Maintaining intravenous volume mitigates hypothermia-induced myocardial dysfunction and accumulation of intracellular Ca2+

Abstract

Previous research exploring pathophysiological mechanisms underlying circulatory collapse after rewarming victims of severe accidental hypothermia has documented post-hypothermic cardiac dysfunction and hypothermia-induced elevation of intracellular Ca²⁺ concentration ([Ca²⁺]_i) in myocardial cells. The aim of the present study was to examine if maintaining euvolaemia during rewarming mitigates cardiac dysfunction and/or normalizes elevated myocardial [Ca²⁺]<sub_i. A total of 21 male Wistar rats (300 g) were surface cooled to 15◦C, then maintained at 15◦C for 4 h, and subsequently rewarmed to 37◦C. The rats were randomly assigned to one of three groups: (1) non-intervention control (n = 7), (2) dextran treated (i.v. 12 ml/kg dextran 70; n = 7), or (3) crystalloid treated (24 ml/kg 0.9% i.v. saline; n = 7). Infusions occurred during the first 30 min of rewarming. Arterial blood pressure, stroke volume (SV), cardiac output (CO), contractility (dP/dt_max) and blood gas changes were measured. Post-hypothermic changes in [Ca²⁺]_i were measured using the method of radiolabelled Ca²⁺ ( ⁴⁵Ca²⁺). Untreated controls displayed post-hypothermic cardiac dysfunction with significantly reduced CO, SV and dP/dt_max. In contrast, rats receiving crystalloid or dextran treatment showed a return to pre-hypothermic control levels of CO and SV after rewarming, with the dextran group displaying significantly better amelioration of post-hypothermic cardiac dysfunction than the crystalloid group. Compared to the post-hypothermic increase in myocardial [Ca²⁺]_i in non-treated controls, [Ca²⁺]_i values with crystalloid and dextran did not increase to the same extent after rewarming. Volume replacement with crystalloid or dextran during rewarming abolishes posthypothermic cardiac dysfunction, and partially mitigates the hypothermia-induced elevation of [Ca²⁺]_i.