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

Abstract

It has been implied that the increase of myocardial extracellular potassium activity [( K+]e) in the early stage of acute myocardial ischemia is a major cause of the increased likelihood of arrhythmia after acute coronary artery occlusion. There is also experimental evidence that some calcium antagonists reduce the occurrence of ischemia-induced early ventricular arrhythmias. In order to clarify the antiarrhythmic effect of gallopamil during the early phase of acute LAD occlusion, the influence of this calcium antagonist on the time course of [K+]e during acute ischemia was measured in open-chest anesthetized dogs using a K+-selective surface multielectrode. The regional myocardial blood flow was determined with 9 micron radioactive tracer microspheres. After application of gallopamil (bolus 25 micrograms/kg and infusion 2.5 micrograms/kg.min for 30 min) the maximal and mean rate of rise of [K+]e as well as the plateau of [K+]e reached during ischemia were significantly diminished compared with the control occlusions. 90 min after gallopamil, the rate of rise of [K+]e as well as the plateau of [K+]e reached were still significantly reduced, but 180 min after the gallopamil application, no significant differences between the time course of [K+]e and that of the two control occlusions could be found. Gallopamil significantly elevated myocardial blood flow in the non-ischemic area, but did not influence blood flow in the ischemic region. While collateral perfusion remains unchanged, the slowed and reduced increase of myocardial [K+]e during acute coronary artery occlusion may be an important component of the antiarrhythmic effect of gallopamil during early ischemia.

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

“…The loss of potassium has been used to monitor directly the reversible cellular injury during global ischemia. The time course of change of [K+]out during ischemia found in the present study is in close agreement with other reports [1,2,4,14] and is in accordance with findings that the rise in [K÷]out during consecutive short periods of reversible ischemia was reproducible [6][7][8][9]. The fact that in our model the second and the third period of ischemia were identical is in agreement with these reports [6][7][8][9]33].…”

“…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.…”

“…The low-calcium experiments were performed to support these results. Studies with verapamil and gallopamil (closely related to verapamil) demonstrate that these drugs also diminished the plateau value of [K+]out compared with control conditions [6,9]. In our model, we only measured a retardation of the rise of [K+]uut and did not observe a significant reduction of the plateau value of [K+]out .…”

“…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.…”

Class IV Antiarrhythmic Agents: New Compounds Using an Old Strategy

“…In open-chest anesthetized dogs D600 significantly elevated myocardial blood flow in the non-ischemic area, but did not influence blood flow in the ischemic region [251] in contrast to the effect of verapamil, which either increased CF to the ischemic area [112] or caused a coronary steal from the ischemic area of the myocardium [128]. Ischemia and reperfusion-induced arrhythmias were reduced by D600 in rats [252], dogs [253] and guinea-pigs [254].…”