Haemodynamic and metabolic changes induced by repeated episodes of hypoxia in pigs

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Abstract
Background: Repeated hypoxia and surgical trauma trigger a potent neuroendocrine response and their association is thought to play a pivotal role in the pathogenesis of multi‐organ dysfunction. We investigated the cardiovascular and metabolic responses to repeated acute hypoxia in anaesthetised and surgically instrumented pigs. Methods: Under ketamine‐midazolam anaesthesia, 15 pigs were surgically instrumented for measurements of cardiac output, vascular pressures and organ blood flows. Lactate production and O2 uptake were determined in the brain, liver, kidney and intestine. Ten animals were subjected to two 12‐min periods of ventilatory hypoxia (FIO2=7%) followed by re‐oxygenation and 5 animals underwent 120–min normoxic ventilation (Control group). Results: Both hypoxic challenges produced a comparable release of catecholamines that was associated with increased cardiac output and redistribution of blood flow away from the intestinal and renal areas towards the brain and the liver; O2 uptake was markedly reduced in the intestine (– 56 ± 10%, P < 0.05) and least affected in the brain and the kidney (– 19±12% and — 23±21%, respectively). During the second hypoxic test, lethal cardiovascular depression occurred in 5 animals; these non‐survivors demonstrated impaired hyperdynamic response and incomplete recovery of intestinal O2 uptake during the first hypoxia/reoxygenation test. In the Control group, normoxic ventilation was not associated with significant haemodynamic and metabolic changes. Conclusion: Intraoperative hypoxia causes marked heterogeneity in organ blood flow and metabolism. The inability to develop a hyperdynamic cardiovascular response during a first hypoxic event, as well as a persistent intestinal O2 debt following re‐oxygenation, predict the occurrence of death during the second hypoxic insult.