Myocardial infarct size. Part 2. Comparison of anti-infarct effects of beta-blockade, glucose-insulin-potassium, nitrates, and hyaluronidase

Based on the principles discussed in the first part of this review, the following interventions (Table I) could be expected to limit infarct size: (1) relief of vascular obstruction, (2) increased collateral flow or diffusion to the ischemic zone, (3) relief of the load on the heart, thereby promoting a more favorable balance between the oxygen supply and demand, (4) catecholamine antagonism, and (5) specific metabolic measures. Table I lists those agents tested in patients for therapeutic effects on indices of infarct size. Because the role and exact nature of the vascular obstruction is so controversial, agents acting at that level have been omitted from further consideration, and one agent has been selected from each of the remaining categories (2 to 5) of Table I.Thus the four anti-infarct agents selected for consideration in further detail are: β-blockade, glucose-insulin-potassium, nitrates, and hyaluronidase. β-blockade is selected because of the exceptionally full experimental and clinical studies now available and because of a combined hemodynamic and metabolic action. Glucoseinsulin-potassium is selected as one of the first interventions introduced, and now well studied over many years; it is an agent likely to counteract undesirable metabolic changes in acute infarction. Glucose-insulin-potassium is compared with the use of a nicotinic acid analog which also has an antilipolytic action. Nitrates are selected because of their dual mechanism of action, both by causing coronary vasodilation and by reducing the pre- and afterload on the heart. In addition, nitrates, as therapeutic agents, are well known to all practicing cardiologists. Nitroprusside is considered together with the nitrates, although nitroprusside has a more definitive effect on the afterload than do nitrates. Finally, hyaluronidase is chosen as a well-investigated agent with minimal side effects and no known hemodynamic mode of action.Other promising agents have been omitted, although of great potential interest, because of the limited number of patient studies available. For example, the effects of steroids are well documented in experimental preparations. Although they diminish the features of acute ischemic injury, probably acting by means of “membrane stabilization,” they also inhibit wound healing¹³⁰ and hence increase the risk of ventricular rupture or aneurysm² (See also Table I, references 250, 251, 256, and 257). Another interesting category of agents, the calcium antagonists, are only now being studied in patients.