Background The sympathoadrenal and the renin-angiotensin systems are involved in blood pressure regulation and are known to be markedly activated during cardiac surgery. Because unexpected hypotensive events have been reported repeatedly during anesthesia in patients chronically treated with angiotensin-converting enzyme (ACE) inhibitors, the authors questioned whether renin-angiotensin system blockade would alter the hemodynamic control through attenuation of the endocrine response to surgery and/or through attenuation of the pressor effects of exogenous catecholamines. Methods Patients with preserved left ventricular function undergoing mitral valve replacement or coronary revascularization were divided into two groups according to preoperative drug therapy: patients receiving ACE inhibitors for at least 3 months (ACEI) group, n = 22) and those receiving other cardiovascular drug therapy (control group, n = 19). Anesthesia was induced using fentanyl and midazolam. Systemic hemodynamic variables were recorded before surgery, after anesthesia induction, during sternotomy, after aortic cross-clamping, after aortic unclamping, as well as after separation from cardiopulmonary bypass (CPB) and during skin closure. Blood was sampled repeatedly up to 24 h after surgery for hormone analysis. To test adrenergic responsiveness, incremental doses of norepinephrine were infused intravenously during hypothermic CPB and after separation from CPB. From the dose-response curves, pressor (defined as mean arterial pressure changes), and vasoconstrictor (defined as systemic vascular resistance changes) effects were analyzed, and the slopes and the dose of norepinephrine required to increase mean arterial pressure by 20% were calculated (PD(20)). Results At no time did the systemic hemodynamics and the need for vasopressor support differ between the two treatment groups. However, for anesthesia induction, significantly less fentanyl and midazolam were given in the ACEI group. Although plasma renin activity was significantly greater in the ACEI group throughout the whole 24-h study period, plasma concentrations of angiotensin II did not differ between the two groups. Similar changes in catecholamines angiotensin II, and plasma renin activity were found in the two groups in response to surgery and CPB. The pressor and constrictor effects of norepinephrine infusion were attenuated markedly in the ACEI group: the dose-response curves were shifted to the right and the slopes were decreased at the two study periods; PD(20) was significantly greater during hypothermic CPB (0.08 micro/kg in the ACEI group vs. 0.03 micro/kg in the control group; P < 0.05) and after separation from CPB (0.52 micro/kg in the ACEI group vs. 0.1 micro/kg in the control group; P < 0.05). In both groups, PD(20) was significantly less during hypothermic CPB than in the period immediately after CPB. Conclusions Long-term ACE inhibitor treatment in patients with preserved left ventricular function alters neither the endocrine response nor the hemodynamic stability during cardiac surgery. However, a significantly attenuated adrenergic responsiveness associated with incomplete blockade of the plasma renin-angiotensin system supports the hypothesis that inhibition of angiotensin II generation and of bradykinin degradation within the vascular wall mediates some of the vasodilatory effects of ACE inhibitors.
Abstract The haemodynamic effects of angiotensin II and noradrenaline were studied in the rat kidney. These pressors were given by intravenous infusion in stepwise increasing doses. Intrarenal haemodynmaics were analyzed by the 13 3enon washout technique, 85krypton autoradiography and silastic casting of the renal vascular tree. Angiotensin II induced significant changes in intrarenal haemodynamies before any changes in systemic blood pressure were detected. The decrease in mean renal blood flow (2.91 ml.min ‐1 .g ‐1 in controls, 1.76 ml.min ‐1 .g ‐1 in rats given 50 μg of angiotensin Il.kg ‐1 .h ‐1 ) reflects a reduction in component I blood flow rate (from 3.9 to 2.9 ml.min ‐1 .g ‐1 ) as well as a decrease in the fraction of total renal blood flow supplied to component I of the washout curve (from 84% to 62%). With noradrenaline an increase in total renal resistance occurred simultaneously with the elevation of mean arterial blood pressure. The resulting reduction in mean renal blood flow (from 2.76 ml.min ‐1 .g ‐1 in controls to 1.55 ml.min ‐1 .g ‐1 in rats given 1000 yg of noradrenaline kg ‐1 . h ‐1 ) reflects a decrease in component I blood flow rate with lower infusion rates and a drop in component I flow fraction (from 82% to 52%) with higher doses. In contrast to canine kidneys, no evidence for a patchy cortical vasoconstriction was found in the rat. Using autoradiography it was possible to attribute component I to the renal cortex and subcortical area of the kidney.
