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Protective effect of propranolol on mitochondrial function in the ischaemic heart.

ABSTRACT: 1. The present study was aimed to determine whether propranolol improves contractile function of the ischaemic/reperfused heart through protection of the mitochondrial function during ischaemia. 2. Isolated perfused rat hearts were subjected to 35-min ischaemia followed by 60-min reperfusion. Pre-treatment with propranolol at the concentrations of 10 to 100 microM for the final 3 min of pre-ischaemia resulted in the improvement of ischaemia/reperfusion-induced contractile dysfunction, release of creatine kinase (CK) into perfusate, and decrease in myocardial high-energy phosphates. Propranolol also attenuated ischaemia-induced accumulation in Na+, suggesting that cytosolic sodium overload during ischaemia was prevented by propranolol. 3. The mitochondrial oxygen consumption rate of skinned bundles from the perfused heart decreased at the end of ischaemia and it further decreased at the end of reperfusion. These decreases were cancelled by treatment with propranolol. A release of cytochrome c from the perfused heart was observed during ischaemia, and this release was suppressed by treatment with propranolol. 4. To elucidate the direct effect of propranolol on mitochondria, the mitochondria were isolated from normal hearts and their activities were determined in the presence of various concentrations of Na+ and propranolol. The addition of sodium lactate, which mimicked sodium overload in the ischaemic heart, reduced the state 3 respiration, whereas this reduction was not attenuated by the presence of propranolol. 5. These results suggest that cardioprotection of propranolol may be exerted via attenuating Na+ influx into cardiac cells followed by prevention of the mitochondrial dysfunction in the ischaemic heart, leading to improvement of energy production of the heart during reperfusion.

SUBMITTER: Iwai T

PROVIDER: S-EPMC1573362 | biostudies-other | 2002 Jun

REPOSITORIES: biostudies-other

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Protective effect of propranolol on mitochondrial function in the ischaemic heart.

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