Electrical changes produced by injury to the rat myocardium in vitro and the protective effects of certain antiarrhythmic drugs.
Glass microelectrodes were used to record intracellular electrical activity from rat isolated and superfused atrial myocardium during external electrical stimulation. 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 O2 (hypoxia). 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. The only component of SI which separately caused electrical changes similar to those of the full simulation was hypoxia. Addition to the superfusate of verapamil (0.5 micrograms ml-1), sulphinpyrazone (1-20 micrograms ml-1) or indomethacin (10-20 micrograms ml-1) attenuated many of the SI-induced electrical changes, although indomethacin was much less effective than the other two drugs. 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.
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology; D003327:Coronary Disease / Q000517:prevention & control*; D004558:Electric Stimulation; D006329:Heart Conduction System / Q000187:drug effects*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D010100:Oxygen / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013442:Sulfinpyrazone / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D014700:Verapamil; D010100:Oxygen; D002118:Calcium; D013442:Sulfinpyrazone; D007213:Indomethacin