Hypoxia-hypotension decreases pressor responsiveness to exogenous catecholamines after severe traumatic brain injury in rats

Objective. To quantify the phenylephrine pressor responsiveness after sever e brain injury combined with hypoxia-hypotension, and to study the respecti ve roles of brain injury and hypoxia-hypotension in the observed alteration . Design: Randomized study. Setting. Accredited animal laboratory. Subjects: Adult Sprague Dawley rats. Interventions: Anesthetized animals were assigned to control, brain injury, hypoxia-hypotension, and brain injury combined with hypoxia-hypotension gr oups. Brain injury was induced with an impact-acceleration device. During t he 15-min hypoxia-hypotension, arterial oxygen pressure was decreased to 40 torr (5.3 kPa) and mean arterial pressure to 30 mm Hg. Thirty-six of the 5 3 included rats were alive at the end of hypoxia-hypotension (nine animals per group). In an additional group (Hypo, n = 8), mean arterial pressure wa s lowered to the level observed in brain injury combined with hypoxia-hypot ension with pentobarbital infusion. Sixty minutes after injuries (T60), ani mals received 0.1, 1, and 10 mug/kg phenylephrine in a random order. Presso r responsiveness to phenylephrine was defined as maximal postinjection minu s preinjection mean arterial pressure. Measurements and Main Results, During hypoxia-hypotension, mortality was hi gher and residual restored blood volume was lower (p < .01) in the animals with brain injury and hypoxia-hypotension compared with hypoxia-hypotension alone. At T60, mean arterial pressure (mm Hg) was lower (p < .01) in the b rain injury group (83 +/- 22) compared with controls (110 +/- 10) and in br ain injury combined with hypoxia-hypotension (76 +/- 18) compared with cont rols and hypoxia-hypotension (107 +/- 14). Pressor responsiveness (mm Hg) t o 1 and 10 mug/kg phenylephrine was less (p < .05) in brain injury combined with hypoxia-hypotension (15 +/- 6 and 44 +/- 8) and hypoxia-hypotension ( 15 +/- 3 and 44 +/- 8) compared with controls (26 +/- 2 and 57 +/- 11). No significant difference was observed for phenylephrine pressor responsivenes s between controls and the Hypo group (25 +/- 5 and 66 +/- 7). Conclusions, Combination of brain injury and hypoxia-hypotension induces a severe hemodynamic alteration associated with a decreased pressor responsiv eness to phenylephrine. Transient hypoxia-hypotension is responsible for th e depressed alpha -1 adrenergic reactivity.