VASCULAR ENDOTHELIAL DYSFUNCTION CONTRIBUTES TO MYOCARDIAL DEPRESSIONIN ISCHEMIA-REPERFUSION IN THE RAT

Endocardial and vascular myocardial capillary endothelium has been sho wn to modulate the contractile characteristics of myocardium by alteri ng myofibrillar affinity for calcium. Although the release of endothel ial-derived substances that modify myocardial contractility has been s hown to be altered in certain physiologic and pathologic situations, u ntil now no study has evaluated whether the direct modulatory effects of endothelium on its subjacent myocardium were altered in pathologic situations and contributed to loss of contractile function. This study was designed to evaluate whether the direct contractile modulatory ef fects of endocardial and (or) vascular endothelium were altered and wh ether these alterations contributed to contractile dysfunction in a mo del of ischemia-reperfusion. Sixty-two perfused rat hearts as Langendo rff preparations were randomized to no intervention, intracoronary Tri ton X100 injection (to render vascular endothelium dysfunctional), isc hemia (30 min)-reperfusion (20 min), and ischemia-reperfusion followed by intracoronary Triton X100 injection. Coronary endothelial-dependen t vascular reactivity and vascular smooth muscle reactivity were asses sed by serotonin and sodium nitroprusside, respectively. Myocardial da mage was assessed by coronary effluent creatine phosphokinase and by m orphologic studies. Papillary muscles were then excised and contractil e characteristics evaluated at varying extracellular calcium concentra tion prior to and after endocardial endothelial removal with Triton X1 00. All three interventions eliminated all coronary vascular response to serotonin but did not modify response to nitroprusside. Creatine ph osphokinase values rose only in hearts with ischemia-reperfusion, and only minor morphologic changes occurred, mostly in hearts with ischemi a-reperfusion. Papillary muscles from hearts with intracoronary Triton X100 injection had lower contractile indices compared with normal con trols (total tension 4.0 vs. 4.6 g/mm(2), p < 0.01) and an abbreviatio n of contraction duration. Increasing extracellular calcium concentrat ion from 0.7 to 3.25 mM eliminated these differences. Similar but more marked decreases in contractile indices and twitch duration were note d in the two ischemia-reperfusion groups, but consistent with some myo cardial damage being present, increasing extracellular calcium concent ration to 3.25 or 7 mM did not fully eliminate these differences. In b oth ischemia-reperfusion groups and the intracoronary Triton X100 grou p, the relative increase in total tension with increasing extracellula r calcium concentrations was similar (35 to 38%) and greater than that of the control group (25%), consistent with dysfunction of vascular e ndothelium contributing to myocardial dysfunction in the three interve ntion groups. Endocardial endothelial removal had a similar effect in all four groups, suggesting that dysfunction of endocardial endotheliu m does not play a role in this model. We conclude that vascular but no t endocardial endothelial dysfunction contributes to the myocardial dy sfunction that occurs during ischemia-reperfusion injury.