Abstract
"Uncontrolled bleeding," "a controlled prefixed bleeding volume," or "controlled decrements in blood pressure" are traditional models of experimental hemorrhagic shock. They are influenced by compensatory mechanisms and do not adequately reflect the severity of the cellular insult as a major target for therapeutic strategies. The aim of this study was to develop an animal model that uses oxygen debt (OD) and metabolic acidemia as indicators of hemorrhage severity. Twenty-five female pigs (mean weight: 23.8 kg) were anesthesized and randomized to 1 of 5 groups of increasing OD (<50 through >120 mL/kg). The predetermined OD was accrued by hemorrhage uniformly over 60 min and followed by retransfusion. The animals were allowed to recover under anesthesia for 200 min and were then observed for 3 days. The extent of metabolic derangements were quantified by arterial base excess (BE) and plasma lactate (LAC) measurements. OD, BE, and LAC were shown to be superior as predictors of outcome in comparison with traditional variables ("bleeding volume," "blood pressure," "cardiac output") in correlation and regression. Of the analyzed predictors of outcome, BE and LAC showed the highest correlation to levels of OD (r = -0.78, 0.8 respectively; P < 0.0001), and regression models were developed. The LD50 for OD was 95.0 mL/kg, for BE -15.3 mmol/L and for LAC 7.7 mmol/L. By using the developed regression models, it is possible to estimate accurately the actual level of OD from BE and LAC values obtained during hemorrhagic shock. OD, BE, and LAC appear to be optimal indicators of severity for a pig hemorrhagic shock model.
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