Graf B M, Fischer B, Martin E, Bosnjak Z J, Stowe D F
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA.
J Cardiovasc Pharmacol. 1997 Jan;29(1):1-7. doi: 10.1097/00005344-199701000-00001.
8-Arginine vasopressin (AVP) is a powerful coronary vasoconstrictor as well as peripheral vasoconstrictor, but AVP also is reported to have negative cardiac inotropic and chronotropic effects in vitro and in vivo. Our aim was to examine the direct effects of coronary vasoconstriction by AVP on cardiac function and metabolism in isolated guinea pig hearts perfused either at a constant perfusion pressure (CPP) of 55 mm Hg or at a constant coronary flow (CCF) equal to the initial natural flow at constant pressure. Coronary vasoconstriction was elicited by perfusing hearts with increasing concentrations of AVP in random order. Variables assessed were atrial heart rate (HR), atrioventricular (AV) conduction time, left ventricular pressure (LVP), coronary flow, inflow and outflow O2 tensions, O2 delivery (Do2), oxygen consumption (MVo2), percentage oxygen extraction (%O2E) and cardiac efficiency (HR-LVP/MVo2). We found that AVP increased coronary vascular resistance more at CCF than at CPP. The decrease in coronary flow, as a function of AVP at CPP, produced concentration-dependent decreases in heart rate, LVP, and MVo2, a decrease in Do2/MVo2, increases in AV conduction time and %O2E, and no significant change in cardiac efficiency. In contrast, the increase in perfusion pressure as a function of AVP at CCF caused no change in HR and AV conduction time, much smaller decreases in LVP and Do2/MVo2, a smaller increase in %O2E, an increase rather than a decrease in MVo2, and a decrease in cardiac efficiency. Our results indicate that larger decreases in HR, LVP, MVo2, and Do2/MVo2, and the larger increases in AV conduction time and %O2E with the AVP-induced decrease in CF at CPP are consistent with myocardial depression resulting from reduced global perfusion. However, cardiac efficiency was maintained at CPP because the decreased HR and LVP product (cardiac work) matched the decrease in MVo2. At CCF, AVP did not directly produce myocardial depression, but the small time-dependent decrease in LVP over time was not matched by the increase in MVo2, so that cardiac efficiency was not maintained. The demonstration of an increase in MVo2 despite no change or a decrease in cardiac work by coronary vasoconstriction with AVP at CCF, but not at CPP, suggests that cardiac O2 use is dependent more on maintenance of CF, despite increased resistance to perfusion, rather than on maintenance of perfusion pressure. Our data agree that Gregg's phenomenon results from a hydraulic effect to distend coronary vasculature because when flow is not allowed to decrease during vasoconstriction, MVo2 increases even though HR is unchanged and LVP is slightly decreased. This is supported by the finding that AVP does not increase coronary vascular resistance during CCF as much as during CPP, so that O2 supply is better maintained to match MVo2.
8-精氨酸加压素（AVP）是一种强效的冠状动脉血管收缩剂以及外周血管收缩剂，但据报道，AVP在体外和体内也具有负性心肌变力和变时作用。我们的目的是研究在以55 mmHg的恒定灌注压力（CPP）或等于恒定压力下初始自然流量的恒定冠状动脉流量（CCF）灌注的离体豚鼠心脏中，AVP引起的冠状动脉血管收缩对心脏功能和代谢的直接影响。通过以随机顺序用浓度递增的AVP灌注心脏来引发冠状动脉血管收缩。评估的变量包括心房心率（HR）、房室（AV）传导时间、左心室压力（LVP）、冠状动脉流量、流入和流出氧张力、氧输送（Do2）、氧消耗（MVo2）、氧提取百分比（%O2E）和心脏效率（HR-LVP/MVo2）。我们发现，与CPP相比，AVP在CCF时使冠状动脉血管阻力增加得更多。在CPP时，作为AVP函数的冠状动脉流量减少导致心率、LVP和MVo2呈浓度依赖性降低，Do2/MVo2降低，AV传导时间和%O2E增加，心脏效率无显著变化。相比之下，在CCF时，作为AVP函数的灌注压力增加并未导致HR和AV传导时间发生变化，LVP和Do2/MVo2的降低幅度小得多，%O2E的增加幅度较小，MVo2增加而非降低，心脏效率降低。我们的结果表明，在CPP时，随着AVP诱导的CF降低，HR、LVP、MVo2和Do2/MVo2的更大降低以及AV传导时间和%O2E的更大增加与整体灌注减少导致的心肌抑制一致。然而，在CPP时心脏效率得以维持，因为降低的HR和LVP乘积（心脏功）与MVo2的降低相匹配。在CCF时，AVP并未直接导致心肌抑制，但随着时间推移LVP的小幅度时间依赖性降低与MVo2的增加不匹配，因此心脏效率未得到维持。在CCF而非CPP时，尽管冠状动脉血管收缩导致心脏功无变化或降低，但MVo2增加，这表明心脏氧利用更多地依赖于CF的维持，尽管对灌注的阻力增加，而不是依赖于灌注压力的维持。我们的数据表明，格雷格现象是由液压效应使冠状动脉血管扩张引起的，因为当血管收缩期间流量不允许减少时，即使HR不变且LVP略有降低，MVo2也会增加。这一发现得到了支持，即AVP在CCF期间增加冠状动脉血管阻力的程度不如在CPP期间大，因此氧供应能更好地维持以匹配MVo2。
