Uncomplicated rapid posthypothermic rewarming alters cerebrovascular responsiveness.
OBJECTIVE
Recently, we focused on the cerebrovascular protective effects of moderate hypothermia after traumatic brain injury, noting that the efficacy of posttraumatic hypothermia is related to the rate of posthypothermic rewarming. In the current communication, we revisit the use of hypothermia with varying degrees of rewarming to ascertain whether, in the normal cerebral vasculature, varying rates of rewarming can differentially affect cerebrovascular responsiveness.


METHODS
Pentobarbital-anesthetized rats equipped with a cranial window were randomized to 3 groups. In 1 group, a 1-hour period of hypothermia (32 degrees C) followed by slow rewarming (over 90 minutes) was used. In the remaining 2 groups, either a 1- or 2-hour period of hypothermia was followed by rapid rewarming (within 30 minutes). Vasoreactivity to hypercapnia and acetylcholine was assessed before, during, and after hypothermia. Additionally, the vascular responses to sodium nitroprusside (SNP) and pinacidil, a K(ATP) channel opener, were also examined.


RESULTS
Hypothermia itself generated modest vasodilation and reduced vasoreactivity to all utilized agents. The slow rewarming group showed restoration of normal vascular responsivity. In contrast, hypothermia followed by rapid rewarming was associated with continued impaired responsiveness to acetylcholine and arterial hypercapnia. These abnormalities persisted even with the use of more prolonged (2-hour) hypothermia. Furthermore, posthypothermic rapid rewarming impaired the dilator responses of SNP and pinacidil.


CONCLUSIONS
Posthypothermic rapid rewarming caused cerebral vascular abnormalities, including a diminished response to acetylcholine, hypercapnia, pinacidil, and SNP. Our data with acetylcholine and SNP suggest that rapid rewarming most likely causes abnormality at both the vascular smooth muscle and endothelial levels.
Ueda
Yuji
Y
Department of Anatomy and Neurobiology, Medical College of Virginia Campus of Virginia Commonwealth University, Richmond, VA 23298-0709, USA.
Suehiro
Eiichi
E
Wei
Enoch P
EP
Kontos
Hermes A
HA
Povlishock
John T
JT
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002245:Carbon Dioxide / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D006935:Hypercapnia / Q000503:physiopathology; D007036:Hypothermia, Induced / Q000379:methods*; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D020110:Pinacidil / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017694:Rewarming / Q000009:adverse effects* / Q000379:methods*; D013997:Time Factors; D014654:Vascular Patency / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology; D014666:Vasomotor System / Q000187:drug effects / Q000502:physiology*
D014665:Vasodilator Agents; D002245:Carbon Dioxide; D009599:Nitroprusside; D020110:Pinacidil; D000109:Acetylcholine