft circumflex branch followed the coronary gro-ove caudally and crossed the left ventricular bor-der to reach the atrial surface of the heart. Alongits course, it gave off several branches and endedclose to the origin of the interventricular subsi-nuosal groove. The collateral branches of the leftcircumflex branch can be classified as atrial andventricular (Table 3). According to their originand distribution, the left atrial branches arenamed proximal (located on the auricular surfa-ce), intermediate (close to the left border) anddistal (on the atrial surface) (Figure 6).

The proximal branches to the left atrium(Figure 6A) were single or multiple. They werethe widest and longest of the atrial branches.When they were multiple, the first branch wasalways the largest. The proximal branches sup-plied mainly the left auricle, the dorsal surface ofthe left atrium, and usually the pulmonary veinstoo. In 4 out of 23 hearts, the proximal branchbifurcated: one branch reaching the left atriumand the other running between the aorta and thebase of the left atrium to finish at the most cau-dal part of the right atrium, at the interatrial sep-tum and at the vena cava. There was usually onesingle intermediate atrial branch (Figure 6A).When this branch was absent, it was replaced byother atrial branches. The intermediate atrialbranch supplied the caudal-most area of the left

atrium and then sometimes continued to theauricle. In 8 out of 23 hearts, it also contributedto the blood supply of the pulmonary veins. Thedistal atrial branches (Figure 6B) were the thin-nest and shortest of the atrial branches. Theywere usually multiple. These vessels spread tothe base of the atrium, but could also run dor-sally to the pulmonary veins (observed in 6hearts) or to the caudal vena cava and interatrialseptum (in 8 samples).

The left ventricular branches, classified asproximal, of the left ventricular border and distalwere wider and more numerous than the corres-ponding atrial branches (Figure 7). The proximalbranches to the left ventricle (Figure 7A) werelarge and long. They ran obliquely towards thecaudal border and apex of the heart, supplyingthe dorsal-most part of the auricular surface ofthe left ventricle. They were longer when run-


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Fig. 6.- Corrosion casts of coronary arteries in the pig. A- Auricular surface; B- Atrial surface.LC- Left Circumflex branch; PLA- Proximal branch to Left Atrium; ILA- Intermediate branch to Left Atrium; DLA- Distal branch to LeftAtrium.

Table 3.- Frequency of the number of branches emerging from theLeft Circumflex Branch.

Table 3.- ++ More common; + Less common; - Not observed.

ning parallel to the muscle fibers and to the leftventricular branches from the interventricularparaconal branch. In 4 out of 23 hearts, the pro-ximal branch to the left ventricle was very large,as the circumflex branch continued as a proxi-mal branch to the left ventricle and gave offanother branch which followed the caudal partof the coronary groove. The branch to the leftventricular border (Figure 7A) followed the cau-dal border of the heart towards the apex, butnever reached it. It was large and, in 3 samples,it was actually the continuation of the left cir-cumflex branch itself. When this branch wasabsent, the left ventricular border was suppliedby the proximal branch to the left ventricle. Thedistal branches to the left ventricle (Figure 7B)were usually shorter and thinner and suppliedthe left ventricular wall between the left ventri-cular border and the interventricular subsinuosalgroove, i.e., the atrial surface of the left ventricle.In 5 out of 23 hearts, one of these branches waswider as it continued and ended the left circum-flex branch.

2.2. Right coronary artery (RCA)The right coronary ostium was located at the

right sinus of the aortic bulbus, above the rightsemilunar valve. In one of the hearts, two rightcoronary ostia were identified.

The RCA ran between the right atrium and thebase of the pulmonary trunk and then followedthe right part of the coronary groove until it rea-ched the interventricular subsinuosal groove.The length of the RCA was similar to that of theleft circumflex branch. When one of these bran-

ches was shorter, the other ran a longer distanceon the coronary sulcus.

Once the interventricular subsinuosal groovehad been reached, the RCA gave off a shortatrioventricular branch to the septa and thencontinued as an interventricular subsinuousbranch descending along this groove (Figure8A). Like the left circumflex branch, the RCAgave off two types of branches: to the rightatrium and to the right ventricle wall, as seen inTable 4 (Figure 8B, Diagram 2).

The right atrial branches were ascendant andvery thin (Figure 9). The first one, called the pro-ximal branch to the right atrium, was usuallywider (Figure 9A and B). It was either single ordouble. When absent, it was compensated byother branches. This branch supplied the rightauricle and in most cases ran dorsally betweenthis auricle and the walls of the aorta to spreadover the cranial vena cava (in 13 samples), thepulmonary veins (in 6 samples) and the caudalvena cava (in 4 samples). In 5 hearts, it also sup-plied the interatrial septum. The intermediateatrial branch (Figure 9A and B) was also single ordouble. It spread mainly over the cranial-mostwall of the right atrium and then sometimes rea-ched its auricle. In some cases (4 hearts), it ranalong the cranial wall of the aorta to give off bran-ches to the cranial vena cava. The distal atrialbranches (Figure 9A and B) were very thin. Theyspread over the base of the right atrium and, in 8samples, they also supplied the cranial vena cava.

The right ventricular branches were largerthan the atrial ones, but not as much as the left


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Fig. 7.- Corrosion casts of coronary arteries in the pig. A- Auricular surface; B- Caudal Border.LC- Left Circumflex branch; PLV- Proximal branch to Left Ventricle; LVB- branch to Left Ventricular Border; DLV- Distal branch to LeftVentricle.

ventricular branches (Figure 10). The rightbranch to the conus arteriosus (Figure 10A andB), unlike the left one, was easily identified, spre-ading to the right side of this structure. The pro-ximal branch to the right ventricle (Figure 10Aand B), slightly wider than the branch to theconus arteriosus, supplied the auricular surface ofthe right ventricle. In 7 hearts, these two bran-ches arose together from the right coronaryartery. The branch to the right ventricular border(Figure 10A) was quite large and sometimes dou-ble. It extended towards the apex of the heartwithout reaching it. The distal branches to theright ventricle (Figure 10C), usually multiple,short and thin, supplied a small area between theright ventricular border and the interventricularsubsinuosal groove, i.e., the dorsal-most part ofthe right ventricle wall on the atrial surface.

As stated above, the RCA gave off an atrio-ventricular branch before continuing as an inter-ventricular subsinuous branch on this groove.

2.2.1. Atrioventricular branchThe atrioventricular branch was very thin, but

usually easy to recognize (except in 2 heartswhere it was indistinct from the other right sep-tal branches). The atrioventricular branch turnedmedially towards the septa and/or continuedcaudally for a short course on the coronary gro-ove. It divided into 2 or 3 thinner branches toparticipate in the blood supply to both the inter-ventricular and interatrial septa and also to asmall part of the dorsal wall of the left ventricle


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Fig. 8.- Corrosion casts of coronary arteries in the pig. A- Base of the heart; B- Atrial surface.RCA- Right Coronary Artery; AV- Atrioventricular branch; IVS- Interventricular Subsinuous branch; A- Atrial branch; V- Ventricularbranch; RV- Right Ventricular branch; LV- Left Ventricular branch.

Table 4.- Frequency of the number of branches arising from theRight Coronary Artery.

Table 4.- ++ More common; + Less common; - Not observed.

Diagram 2.- Branches of the Right Coronary Artery. AV- Atrioventricular; IV- Interventricular; LV- Left Ventricular;RS- Right Septal; RV- Right Ventricular; RA- Right Atrium; RV-Right Ventricle; Prox.-Proximal; R- Right; Art.- Arterial.


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Fig. 9.- Corrosion casts of coronary arteries in the pig. A- Base of the heart; B- Cranial Border.RCA- Right Coronary Artery; PRA- Proximal branch to Right Atrium; IRA- Intermediate branch to Right Atrium; DRA- Distal branchto Right Atrium.


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Fig. 10.- Corrosion casts of coronary arteries in pig. A- Cranial Border; B- Base of the heart; C- Atrial Surface.Fig. 10.- RCA- Right Coronary Artery; IVS- Interventricular Subsinuous branch; rCA- Right branch to Conus Arteriosus; PRV- Proximal branch

to Right Ventricle; RVB- branch to Right Ventricular Border; DRV- Distal branch to Right Ventricle.

close to the coronary groove (Figure 11). At leastin 2 hearts, it also gave off a branch to the cau-dal vena cava.

2.2.2. Interventricular subsinuous branchThis branch was wide and was the continua-

tion of the RCA, describing a wavy course alongthe interventricular subsinuosal groove andending close to the apex of the heart. Thisbranch was always shorter than the interventri-cular paraconal branch. In fact, the shorter theinterventricular subsinuous branch, the longerthe other one.

Like the interventricular paraconal branch,the interventricular subsinuous branch gave off3 types of divisions: the right ventricular, leftventricular and right septal branches, as seen inTable 5 (Figure 12). The right ventricular bran-ches (Figure 12A) were usually the largest andran obliquely to the right ventricular border,supplying this wall of the right ventricle. Theleft ventricular branches (Figure 12A) wereshorter and thinner. They coursed towards theleft ventricular border. In most cases, they hada distal origin at the interventricular subsinuousbranch. Proximally, the dorsal wall of the left


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Fig. 11.- Corrosion cast of coronary arteries in the pig - base of theheart.

Fig. 11.- RCA- Right Coronary Artery; IVS- InterventricularSubsinuous branch; AV- Atrioventricular branch.

Fig. 12.- Corrosion casts of coronary arteries in pig. A- Atrial Surface; B- Caudal Border.Fig. 12.-RCA- Right Coronary Artery; AV-Atrioventricular branch; IVS- Interventricular Subsinuous branch; LV- Left Ventricular branch; RV-

Right Ventricular branch; RS- Right Septal branch.

ventricle was supplied either by the distal ven-tricular branches (in 10 hearts) or by divisionsfrom the atrioventricular branch (in 4 hearts).The right septal branches (Figure 12B) weremore uniform and numerous. They plungedinto the interventricular septum to supply itsright peripheral part. They were as short andramified as their counterparts, the left septalbranches.


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Fig. 13.- Corrosion casts of coronary arteries in pig.Fig. 13.- A- Anastomosis between one Distal branch to Left Ventricle and one Right Septal branch at the subatrial papillary muscle; B-

Anastomosis between the branch to Left Ventricular Border and one Right Septal branch at the subatrial papillary muscle

Table 5.- Variations in the number of branches emerging from theInterventricular Subsinuous Branch.

3. Inter-arterial anastomoses

3.1. Corrosion castsThe anastomoses between the branches of

the RCA and LCA were thin but macroscopicallyvisible (Figure 13). They did not occur betweenthe main branches from the coronary arteries,but between thinner branches. Each heart pre-sented on average 2 anastomoses. In 2 samples,we identified 4 anastomoses in each. Only inone heart were these inter-arterial connectionsnot recognized.

Most of these anastomoses occurred betwe-en the branches that supplied the papillarymuscles. Thirty per cent of all anastomoseswere observed between branches to the suba-trial papillary muscle at the left ventricle (leftventricular branches connecting to right septalbranches) (Figure 13A and B). At the majorpapillary muscle, in the right ventricle, theanastomoses occurred between the trabecularbranch and the right ventricular branches (20%of the total of anastomoses identified) (Figure13C and D).


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Fig. 13.- C and D- Anastomosis between the Trabecular branch and the branch to the Right Ventricular Border at the major papillary muscle

Another 20% were connections between theatrioventricular branch and other branches:namely, the interventricular septal branch, thetrabecular branch and the distal branches to theleft ventricle (Figure 13E). Other less commonanastomoses were observed between oppositeatrial branches and between opposite septalbranches.

3.1.1. Blood supply to papillary musclesBecause most of the anastomoses occurred

on the papillary muscles, it seemed importantto describe their blood supply. The branchesthat most commonly supplied each papillarymuscle were identified and percentages werecalculated.

At the left ventricle, the subauricular papillarymuscle was supplied by left ventricular branchesfrom the interventricular paraconal branch (65%)or by proximal branches to the left ventricle(35%). The subatrial papillary muscle was sup-plied by right septal branches (45%), by the endof the left circumflex branch (25%), by distalbranches to the left ventricle (20%), by thebranch to the left ventricular border (4%), by theinterventricular septal branch (3%) or even bythe atrioventricular branch (3%).

At the right ventricle, when the major papi-llary muscle was identified it was supplied by

the branch to the right ventricular border (55%),by proximal (20%) or by distal (20%) branches tothe right ventricle, or also by the end of the rightcoronary artery (5%).

3.2. Scanning electron microscopy The 3 anastomotic samples obtained from

corrosion casts were analysed. We observed thatthe diameter of the branches was always greaterthan 100 mm (between 300 and 600 mm), indica-ting that all of them were small arteries.

There was no evidence of any constrictions orsphincters on the surface of the anastomoticarea. The diameter of these branches did notshow any changes, throughout the course fromthe branch from the RCA, along the anastomoticarea, to the branch from the LCA (Figure 14).

At higher magnification, 3 different areaswere observed: one in the branch from the RCA;another in the transitional area, and another inthe branch from the LCA. In all of them, the sur-face showed longitudinal folds and sulci (Figure14: Z1, Z2 and Z3). These irregularities are evi-dence of the contraction of the wall of the arte-ries due to low viscosity of the methyl met-hacrylate. The impressions of the endothelialnuclei were always elongated, oriented parallelto the longer axis of the vessel. This feature istypical of arterial vessels.


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Fig. 13.- E- Anastomosis between the Interventricular Septal branch and the Atrioventricular branch.Fig. 13.- IVS- Interventricular Subsinuous branch; LC- Left Circumflex branch; RCA- Right Coronary Artery; IVP- Interventricular Paraconal

branch; RVB- branch to Right Ventricular Border; T- Trabecular branch; AV- Atrioventricular branch; IVS- Interventricular Septalbranch.

DISCUSSION

The present data on the microanatomy of thecoronary arterial supply of the pig heart are dis-cussed at two levels: i) comparison with pre-vious reports on the arterial supply of the pigheart; ii) major differences in heart arteries bet-ween pigs and humans.

Anatomical terms are different in Human andVeterinary Medicine. The major differencesregarding the heart arteries are that the interven-tricular paraconal branch in veterinary anatomyis always named interventricular anterior branch(or anterior descending) in human anatomy andthe interventricular subsinuous branch is alsonamed interventricular posterior branch (or pos-


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Fig. 14.- Electron micrographs of anastomosis in a corrosion cast of coronary arteries in the pig. Z1- transitional anastomotic area; Z2- branchfrom Right Coronary Artery; Z3- branch from Left Coronary Artery.

terior descending). The collateral branches havedifferent designations too, depending on theauthor, either as human or veterinary anatomists.Therefore, it does not seem very important tomention each of these terms. We chose the onesproposed by the Nomenclatura Anatomica Vete-rinaria (Simoens and De Vos, 1999) and someveterinary anatomy books: Schummer et al.(1981), Getty (1986), Ghoshal (1986), Barone(1996), Dyce et al. (1997) and Evans (1993).

1. Neither the LCA nor RCA is dominant in thesuperficial arterial supply of the pig heart in con-trast with the right dominance in the humanheart.

The meaning of dominance regarding the vas-cular territory of a coronary artery must first bedefined. In fact, some authors consider that acoronary artery is dominant when its superficialdistribution is broader, while other authors usedominance to refer to the ventricular mass sup-plied by the artery.

Concerning superficial arterial distribution,three different concepts may be considered.According to Gabella (1999), Crick et al. (1998),Weaver et al. (1986), Christidès and Cabrol (1976),and Kamimura et al. (1996), right or left domi-nance of the coronary system is given to theartery that originates the interventricular posterior(subsinuous) branch. Alternatively, Hadziselimo-vic et al. (1980) consider that the dominant arteryis the one going beyond the crossing between theinterventricular subsinuosal groove and the coro-nary groove, the so-called “cardiac cross”. Grandeet al. (1994) and Dodge et al. (1993) integratedthese definitions on proposing that there is rightdominance when the right coronary artery givesoff the interventricular posterior (subsinuous)branch and supplies the posterior (atrial) surfaceof the left ventricular wall (in this case, the left cir-cumflex branch is of a “short” type, and does notreach the cardiac cross). There is left dominancewhen the interventricular posterior (subsinuous)branch is given off by the LCA, and these authorsconsider that there is no dominance when theinterventricular posterior (subsinuous) branch ari-ses from the RCA and the left circumflex branchis “long”.

In the present study no interventricular subsi-nuous branch was seen to spring from the LCAor from any other branch following a parallelcourse to the interventricular subsinuous brancharising from the RCA. In light of this, and becau-se each coronary artery ran a similar distancealong the coronary groove and each one gaveoff an interventricular branch, regarding thesuperficial arterial supply, it may be assumedthat there is no dominance of the coronary arte-ries in the pig. This observation is in agreementwith previous observations by several authors,e.g. Barone (1996), Getty (1986), Ghoshal (1986)

and Schummer et al. (1981). In contrast, Weaveret al. (1986) and Crick et al. (1998) stated thataround 80% of domestic pigs presented rightdominance in the distribution of the coronaryarteries in the heart. A possible explanation forthis interpretation may be found in their assump-tion that there was no dominance only whenboth coronary arteries gave off branches runningalong the interventricular subsinuosal groove.

In human hearts, the studies by Hadziselimo-vic et al. (1980), Grande et al. (1994), Dodge etal. (1993), Christidès and Cabrol (1976), Barone(1996) and Lumb and Singletary (1962) reportedhigh percentages (63% a 93%) of hearts withright dominance. These authors observed thatthe RCA often gave off the interventricular pos-terior (subsinuous) branch and spread over theposterior (atrial) surface of the left ventricle.They also noticed that the left ventricular branchwas usually short, ending close to the left ventri-cular border. Interestingly, in different editionsof Gray’s classical textbook of Human GrossAnatomy (35th and 38th) there are different state-ments concerning the organization of humancoronary arteries. In fact, Williams and Warwick(35th edition) say that in the human heart theinterventricular posterior (subsinuous) brancharises most frequently from the RCA and spreadsto the right and posterior (atrial) walls of bothventricles. Later, Gabella (38th edition) states thatin most cases (70%), there is left dominance ofthe coronary arterial supply in human hearts. Inthe remaining 30%, the same author reports thatthe interventricular posterior (subsinuous)branch proceeded from both coronary arteries orcould be absent.

2. Regarding the volume of myocardium suppliedby the coronary arteries, the LCA is dominant inboth species

The LCA was usually wider and proportio-nally larger than the RCA and this differencereflected the greater left ventricular mass in com-parison to the right one in the pig heart. Weobserved that in 12 animals the LCA was widerthan the right one; only in 2 hearts was theopposite observed. The remaining 9 hearts pre-sented a LCA and a RCA of the same calibre.Considering that a higher calibre of one coronaryartery supplies a greater myocardial volume(according to Vieweg et al., 1976), then the LCAis the dominant coronary artery in the pig heart.There is also left dominance in the human heart,but it is less significant because the differencebetween the right and left ventricular masses isnot so marked in this species (Gabella, 1999;Crick et al., 1998; Ghoshal, 1986).

Studies by Elízaga et al. (1985), White andBloor (1981) and Kassab and Fung (1994) con-firm the left dominance (in terms of ventricularmass supplied) in the pig heart. All these authorsconsidered the existence of three independent


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coronary arteries (the RCA, the interventricularparaconal branch and the left circumflexbranch). In the study by White and Bloor (1981),only 38% of the heart tissue was supplied by theRCA. Kassab and Fung (1994) studied the arran-gement of the coronary capillaries in pigs. Theseauthors calculated a total number of 1187 capi-llaries arising from the RCA; 1273 capillaries fromthe interventricular paraconal branch, and 516from the left circumflex branch. These numbersdocument left coronary dominance, since addi-tion of the two last figures show that the LCAcontributes with 1789 capillaries, while the RCAonly gives off 1187.

3. The existence of a single coronary ostium isvery rare. The presence of supranumerary ostia isalso not usual in pigs, but occurs with some fre-quency in humans, especially at the right aorticsinus

Barone (1996) and Ghoshal (1986) reportedthat in some animal species, although seldom,both coronary arteries may spring from a com-mon trunk. This vascular architecture was notobserved in any of our samples.

In the human heart, Grande et al. (1982)observed some variation in the localisation ofcoronary ostia: in a total of 710 hearts, theyfound that both coronary arteries proceededfrom the same aortic sinus in 2% of cases. Gabe-lla (1999) and Santos et al. (1991) also describedrare situations in human patients in which thecoronary arteries sprung from the same sinus.

The presence of supranumerary coronaryostia is more usual than the existence of a singleostium for both coronary arteries, both inhumans and in domestic animal species (Chris-tidès and Cabrol, 1976; Gabella, 1999).

We identified two right coronary ostia in onesample, from which proceeded the right branchto the conus arteriosus and the RCA itself. Wenever recognized more than one left coronaryostia. Barone (1996), however, described “twobranches of the LCA arising side by side or veryclosely on the aorta”. That author considers thissituation very rare in domestic animal species,and never reports the possibility of supranume-rary ostia at the right aortic sinus.

In human hearts, most authors agree thatsupranumerary ostia are more commonly found atthe right than at the left aortic sinus (Gabella,1999; Edwards et al., 1981). Three different pat-terns were described by Edwards et al. (1981):one in which the right branch to the conus arte-riosus proceeded from the aorta; a second one inwhich this branch and the RCA arose from thesame ostium; and a third one in which only theRCA arose from the right aortic sinus. Regardingthe left sinus, there may be two ostia for each ofthe main branches: the interventricular anterior(paraconal) branch, and the left circumflex branch(Gabella, 1999). In their studies of 710 human

hearts, Grande et al. (1982) found two ostia in87% of cases, but they identified supranumeraryostia (3 or 4) in 12% of cases, the majority of themat the right sinus. The same authors observed oneexceptional case in which 5 ostia were present.

4. Three major differences in LCA branching bet-ween the pig and human heart

Our observations in the distribution of thecollateral branches of the LCA in the pig revea-led 3 major differences in comparison with theirorganization in humans:

a.- Absence of the left branch to the conus arte-riosus in the pig. This branch was described byBarone (1996) and Schummer et al. (1981), but inour study it was only recognized in 3 of thehearts. This left branch to the conus arteriosus isnot mentioned in the Nomenclatura AnatomicaVeterinaria (Simoens and De Vos, 1999). Inhumans, however, the prevalence of this branchis quite high (Christidès and Cabrol, 1976). Gran-de et al. (1994) identified two left branches to theconus arteriosus in all of 70 hearts.

b.- Lack of a distinct diagonal branch in thepig hearts, as reported by Barone (1996). Weobserved that this branch could be double or tri-ple, or mingled with the rest of the ventricularbranches due to their similar caliber. TheNomenclatura Anatomica Veterinaria (Simoensand De Vos, 1999) does not report any diagonalbranches. Schummer et al. (1981) consider thatthere are two larger ventricular branches and callthem proximal and distal collateral branches.

Diagonal branches of the LCA are usuallyconsidered in the human heart. The Nomencla-tura Anatómica Humana (Feneis and Dauber,2000) calls them lateral branches. Dodge et al.(1993) and Christidès and Cabrol (1976) considerthat these branches include the two or three firstleft ventricular branches from the interventricularanterior (paraconal) branch and they are thewidest and longest. On the other hand, Grandeet al. (1994) described a diagonal branch as theone arising from the LCA when it ends as a tri-furcation. Grande et al. (1994) and Gabella(1999) identified this branch in 33-50% of cases.

c - The length of the left circumflex branch.This branch had a very constant length: alwaysthe “long” type in the pig heart. It gave off distalatrial and ventricular branches and usuallyended at the cardiac cross. This branch neverfollowed the interventricular subsinuous groove.

In contrast, in humans this branch is not cons-tant in terms of length. It may end close to theventricular border (in most cases) or reach andfollow the interventricular posterior (subsinuous)branch (Gabella, 1999; Barone, 1996; Grande etal., 1994; Dodge et al., 1993; Hadziselimovic etal., 1980; Christidès and Cabrol, 1976, Lumb andSingletary, 1962). Christidès and Cabrol (1976)identified distal branches to the left atrium inonly 50% of cases, explained by the shortness of


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the left circumflex branch. For the same reason,the Nomenclatura Anatómica Humana (Feneisand Dauber, 2000) also reports that the distalbranches to the left ventricle are not constant.

It seems relevant to point out the importanceof the interventricular septal branch arising fromthe LCA. The Nomenclatura Anatomica Veterina-ria (Simoens and De Vos, 1999) and Barone(1996) do not mention any interventricular sep-tal branch in the pig heart. Christensen and Cam-peti (1959), quoted by Ghoshal, 1986 andSchummer et al. (1981) are the only authors whodistinguished it from the other left septal bran-ches. They report that it spreads to the centralpart of the interventricular septum.

We found that the interventricular septalbranch is responsible for more than one third ofthe blood supply of the septum, especially itsmost dorsal and central part. The other left sep-tal branches supplied the left periphery and api-cal part of the septum. The remaining part of theinterventricular septum was supplied by divi-sions from the interventricular subsinuousbranch and atrioventricular branch. The LCAthus had a higher contribution (60 to 80%) to theblood supply of the septum compared to that ofthe RCA (Barone, 1996; Weaver et al., 1986).

This branch is present in human hearts andhas a similar distribution. It is mentioned byseveral authors (Dodge et al., 1993; Christidèsand Cabrol, 1976; Williams and Warwick, 1973;Lumb and Singletary, 1962).

5. Three major differences in RCA branching bet-ween the pig and human heart.

Regarding the RCA and in agreement with theNomenclatura Anatomica Veterinaria (Simoensand De Vos, 1999), Barone (1996) and Getty(1986), we did not consider a right circumflexbranch. We describe the course of the RCA asbeginning in the aortic sinus, following the rightpart of the coronary groove until it bifurcates inan atrioventricular branch and an interventricularsubsinuous branch. However, Schummer et al.(1981) describe a right coronary artery arisingfrom the right aortic sinus, its right circumflexbranch that first follows the right part of thecoronary groove and then as an interventricularsubsinuous branch through this groove until theapex of the heart.

We identified two differences between thebranches of the RCA in pigs and humans:

a.- The collateral branches of the RCA are lessdeveloped than those from the LCA in the pig.This situation also occurs in humans (Barone,1996), although the difference between the rightand left ventricular mass is not as significant asin the pig.

b.- The extent of the atrioventricular branch. Inthe pig, it spreads only to a restricted area closeto the cardiac cross while in humans it usuallycontinues along the coronary groove, almost rea-

ching the left ventricular border. Barone (1996)reports that the atrioventricular branch is almostrudimentary in pigs in comparison with humans.

With the exception of Schummer et al. (1981),most authors do not mention that in pig heartsthe atrioventricular branch, besides spreading toboth interatrial and interventricular septa, alsobranches over the adjacent left ventricular wall.Our observations also revealed that in at leasttwo hearts the atrioventricular branch gave off abranch to the caudal vena cava.

Another particular feature not mentioned inprevious studies is the fact that the proximalbranch to the right ventricle could arise from acommon branch with the right branch to theconus arteriosus. We identified this commontrunk in 30% of the pig hearts studied.

6. As in humans, the inter-coronary anastomosesin the pig are common. They usually occur sub-endocardially

In the pig heart, anastomoses were multipleand small, usually involving small arterioles. Inmore than 70% of the samples, these anastomo-ses occurred sub-endocardially, especially bet-ween branches that supplied the papillary mus-cles and the interventricular septum. The other30% were more superficial anastomoses: betwe-en opposite atrial branches, or between theatrioventricular branch and distal branches to theleft ventricle.

In contrast with our observations, Stowe et al.(1978), Schaper et al. (1990), Sakai et al. (1985)and Elízaga et al. (1985) claim that inter-coronaryanastomoses in the pig are virtually inexistentbecause they are capillary connections. This con-clusion was probably based on observationsdone epicardially, where there are only a fewand very small anastomoses in the pig. Dyce etal. (1997), Barone (1996), Schummer et al. (1981)and Fedor et al. (1978) support our results. Baro-ne (1996) reports that in most species the distri-bution of branches from coronary arteries is of aterminal type, i.e., their final divisions presentvery thin, almost microscopic anastomoses. Inthe pig, however, this author defends the notionthat they are macroscopic and numerous.Schummer et al. (1981) and Fedor et al. (1978)add that they are more common between smallbranches of sub-endocardial arteries.

In their study of coronary capillary arrange-ment in pigs, Kassab and Fung (1994) identifiedseveral types of connections. The most interes-ting one was the H type, which allows the fluidsin two parallel vessels to communicate. Theyreported that these anastomoses are very impor-tant and serve different functions: they make thedistribution pressure in the capillary networkmore uniform; they may affect the transport ofoxygen if there are countercurrent flows prevai-ling; and they may serve as a mechanical sup-port for capillaries during ventricular contraction.


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Christidès and Cabrol (1976) and Reig-Vilallongaet al. (1988) suggest that these anastomosesbecome functional only when the system is uns-table, i.e., when one coronary system is defi-cient, these connections allow the blood to flowfrom the other coronary artery.

Hadzziselimovic and Secerov (1979) studied alltypes of anastomoses (inter-arterial, intra-arterial,arterio-venous and veno-venous) in 100 humanhearts. They identified inter-arterial anastomosesin 33% of cases, but they did not mention theirposition. Gabella (1999) reports the existence ofanastomoses at all levels: sub-epicardial, myo-cardial and sub-endocardial. Although some ofthe techniques used were not the most appro-priate, several other studies in human heartsmention anastomoses at the cardiac cross, at theapex, and at the conus arteriosus (Williams andWarwick, 1973; Christidès and Cabrol, 1976;Hadzziselimovic et al., 1980). Christidès andCabrol (1976) and Reig-Vilallonga et al. (1988)also identified anastomoses between right andleft septal branches. Reig-Vilallonga et al. (1988)examined 100 human hearts and recognizedinter-coronary anastomoses in 96 of them, ofwhich 76% were located at the supraventricularcrest. This study reinforces the similarity betwe-en the hearts of pigs and humans, provided thatmost of the connections happen between sub-endocardial branches, as we observed in ourstudy of the pig heart.

The fact that the anastomoses identified by uswere located mostly at the papillary muscles issomewhat intriguing. This prompted us to per-form a more detailed analysis of the bloodsupply to these structures. With the exception oftwo articles (Teixeira Filho et al., 2001 andLorenz and Guski, 1990), this issue does notseem to be addressed. The first authors studiedthe blood supply to the papillary muscles inoxen and the second authors examined the exis-ting vessels at the trabecula septomarginalis inpigs, goats and oxen.

From comparison of the vascular anatomy ofthe pig and human heart, it may be concludedthat the similarities are greater than the differen-ces in the anatomical arrangement of the coro-nary arteries. The most important similarities are:

• The myocardial volume supplied by theLCA is higher and therefore dominant as compa-red to the RCA;

• The coronary arteries arise from the aorticbulbus in a similar way in both species;

• The LCA is very short and divides into aninterventricular paraconal (anterior) branch anda left circumflex branch. These latter give offcollateral branches, mainly to the left atrium andventricle;

• The interventricular paraconal (anterior)branch gives off proximally a wider left septalbranch, the interventricular septal branch, which

spreads to the most dorsal and central part of theseptum;

• The RCA supplies mainly the right atriumand ventricle, always continuing as an interven-tricular branch in the pig and, in most cases, alsoin humans;

• The atrioventricular branch supplies a smallarea of the interventricular septum, dorsally andto the right;

• The anastomoses between the branches fromthe coronary arteries are common and occur bet-ween small arteries, usually sub-endocardially.

From the differences between the coronarycirculation in the pig and in humans, we pointout the following:

• In the pig, each of the coronary arteriesruns a course of a similar length and gives off aninterventricular branch. In humans, however, thelength and origin of the interventricular posterior(subsinuous) branch are highly variable;

• There is right coronary dominance in mosthuman hearts, but there is no dominance in thehearts of pigs as regards to the surface distribu-tion of the coronary arteries;

• In the pig, the right atrial and ventricularbranches are less developed than their counter-parts, the left atrial and ventricular branches. Inhumans, this difference is not so clear;

• It is not possible to recognize diagonalbranches or left branches to the conus arteriosusin the pig.

We may therefore conclude that, from a strictlyanatomical point of view, it is not possible to findimportant reasons for objecting to the compatibi-lity between the hearts of these two species. Onthe other hand, the type of coronary dominancepresent in a specific human heart and the calibresof its coronary arteries should be analysed whenconsidering the need for xenotransplantation of apig heart to a human patient.

ACKNOWLEDGEMENTS

The authors are grateful to Dr M. Costa, Mr E.Monteiro and Mr C. Frias for the expert technicalassistance; Mr D. Monteiro for the artwork, and DrA. Roldão for photographic work. This researchwas funded by the FCT.

REFERENCES

BARONE R (1996). Angiologie. In: Anatomie comparée desmammifères domestiques. Vigot Frères, Paris, 5: 5-443.

CHRISTIDÈS C and CABROL C (1976). Anatomie des artèrescoronaires du cœur. Lafarge, Paris, pp 9-119.

COOPER DK, KEOGH AM, BRINK J, CORRIS PA, KLEPETKO W,PIERSON RN, SCHMOECKEL M, SHIRAKURA R and WARNER SL(2000). Report of the Xenotransplantation AdvisoryCommittee of the International Society for Heart andLung Transplantation: the present status of xenotrans-


86

plantation and its potential role in the treatment of end-stage cardiac and pulmonary diseases. J Heart LungTransplant, 19: 1125-1165.

COOPER DKC (1996). Xenotransplantation – State of the Art.Front Biosci, 1: d248-265.

COOPER DKC, GOLLACKNER B and SACHS DH (2002). Will thepig solve the transplantation backlog? Annu Rev Med,53: 133-147.

CRICK SJ, SHEPPARD MN, HO SY, GEBSTEIN L and ANDERSON RH(1998). Anatomy of the pig heart: comparisons with nor-mal human cardiac structure. J Anat, 193: 105-119.

DODGE JT JR, BROWN BG, BOLSON EL and DODGE EHT (1993).Diâmetro do lúmen de artérias coronárias humanas nor-mais. Circulação, 13: 111-130.

DYCE KM, SACK WO and WENSING CJG (1997). O SistemaCardiovascular. In: Tratado de Anatomia Veterinária,2nd edition. Guanabara Koogan S.A., Rio de Janeiro, pp171-179.

EDWARDS BS, EDWARDS WD and EDWARDS JE (1981). Aortic ori-gin of conus coronary artery. Evidence of postnatalcoronary development. Br Heart J, 45: 555-558.

ELÍZAGA J, GARCÍA DORADO D, GALIÑANES M, SOLARES J and FER-NÁNDEZ AVILÉS F (1985). Estudio cuantitativo de las dife-rencias en los territorios de distribución de las arteriascoronarias epicárdicas en el perro y en el cerdo. Rev EspCardiol, 38: 348-350.

EVANS HE (1993). The Heart and Arteries. In: Miller’s Ana-tomy of the Dog, 3rd edition. W.B. Saunders Company,Philadelphia, pp 586-601.

FEDOR JM, MCINTOSH DM, REMBERT JC and GREENFIELD JC JR(1978). Coronary and transmural myocardial blood flowresponses in awake domestic pigs. Am J Physiol, 235:H435-444.

FENEIS H and DAUBER W (2000). Corazón e Arterias. In:Nomenclatura anatómica ilustrada, 4th edition. MassonS.A., Barcelona, pp 184-193.

GABELLA G (1999). Cardiovascular System. In: Gray’s Ana-tomy, 38th edition. Churchill Livingstone, London, pp1505-1510.

GETTY R (1986). Generalidades sobre o coração e os vasossanguíneos. In: Sisson/Grossman Anatomia dos ani-mais domésticos, 5th edition. Guanabara Koogan, Riode Janeiro, 1; 153-162.

GHOSHAL NG (1986). Coração e artérias do suíno. In: Sis-son/Grossman Anatomia dos animais domésticos, 5th edi-tion. Guanabara Koogan, Rio de Janeiro, 2; 1224-1227.

GRANDE N, CASTELO BRANCO N and RIBEIRO A (1982). Coro-nary arterial circulation in the Bantu. Ohio Acad Sci, 82:146-151.

GRANDE NR, TAVEIRA D, SILVA AC, PEREIRA AS and ÁGUAS AP(1994). Anatomical basis for the separation of four car-diac zones in the walls of human heart ventricles. SurgRadiol Anat, 16: 355-361.

HADZ ISELIMOVIC H and SECEROV D (1979). Superficial anasto-moses of blood vessels in the human heart. Acta Anat(Basel), 104 (3): 268-278.

HADZISELIMOVIC H, DILBEROVIC F and OVCINA F (1980). Bloodvessels of the human heart: coronarography and dissec-tion. Acta Anat, 106: 443-449.

HAMMER C (1998). Physiologic obstacles after xenotrans-plantation. Ann N Y Acad Sci, 862: 19-27.

HAMMER C (2001). Xenotransplantation: perspectives andlimits. Blood Purif, 19: 322-328.

IGAZ P (2001). Recent strategies to overcome the hyperacu-te rejection in pig to human xenotransplantation. Yale JBiol Med, 74: 329-340.

KAMIMURA R, SUZUKI S, NOZAKI S, SAKAMOTO H, MARUNO H andKAWAIDA H (1996). Branching patterns in coronary arteryand ischemic areas induced by coronary arterial occlu-sion in the CLAWN miniature pig. Exp Anim, 45: 149-153.

KASSAB GS and FUNG YC (1994). Topology and dimensionsof pig coronary capillary network. Am J Physiol, 267:H319-325.

LORENZ G and GUSKI H (1990). Histotopographic and morp-hometric studies of the intramural coronary arteries inthe trabecula septomarginalis of swine and pigmy goats.Zentralbl Allg Pathol, 136: 87-95.

LUMB G and SINGLETARY HP (1962). Blood supply to the atrio-ventricular node and bundle of His: a comparative studyin pig, dog, and man. Am J Pathol, 41: 65-71.

PLATT J, DISESA V, GAIL D and MASSICOT-FISHER J (2002).Recommendations of the National Heart, Lung, andBlood Institute Heart and Lung XenotransplantationWorking Group. Circulation, 106: 1043-1047.

REIG-VILALLONGA J, LONCAN-VIDAL MP and DOMENECH-MATEU

JM (1988). Coronary arterial anastomoses. Study of theirdistribution in adult hearts specially emphasizing thecrista supraventricularis. Anat Anz, 166: 285-295.

SAKAI K, WATANABE K and MILLARD RW (1985). Defining themechanical border zone: a study in the pig heart. Am JPhysiol, 249: H88-94.

SAMSTEIN B and PLATT JL (2001). Physiologic and immunolo-gic hurdles to xenotransplantation. J Am Soc Nephrol,12: 182-193.

SCHAPER W, SHARMA HS, QUINKLER W, MARKERT T, WUNSCH Mand SCHAPER J (1990). Molecular biologic concepts ofcoronary anastomoses. J Am Coll Cardiol, 15: 513-518.

SCHUMMER A, WILKENS H, VOLLMERHAUS B and HABERMEHL KH(1981). Heart. In: Nickel R, Schummer A, Seiferle E(eds). The Anatomy of the Domestic Animals. Springer-Verlag, New York, 3; 15-70.

SIMOENS PJ and DE VOS NR (1999). Angiologia. In: Nomen-clatura Anatômica Veterinária Ilustrada. Manole Ltda,São Paulo, pp 234-243.

STOWE DF, MATHEY DG, MOORES WY, GLANTZ SA, TOWNSEND

RM, KABRA P, CHATTERJEE K, PARMLEY WW and TYBERG JV(1978). Segment stroke work and metabolism dependon coronary blood flow in the pig. Am J Physiol, 234:H597-607.

TEIXEIRA FILHO A, ROLL C, SOARES CL and CARAMBULA SF(2001). The blood supply of the papillary muscles of theleft ventricle in the Hereford cattle. Ital J Anat Embryol,106: 293-298.

VIEWEG WV, ALPERT JS and HAGAN AD (1976). Caliber anddistribution of normal coronary arterial anatomy. CathetCardiovasc Diagn, 2: 269-280.

WEAVER ME, PANTELY GA, BRISTOW JD and LADLEY HD (1986).A quantitative study of the anatomy and distribution ofcoronary arteries in swine in comparison with other ani-mals and man. Cardiovasc Res, 20: 907-917.

WHITE FC and BLOOR CM (1981). Coronary collateral circu-lation in the pig: correlation of collateral flow with coro-nary bed size. Basic Res Cardiol, 76: 189-196.

WILLIAMS PL and WARWICK R (1973). Angiology. In: Gray’sAnatomy, 35th edition. Jarrold and Sons Ltd, Norwich,pp 616-619.

ZHANG Z, BÉDARD E, LUO Y, WANG H, DENG S, KELVIN D andZHONG R (2000). Animal models in xenotransplantation.Exp Opin Invest Drugs, 9: 1-17.


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