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 Ca 2+ concentration ([Ca 2+ ] 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 [Ca 2+ ] 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 [Ca 2+ ] i were measured using the method of radiolabelled Ca 2+ ( 45 Ca 2+ ). 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 [Ca 2+ ] i in non-treated controls, [Ca 2+ ] 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 [Ca 2+ ] i .

Enhanced Blood Clotting After Rewarming From Experimental Hypothermia in an Intact Porcine Model

“…After rewarming we found a restoration of most hemodynamic parameters to within pre-hypothermic baseline values. However, SV remained significantly reduced, which may indicate the presence of a myocardial contractile dysfunction induced by hypothermia and rewarming, previously reported in several studies (Filseth et al, 2010;Han et al, 2010;Nilsen et al, 2021).…”

The Protective Role and Mechanism of Mild Therapeutic Hypothermia Protection on Brain Cells

“…The modulation of calcium levels by hypothermia has been observed in several animal models. [13][14][15] Calcium levels can also be affected by peroxide. 11,12 However the interplay between therapeutic hypothermia and peroxide is unknown.…”

“…11,12 Hypothermia treatment has been shown to modulate calcium levels in several animal models. [13][14][15] Therefore, it is reasonable to speculate that therapeutic hypothermia may protect against brain cell injury by regulating Ca 2+ levels in cells exposed to peroxide. However, the interplay between therapeutic hypothermia and peroxide is unknown.…”

Physiological Impact of Hypothermia: The Good, the Bad, and the Ugly

“…These effects most likely explain the depression in left ventricular contractile function after rewarming, which underlies the reduction of cardiac output and systemic arterial pressure (190). These models have also been used to screen the potential beneficial effects of different pharmacologic interventions to alleviate hypothermia-rewarming induced cardiac dysfunction in vivo (45,47,49,62,98,133,196,197).…”