Effects of preconditioning on myocardial interstitial levels of ATP and its catabolites during regional ischemia and reperfusion in the rat |
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Authors: | AI Kuzmin AV Gourine AI Molosh VL Lakomkin G Vassort |
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Institution: | (1) Institute of Experimental Cardiology, National Cardiology Research Centre, 3rd Cherepkovskaya Street 15A, Moscow 121552, Russia, RU;(2) Belorussian Research Institute of Cardiology, R. Luxemburg Street 110, Minsk, Republic of Belarus, BY;(3) Laboratoire de Physiopathologie, Cardiovasculaire, INSERM U-390, CHU Arnaud de Villeneuve, F-34295 Montpellier Cédex, France, FR |
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Abstract: | The interstitial accumulation of adenine nucleotide breakdown products (ANBP) in the myocardium during ischemia has been
shown to provide a useful index of the ischemic injury, whereas reperfusion ANBP washout rate has been regarded as an index
of reperfusion damage. The purpose of this study was, using cardiac microdialysis, to examine in the rat model of regional
ischemia/reperfusion the relationship between the duration of ischemia and these indices and to assess the profile of interstitial
ATP concentrations and the beneficial effects of ischemic preconditioning (IP). The rats underwent 10, 20, 30 or 40 min of
coronary artery occlusion and 50 min of reperfusion. Regional ischemia, with its duration, provoked a progressive increase
in dialysate ANBP in the ischemic zone. The rate of purine washout during reperfusion exponentially declined with an increase
in duration of the ischemic period. IP, induced by three 5-min episodes of ischemia, each separated by 5 min of reperfusion,
significantly reduced the accumulation of ANBP during the 30-min period of sustained ischemia and resulted in a marked acceleration
of reperfusion ANBP washout, indicating the improvement of postischemic microcirculation. These effects were suggested to
be, at least in part, responsible for the infarct size limitation observed. Using the relationship between the duration of
ischemia and ANBP washout rate, it could be demonstrated that IP produced similar facilitation of purine washout as shortening
of the ischemic period in nonpreconditioned rats from 30 to approximately 7 min. Regional 20-min ischemia induced an early
peak increase in interstitial fluid ATP which correlated with the maximal incidence of ventricular arrhythmias, whereas IP
abolished both ATP release and arrhythmias during the sustained ischemia. These findings suggest that ATP may be an important
mediator of ischemia-induced ventricular arrhythmias.
Received: 20 April 1999, Returned for 1. revision: 11 May 1999, 1. Revision received: 23 June 1999, Returned for 2. revision:15
July 1999, 2. Revision received: 27 September 1999, Accepted: 29 September 1999 |
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Keywords: | Cardiac microdialysis – adenine nucleotide breakdown products – ATP – ischemia/reperfusion – preconditioning |
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