Post-hypothermic cardiac left ventricular systolic dysfunction after rewarming in an intact pig model

Abstract

IntroductionWe developed a minimally invasive, closed chest pig model with the main aim to describe hemodynamic function during surface cooling, steady state severe hypothermia (one hour at 25°C) and surface rewarming.MethodsTwelve anesthetized juvenile pigs were acutely catheterized for measurement of left ventricular (LV) pressure-volume loops (conductance catheter), cardiac output (Swan-Ganz), and for vena cava inferior occlusion. Eight animals were surface cooled to 25°C, while four animals were kept as normothermic time-matched controls.ResultsDuring progressive cooling and steady state severe hypothermia (25°C) cardiac output (CO), stroke volume (SV), mean arterial pressure (MAP), maximal deceleration of pressure in the cardiac cycle (dP/dtmin), indexes of LV contractility (preload recruitable stroke work, PRSW, and maximal acceleration of pressure in the cardiac cycle, dP/dtmax) and LV end diastolic and systolic volumes (EDV and ESV) were significantly reduced. Systemic vascular resistance (SVR), isovolumetric relaxation time (Tau), and oxygen content in arterial and mixed venous blood increased significantly. LV end diastolic pressure (EDP) remained constant. After rewarming all the above mentioned hemodynamic variables that were depressed during 25°C remained reduced, except for CO that returned to pre-hypothermic values due to an increase in heart rate. Likewise, SVR and EDP were significantly reduced after rewarming, while Tau, EDV, ESV and blood oxygen content normalized. Serum levels of cardiac troponin T (TnT) and tumor necrosis factor-alpha (TNF-α) were significantly increased.ConclusionsProgressive cooling to 25°C followed by rewarming resulted in a reduced systolic, but not diastolic left ventricular function. The post-hypothermic increase in heart rate and the reduced systemic vascular resistance are interpreted as adaptive measures by the organism to compensate for a hypothermia-induced mild left ventricular cardiac failure. A post-hypothermic increase in TnT indicates that hypothermia/rewarming may cause degradation of cardiac tissue. There were no signs of inadequate global oxygenation throughout the experiments.

Hypothermia/rewarming disrupts excitation-contraction coupling in cardiomyocytes

“…These results in isolated cardiomyocytes are consistent with the contractile dysfunction induced by H/R in rat papillary muscle (14), and the left ventricular dysfunction induced by H/R in rat heart (10,16,38,40). These results are also consistent with the clinical observation of ventricular dysfunction during rewarming shock following accidental hypothermia (21).…”

Role of calcium desensitization in the treatment of myocardial dysfunction after deep hypothermic circulatory arrest

“…Experimental models of deep hypothermia and rewarming confirm and explain these clinical findings [15,16]. In an experimental animal model of DHCA, left ventricle contractility, relaxation and afterload were markedly, but transiently, depressed early after reperfusion and mildly depressed late after reperfusion [17].…”

Altered pharmacological effects of adrenergic agonists during hypothermia

“…During cooling, studies on isolated papillary muscle show a positive inotropic effect of hypothermia per se [70]. In the intact pig however, cooling induce a reduction of cardiac contractile function and SV [33]. Lewis and colleagues showed that the inotropic effect of increasing heart rate during normothermic conditions in man, is lost at a core temperature of 33 °C [71], independent of pharmacologic interventions.…”

“…Increased levels of cAMP will increase such PKA-mediated Ser 23/24 phosphorylation and give a negative inotropic effect. Such phosphorylation will also enhance cardiac relaxation [32], which is normalized during rewarming from hypothermia as diastolic function is restored [33]. Thus, favorable or harmful effects of β 1 -agonists administration in hypothermic subjects appears associated to inotropic rather than lusitropic properties, as hypothermia-induced cardiac dysfunction is an isolated impairment of systolic function [1].…”