Tolerance of isolated rat hearts to low-flow ischemia and hypoxia of increasing duration: protective role of down-regulation and ATP during ischemia.
We tested the hypothesis that down-regulated hearts, as observed during low-flow ischemia, adapt better to low O2 supply than non-down-regulated, or hypoxic, hearts. To address the link between down-regulation and endogenous ischemic protection, we compared myocardial tolerance to ischemia and hypoxia of increasing duration. To that end, we exposed buffer-perfused rat hearts to either low-flow ischemia or hypoxia (same O2 shortage) for 20, 40 or 60 min (n = 8/group), followed by reperfusion or reoxygenation (20 min, full O2 supply). At the end of the O2 shortage, the rate-pressure product was less in ischemic than hypoxic hearts (p < 0.0001). The recovery of the rate-pressure product after reperfusion or reoxygenation was not different for t = 20 min, but was better in ischemic than hypoxic hearts for t = 40 and 60 min (p < 0.02 and p < 0.0002, respectively). The end-diastolic pressure remained unchanged during low-flow ischemia (0.024 +/- 0.013 mmHg x min(-1)), but increased significantly during hypoxia (0.334 +/- 0.079 mmHg x min(-1)). We conclude that, while the duration of hypoxia progressively impaired the rate-pressure product and the end-diastolic pressure, hearts were insensitive of the duration of low-flow ischemia, thereby providing evidence that myocardial down-regulation protects hearts from injury. Excessive ATP catabolism during ischemia in non-down-regulated hearts impaired myocardial recovery regardless of vascular, blood-related and neuro-hormonal factors. These observations support the view that protection is mediated by the maintenance of the ATP pool.
Milano
G
G
Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Corno
A F
AF
de Jong
J W
JW
von Segesser
L K
LK
Samaja
M
M
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D015536:Down-Regulation; D006321:Heart / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia; D007511:Ischemia; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000255:Adenosine Triphosphate; D010100:Oxygen