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Regional Blood Flow --- Cardiac Output

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Background. Adenosine, a physiologic coronary vasodilator, has been proposed to regulate coronary circulation according to myocardial oxygen demand. In the present study, we have investigated the mechanisms of adenosine formation and utilization in isolated rabbit cardiomyocytes, and in particular the existence and the role of substrate cycling between AMP and adenosine in the regulation of its concentration.
Methods and results. Rabbit cardiomyocytes were isolated after isolated after collagenase perfusion and incubates in HEPES-buffered Krebs Henseleit solution at 37°C, pH 7,4, in control and during ATP depletion achieved by inhibiting glycolysis with 5 mM iodoacetate. Under control conditions, adenosine accumulated at a rate of 4 pmol/min/106 cells. The 13-fold elevation of adenosine accumulation induced by iodotubercidin (ITu), an inhibitor of adenosine kinase, shows that adenosine is normally recycled into AMP. This recycling involves 95 % of the adenosine formed. When cellular ATP was depleted, adenosine accumulated at the rate of 335 pmol/min/106 cells and was no longer rephosphorylated after 20min, as shown by the absence of effect of ITu after the time interval. Moreover, adenosine was deanimated as indicated by the 2-fold increase of its accumulation induced by deoxycoformycin (dCF), an inhibitor of adenosine deaminase. Both in control conditions and in ATP depletion, adenosine-dialdehyde, an inhibitor of S-adenosyl-homocysteine (SAH)-hydrolase, had no significant effect on adenosine formation, indicating that the transmethylation pathway is not an important source of adenosine in rabbit cardiomyocytes.
Conclusions. The results indicate that recycling of adenosine into AMP is essential for the maintenance of low, non-vasodilatory concentrations of the nucleoside under control conditions, and that interruption of the recycling plays an important role in elevating adenosine during ATP depletion

Substrate Cycling --- Adenosine --- Adenosine Triphosphate --- Regional Blood Flow

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Regional Blood Flow --- Coronary Vessels --- Coronary Vessels --- Myocardium --- Heart

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Arteriosclerosis Obliterans --- Leg --- Regional Blood Flow --- diagnosis --- blood supply

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Neuropathology --- Semiology. Diagnosis. Symptomatology --- Pathology of the circulatory system --- Regional blood flow --- Radioisotope scanning --- Cerebral circulation --- Measurement --- Regional blood flow - Measurement