Shock-induced enhanced capillary permeability is associated with alterations in the interstitial matrix composition and contributes to organ damage. This study was designed to evaluate albumin extravasation in various organ tissues during severe, hemorrhagic shock without fluid resuscitation and reperfusion. Target value of hemorrhagic shock was a reduction of cardiac output (CO) by 50% induced by removal of blood. Twelve anesthetized Sprague-Dawley rats (260-325 g) kept under continuous hemodynamic monitoring were randomly assigned to a group of hemorrhagic shock (n = 6) and a control group of normovolemic animals (n = 6). After 30 min of shock 50 mg/kg b.w. Evans blue (EB) was injected intravenously followed by an incubation period of 20 min. Exsanguination and wash out of the intravascular space was performed by a pressure-controlled perfusion with heparinized saline before harvesting organs to quantify albumin-bound EB extravasation. We found that withdrawal of 4.7 +/- 0.4 mL (mean, +/-SEM) blood, which accounts for 21.1% of the calculated total blood volume, resulted in a reduction of CO from 36.1 +/- 3.1 to 19.4 +/- 2.7 mL/min. Simultaneously, MAP decreased from 98 +/- 6 to 40 +/- 1 mmHg. In hemorrhaged rats, the interstitial concentration of EB in lung and kidney was significantly higher than observed in intact animals, whereas heart, spleen, liver, ileum, skeletal muscle, and skin showed no significant microvascular damage. We conclude that despite the absence of fluid resuscitation and reperfusion, microvascular damage in lung and kidney is evident within the first thirty minutes of hemorrhagic shock.

This observation of increased microvascular albumin extravasation should be borne in mind for any interventional use of candesartan or enalaprilat during circulatory stress.

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Respiratory depression and apnoea during anaesthesia may lead to hypoxia and myocardial ischaemia. A self-inflating miniature bag-mask device was assembled combining characteristics from the Ambu-bag and the Kuhn-system. This bag-mask device permitted ventilation during anaesthesia-induced apnoea in rats until a safe airway by tracheotomy was achieved.