Cardiopulmonary bypass (CPB) causes activation of platelets, white cells, and blood proteins leading to a systemic inflammatory response (CPB-SIRS) associated with multiple organ failure (MOF). The cause is contact of blood with the foreign surfaces of the heart lung machine, initiating hemolysis and activation of leukocytes, platelets, thrombin, and complement. Unlike CPB, this response is minimal during extracorporeal membrane oxygenation (ECMO), even after days or weeks of extracorporeal circulation. ECMO has essentially the same characteristics as CPB, except with ECMO there is no air interface in the bypass circuit, which suggests that the mechanism of hemolysis and SIRS may be related to the blood/air interface. Mixing of heparinized blood with air is inevitable durin CPB in the open venous reservoir and during cardiotomy suction. We hypothesize that blood/air exposure is the primary cause of CPB-SIRS. Although air is the largest source of blood/foreign surface interaction during CPB, the relation to blood activation has not been extensively studied. We hypothesize that air exposure causes platelet and WBC activation in a dose related fashion (Specific Aim 1). We hypothesize that air-related activation causes SIRS and organ dysfunction (Specific Aim 2). If air exposure is inevitable in cardiac surgery, and is a major cause of SIRS, what would be the clinical application of this finding? Our studies have shown that surface-generated nitric oxide prevents platelet and WBC activation by plastic surfaces. One clinical study suggested that NO in the sweep gas to the membrane lung during CPB minimized SIRS and MOF. What would be the effect of NO on the activation of platelets and neutrophils by air? That is addressed in Specific Aim 3.
This project will determine the effects of blood/air interfaces the cause of systemic inflammation during cardiopulmonary bypass (CPB), and evaluate inhibition bi nitric oxide. We expect the results of the proposed studies will support expanded research efforts to further optimize CPB components in a large animal model as the next step towards prospective randomized clinical trials.
|Qin, Yu; Zajda, Joanna; Brisbois, Elizabeth J et al. (2017) Portable Nitric Oxide (NO) Generator Based on Electrochemical Reduction of Nitrite for Potential Applications in Inhaled NO Therapy and Cardiopulmonary Bypass Surgery. Mol Pharm 14:3762-3771|
|Trahanas, John M; Witer, Lucas J; Alghanem, Fares et al. (2016) Achieving 12 Hour Normothermic Ex Situ Heart Perfusion: An Experience of 40 Porcine Hearts. ASAIO J 62:470-6|