ABSTRACTS

KINETICS OF ANTIARRHYTHMIC EFFECTS OF BRETYLIUM: CORRELA- TION WITH MYOCARDIAL. DRUG CONCENTRATIONS. Jeffrey L. Anderson, M.D.; Eugene Patterson; Marilyn Conlon: Stanis- law Pasyk, M.D.: Benedict R. Lucchesi, PhD,M.D., Univer- sity of Michigan, Ann Arbor, Michigan.

In order to study the relative importance of myocardial (&,,) vs serum (C,) drug concentrations in predicting anti-

arrhythmic effects of bretylium tosylate (BT). kinetic studies were performed in 27 dogs after bolus injection of

saline, bretylium 6mplkg (BT-6) or Zmp/kg (BT-2). Paral- lel determinations of drug concentrations (Cm,&) and antiarrhythmic effects (ventricular effective refractory period [ERP], repetetive ventricular respite [RVR], and ventricular fibrillation threshold [VFT]) were made with- out and with '2 min of coronary ischemia (I). C, fell rapidly after IV BT, whereas C, rose gradually, peaking at 1.5-6hrs. C,:C, rose progressively (1.2+.3 [SEMI at 30 min, 6.4tl.O at 12 hr: (n=7,BT-61). ERP.RVR and VFT followed c, rather than C,, with peak effects (increases)

at 3 hrs. These kinetic results were similar with or without I and for both doses of BT. I" contrast, parameters for saline controls did not vary with time. Selected results i: SEM (msec) for BT-2 (n=6) are

representative:

t (h) 0 .03 .5

ERP 154fl 157+3

RVR 1.2to.2 2.8kl.l 2.5f0.8 VFT 3.6f.5 7.5t2.5 10.3f2.7*

t (hj1.5 3 12 EkP 167f3** 175+6** 163*3 RVR 4.0t1.1* 5.421.9* 4.3+1.0* VFT 15.4+3.4** 23.5+5.4*X 15.8+2.1X*

* p i .05, ** p i .Ol "S 0 value These kinetic studies quantitate the prolonged antifib-

rillatory effect of BT, withits delayedmaximum, and em- phasizetheimportanceof Cmin determiningthisbehavior.

REPERFUSION ARRHYTHMIAS: DIFFERENTIAL EFFECT OF LIDCCAINE ON REE!!TRY AND ENHANCED AUTCMATICITY

Glenn Kabell, PhD; Benjamin J. Scherlag, PhD, FACC; Ronald R. Hope, MD, FACC; Ralph Lazzara, MD, FACC, Veterans Adm and University Hospitals, University of Oklahoma, Oklahoma City, Oklahoma

We studied the effects of reperfusion (R) in 31 dogs fol- lowing a 30-45 rain period of left anterior descending cor- onary artery (LAD) occlusion using ECG and composite electrogram recordings. One-stage R in 14 of 16 dogs pro- duced ventricular arrhythmias (VA) which degenerated into ventricular fibrillation (VF) within 60 sec. The onset of VA was associated with continuous electrical activity (CEA) in epicardial and intramural electrograms recorded fr?m the reperfused zone (RZ). Vagal slowing during R (72-S/ min) did not prevent VF (8 of 8 dogs) and escape beats were often followed by one or more coupled ectopic beats associated with CEA. Rapid atria1 pacing (270/min) also did not prevent the appearance of CEA-related VA and VF (4 of 4 dogs) nor did 4 mg/kg lidocaine (10 of 11 dogs). In 4 untreateddogs resuscitated by DC cardioversion ((40 Watt-set) VA were observed in the absence of CEA in local electrograms. I" all cases VA were reversibly suppressed by reocclusion of the LAD suggesting these VA did not re- sult from DC shock. In another group of 15 dogs R was performed in 2 stages resulting in no VF but in 8 of 15 dogs VA were observed beginning 2-3 min after R and last- ing 20-30 min. Atria1 pacing suppressed VA and idioven- tricular rate averaged 164+10/min vs 55tlO/min pre-R con- trol. The earliest site of activation indicated automatic foci in the subendocardium of the RZ. Lidocaine (2-4 mg/ kg rapidly (< 90 set) restofed normal sinus rhythm and suppressed automaticity (72-11/&n) as did LAD reocclu- sion (52+6/min). We conclude that both reentry and en- hanced automaticity play a role in VA due to R. Lidocaine suppresses automatic but not reentrant VA.

EFFECTS OF ETHMOZINE AND LIDOCAINE ON VENTRICULAR FIBRIL-

Columbia Univ., College of Physicians & Surgeons, NY, NY Lidocaine (L) and ethmozine (E) are both effective in sup- pressing ventricular arrhythmias. We induced single and

LATION AND DEFIBRILLATION I&' ANESTHETIZED DOGS. Susan Fox,

multiple ventricular premature beats (VPB) and fibrilla-

Bruce Hoffman, Michael Rosen MD, FACC, Brian Hoffman MD,

tion electrically in 9 mongrel dogs 1 to 6 weeks following surgical placement of electrodes on the ventricles and studied E and L effects on the VF'B and ventricular fibril-

lation and defibrillation thresholds. The effects of the drugs on threshold (mamps) were as follows: (*P<.O5)

Joseph F. Spear, PhD, FACC; Eric L. Michelson, MD; E.Neil Moore. DVM. PhD. FACC: Universitv of Pennsvlvania and

TEMPORAL DISPERSION OF REFRACTORINESS: LACK OF CORRELA- TION WITH ANTIARRHYTHMIC EFFICACY IN A MODEL OF CHRONIC INFARCTION

I I ,

Lankenau Hospital, Philadelphia, Pennsylvania

A chronic infarction model has been developed using occlu- sion of the mid or distal left coronary artery modified by a reperfusion stage. Three to 30 days after surgery ei- ther sustained ventricular tachycardia (VT, 3 dogs) and/ or fibrillation (VF, 3 dogs) was initiated using routine methods of programmed electrical stimulation. Strength in- terval curves were constructed using unipolar cathodal stimulation via plunge electrodes during ventricular pac- ing at a cycle length of 300 msec. Measurements were made at 26 normal and/or infarcted sites distributed over the left ventricle in these 6 dogs. The temporal dispersion of both effective (ERP) and relative refractory periods (RRP) was determined before and after infusion of 15-30 mg/kg procainamide (PA) and correlated with its effect on the inducibilitv of VT and VF 20-30 min after infusion.

Single VPB Multiple VPB V. Fib. V. Defib. Cont. Drug Cont. Drug Cont. Drug Cont. Drug

L M 6.3 +5.4* 10.4 +7.7* 14.9 +15.7* 02.4 +36.6 SD 2.6 5.6 3.7 5.9 3.2 6.3 20.4 67.1

E M 7.6 +4.0* 12.5 +3.7* 18.7 + 2.1 90.0 t21.7 SD 3.2 3.8 4.4 2.4 7.4 2.4 27.7 47.7

L and E significantly increased the threshold for inducing single and multiple VPB's. L significantly increased the ventricular fibrillation threshold; E did not. With re- spect to defibrillation threshold, neither drug affected this to a statistically significant degree. However, for L, 4 dogs showed no change in defibrillation threshold, another 4 could not be fibrillated (and hence, defibrilla- tion threshold could not be tested); and only in one dog was a" increase in defibrillation threshold seen. I" com- parison, with E, defibrillation threshold increased in 4 dogs and decreased in two. Another 2 dogs could not be defibrillated after E. We concluded that both L and E are effective drugs when used for the suppression of,VPB's. L had more of a" antifibrillatory effect than E and - whereas L did not alter defibrillation threshold - this appeared to increase with E.

Dispersion of: ERP (msec) RRP (msec)

Pre PA 40.5 + 41 54.6 + 37 (mean + SD)

Post PA- (p=NS) (p=NS)

43.3 + 38 55.1 ) 39

While mean dispersion of ERP and RRP were unchanged after PA, PA did prevent reinitiation of VF in 3/3 dogs, and had salutory effects on VT in 3/3 dogs (4 cycle length, episodes nonsustained). We conclude that (1) dispersion

of refractoriness characterizes chronic infarction, (2) the antiarrhythmic effects of PA cannot be explained sim- ply by its effects on dispersion of refractoriness, and (3) measurements of dispersion of refractoriness have limitations in the study of arrhythmogenesis.

474 February 1980 The American Journal of CARDIOLOGY Volume 45