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

Abstract

1 Glass microelectrodes were used to record intracellular electrical activity from rat isolated and superfused atrial myocardium during external electrical stimulation. 2 After 2 h in normal oxygenated physiological salt solution the muscle was exposed for 30 min to a superfusate simulating the composition of extracellular fluid during myocardial ischaemia (SI). This fluid contained lactate (20 mM), a raised potassium concentration (7 mM), no glucose and a pH lowered to 6.4, and was gassed with N2 in place of 02 (hypoxia). 3 During SI the diastolic threshold voltage for stimulation increased, the speed of action potential conduction between the right and left atria slowed, and both the effective and functional refractory periods of the right atrium shortened, as did the duration of the right atrial action potential. 4 The only component of SI which separately caused electrical changes similar to those of the full simulation was hypoxia.5 Addition to the superfusate of verapamil (0.5figmimP), sulphinpyrazone (1-20 igml-1) or indomethacin (10-20p1gmlm') attenuated many of the SI-induced electrical changes, although indomethacin was much less effective than the other two drugs. 6 Lowering the calcium concentration of the superfusate from 2 mM to 0.5 mM protected against the SI-induced electrical changes that were inhibitable with sulphinpyrazone and verapamil.

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

“…Exposure of the myocardium to SI produced a pattern of electrical changes similar to that described previously (Northover, 1987). There was a progressive slowing of CV and a shortening of both action potential duration and refractory periods.…”

“…There was a progressive slowing of CV and a shortening of both action potential duration and refractory periods. The shortened action potential duration contributes to, but does not fully account for, the shortened refractory period, as discussed more fully in a previous paper from this laboratory (Northover, 1987). Shortening of refractory periods was most marked 12-15 min after the beginning of SI.…”

“…In SI of cardiac muscle in vitro, conduction velocity (CV) of action potentials is reduced, as are both action potential duration and refractory periods (Ferrier et al, 1985;Northover, 1987). These changes probably constitute the electrical basis for at least some of the disturbances of rhythm that characterize myocardial ischaemia in vivo (Northover, 1986).…”

“…These changes probably constitute the electrical basis for at least some of the disturbances of rhythm that characterize myocardial ischaemia in vivo (Northover, 1986). Pretreatment with sulphinpyrazone protects the myocardium against these electrical changes (Northover, 1987). It was of interest to discover whether sulphinpyrazone also protects the myocardium against the structural and mechanical changes produced by SI and whether other non-steroidal anti-inflammatory agents share these properties.…”

Modification by hypoxia, hyperkalaemia and acidosis of the cardiac electrophysiological effects of a range of antiarrhythmic drugs

“…propranolol and verapamil, were also investigated. Propranolol was studied because its effects during simulated myocardial ischaemia have not been described and verapamil because conflicting results have been obtained with respect to its action under ischaemic conditions (Dersham & Han, 1981;Northover, 1987).…”