Electrophysiologic consequences of chronic experimentally induced left ventricular pressure overload.

Cardiac electrophysiologic alterations were evaluated 1 to 8 months after partial supracoronary aortic constriction in cats. This procedure induced left ventricular systolic hypertension and hypertrophy with marked connective tissue infiltration. In situ, premature ventricular complexes were observed during or after vagal slowing of sinus rate in 8 (26%) of the 31 experimental animals, while an additional 3 of the 31 developed ventricular fibrillation. No arrhythmias were recorded in 31 normal or 7 sham-operated cats. In vitro, 29% of the left ventricular preparations from cats with pressure overload and 5% from control cats showed spontaneous ectopic activity. During stimulation at cycle lengths of 800 to 1,000 ms, multiple site impalements of subendocardial muscle cells within fibrotic regions revealed heterogeneous electrical abnormalities. These included short action potential duration, low amplitude action potentials generated from low resting potentials, split upstrokes and electrically silent areas. Impalements in nonfibrotic areas of the left ventricle showed prolongation of muscle action potential duration. Long-term disturbances in cellular electrophysiologic properties may favor the development of arrhythmias and thereby contribute to sudden cardiac death in left ventricular hypertension and hypertrophy.

Electrophysiological effects of alprenolol on depressed canine myocardium.

The electrophysiological effects of the beta-adrenergic antagonist, alprenolol, were compared in normal and depressed canine myocardium. Both (+) and (+/-)-alprenolol (5 x 10(-6) and 10(-5) mol.litre-1) decreased action potential amplitude and Vmax in Purkinje fibres superfused with Tyrode's solution in tissue bath. These concentrations shortened action potential duration and effective refractory period of Purkinje fibres but prolonged those of ventricular muscle. Alprenolol more markedly decreased Vmax and sometimes prevented action potential propagation in Purkinje fibres overlying infarcted regions. Similar depressant actions were noted in Purkinje fibres depolarised by exposure to 9 mmol.litre-1 K+. Depolarised and diseased myocardium is more sensitive to alprenolol and the drug's membrane depressant actions may be significant in terminating arrhythmias in such tissue.

Computer analysis of biological signals.

A microcomputer program was written in Basic that analyzes previously digitized biological signals. The program determines the maximum and minimum amplitudes, the upstroke velocity, the frequency, and the duration of the signal. In addition, the program has capabilities of signal averaging, graphing the signal on a CRT, smoothing of signals obscured by noise, and analyzing unipolar or bipolar signals. This program should be useful to physiologists because of its flexibility in analyzing a large variety biological signals, and modular construction that is easily modified.

Acute deleterious effects of cocaine on cardiac conduction, hemodynamics, and ventricular fibrillation threshold: effects of interaction with a selective dopamine D1 antagonist SCH 39166.

Cocaine has demonstrated cardiotoxicity that has led to sudden death by unknown mechanisms. SCH 39166, a selective dopaminergic D1-receptor antagonist, suppresses the compulsive drug-intake actions of cocaine in primates. This study examined the cumulative toxic effects of cocaine after the long-term administration of SCH 39166. After pretreatment with oral placebo/SCH 39166 for 5 days, an i.v. infusion of 0.25 mg/kg/min of cocaine HCl was delivered to 14 anesthetized dogs, and cardiac conduction, arterial blood pressure, ventricular refractoriness, and arrhythmogenesis were examined. The cocaine infusion was stopped when QRS width increased by 20% from baseline (QRS20). In Coc + Placebo regimen, the QRS and His-Ventricular (HV) intervals showed a dose-dependent lengthening. Initially, the mean blood pressure (MBP) increased followed by a precipitate decrease at a mean dose of 2.03 +/- 0.5 mg/kg of cocaine. At QRS20, the ventricular effective refractory period (ERP) increased significantly, whereas the ventricular fibrillation threshold (VFT) showed a significant reduction from the baseline. In Coc + SCH, the QRS, HV intervals, and ERP increased similarly, but the decrease in MBP was attenuated, and the VFT was increased. A relatively small infusion of cocaine causes a hemodynamic compromise. The His-ventricular conduction delay and lengthened ERP suggest a predominant direct local anesthetic effect. Cocaine additionally decreased the VFT, suggesting an increased susceptibility to VF. SCH 39166 did not potentiate the cardiotoxic effects of cocaine. It displayed a protective trend by suppressing the arrhythmogenic effects and the hemodynamic compromise caused by cocaine.

Effective defibrillation in pigs using interleaved and common phase sequential biphasic shocks.

Previous studies have shown that low internal defibrillation thresholds (DFTs) can be attained by using two pairs of electrodes and combining biphasic shocks with sequential timing. The purpose of this two-part study was to test the defibrillation efficacy of two new shock sequences, an interleaved biphasic, and a common phase sequential biphasic, that utilized two pairs of electrodes and were developed from the concept of sequential biphasic shocks. In the first part, defibrillation catheters were placed in the right ventricle and the superior vena cava of six anesthetized pigs. A small patch electrode was placed on the LV apex through a subxiphoid incision and a cutaneous patch was placed on the left thorax. The mean DFT energies for the interleaved biphasic (5.2 +/- 0.4 J) and the common phase sequential biphasic waveforms (5.4 +/- 0.4 J) were substantially less (P < 0.0001) than those for either the sequential monophasic (10.6 +/- 1.0 J) or single biphasic waveforms (9.0 +/- 1.0 J). In the second study, which used nine anesthetized pigs, the importance of phase reversal was demonstrated by the finding that the DFT energy of a common phase sequential biphasic shock (6.2 +/- 0.4 J) was much less than a common phase sequential monophasic shock (17.9 +/- 1.3 J, P < 0.0001); furthermore, the average DFT for four common phase sequential biphasic configurations (5.7 +/- 0.2 J) was much less than for a configuration that was similar except that current flow was not reversed in one phase so that no biphasic effect was present (19.7 +/- 1.2 J). The efficacy of common phase sequential biphasics was comparable to that of sequential biphasics. The effectiveness of sequential biphasics, interleaved biphasics, and common phase sequential biphasics is possibly due to two mechanisms: (A) an increase in the potential gradient during a later phase in regions that were low during the first phase, and (B) the exposure of most of the myocardium to a biphasic shock that reduces the minimum extracellular potential gradient needed to defibrillate.

Defibrillation electrode configurations developed from cardiac mapping that combine biphasic shocks with sequential timing.

Previous canine mapping studies of the transvenous defibrillation lead configuration of right ventricle (RV) to left R2 patch (P) revealed regions of low potential gradient in the left ventricular apex (A) and the right ventricular outflow tract (O). Thus 16 new lead configurations were tested in eight dogs, which incorporated electrodes in A and O to raise the gradient. When used in conjunction with two sequential biphasic shocks, the average defibrillation threshold energy from these configurations was 57% lower than that produced by a single biphasic shock delivered through RV-->P (phase 1 cathode-->anode, p < 0.001). Of the 16 configurations tested, the most effective was RV-->P followed by A-->O. When the shocking order of this configuration was reversed in another eight dogs, no difference in defibrillation efficacy was noted. In individual configurations of RV-->P and A-->O that used a single biphasic shock, defibrillation was not effective. Finally, when two sequential biphasic shocks were delivered to the same two electrodes in seven other dogs, the defibrillation efficacy was low. Thus configurations that use two sequential biphasic shocks can produce low defibrillation thresholds when the shocks are delivered to two different sets of electrodes. The high efficacy may be caused by one shock increasing the potential gradient in regions of low potential gradient that are produced by the other shock.

Defibrillation with low voltage using a left ventricular catheter and four cutaneous patch electrodes in dogs.

The purpose of this study was to determine a lower limit of defibrillation thresholds (DFTs) that could be used to evaluate nonthoracotomy lead configurations for implantable defibrillators. A lead configuration that consisted of a left ventricular catheter and four circumferential cutaneous patches was tested because it was hypothesized to create a relatively uniform electric field for defibrillation. In eight anesthetized dogs, three 8F defibrillating catheters with 6 cm platinum clad titanium tips were inserted into the right ventricle (R), right ventricular outflow tract (O), and left ventricle (L). Four cutaneous patch electrodes (4P), each with a surface area of 42 cm2, were placed on the left lateral, right lateral, anterior and posterior thorax. DFTs for ten lead configurations, consisting of different combinations of these electrodes, were evaluated. DFTs were determined by using a modified Purdue technique and applying a single capacitor biphasic shock with both phases 6 ms in duration after 15 sec of electrically induced fibrillation. The L(-)----4P+ configuration produced a lower DFT than R(-)----4P+ (3.2 +/- 1.6 J vs 8.0 +/- 4.2 J, P less than 0.001) with reduced current (2.6 +/- 0.7 A vs 4.1 +/- 1.2 A, P less than 0.001). Lowering the impedance by a mean of 40%, configurations that used four patches produced lower DFTs than those that used a single left lateral patch. The use of an O catheter produced lower DFTs only when used in conjunction with an R catheter.(ABSTRACT TRUNCATED AT 250 WORDS)