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Biomedical subjects

V Elharrar

Publications and source records attributed to V Elharrar.

35 records · Page 2Linked to original sources
PubMed1978

Slow-channel depolarization: mechanism and control of arrhythmias.

The secondary inward current that flows through the slow channel is probably carried primarily by calcium ions. This current is responsible, in part, for the plateau phase of the cardiac action potential. Inward calcium current through the slow channel is essential to excitation-contraction coupling, and enhancement of this current exerts a positive inotropic effect. Transmembrane electrical potentials generated as a consequence of this slow inward current, so-called slow-channel depolarizations or slow responses, have been useful models in recent studies of cardiac autonomic interactions. The significance of the slow response in ventricular arrhythmias remains controversial and awaits more definitive experiments. The role of slow-channel depolarization as a basis for SA and AV nodal electrical activity is suggested by the electrophysiological similarities between these tissues and slow responses produced in vitro. This hypothesis is supported by the responses of these nodal tissues to interventions that augment of impede the slow inward current. More direct evidence in support of this notion may not be obtainable in the near future, since the critical voltage-clamp studies of ionic currents in SA and AV nodes are not technically feasible at this time.

Action Potentials↗
PubMed1978

Effects of aprindine HCl on slow channel action potentials and transient depolarizations in canine Purkinje fibers.

The electrophysiologic effects of aprindine hydrochloride were studied on normal Purkinje fibers, on Purkinje fibers superfused with Tyrode's solution containing 22 mM KCl and isoproterenol (1 X 10(-5) M) and on transient depolarizations induced by exposure to acetylstrophanthidin (1.7--2 X 10(-7) M). Aprindine (3 X 10(-6) M) significantly reduces the action potential amplitude and dV/dtmax and shortens the action potential duration but does not alter the resting membrane potential. Transient depolarizations were suppressed by aprindine at a dose of 2 X 10(-6) M. Isoproterenol (1 X 10(-5) M) failed to restore the transient depolarizations after suppression with aprindine. Slow responses induced in K-depolarized, isoproterenol-treated fibers were unchanged by aprindine (3 X 10(-6)-1 X 10(-5) M) in the presence as well as in the absence of acetylstrophanthidin. These experiments suggest that aprindine does not have slow channel blocking properties and that an inward current through the slow channel cannot be considered as the sole basis of the digitalis-induced transient depolarization.

Action Potentials↗
PubMed1977

Influence of excitability on the ventricular fibrillation threshold in dogs.

The influence of the excitability threshold on the ventricular fibrillation threshold was studied in dogs during myocardial ischemia and potassium and aprindine infusion. Interventions that influenced excitability threshold were associated with similar changes in ventricular fibrillation threshold although the percent change in both values differed. Although it is possible that the interventions studied caused parallel but independent changes in excitability threshold and ventricular fibrillation threshold, it is likely that the excitability threshold influences the ventricular fibrillation threshold. An increase in excitability threshold could result in an increase in ventricular fibrillation threshold in spite of an increase in the actual tendency of the heart to fibrillate spontaneously. Such discordance between the "electrical stability of the heart" and the ventricular fibrillation threshold was found during myocardial ischemia.

Animals↗
PubMed1977

Effect of drugs on conduction delay and incidence of ventricular arrhythmias induced by acute coronary occlusion in dogs.

The effects of various drugs on delayed activation of the ischemic myocardium and the incidence of ventricular arrhythmias were studied in 34 open-chest anesthetized dogs. The left anterior descending coronary artery was occluded for 6 minutes before and 42 minutes after administration of aprindine (2.85 mg/kg body weight), quinidine (8 mg/kg) and verapamil (0.2 mg/kg) and during infusion of isoproterenol (0.2 microng/min). The time intervals from the onset of the QRS complex to the major deflection of the bipolar electrograms recorded within the normal and ischemic zones were measured at cycle lengths of 500, 400 and 300 msec and were correlated with the development of ventricular arrhythmias. At a cycle length of 500 msec, aprindine increased by 19.5 msec the delay in activation time produced by coronary ligation alone (P less than 0.05), whereas verapamil reduced by 10 msec the extent of ischemia-induced conduction delay (P less than 0.05). The delay in activation time in the ischemic zone was not significantly altered by quinidine or isoproterenol. The incidence of ventricular arrhythmias was increased by aprindine (from 1 in 11 to 8 in 11 dogs), decresed by verapamil (from 3 in 7 to 0 in 7 dogs) and was not changes by quinidine or isoproterenol. Thus, delayed activation of the ischemic myocardium appears to play an important role in the genesis of early arrhythmias due to myocardial ischemia, and drugs that significantly depress conduction in the ischemic myocardium may predispose to the development of ventricular arrhythmia whereas those that improve conduction may be protective. Contrary to their effects on slow channel-dependent conduction, verapamil improved and isoproterenol worsened conduction during ischaemia.

Animals↗
PubMed1977

Alterations in canine myocardial excitability during ischemia.

Changes in the ventricular diastolic excitability threshold following occlusion of the left anterior descending coronary artery (LAD) were studied in open-chest anesthetized dogs by using a new automatic threshold-following pacemaker (ATFP). The ATFP measures the diastolic excitability threshold by successively decreasing the duration of regularly occurring pacing stimuli until the ventricle fails to respond. Under control conditions, the threshold stimulus duration was 60 +/- 4 (mean +/- SEM) musec. In the first 1-3 minutes following occlusion of the LAD, the diastolic excitability threshold in the ischemic zone (IZ) decreased to 51 +/- 5 musec and then rapidly increased to 600 musec at 5 minutes. The initial decrease in excitability threshold at IZ could be abolished by elevating the serum K+ concentration prior to the LAD occlusion. These changes in excitability threshold at IZ could be prevented by infusing nonoxygenated solutions into the LAD at a site distal to the occlusion. As the excitability threshold increased in IZ during ischemia, the earliest time at which IZ could be reactivated by a stimulus with a voltage equal to twice the preligation diastolic voltage threshold was increased. In nine of 16 dogs, after 5 minutes of LAD ligation, the IZ to normal zone (NZ( activation time (when stimulating at IZ) exceeded the NZ to IZ activation time (when stimulating at NZ) by an average of 9 msec. We also found that in four dogs the NZ to IZ activation time exceeded the IZ to NZ activation time by an average of 10 msec. We conclude from these findings that a gradient of increasing excitability threshold exists as one moves from normally perfused toward more ischemic tissue, passing through a heterogenous border zone that manifests some areas which have a decreased excitability threshold and other areas which have an increased excitability threshold, and that these changes in excitability importantly influence the determination of refractory period durations and conduction times.

Animals↗
PubMed1977

Accelerated ventricular escapes induced in the intact dog by barium, strontium and calcium.

Accellerated ventricular escapes (AVE) were produced with infusion of BaCl2, SrCl2 and CaCl2. AVE demonstrated overdrive acceleration rather than overdrive suppression, i.e., faster pacing rates caused shorter escape intervals. BaCl2 (mean 20.2 mumol/kg) produced AVE in 18 of 23 dogs and a decrease in mean serum potassium (K+). SrCl2 alone (mean 2494 mumol/kg) did not produce AVE in 5 dogs and K+ was unchanged. When insulin and glucose were infused to lower K+ and SrCl2 was infused 30 minutes later, AVE was demonstrated in 7 of 10 dogs. CaCl2 alone (mean 1628 mumol/kg) produced AVE in 3 of 5 dogs and CaCl2 (mean 1733 mumol/kg) infused 30 minutes after insulin and glucose produced AVE in 4 of 4 dogs. This study demonstrates that AVE previously produced with cardiac glycosides can also be induced by infusion of barium, strontium and calcium.

Animals↗
PubMed1976

The effects of acetylstrophanthidin on the response of the AV junction to adrenergic stimulation studied in dogs.

The response of the AV junction to adrenergic stimulation was studied in 35 anesthetized open-chest dogs before and after the injection of acetylstrophanthidin (5mug) directly into the AV node artery. An AV junctional rhythm was obtained under control conditions by injecting norepinephrine (n = 9) or isoproterenol (n = 8) into the AV node artery and by stimulation of the left stellate ganglion (n = 11) after selectively injecting propranolol into the sinus node artery. Acetylstrophanthidin brought about various degrees of conduction block from simple PR interval prolongation to complete heart block, and decreased the chronotropic response of the AV junction to adrenergic stimulation. In seven animals the appearance of a spontaneous second degree AV block did not reduce the AV junctional response to adrenergic stimulation. Acetylstrophanthidin also reduced the ventricular acceleration produced by adrenergic stimulation during atrial fibrillation. These results suggest that the anti-adrenergic effect of cardiac glycosides may not only be involved in the mechanism of AV conduction disturbances during digitalis intoxication, but may also play a role in slowing the ventricular rate during atrial fibrillation.

Animals↗
PubMed1975

Catecholamine-ouabain interaction on the isolated perfused rat heart.

The effect of catecholamine-depleting pretreatments, reserpine, and 6-hydroxydopamine (6-OH-DA) on left ventricular pressure (LVP) and the inotropic response to graded doses of ouabain (up to 300 mug/0.05 ml) was studied in isolated perfused rat and guinea-pig hearts. In rats, reserpine and 6-OH-DA depleted the cardiac content of catecholamine, but did not increase initial LVP and did not reduce the inotropic response to the highest dose of ouabain. It is concluded that in isolated rat hearts, these catecholamine-depleting pretreatments nearly abolish the inotropic response to ouabain, and this effect appears to be mediated mainly through an increase in initial LVP. The reason why catecholamine depletion failed to increase initial LVP in guinea pigs remains unexplained.

Animals↗
PubMed1975

Effects of aprindine HCL on cardiac tissues.

The effects of aprindine HCL on cardiac tissues were studied in anesthetized, open-chest dogs pretreated with atropine (0.8 mg/kg) and propranolol (1.0 mg/kg). Aprindine (10(-5)-10(-3) g/ml), injected into the sinus node artery, decreased the spontaneous sinus rate; when injected into the atrioventricular nodal artery, aprindine (10(-4) g/ml) prolonged the conduction time and functional refractory period of the atrioventricular node. Intravenous administration of aprindine (1.4, 2.8 and 4.2 mg/kg cumulative dose) prolonged atrial and ventricular conduction time and prolonged the effective refractory period of both tissues. The results from this study indicate that aprindine has a negative dromotropic effect on all cardiac tissue.

Animals↗
PubMedDate not supplied

Frequency-dependent effects of several class I antiarrhythmic drugs on Vmax of action potential upstroke in canine cardiac Purkinje fibers.

Vmax of the action potential upstroke in canine cardiac Purkinje fibers was studied in the presence of seven class I antiarrhythmic drugs--lidocaine (4 micrograms/ml), mexiletine (4 micrograms/ml), propranolol (0.9 micrograms/ml), procainamide (30 micrograms/ml), quinidine (5 micrograms/ml), flecainide (4 micrograms/ml), and disopyramide (3.1 micrograms/ml)--at constant cycle lengths (CCL) and after abrupt changes in cycle length (ACCL). The time constant of Vmax recovery after ACCL at a basic cycle length of 500 ms was 0.09 +/- 0.01 s for lidocaine, 0.18 +/- 0.03 s for mexiletine, 1.35 +/- 0.20 s for propranolol, 4.4 +/- 0.8 s for procainamide, 8.3 +/- 1.2 s for quinidine, 11.0 +/- 0.9 s for flecainide, and 37.9 +/- 9.4 s for disopyramide. These values were similar to those reported by others in guinea pig papillary muscle, and, with the exception of flecainide, conformed to the scheme proposed by Courtney (J Mol Cell Cardiol 1980; 12:1273-86) based on the molecular weight and lipid solubility hypothesis. Each drug altered the Vmax differently at CCL from after ACCL at the same diastolic intervals. The magnitude of these differences and the range of diastolic intervals at which they were present varied among different drugs. These observations explain differences in the drug effects on the Vmax of the regularly and prematurely occurring depolarizations. In the presence of lidocaine and mexiletine, the recovery kinetics of Vmax were not altered by CCL within the 300-1,500-ms range, and the magnitude of Vmax depression was not influenced by action potential duration within the 200-270-ms range.

Action Potentials↗
PubMedDate not supplied

Effect of antiarrhythmic drugs on the cycle length-dependent action potential duration in dog Purkinje and ventricular muscle fibers.

We examined the steady-state action potential duration (APD) within a wide range of cycle lengths (CL) in cardiac dog Purkinje (P) and ventricular (V) muscle fibers in the presence of: lidocaine (L) 4 and 8 micrograms/ml, mexiletine (M) 4 and 8 micrograms/ml, flecainide (F) 1 and 4 micrograms/ml, disopyramide (D) 3.1 and 10 micrograms/ml, quinidine (Q) 2.5, 5, and 10 micrograms/ml, bretylium tosylate (B) 5 and 10 micrograms/ml, and sotalol (S) 5 micrograms/ml. In the P fibers, all drugs except for B and S shortened plateau duration, increased slope of phase 2 and decreased slope of phase 3 repolarization, and either shortened (L, M, Q, F) or prolonged (D) APD. B and S lengthened APD and did not change significantly the slopes of phase 2 and 3 of repolarization. Each drug altered the relation between APD and Cl according to one of the following three patterns: (a) L, M, Q, and F shortened APD more at long than at short CL; (b) D lengthened APD more at short than at long CL; (c) B and S lengthened APD more at long that at short CL. In the V fibers, APD was lengthened by F, Q, and B, and shortened by L and M. The drug-induced changes in the relation between APD and CL were as in the P fibers. The results suggest that the drug-induced changes in the relation between APD and CL can be predicted from the drug effects on the course of repolarization.

Action Potentials↗