JOURNAL OF SURGICAL RESEARCH 13, 24-27 (1972)

CEREBRAL ISCHEMIA DURING CARDIAC RESUSCITATION

DAVID YASHON, M.D., GEORGE E. LOCKE, M.D., DUANE DONOVAN, M.D., AND

WILLIAM E. HUNT, M.D.

CARDIAC MASSAGE HAS BEEN SHOWN EXPERIMENTALLY and clinically to be effective in maintaining circulation [4, 8, 91. Although cardiac resuscitation, both open and closed, is routinely performed in emergency conditions, the extent of cerebral ischemia during prolonged manual circulatory support has not been investigated. Viability of the brain and spinal cord are of prime importance during cardiac arrest since the central nervous system to a great extent determines quality of survival. Maintenance of adequate cerebro- vascular perfusion is a requisite because the existing disease in a compromised somatic organ may be transient or therapeutically re- versible.

Glucose is the primary substrate in suste- nance of cerebral biochemical processes. During homeostatic conditions glucose is metabolized via t,he Emden-Meyerhoff and Krebs’ path- ways with production of energy. Lactate accu- mulates consequent to ischemia and is an ex- cellent indicator of extent of oxygen debt [6]. Normally little or no lactate is produced [5].

In a previous study it had been determined that during ventricular fibrillation and cardiac massage intracranial pressure [12] as well as cerebral cortical electrical activity could be maintained for over an hour [12, 151. While cerebral electrical activity is one means of as- sessing brain viability [12, 131, it has recently been asserted that in brain and other organs extent of anaerobic metabolism may bear a

From the Division of Neurological Surgery; De- partment of Surgery; College of Medicine; Ohio State University; 410 West Tenth Avenue; Colum- bus, Ohio 43210.

Submitted for publication December 4, 1971.

24 Copyright Q 1972 by Academic Press, Inc. All rights of mproduet,ion in any form reserved.

relationship to meaningful survival [3, 111. Ac- cordingly, the model utilized in assessment of brain clcctrical activity [12, 151 was employed in this study for determination of cerebral tis- sue lactate accumulation during adequate car- diac resuscitation.

MATERIALS AND METHODS

Nine large mongrel dogs were fully anesthe- tized with iv pentobarbital (30 mg/kg) and intubated. Throughout the experiments the an- imals were vent,ilated on a Harvard respirator utilizing room air by positive pressure. End tidal % CO2 was kept between 45% during preparation to ensure respiratory homeostasis. A right thoracotomy through the fourth inter- co&al space was performed and the pericar- dium was opened and the heart dislocated. Prior to ventricular fibrillation a craniectomy was performed employing hemostatic neuro- surgical techniques. The dura was reflected widely but venous sinuses were not disturbed. A brain sample of about 1 cc of the left frontal lobe was rapidly excised for control analysis utilizing sharp dissection. At time intervals fol- lowing fibrillation indicated in Table 1, blocks of cerebral tissue were similarly excised from left parieto-occipital lobe, right frontal lobe, and right parieto-occipital lobe. It had pre- viously been demonstrated that craniectomy, exposure, and removal of brain well-away from the midline and major vasculaturc does not in itself cause elevation of cerebral tissue lactate [5]. The excised tissue was immediately immersed in liquid nitrogen and tissue re- moval to immersion in liquid nitrogen usually required 7 but always less than 10 set [Q]. A

YASHOK ET AL.: CEREBRAL ISCHEMIA

0.5-1.0-g sample of frozen cerebral tissue was added to 6% (w/v) perchloric acid and ho- mogenized in preweighed glass homogenizers. I,actate determinations were performed on the aqueous extracts utilizing a lactate dehydro- genase method [I]. Determination, employing a Beckman DU-2 spectrophotometer, of the conversion of NAD to NADH was used for the final measurement [l]. Ventricular fibrilla- tion Teas induced by a method similar to that of Kennedy and Michel [7] by direct atri- al-ventricular application of 10 V ac for a period of 2 sec. Continual ventricular fibrilla- tion was verified by electrocardiography and palpation. Cardiac massage was performed utilizing the open method [4, lo] with a rate of 48-72 beats/min. Aortic arterial systolic blood pressure, recorded via strain gauge was main- tained between 80 and 125 mm Hg. In a sepa- rate study lactate did not accumulate at mean arterial pressure of 80 mm Hg under normal conditions [17]. Vital parameters were re- corded simultaneously on a Sanborn poly- graph. During control and experimental peri- ods pO2, pH, pCO-, and lactate were deter- mined in arterial blood for estimation of ade- quacy of oxygenation and ventilation.

Table 1. Lactate Accumulation During Cardiac Resuscitation

Time Lactate Dog Time Lactate. after mmole/kg number after mmole/kg

cardiac cardiac fibril- fibril- lation lation (mins) (min)

1 3.34

2 8.14 5 4.09

5 3.76 5 3.98 5 5.61

5 6.37 7 9.07

10 4.47

10 5.57 10 4.07 10 4.76

10 7.fxi 10 12.43

10 8.18

10 9.G9

RESULTS

See Table 1 and Fig. 1. Arterial POZ was above 85 mm Hg during preparation but ranged from 73 mm Hg to 36 mm Hg during

massage. In some instances with low arterial PO2 lactate accumulation was moderate to low. There was considerable variability as to extent of arterial oxygenation in individual ex- periments, although arterial blood lactate gen- erally paralleled cerebral lactate concentra- tion. Despite adequate circulatory support as evidenced by blood pressure criteria consider- able cerebral ischemia was present,.

. AVERAGE

‘*- 1 RANGE

16-

14-

6-

4- I .

2-

Dog num-

ber

1 15 6.17 3 1 15 13.01 4

1 15 10.99 5 2 15 8.06 9

3 15 6.60 6

4 15 6.69 2

5 20 10.06 9

1 20 12.64 6

6 20 12.38 8 2 20 10.34 7

7 20 8.21 2

8 25 9.48 9

9 25 8.19 6

3 30 14.20 8

4 30 15.27 7

5 40 18.37 8

40 16.04 7

I” ’ ’ ’ I I 1 I I

12 57 IO 15 20 25 30 40 CONiROL TIME (minutes)

Fig. 1. Cerebral lactate accumulation during cardiac resuscitation.

26 JOURNAL OF SURGICAL RESEARCH, VOL. 12, NO. 7, JULY 1972

DISCUSSION

Many patients, successfully resuscitated after cardiac arrest, have complete cerebral re- covery even after prolonged circulatory assist- ance. In this study by 30-40 min cerebral tis- sue lactate had accumulated to levels seen at 10 min of complete cerebral anoxia [14] and after 60 min of oligemic hypotension at mean arterial pressures of 30 mm Hg. Nevertheless, cerebral electrical activity was sustained both at 1 hr in the identical resuscitative model [15] and at 1 hr of oligemic hypotension [16]. The same level of cerebral tissue lactate at 10 min of total cerebral circulatory arrest was incom- patible with meaningful canine survival [2] and about 50% of the dogs will not survive 60 min of oligemic hypotension at 30 mm Hg mean arterial pressure. It is obvious that mul- tiple parameters of cerebral viability are oper- ant in organs as complex as brain.

This investigation has clarified the issue of whether during ideal conditions adequate cere- bral perfusion and oxygenation can be main- tained utilizing artificial manual massage. It can be seen (Fig. 1) that cerebral ischemia occurs as early as 5 min. What is important, however, is that there is a diminution in accu- mulated lactate compared to studies of total cerebral ischemia [14] at that time indicating its definite protective effect. Also compared to studies of oligemic hypotension (30-40 mm Hg mean arterial pressure) improvement of is- chemia [5] is noted, particularly by 30 min.

In artificial manual sustenance of body cir- culation the longer it was necessary to reestab- lish circulation the poorer the prognosis. Rarely, after 15-20 min of artificial massage, do patients survive. This may be reflected in cerebral tissue lactate after 30 min in which marked elevation occurred and is at variance with work employing the identical model in which electrical activity was maintained up to an hour [16].

SUMMARY

The adequacy of cardiac massage during ventricular fibrillation for prevention of cere- bral ischemia was assessed in dogs. Systolic blood pressure was maintained above 80 mm Hg and extent of cerebral tissue lactate accu-

mulation was determined for periods up to 40 min. Lactate, as an indicator of hypoxia, was present in large amounts but protection, as compared to levels present during circulatory arrest and oligemic hypotension (30 mm Hg), was demonstrated.

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YASHON ET AL.: CEREBRAL IWHEMIA 27

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