Pharmacologic modification of myocardial ischemia.

Abstract

SUMMARY The value of three agents in reducing the area of myocardial ischemia in rabbit hearts perfused with crystalloid solution was examined. Ten hearts received crystalloid solution with methylprednisolone (M), 0.25 mg/ml; 18 with hyaluronidase (H), 4 U/mi; and 10 with propranolol (P), 1 g.g/ml.Thirty-six hearts served as controls. The mitral valves were excised, the hearts were paced at 240 beats/min and a coronary artery was ligated. The ischemic area was evaluated by nicotinamide adenine dinucleotide autofluorescence photography, an intrinsic, high-resolution display of anoxic tissue. The ischemic area was determined by computer from standardized photographs. Myocardial oxygen consumption (MVO2) was determined and photographs were taken before and at 10-minute intervals after ligation. At 60 minutes, each heart was perfused with rhodamine dye and quick-frozen. In hearts treated with M and H, coronary blood flow increased by 151% (51.7 ± 3 to 77.9 ± 3 ml/min) and 150% (48.3 ± 2 to 72.3 ± 2 m/min), respectively (p < 0.001), whereas in hearts treated with U and P, coronary flow decreased at 60 minutes. In the control hearts, the ischemic area did not change between 5 and 40 minutes of ischemia. The ischemic area of H-treated hearts decreased from 136 ± 4 mm2 to 110 ± 9 mm2 between the postligation control and the end of the experiment (p < 0.01). The ischemic area of M-treated hearts decreased from 131 ± 5 mm2 to 113 ± 5 mm2 (p < 0.05). P produced no change in ischemic area (p > 0.4). There was no change in the oxygen-diffusion zone of P-treated or control hearts (439 ± 13 vs 383 ± 12 ,c, p > 0.1). The oxygendiffusion zone between perfused and anoxic tissue in the M and H hearts increased from 383 ± 12 ,u to 861 + 76 ,u and 681 ± 62 ,i, respectively (p < 0.001). We conclude that significant volumes of myocardium remain normoxic within nonperfused areas of M-, P-and H-treated hearts.LIMITING myocardial necrosis during an evolving myocardial infarction is of major clinical significance because the extent of damage after coronary artery occlusion is a strong determinant of patient survival." 2 Numerous studies have investigated the character, extent and reversibility of myocardial ischemic injury, but the nature of the transition from reversible to irreversible damage remains obscure. In this study, we used nicotinamide adenine dinucleotide (NADH) fluorophotography9 to evaluate the influence of three pharmacologic agents on limiting infarct size. Hyaluronidase, an oxygen-diffusion facilitator; methylprednisolone, a steroidal antiinflammatory agent; and propranolol, an agent for reducing oxygen demand, were administered after acute coronary ligation in the isolated, perfused rabbit heart. Methods and

Myocardial surface oxygen pressure across the border zone in the pig during acute coronary artery occlusion. A comparison of pretreatment with metoprolol or isoprenaline

“…The net result, under most but not all conditions, is a reduction in myocardial oxygen demand. Many experimental studies indicate the possibility of beta-blockade reducing infarct size (5,16,21,23,26) but some show conflicting results (7,32).…”