Cellular protection during myocardial ischemia: the development and characterization of a procedure for the induction of reversible ischemic arrest.

An isolated perfused working rat heart model was used to investigate the extent to which various protective agents, used either singly or in combination, were able to increase the resistance of the heart to periods of transient ischemia. The aim of the studies was to develop a solution which, if infused into the coronary vessels just prior to the onset of ischemia, would rapidly induce arrest and would also counteract several of the deleterious cellular changes known to occur during myocardial ischemia. Agents with induce cardiac arrest, modify cellular ion loss, affect substrate utilization, energy production and energy stores, affect coronary vessel diameter and cell swelling, prevent dysrhythmias, and affect metabolic rate were investigated. The additive effects of these agents were evaluated. An aqueous solution was formulated which contained high concentrations of potassium and magnesium, in combination with adenosine triphosphate, creatine phosphate and procaine. This solution increased the recovery of the ischemic (37 degrees C for 30 min) rat heart from 0% to 93%. The safe period of ischemia could be further increased by the use of hypothermia.