Effects of verapamil on the extracellular K+rise during myocardial ischaemia in dogs

Abstract

The effects of verapamil on the [K+]o rise produced by myocardial ischaemia were assessed in 26 open chest mongrel dogs. Ischaemia was produced by intermittent occlusion of the LAD artery (15 dogs) or by reduction of flow of the cannulated LAD (11 dogs). Specially constructed valinomycin K+ sensitive electrodes were inserted into the mid myocardium in the central zone of ischaemia (CZ); in the margin (MZ) and in the nonischaemic zone (NZ). Occlusion of the coronary artery under controlled conditions produced significant [K+]o rise, greater in the CZ than in the MZ. During the infusion of verapamil the ischaemic [K+]o rise was substantially reduced in both zones. During controlled 75% reduction of coronary flow the [K+]o reached a plateau that remained stable until reperfusion was re-established. During verapamil infusion, the plateau showed a steady decline, both in the CZ and in the MZ. The changes in [K+]o produced by verapamil, during myocardial ischaemia are probably due to: coronary dilatation of the marginal arteries and+or to a reduction of the late cellular K+ conductance due to a decrease in the intracellular Ca2+, produced by verapamil.

Effects of the calcium antagonist gallopamil on the increase of myocardial extracellular potassium activity during LAD occlusion in dogs

“…This antiarrhythmic effect of calcium antagonists could therefore be due to the reduced ischemia-induced calcium influx into the cells and/or the preservation of ATP. The calcium antagonists gallopamil (as our results substantiate), verapamil (13,31,36,37), and diltiazem (3) delay and reduce the potassium loss during ischemia. In this way the decrease of the membrane potential is delayed and diminished during early ischemia and the alterations, as well as the inhomogeneities, of electrophysiological properties of the ischemic myocardium appear delayed and diminished too.…”

“…The results of other studies have suggested that the estimation of [K+]~ could be a marker of acute myocardial ischemia (22,32). Currently, the effects of verapamil (13,30,31,36,37), diltiazem (3), and now of gallopamil, on the time course of [K+]~ are known but the mode of action of gallopamil and other calcium antagonists in reducing the extracellular potassium accumulation and preventing the occurrence of VA during ischemia has not been clarified.…”

The effects of calcium antagonists on extracellular potassium accumulation during global ischaemia in isolated perfused rat hearts

“…At higher concentrations, all three Ca antagonists further diminished the potassium loss to a similar extent. The ability to slow potassium loss appears to be in agreement with the limited number of experimental studies in other models [5][6][7][8][9]. The fact that cardiodepression after treatment with low Ca 2÷ did not reduce the loss of potassium indicates that cardiodepression and cardioprotection may be fully dissociated and supports our finding with non-cardiodepressant concentrations of the Ca antagonists.…”

“…A few recent studies have indicated that Ca antagonists can slow the loss of K ÷ caused by ischemia [6][7][8][9]. However, little attention has been paid to the influence of Ca antagonists in various cardiodepressant concentrations, since negative inotropic activity may be an important adverse reaction of these drugs.…”

Effects of verapamil on ischemia-induced changes in extracellular K+, pH, and local activation in the pig.

“…Various drugs, including the calcium channel-blocking agents, are capable of suppressing these arrhythmias.14 15 Although the mechanism(s) by which the calcium-blocking agents suppress arrhythmias remains uncertain, several potentially antiarrhythmic effects of various members of this class of agents have been demonstrated in the setting of acute ischemia. These include (1) a decrease in the size of an experimental infarct zone,16 (2) a lessening in the delay in local activation, '7-20 (3) metabolic protection of the ischemic tissues,2' 24 and (4) a decrease in the rate of [K']e accumulation.25 27 However, the effects of calcium blockers on the metabolic, electrical, and ionic changes during ischemia have not been correlated in the same experimental preparation. Nor have these effects been demonstrated in an experimental preparation with low collateral flow, such as the pig.28 '29 We have recently reported that serial 10 min coronary occlusions in the swine heart in situ provide a useful method of studying the ischemia-induced changes in myocardial [K] Miniature K'-sensitive and H+-sensitive plunge electrodes, modified from earlier designs,10 were fashioned by methods described in detail elsewhere.…”