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J Thorac Cardiovasc Surg 1994;108:1092-1099
© 1994 Mosby, Inc.

CARDIOPULMONARY BYPASS, MYOCARDIAL MANAGEMENT, AND SUPPORT TECHNIQUES

Pulmonary microvascular responses to protamine and histamineEffects of cardiopulmonary bypass

Boston, Mass.

Supported by National Heart, Lung, and Blood Institute grant HL 46716, American Heart Association (Massachusetts Affiliate) grant 13-501-912, and a grant from the American College of Chest Physicians.

Received for publication Feb. 25, 1994. Accepted for publication June 14, 1994. Address for reprints: Frank W. Sellke, MD, Division of Cardiothoracic Surgery, Beth Israel Hospital, Dana 905, 330 Brookline Ave., Boston, MA 02215

Abstract

Total cardiopulmonary bypass with associated reduced pulmonary blood flow causes significant alterations of endothelium-dependent pulmonary microvascular responses after resumption of normal perfusion. To determine if this change in pulmonary vascular reactivity may influence the responses of pulmonary arterioles to protamine and histamine, we examined isolated pulmonary microvessels after cardiopulmonary bypass. Sheep were heparinized, cannulated, and placed on either total bypass without ventilation or partial bypass (70% of baseline pulmonary arterial flow) with continued ventilation. After 90 minutes, sheep were separated from cardiopulmonary bypass and the lungs were perfused normally for 60 minutes. Vessels from noninstrumented sheep were used as controls. Peripheral pulmonary arterioles (90 to 190µm) were cannulated, pressurized (20 mm Hg) in a no-flow state, and examined with video microscopy. After precontraction of vessels with the thromboxane A₂analog U46619 by 18% to 25% of the baseline diameter, vasoactive agents were applied. Protamine sulfate, histamine, heparin, and the protamine-heparin complex caused significant dose-dependent relaxations of control pulmonary microvessels. These relaxation responses were substantially reduced or converted to contractile responses in endothelium-denuded vessels, which suggests that these relaxations are mediated through endothelium-dependent mechanisms. After partial bypass, responses to protamine and histamine were slightly reduced compared with the respective responses of control vessels, whereas the relaxation to protamine-heparin complex was not significantly altered. After total bypass, relaxation responses to protamine and protamine-heparin complex were markedly reduced, whereas histamine induced contraction of pulmonary microvessels. Endothelium-independent relaxation to sodium nitroprusside was not affected by partial cardiopulmonary bypass and was slightly reduced after total bypass. A reduced direct vascular relaxation response to protamine and increased contractile response to histamine (or other humoral substances released during the systemic administration of protamine sulfate) may contribute to the elevation of pulmonary vascular resistance during infusion of protamine after cardiopulmonary bypass. (J THORACCARDIOVASCSURG1994;108:1092-9)

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