Selective enhancement of function of stunned myocardium by increased flow.

Abstract

Although augmentation of flow does not improve the performance of normal myocardium, the hyperemic response after brief coronary occlusion is associated with transient hyperfunction in the previously ischemic region. In this study we assessed the effect of vasodilator-enhanced coronary blood flow on the systolic function of postischemic stunned myocardium. In 18 open-chest, anesthetized dogs the anterior descending artery was occluded for 5 min, followed by a 10 min period of reflow, repeated 12 times with a final 90 min recovery period. After the recovery period, either 0.06 mg/min dipyridamole (n = 6), 1 mg/min papaverine (n = 6), or 1.5 ,g/kg/min nitroglycerin (n = 6) was infused intravenously for 15 min. Regional myocardial blood flow, which had returned to normal before administration of vasodilator, was increased 150% above baseline by dipyridamole and 80% by papaverine, but was unchanged by nitroglycerin. Segmental shortening decreased after repeated occlusions: from 17.5% to 0.9% in the group later treated with dipyridamole, from 18.6% to 6.7% in the papaverine group, and from 19.2% to -1.9% in the nitroglycerin group (p < .005 for all groups). Segmental shortening increased to 8.8% after dipyridamole, 13.6% after papaverine, and 5. 1 % after nitroglycerin (p < .05 for all groups), although the load-independent end-systolic pressure-length relationship (ESPLR) showed a significant shift to the left, reflecting enhanced performance, only after dipyridamole and papaverine. For all dogs combined, the percent improvement in ESPLR was correlated with the percent increase in flow (R = -. 73, p < .001). Performance was unchanged in the control region despite similar augmentation of flow. This study demonstrates that the function of postischemic myocardium can be selectively enhanced by augmentation of coronary blood flow to levels greater than normal.Circulation 74, No. 4, 843-851, 1986

Intravenous Nicorandil in Conjunction With Coronary Reperfusion Therapy is Associated With Better Clinical and Functional Outcomes in Patients With Acute Myocardial Infarction.

“…Nicorandil also reduces neutrophil infiltration into the ischemic myocardium 18,19 and attenuates the activity of neutrophils, which would attenuate the microvascular injury caused by neutrophils, leading to maintenance of myocardial blood flow. In addition, vessels less than 100 m in diameter are sensitive to nicorandil and dilate to increase the blood flow, 20 which would augment the functional improvement of stunned myocardium, 21 and was reflected in the lower frequency of no-reflow in the nicorandil group than in the control group in patients with an anterior AMI. The benefit of nicorandil treatment also may be related to a hemodynamic effect that is characterized by a reduction of preload and/or afterload.…”

Medical and Cellular Implications of Stunning, Hibernation, and Preconditioning

“…2 Indeed, myocardial stunning might be regarded not as a single entity but instead as a phenomenon. At the experimental level, the available observations can be grouped into six categories 2 : (1) stunning after a single, completely reversible episode of regional ischemia in vivo (eg, a coronary occlusion Ͻ20 minutes in the dog), as originally described by Heyndrickx et al [3][4][5][6] ; (2) stunning after multiple, completely reversible episodes of regional ischemia in vivo (eg, repeated 5-or 10-minute coronary occlusions in the dog) [7][8][9][10][11] ; (3) stunning after a partly reversible (no necrosis) plus partly irreversible (some areas of necrosis) episode of regional ischemia in vivo (eg, a coronary occlusion Ͼ20 minutes but Ͻ3 hours in the dog) 12,13 (this category may be relevant to patients who receive thrombolysis or angioplasty for acute myocardial infarction and then demonstrate delayed recovery of function of the salvaged tissue); (4) stunning after global ischemia in vitro (isolated heart preparations) 14 -19 ; (5) stunning after global ischemia in vivo (cardioplegic arrest) 20 -23 ; and (6) stunning after exercise-induced ischemia (high-flow ischemia). 24 -26 Because of the heterogeneity of these settings, it is possible that findings developed in one setting may not be applicable to another.…”

Mechanism of myocardial "stunning".

“…[15][16][17][18][19] The largest decrease in contractility occurs after the first occlusion; with subsequent occlusions, the additional decrements in mechanical performance become progressively smaller. 20 (Whether repetitive ischemia also has a cumulative effect on the time to complete recovery, however, remains unclear.)…”