Cardiac function during mild hypothermia in pigs: increased inotropy at the expense of diastolic dysfunction

Abstract

The induction of mild hypothermia (MH; 33 degrees C) has become the guideline therapy to attenuate hypoxic brain injury after out-of-hospital cardiopulmonary resuscitation. While MH exerts a positive inotropic effect in vitro, MH reduces cardiac output in vivo and is thus discussed critically when severe cardiac dysfunction is present in patients. We thus assessed the effect of MH on the function of the normal heart in an in vivo model closely mimicking the clinical setting. Ten anaesthetized, female human-sized pigs were acutely catheterized for measurement of pressure-volume loops (conductance catheter), cardiac output (Swan-Ganz catheter) and for vena cava inferior occlusion. Controlled MH (from 37 to 33 degrees C) was induced by a vena cava inferior cooling catheter. With MH, heart rate (HR) and whole body oxygen consumption decreased, while lactate levels remained normal. Cardiac output, left ventricular (LV) volumes, peak systolic and end-diastolic pressure and dP/dt(max) did not change significantly. Changes in dP/dt(min) and the time constant of isovolumetric relaxation demonstrated impaired active relaxation. In addition, MH prolonged the systolic and shortened the diastolic time interval. Pressure-volume analysis revealed increased end-systolic and end-diastolic stiffness, indicating positive inotropy and reduced end-diastolic distensibility. Positive inotropy was preserved during pacing, while LV end-diastolic pressure increased and diastolic filling was substantially impaired due to delayed LV relaxation. MH negatively affects diastolic function, which, however, is compensated for by decreased spontaneous HR. Positive inotropy and a decrease in whole body oxygen consumption warrant further studies addressing the potential benefit of MH on the acutely failing heart.