Lung Injury after CardioPulmonary Bypass

PI:  Irving Kron, MD

CPB research group: Sheila Hammond, Sara Hennessy, Lucas Fernandez, & Ashish Sharma

Summary: Cardiopulmonary bypass (CPB) often induces systemic inflammatory response syndrome (SIRS) characterized by alterations in cardiovascular and pulmonary function. When acute lung injury occurs after CPB, significant mortality can occur. Although the lungs are typically most affected, SIRS can affect multiple organs leading to liver, kidney or neurological insufficiencies. SIRS is thought to result from interactions of blood components with the artificial circuit as well as from pulmonary ischemia-reperfusion (IR) injury. It is known that CPB involves activation and sequestration of neutrophils which release cytotoxic contents resulting in tissue injury. We believe that the lungs are the pivotal organ which determines the severity of SIRS and ultimate mortality. Our laboratory has shown that adenosine A2A receptor (A2AR) activation attenuates lung IR injury. We have also shown that CPB in rats results in lung injury and induction of TNF-alpha, IFN-gamma, IL-6, and IL-1beta, which are prevented by A2AR activation. We believe that A2AR activation attenuates CPB-induced lung injury by directly inhibiting neutrophil activation and infiltration. We have demonstrated that lung IR injury leads to cardiac dysfunction which can be ameliorated by A2AR activation, and we have also shown that IR is mediated by TNF-alpha produced from activated alveolar macrophages which leads to neutrophil chemotaxis and tissue injury. Our research project is evaluating if lung injury and neutrophil infiltration after CPB is initiated by alveolar macrophage activation via TNF-alpha. In addition, we are testing whether A2AR activation prevents CPB-induced lung injury predominantly via inhibition of neutrophil activation. This project utilizes an established rat model of CPB.