Bradykinin receptor antagonism could reduce the hypotensive response to CPB. Low systemic vascular resistance (SVR) commonly occurs during and early after CPB. It is usually transient and easy to treat. Occasionally, patients have a more severe and persistent fall in SVR, referred to postoperative vasodilatory shock. Risk factors for vasodilatory shock includes the preoperative use of ACE inhibitors, low left ventricular ejection fraction and heart failure syndrome. Treatment is frequently required to maintain adequate perfusion pressure during CPB and to establish satisfactory hemodynamics when ready to separate the patient from bypass. This usually entails counteracting the effect of the vasodilatory mediators by administration of drugs such as norepinephrine or phenylephrine. Although usually effective and safe, these drugs can redistribute blood flow in such a way as to compromise the splanchnic and renal circulation. Several mediators are thought to be responsible for producing postoperative shock, including bradykinin. For example, there is an inverse correlation between bradykinin concentrations and mean arterial pressure during CPB, suggesting that bradykinin is an important mediator in the decrease in SVR. We and others have shown that bradykinin induces vasodilation through its B2 receptor. In contract, B1 receptor stimulation does not cause vasodilation. As outlined under PRELIMINARY STUDIES, we have demonstrated that endogenous bradykinin contributes to protamine-related hypotension following CPB and that bradykinin receptor antagonism administered just prior to protamine attenuates this hypotensive response. In Specific Aim 2 we will test the hypothesis that bradykinin receptor antagonism modulate the hemodynamic changes observed during CPB.