University of Louisville
Effects of Normothermia Versus Hypothermia on Serum Complement Activation and Cytokine Production During Simulated Cardiopulmonary Bypass
Institution
University of Louisville
Faculty Advisor/ Mentor
Claudio Maldonado
Abstract
It is well known that during cardiopulmonary bypass (CPB) surgery, serum complement is activated and can lead to a significant systemic inflammatory response, resulting in adverse effects to the patient. CPB is a procedure that involves the use of the Heart-Lung machine, which replaces heart and lung function while the heart is being repaired. As blood comes into contact with pump tubing and other foreign materials, the complement alternative pathway is activated and results in the production of two potent pro-inflammatory anaphylatoxins; C3a and C5a, which bind to their corresponding cellular receptors on monocytes and are thought to modulate the production of pro-inflammatory cytokines. In the course of CPB, the heart is intentionally arrested and the patient’s temperature is lowered (cardioplegia) to decrease cellular metabolism to mitigate ischemia/reperfusion injury. Yet, a recent report using an in vitro model simulating sepsis has demonstrated that temperature modulates the production levels of inflammatory cytokines in whole blood. Contrary to popular belief, hypothermia (28°C) has been reported to actually increase pro-inflammatory cytokine production compared to normothermia (37°C) or hyperthermia (40°C), suggesting that hypothermia over-stimulates inflammatory cytokine production, which potentially have deleterious consequences in patients. To our knowledge the effects of hypothermia on foreign body complement activation and pro-inflammatory cytokine production in a simulated model of CPB has not been studied. Thus, the clinical question that I sought to answer was whether cardioplegia during CPB increased over-stimulation of proinflammatory cytokines promoting an inappropriate inflammatory response that is potentially harmful to patients.
Effects of Normothermia Versus Hypothermia on Serum Complement Activation and Cytokine Production During Simulated Cardiopulmonary Bypass
It is well known that during cardiopulmonary bypass (CPB) surgery, serum complement is activated and can lead to a significant systemic inflammatory response, resulting in adverse effects to the patient. CPB is a procedure that involves the use of the Heart-Lung machine, which replaces heart and lung function while the heart is being repaired. As blood comes into contact with pump tubing and other foreign materials, the complement alternative pathway is activated and results in the production of two potent pro-inflammatory anaphylatoxins; C3a and C5a, which bind to their corresponding cellular receptors on monocytes and are thought to modulate the production of pro-inflammatory cytokines. In the course of CPB, the heart is intentionally arrested and the patient’s temperature is lowered (cardioplegia) to decrease cellular metabolism to mitigate ischemia/reperfusion injury. Yet, a recent report using an in vitro model simulating sepsis has demonstrated that temperature modulates the production levels of inflammatory cytokines in whole blood. Contrary to popular belief, hypothermia (28°C) has been reported to actually increase pro-inflammatory cytokine production compared to normothermia (37°C) or hyperthermia (40°C), suggesting that hypothermia over-stimulates inflammatory cytokine production, which potentially have deleterious consequences in patients. To our knowledge the effects of hypothermia on foreign body complement activation and pro-inflammatory cytokine production in a simulated model of CPB has not been studied. Thus, the clinical question that I sought to answer was whether cardioplegia during CPB increased over-stimulation of proinflammatory cytokines promoting an inappropriate inflammatory response that is potentially harmful to patients.