Copyright © 2006, European Society of Cardiology
Hyperoxic and hyperbaric-induced cardioprotection: Role of nitric oxide synthase 3
aDivision of Pediatric Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, United States
bDepartment of Plastic Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, United States
cDepartment of Transplant Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, United States
dCenter for Comprehensive Wound Care and Hyperbaric Oxygen Therapy, St. Luke's Medical Center, Milwaukee, WI 53215, United States
* Corresponding author. Division of Pediatric Surgery, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, United States. Tel.: +1 414 456 4644; fax: +1 414 453 9700. Email address: bgcab{at}yahoo.com
Objective: The relative contributions of the fraction of inspired oxygen (FIO2) and atmospheric pressure (ATM) to cardioprotection are unknown. We determined whether the product of FIO2xATM (oxygen partial pressure) controls the extent of hyperoxic+hyperbaric-induced cardioprotection and involves activation of nitric oxide synthase (NOS).
Methods: Adult Sprague Dawley rats (n=10/gp) were treated for 1 h with (1) normoxia+normobaria (21% O2 at 1 ATM), (2) hyperoxia+normobaria (100% O2 at 1 ATM), (3) normoxia+hyperbaria (21% O2 at 2 ATM) and (4) hyperoxia+hyperbaria (100% O2 at 2 ATM).
Results: Infarct size following 25 min ischemia and 180 min reperfusion was decreased following hyperoxia+normobaria and normoxia+hyperbaria compared with normoxia+normobaria and further decreased following hyperoxia+hyperbaria treatment. L-NAME (200 µM) reversed the cardioprotective effects of hyperoxia+hyperbaria. Nitrite plus nitrate content was increased 2.2-fold in rats treated with normoxia+hyperbaria and hyperoxia+hyperbaria. NOS3 protein increased 1.2-fold and association of hsp90 with NOS3 four-fold in hyperoxic+hyperbaric rats.
Conclusions: Cardioprotection conferred by hyperoxia+hyperbaria is directly dependent on oxygen availability and mediated by NOS.
KEYWORDS Hyperbaric oxygen; Nitric oxide; Ischemia; Infarction