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

Abstract

1. Rat isolated and superfused atria were exposed for varying periods to a solution simulating the composition of extracellular fluid during myocardial ischaemia (SI). 2. Atria subjected to SI showed a loss of systolic contractile tension, a rise in diastolic tension, a shortening of electrical refractory periods, a slowing of action potential conduction velocity and disruption of the mitochondrial ultrastructure. All these features were reversible when the muscle was returned to normal superfusate. 3. Atria pretreated with a superfusate containing a calcium channel antagonist, a calmodulin inhibitor or an intracellular calcium antagonist showed fewer features of the response to SI than did controls. 4. Atria pretreated with a superfusate containing various non-steroidal anti-inflammatory agents did not show identical responses to SI. Sulphinpyrazone protected against all features of the response to SI but ibuprofen, flurbiprofen and GP25671 (a metabolite of sulphinpyrazone) had little effect. Flufenamate, phenylbutazone and salicylate enhanced the responses to SI.