Document Detail

Chronic hypoxia induces adaptive metabolic changes in neonatal myocardium.
MedLine Citation:
PMID:  8691889     Owner:  NLM     Status:  MEDLINE    
The effect of chronic hypoxia on neonatal myocardial metabolism remains undefined. With a new neonatal piglet model, we determined changes in myocardial metabolism during global ischemia after chronic hypoxia. Five-day-old piglets (N = 30) were randomly assigned to two groups and exposed to an atmosphere of 8% oxygen or to room air for 28 days before they were killed. Left ventricular myocardium was then analyzed at control and at 15-minute intervals during 60 minutes of global normothermic ischemia to determine high-energy phosphate levels, glycogen stores, and lactate accumulation. Time to peak ischemic myocardial contracture was measured with intramyocardial needle-tipped Millar catheters as a marker of the onset of irreversible ischemic injury. Results showed an initially greater level of myocardial adenosine triphosphate in the hypoxic group (27 +/- 1.2 vs 19 +/- 1.8 micromol/gm dry wt, p = 0.001) and a delay in adenosine triphosphate depletion during 60 minutes of global ischemia compared with the control group. Initial energy charge ratios (1/2 adenosine diphosphate + adenosine triphosphate/adenosine monophosphate + adenosine diphosphate + adenosine triphosphate) were also greater in the hypoxic group (0.96 +/- 0.01 vs 0.81 +/- 0.04, p = 0.01) and remained so throughout global ischemia. Initial glycogen stores were greater in the hypoxic group (273 +/- 13.3 vs 215 +/- 14.7 micromol/gm dry weight, p = 0.02) when compared with the control group. Lactate levels in the hypoxic group were initially higher (19.1 +/- 6.4 vs 8.9 +/- 3.1 micromol/gm dry weight, p = 0.001) compared with control levels and remained elevated throughout 60 minutes of ischemia. Time to peak ischemic contracture was prolonged in the hypoxic group (69.5 +/- 1.8 vs 48.9 +/- 1.4 minutes, p = 0.001) compared with the controls group. These data show that chronic hypoxia results in significant myocardial metabolic adaptive changes, which in turn result in an improved tolerance to severe normothermic ischemia. These beneficial effects are associated with elevated baseline glycogen storage levels and an accelerated rate of anaerobic glycolysis during ischemia.
M D Plunkett; P J Hendry; M P Anstadt; E M Camporesi; M T Amato; J D St Louis; J E Lowe
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of thoracic and cardiovascular surgery     Volume:  112     ISSN:  0022-5223     ISO Abbreviation:  J. Thorac. Cardiovasc. Surg.     Publication Date:  1996 Jul 
Date Detail:
Created Date:  1996-08-23     Completed Date:  1996-08-23     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0376343     Medline TA:  J Thorac Cardiovasc Surg     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  8-13     Citation Subset:  AIM; IM    
Department of Surgery, Duke University Medical Center, Durham, NC, USA.
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MeSH Terms
Animals, Newborn
Anoxia / metabolism*
Chronic Disease
Disease Models, Animal
Glycogen / analysis
Myocardial Contraction
Myocardium / chemistry,  metabolism*
Ventricular Function, Left*
Grant Support
Reg. No./Substance:

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