Although oxygen consumption closely parallels mechanical work in the normal heart, previous studies have found that stunned myocardium may have normal or even increased oxygen consumption despite depressed function. In this study we used microspectrophotometry to measure the oxygen saturations within arteries and veins of less than 100 micron diameter in quick-frozen biopsy samples from normal and regionally stunned myocardium of 10 open-chest anesthetized dogs. Regional myocardial blood flow, measured by radioactive microspheres, was similar in stunned and normal regions, as was mean arteriolar oxygen saturation. However, mean venous oxygen saturation was lower in the stunned region (epicardium 38.0% vs 43.8%, p less than .02; endocardium 36.2% vs 39.5%, p = .12), indicating increased oxygen extraction and consumption, despite a marked reduction in mean systolic segmental shortening from 14.4% to 0.5%. In addition, there was greater vein-to-vein heterogeneity of oxygen saturation in the stunned region, with an excess of veins having low saturations (statistically significant in epicardium, nonsignificant trend in endocardium). Microvascular injections studies with Microfil or drafting ink revealed filling of over 95% of arterioles and 85% of capillaries in the stunned region, similar to the findings in the normal region. Our results are consistent with an inefficient transfer of energy into myocyte contraction or an increased use of energy for noncontractile activities in stunned myocardium. In addition, the finding of increased heterogeneity of oxygen extraction suggests that the injury to stunned myocardium may not be uniform to all contractile elements, but instead may be focally and irregularly distributed.

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

Microvascular obstruction and persistent focal ischemia have been suggested as a possible cause of myocardial dysfunction (stunning) after brief coronary occlusion. Microvascular occlusion should result in a reduction in maximal coronary flow reserve, although resting transmural coronary flow may be maintained by release of local vasodilators, such as adenosine. To test the microvascular occlusion hypothesis, coronary flow reserve was measured in 14 anesthetized dogs, before and after myocardial stunning produced by 10 min of ischemia. Intracoronary adenosine infusion (5,900 microM/min) increased coronary flow to the same degree in normal [195 +/- 20 (SE) ml/min] and stunned (212 +/- 23 ml/min) myocardium. Peak hyperemic flow after 100 s of coronary occlusion was also similar in normal (205 +/- 25 ml/min) and stunned (218 +/- 23 ml/min) myocardium. The adenosine antagonist 8-phenyltheophylline (5 mg/kg) reduced the flow response to exogenous adenosine, but neither resting coronary flow nor peak hyperemic flow in stunned myocardium was altered. In stunned myocardium, myocardial shortening at rest (0.2 +/- 2.0%) increased during reactive hyperemia (to 13.8 +/- 2.5%, P less than 0.01), but shortening promptly returned to basal levels after each hyperemia. These findings indicate that fixed microvascular occlusion is unlikely to be an important factor in the pathogenesis of stunned myocardium and that local adenosine release does not appear to have a compensatory role in coronary vasoregulation in stunned myocardium.

Stunned myocardium can be produced by repeated short episodes of ischemia. Histochemical and ultrastructural abnormalities such as sarcomere lengthening and myofiber thinning have been noted in myocardium soon after the onset of ischemia and have been attributed to the mechanical stretching that occurs during ventricular systole. To test whether mechanical forces alone could produce the residual dysfunction seen in stunned myocardium, regional dyskinesia was produced in open chest dogs by six repeated intracoronary infusions of either potassium chloride, 0.2 mEq/min for 2.5 minutes, or lidocaine, a 10 mg bolus followed by 1 to 3 mg/min for 5 minutes. These dogs were matched with dogs that had six repeated coronary occlusions of 2.5 and 5 minutes' duration, respectively. Regional function was analyzed using fractional systolic shortening and the load-independent end-systolic pressure-length relation. Both potassium chloride and lidocaine produced regional dyskinesia that was similar to the dyskinesia produced by coronary occlusion. Although regional ventricular function after repeated coronary occlusions remained significantly reduced, function returned completely to normal within 5 minutes after the last drug-induced dyskinesia. In conclusion, regional dysfunction produced by potassium chloride and lidocaine does not produce residual dysfunction despite mechanical forces during systole similar to those seen during coronary occlusion.