S. Holtzer et al., Hypoxia-hypotension decreases pressor responsiveness to exogenous catecholamines after severe traumatic brain injury in rats, CRIT CARE M, 29(8), 2001, pp. 1609-1614
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.