Effects of remote ischemic preconditioning on intestinal oxygenation, microcirculation, and mitochondrial respiration within the second window of organ protection in a rodent hemorrhagic shock model

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Abstract Background In the setting of high-risk surgery, preventive strategies to maintain intestinal tissue integrity are of particular importance, as no bridging organ replacement therapy exists. Remote ischemic preconditioning (RIPC) has been reported to attenuate organ injury under conditions of restricted oxygen delivery. However, its effectiveness in hemorrhagic shock followed by blood transfusion is barely described. This study was designed to investigate the protective effects of RIPC, when applied 24 h prior to hemorrhagic shock, on intestinal tissue oxygenation, microcirculation, and mitochondrial function as key determinants of cell death and organ dysfunction. Methods Male rats received either RIPC, consisting of 4 cycles with 5 min of bilateral hindlimb vascular occlusion and 5 min of reperfusion each, or a sham treatment. After 24 h, animals were subjected to a fixed-pressure hemorrhage (40 ± 5 mmHg; 1 h) followed by shed blood transfusion and a 2 h observation period. Control animals were observed over time without induction of shock. Microvascular measurements and evaluation of intestinal microvascular oxygenation were assessed after median laparotomy. Intestinal microvascular oxygenation (µHbO 2 ) was assessed by white-light spectroscopy. Microvascular perfusion was evaluated using laser Doppler flowmetry and incident dark-field imaging. Mitochondrial function was analyzed by high-resolution respirometry. Results Hemorrhagic shock markedly impaired intestinal microvascular oxygenation and microvascular perfusion. RIPC applied 24 h prior to shock induction did not exert sustained protective effects on intestinal µHbO 2 , microcirculatory perfusion, or mitochondrial function. Conclusions RIPC applied 24 h before hemorrhagic shock failed to improve tissue oxygenation, microcirculation, and mitochondrial function as key determinants of cell survival and organ function. Elucidating the molecular mechanisms underlying RIPC remains essential to enable its effective translation into clinical practice.

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