We tested the hypothesis that down-regulated hearts, as observed during low-flow ischemia, adapt better to low O-2 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 O-2 shortage) for 20, 40 or 60 min (n = 8/group), followed by reperfusion or reoxygenation (20 min, full O-2 supply). At the end of the O-2 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.min(-1)), but increased significantly during hypoxia (0.334 +/- 0.079 mmHg.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.

Tolerance of isolated rat hearts to low-flow ischemia and hypoxia of increasing duration: Protective role of down-regulation and ATP during ischemia / G. Milano, A. Corno, J. de Jong, L. von Segesser, M. Samaja. - In: MOLECULAR AND CELLULAR BIOCHEMISTRY. - ISSN 0300-8177. - 226:1-2(2001), pp. 141-151.

Tolerance of isolated rat hearts to low-flow ischemia and hypoxia of increasing duration: Protective role of down-regulation and ATP during ischemia

M. Samaja
Ultimo
2001

Abstract

We tested the hypothesis that down-regulated hearts, as observed during low-flow ischemia, adapt better to low O-2 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 O-2 shortage) for 20, 40 or 60 min (n = 8/group), followed by reperfusion or reoxygenation (20 min, full O-2 supply). At the end of the O-2 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.min(-1)), but increased significantly during hypoxia (0.334 +/- 0.079 mmHg.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.
Settore BIO/10 - Biochimica
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/181703
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