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

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Abstract

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·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.

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Authors and Affiliations

  1. Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

    Giuseppina Milano, Antonio F. Corno & Ludwig K. von Segesser

  2. Thorax Center, Erasmus University Rotterdam, Rotterdam, The Netherlands

    Jan Willem de Jong

  3. Dipartimento di Medicina Chirurgia e Odontoiatria, Ospedale San Paolo, Via di Rudinì 8, 20142, Milano, Italy

    Michele Samaja

Authors
  1. Giuseppina Milano
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  2. Antonio F. Corno
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  3. Jan Willem de Jong
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  4. Ludwig K. von Segesser
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  5. Michele Samaja
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Correspondence to Michele Samaja.

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Milano, G., Corno, A.F., de Jong, J.W. et al. Tolerance of isolated rat hearts to low-flow ischemia and hypoxia of increasing duration: Protective role of down-regulation and ATP during ischemia. Mol Cell Biochem 226, 141–151 (2001). https://doi.org/10.1023/A:1012708324876

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