Faculty Collaboration Database

Cardioprotection in chronically hypoxic rabbits persists on exposure to normoxia: role of NOS and KATP channels. Am J Physiol Heart Circ Physiol 2005 Jan;288(1):H62-8

Date

08/21/2004

Pubmed ID

15319200

DOI

10.1152/ajpheart.00701.2004

Scopus ID

2-s2.0-11144330066 (requires institutional sign-in at Scopus site)   45 Citations

Abstract

Hypoxia from birth increases resistance to myocardial ischemia in infant rabbits. We hypothesized that increased cardioprotection in hearts chronically hypoxic from birth persists following development in a normoxic environment and involves increased activation of nitric oxide synthase (NOS) and ATP-dependent K (K(ATP)) channels. Resistance to myocardial ischemia was determined in rabbits raised from birth to 10 days of age in a normoxic (Fi(O(2)) = 0.21) or hypoxic (Fi(O(2)) = 0.12) environment and subsequently exposed to normoxia for up to 60 days of age. Isolated hearts (n = 8/group) were subjected to 30 min of global ischemia followed by 35 min of reperfusion. At 10 days of age, resistance to myocardial ischemia (percent recovery postischemic recovery left ventricular developed pressure) was higher in chronically hypoxic hearts (68 +/- 4%) than normoxic controls (43 +/- 4%). At 10 days of age, N(G)-nitro-L-arginine methyl ester (200 microM) and glibenclamide (3 microM) abolished the cardioprotective effects of chronic hypoxia (45 +/- 4% and 46 +/- 5%, respectively) but had no effect on normoxic hearts. At 30 days of age resistance to ischemia in normoxic hearts declined (36 +/- 5%). However, in hearts subjected to chronic hypoxia from birth to 10 days and then exposed to normoxia until 30 days of age, resistance to ischemia persisted (63 +/- 4%). L-NAME or glibenclamide abolished cardioprotection in previously hypoxic hearts (37 +/- 4% and 39 +/- 5%, respectively) but had no effect on normoxic hearts. Increased cardioprotection was lost by 60 days. We conclude that cardioprotection conferred by adaptation to hypoxia from birth persists on subsequent exposure to normoxia and is associated with enhanced NOS activity and activation of K(ATP) channels.

Author List

Fitzpatrick CM, Shi Y, Hutchins WC, Su J, Gross GJ, Ostadal B, Tweddell JS, Baker JE

Author

John E. Baker PhD Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adaptation, Physiological
Adenosine Triphosphate
Animals
Animals, Newborn
Body Weight
Chronic Disease
Cytoprotection
Heart
Hypoxia
Myocardial Ischemia
Myocardium
Nitric Oxide Synthase
Organ Size
Potassium Channels
Rabbits