Effects of Polyamines on Ethylmorphine N-Demethylation in Rat Liver Microsomes

Abstract

Abstract-Effects of calcium antagonists and lidocaine on the conduction delay observed in the ischemic myocardium were studied in 24 open-chest anesthetized dogs. Acute myocardial ischemia was produced by complete occlusion of the left anterior descending coronary artery (LAD) for 5 or 10 minutes. The conduction time was measured from the initial deflection of V waves on the His bundle electrograms to the major deflection of the bipolar electrograms recorded from the ischemic and non-ischemic subepicardium under a constant atrial pacing. LAD occlusion produced conduction delay in the ischemic zone (14.3--2.3 msec, p<0.001) with no effect on the normal zone. This ischemia-induced conduction delay was reversible and rate-dependently increased. Administration of lidocaine (2 mg/kg bolus, 4.3 mg/kg/hr constant infusion) prior to the second occlusion increased conduction delay by 12.9 1.9 msec (p<0.001) whereas diltiazem (0.4 mg/kg i.v.) and verapamil (0.3 mg/kg i.v.) reduced the ischemia-induced conduction delay by 12.74-4.9 msec (p<0.05) and 8.4-4--1.8 msec (p<0.001), respec tively. These results indicate that slow channel blocking agents reduce the conduction delay induced by the myocardial ischemia, in contrast with the prolonging effect of lidocaine.Electrophysiological studies on the ischemic myocardium have shown that ventricular arrhythmias of the early phase are due to the re-entrant mechanism (1, 2). Delayed activation The effects of various antiarrhythmic agents such as lidocaine (8, 9), procainamide (8),

Electrical changes produced by injury to the rat myocardium in vitro and the protective effects of certain antiarrhythmic drugs

“…The slowing of the ROC of myocardial action potentials during ischaemia in vivo and during SI in vitro has been attributed, by many previous workers, to alterations in cellular calcium metabolism (Wojtczak, 1979;Nakaya et al, 1980;Kimura et al, 1982;Gettes et al, 1985). It is well established that conduction of action potentials through the myocardium depends upon a selective flow of ionic current through specialised regions of low electrical resistance between adjacent cells (DeMello, 1982).…”

“…These specialized regions of low electrical resistance are disrupted, lost or occluded when the cytoplasmic calcium concentration rises (DeMello, 1975), as it does during ischaemia, thus slowing the ROC of the action potential. Several groups of workers have demonstrated that slow channel calcium entry blockers of various chemical types (Nakaya et al, 1980;Kimura et al, 1982;Gettes et al, 1985), as well as certain intracellular calcium antagonists (Anno et al, 1986), inhibit the slowing of the ROC of action potentials during exposure of the myocardium to ischaemia or SI. The ability ofverapamil in the present experiments, therefore, to inhibit SI-induced slowing of the ROC extends to the rat the findings in other species.…”

“…Moreover, these extracellular chemical changes, particularly in combination, tend to shorten the duration of myocardial action potentials and their associated refractory periods (Downar et al, 1977;Morena et al, 1980;Cobb et al, 1985;Ferrier et al, 1985) and tend to slow the rate of conduction (ROC) of myocardial action potentials (Nakaya et al, 1980;Kimura et al, 1982;Gettes et al, 1985). These electrical disturbances are arrhythmogenic, particularly when they occur heterogeneously throughout the myocardium (Northover, 1986).…”

Protection of rat atrial myocardium against electrical, mechanical and structural aspects of injury caused by exposure in vitro to conditions of simulated ischaemia

“…Diltiazem and verapamil were shown to protect against all aspects of the response to SI. Previous workers have shown that these agents protect ventricular muscle against ischaemia-induced and hypoxia-induced shortening of refractory periods and slowing of CV (Elharrar et al, 1977;Nakaya et al, 1980;Fujimoto et al, 1981;Kimura et al, 1982;1983;Peter et al, 1982;1983;Gettes et al, 1985;Fleet et al, 1986), against the associated contracture (Henry et al, 1977;Poole-Wilson et al, 1982;1984;Cavero et al, 1983;Fitzpatrick & Karmazyn, 1984;Henry, 1984;Ferrari et al, 1986;Piacenza et al, 1986), and against the mitochondrial structural alterations (Rahamathulla et al, 1983). In the present experiments, verapamil and diltiazem protected the atria only at concentrations which exerted a negative inotropic effect in NS.…”

Suppression by Orally‐administered Nifedipine, Nisoldipine and Niludipine of Early, Life‐threatening Ventricular Arrhythmias Resulting From Acute Myocardial Ischaemia

“…The precise mechanism of this protective action is unclear but there appear to be two main and related possibilities: (i) Nifedipine abolishes abnormal automaticity in Purkinje fibres obtained from canine subendocardium 24 h after acute coronary artery ligation, as well as that induced in normal Purkinje fibres following exposure to barium chloride (Dangman & Hoffman, 1980). (ii) Nifedipine reduces the conduction delay which occurs within 5-10 min of the onset of acute myocardial ischaemia in dogs (Nakaya, Hattori & Kanno, 1980). This could result from a diminished degree of ischaemic injury as a result of increased blood flow, a 'sparing' effect on endogenous energy resources and/or a reduced intracellular sequestration of the metabolic byproducts of ischaemia.…”