Salvage of Myocardium in Acute Ischemia

CLINICIANS have long been concerned that some of the therapeutic measures employed in patients with heart failure caused by myocardial infarction may exert paradoxical effects by causing direct damage to the myocardium. Administration of agents that enhance the inotropic state of the myocardium may increase oxygen demand, and since oxygen supply is critically limited, further ischemic damage to cardiac muscle may result. It is entirely proper that clinicians concern themselves with the possibility that salvage of ischemic myocardium may have a place in the therapy of myocardial infarction. In this issue of CIRCULATION, Maroko and his colleagues have attempted to define factors that may influence the extent of the ischemic process, using as an experimental model dogs with temporary or permanent coronary ligation. Severity of ischemia is assessed from two measurements: (1) height and extent of S-T segment elevation measured from epicardial electrodes within minutes after temporary ligation, and (2) depletion of creatine phosphokinase from the ischemic area 24 hr after permanent ligation. The authors found that inotropic interventions (isoproterenol, glucagon, ouabain, bretylium, and rapid pacing) increased the severity and extent of S-T segment elevation within minutes after ligation, and that, conversely, a cardiac depressant (propranolol) did the opposite. Also, lowering blood pressure by hemorrhage increased ischemia, and raising it with methoxamine decreased ischemia. The results with isoproterenol and propranolol were supported by measurements of levels of myocardial creatine phosphokinase after 24 hr, which showed relatively greater and lesser degrees of depletion than predicted from control experiments. The crucial question these studies seek to