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

Abstract

Introduction Microvascular inflammation occurs during resuscitation following hemorrhagic shock, causing multiple organ dysfunction and mortality. Pre-clinical evidence suggests that hypothermia may have some benefit in selected patients by decreasing this inflammation, but this effect has not been extensively studied. Methods Intravital microscopy was used to visualize mesenteric venules of anesthetized rats in real time to evaluate leukocyte adherence and mast cell degranulation. Animals were randomly allocated to normotensive or hypotensive groups, and further subdivided into hypothermic and normothermic resuscitation (N=6 per group). Animals in the shock groups underwent mean arterial blood pressure reduction to 40-45 mmHg for 1 hour via blood withdrawal. During the first two hours following resuscitation by infusion of shed blood plus double that volume of normal saline, rectal temperature of the hypothermic groups were maintained at 32-34°C, while the normothermic groups were 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 of hypothermic resuscitation compared with normothermic resuscitation: (2.8±0.8 vs 8.3±1.3 adherent leukocytes, p=0.004). Following rewarming, leukocyte adherence remained significantly different between hypothermic and normothermic shock groups: (4.7±1.2 vs 9.5±1.6 adherent leukocytes, p=0.038). Mast cell degranulation index (MDI) was significantly decreased in the hypothermic (1.02±0.04 MDI) vs normothermic (1.22±0.07 MDI) shock groups (p=0.038) after the experiment. Conclusions Induced hypothermia during resuscitation following hemorrhagic shock attenuates microvascular inflammation in rat mesentery. Furthermore, this decrease in inflammation is carried over after rewarming takes place.

Mast cell activation and arterial hypotension during proximal aortic repair requiring hypothermic circulatory arrest

“…[9, 24] In fact, conflicting results have been reported on the temperature-dependency of cytokine release in cardiac cases. [25, 26] Consistent with a previous report[13] our data suggests that MC degranulation is blunted at low temperatures, but, as with Rasmussen et al,[26] other inflammatory markers were not affected (data not included). Our previous work in a rat model of HCA revealed substantial intestinal I/R injury.…”

“…Despite compelling evidence for relevant MC activation in animal models of trauma,[12] hemorrhagic shock,[13] ischemia/reperfusion (I/R) injury [14], but also rat HCA [7] and porcine ECMO [15], corresponding human studies have been lacking. MCs are a ubiquitously present population of potent inflammatory surveillance cells that rapidly respond to inflammatory triggers and tissue stress signals with release of pre-formed and de-novo synthesized proinflammatory, vasoactive, and tissue-disruptive effectors (reviewed in [8]).…”

Induced Hypothermia Preserves the Functional Enterocyte Mass in A Porcine Multiple Trauma Model

“…Different experimental studies have shown that induced hypothermia might be able to attenuate the inflammatory response, reduce organ damage, and improve the outcome of severe trauma (17)(18)(19). The important mechanisms associated with these beneficial effects are maintaining aerobic metabolism and reducing oxygen demand (20,21).…”

Condition of microcirculatory and hemostasis systems in rats after moderate hypothermia

“…Таким образом, было продемонстрировано, что под действием анестезии у экспериментальных животных утрачивается активный контроль терморегуляторных механизмов. Начальная фаза гипотермии сопровождается уменьшением температурного порога в гипоталамусе, в ответ на это центр терморегуляции усиливает периферический ток крови (при нормальных условиях механизм защита от перегрева) [9,10]. Кроме того, непосредственное воздействие общего анестетика на прекапилляры увеличивает ток крови к поверхностным тканям, вызывая перераспределение тепла от внутренних органов к периферическим тканям [2,11].…”

“…На фоне развития вазодилатации увеличивается объем крови в МЦР, что сопровождается увеличением показателя микроциркуляции. Увеличение флакса обусловлено более интенсивным функционированием механизмов активного контроля микроциркуляции и свидетельствует о глубокой модуляции кровотока [5,9,14]. Увеличению показателя флакса также способствует рост амплитуды дыхательных волн, вызванный в свою очередь, как увеличением микроциркуляторного давления, так и развившейся вазодилатацией.…”