Induced Hypothermia During Resuscitation from Hemorrhagic Shock Attenuates Microvascular Inflammation in the Rat Mesenteric Microcirculation

Abstract

Introduction: Hemorrhagic shock is a major cause of morbidity and mortality in trauma patients. Microvascular inflammation occurs during resuscitation following hemorrhagic shock, and is a major cause of multiple organ dysfunction and late mortality. Hypothermia has traditionally been associated with poor outcomes in trauma patients, but pre-clinical evidence suggests that hypothermia may have some benefit in selected patients. Our objective was to evaluate the effect of induced hypothermia on microvascular inflammation during resuscitation from hemorrhagic shock. Methods: Intravital microscopy was used to visualize mesenteric venules of anesthetized rats in real time to evaluate leukocyte adherence per 100 μm venule length and mast cell degranulation. An optical Doppler velocimeter was used to measure centerline red blood cell velocity in order to calculate shear rate. Measurements were obtained at a baseline control period in all animals. Animals then were divided into normotensive or hypotensive groups. Animals in the shock group underwent mean arterial blood pressure reduction to 40-45 mmHg for 1 hour via blood withdrawal. During the first two hours of resuscitation, body temperature of the hypothermic group was maintained at 32-34°C, while the normothermic group was maintained between 36-38°C. The hypothermic group was then rewarmed for the final two hours of resuscitation. Results: Leukocyte adherence was significantly lower after 2 hours in hypothermic resuscitation (n=5) compared with normothermic resuscitation (n=6): (3.4±0.8 vs 8.3±1.3, p=0.011). Upon rewarming, leukocyte adherence was not significantly different between hypothermic and normothermic shock groups: (5.4±1.1 vs 9.5±1.6, p=0.081). No significant elevation was observed in normotensive normothermic (n=3) or hypothermic animals (n=4). Shear rate decreased significantly from the control period after normothermic resuscitation (p<0.05), with no other groups having significant changes. Mast cell degranulation was significantly decreased in the hypothermic (1.02±0.04) vs normothermic (1.22±0.07) shock groups (p=0.038) after the experiment compared to the control measures; no significant degranulation occurred in normotensive animals. Conclusions: Hypothermia during resuscitation attenuates microvascular inflammation in rat mesentery following hemorrhagic shock. Further study is needed to determine the underlying mechanisms of hypothermia in reducing microvascular inflammation during resuscitation, defining optimal degree of hypothermia, and the timing of this innovative therapy.