ABSTRACTS

DEVELOPMENTAL CHANGES IN CARDIAC ACTION POTENTIAI CHARACTERISTICS AND THEIR MODIFICATION BY OUABAIN Allan Hordof MD, Arthur Hodess, and Michael R. Rosen MD, Dept. of Pediatrics, Columbia University College of Physicians and Surgeons, New York, New York

Age related differences in the sensitivity to cardio- active agents and the spectrum of toxic cardiac arrythmias have been well documented. To further elucidate the mech- anisms for these developmental differences, the electro- physiologic properties of canine cardiac Purkinje fibers (PF) were studied using microelectrode techniques. Trans membrane action potential (AP) characteristics of PF from l-7 day old (N), 4-8 week old (P,, and adult (A) mongrel dogs were compared in the control state and after super- fusion of the PF by ouabain ~x~O-~M. All PF were stim- ulated at a 500 msec. cycle length. AP amplitude, dur- ation (APD), resting membrane potential (RI%'), and phase 0 upstroke velocity (V,,,) were significantly greater in A than in N. Values for P ware intermediate between the other groups. Following superfusion with ouabain for 25 minutes there were decreases in AP amplitude, APD, FXP

and "max in PF from all age groups. The changes were greatest in A and least in N, with P intermediate. There was an increase in the slope of phase 4 depolarization in lO/ll A, 7/16 P, and O/12 N. From these observations it is evident that there are significant changes in the AP characteristics of PF as age increases from N to A. The modifications of the AP and of phase 4 depolarization by ouabain are also markedly different between the various age groups, indicating a greater sensitivity of the mature conducting system to digitalis. These age related develop mental changes in the AP characteristics and their mod- ification by ouabain, may account for the clinical differences seen in the tolerance of digitalis and the spectrum of toxic arrythmias observed in the infant age group as compared to older children and adults.

EFFECT OF OVERDRIVE PACING ON VENTRICULAR TACHYCARDIA FOLLOWING ACUTE MYOCARDIAL INFARCTION Francis Hubbard, ND; John V. Temte, MD; Bernard Lawn, MD, FACC, Cardiovascular Research Lab, Dept. of Nutrition, Harvard School of Public Health, Boston, Mass.

Following experimental myocardial infarction, a gradual increase in ventricular automaticity has been thought to precede the late development (4-8 hours) of ventricular tachycardia (VT). In 13 dogs AV block was produced by His bundle ligation and infarction accomplished by balloon occlusion of the left anterior descending artery. An attempt was made to quantitate altered automaticity by serially determining ventricular escape intervals @EL). Following infarction all dogs exhibited nonsustained VT, mean onset 3 hours. Ten dogs developed sustained VT, mean onset 5 hours. VEI was determined before and at hourly intervals post infarction by means of overdrive pacing at rates of 80-220 beats/min. VEI lengthened with in- creasing overdrive rates during the control period. Following coronary occlusion (CO), until the stage of sustained VT, the same idioventricular focus returned after discontinuation of overdrive without significant shortening of the VEI. During the stage of sustained VT, the VT focus emerged after overdrive at a shortened VEI that did not lengthen with increasing pacing rate. Intermittently, however, the VT focus was suppressed following overdrive pacing. Under these circumstances, the idioventricular focus escaped at the lengthened in- terval expected for that pacing rate. If a focus ex- hibiting enhanced automaticity was responsible for the late VT, it must have been protected from the influence of overdrive pacing. The present study indicates an absence of progressive enhancement of ventricular auto- maticity to account for the sustained VT which follows CO in the dog.

EFFECTS OF LIDOCAINE AND VERAPAMIL ON SLOW CHANNEL-DEPEN- DENT AUTOMATIC DEPOLARIZATIONS IN DEPOLARIZED GUINEA PIG VENTRICULAR MYOCARDILJM Sunao Imanishi, MD; Borys Surawicz, MD, FACC; University of Kentucky Medical Center, Lexington, Ky.

Extracellular current pulses of 3-5 set duration applied across two electrically insulated chamber compartments induced rhythmic automatic depolarizations in guinea pig papillary muscles bathed in Tyrode solution. These de- polarizations were considered to be slow channel-depen- dent because: 1) the threshold was about -35 mV, 2) the dV/dt less than 20 V/set, 3) they were suppressed by low Cal+ and MI++, and 4) enhanced by high Cal-+ and isopro- terenol. Recording simultaneous action potentials from both ends of preparation (length 2 1 mm) showed homo- genous and synchronous activity and thereby virtually ruled out the re-entry mechanism. The automatic depola- rizations were not suppressed by lidocaine concentrations ranging from 4-16 pg/ml (8 experiments) and 2 ug/ml vera- pamil concentrations (3 experiments). However, verapamil concentrations 2 3 pg/ml depressed the automaticity (5 experiments). The verapamil-induced suppression was partly restored by increasing extracellular calcium con- centration from 1.8 to 6.8 mM/l. We concluded that slow channel-dependent rhythmic automatic depolarizations in depolarized ventricular myocardium can be suppressed by moderately high doses of verapamil but not by very high doses of lidocaine. These observations may be pertinent

to the treatment of arrhythmias originating in the depo- larized myocardium.

LEFT VENTRICULAR DYSFUNCTION FOLLOM'ING CICARETTE SMOKING IN PATIENTS WITH CORONARY ARTERY DISEASE Abnash C. Jai", MD, FACC; Allen F. Bowyer, MD; Robert J. Marshall, MD, FACC; Hiroaki Asato, MD, West Virginia University School of Medicine, Morgantown, W.Va.

Smoking increases heart rate (R) and arterial pressure (P) and decreases external isometric contraction time (EICT) and pre-ejection period (PEP) in normals. The alteration of systolic time intervals is less well known in coronary artery disease patients. Therefore, determinations of R, P, PEP, EICT, left ventricular ejection time (LVET), and the ratios PEP/LVET and EICT/LVET were obtained in 45 age matched normals (N) and coronary artery disease (CAD) male smokers. The measurements were made before and after smoking two cigarettes in rapid sequence. CAD was confirmed by coronary arteriography for each patient.

Both N and CAD showed slight increases in R and P. Before smoking there was no difference in the ratios between N and CAD (p >.S). After smoking PEP/LVET did not change for the normal group (0.310 to 0.299) (p >.l). After smoking PEP/LVET increased significantly for the CAD

group (0.376 to 0.465) (p c.05). Smoking increased the ratio LVET/EICT in the N group (6.72 to 9.28) (p c.05). In the CAD group LVET/EICT ratio diminished (6.40 to 5.31) (p L.05).

Thus, smoking slightly increased the ventricular function in the normals, but consistently depressed ventricular function in subjects with significant coronary artery disease.

January 1975 The American Journal of CARDIOLOGY Volume 35 145