Effects of graded perfusion and isovolumic work on epicardial and venous adenosine and cytosolic metabolism

Role of K+ ATP channels and adenosine in the regulation of coronary blood flow during exercise with normal and restricted coronary blood flow.

“…The finding that adenosine opposed the hypoperfusion produced by K ϩ ATP channel blockade during exercise but not under resting conditions suggests that, after K ϩ ATP channel blockade, exercise caused further deterioration of the oxygen supply-demand balance, thereby augmenting the release of adenosine into the myocardial interstitial space. This hypothesis is supported by the findings of Berne and co-workers (26), who observed greater increases in interstitial adenosine concentrations in isovolumically beating hearts than in empty beating hearts when both underwent similar coronary blood flow reductions. Moreover, these authors observed excellent inverse correlations between the myocardial oxygen supply-demand balance and interstitial adenosine concentrations (26).…”

“…This hypothesis is supported by the findings of Berne and co-workers (26), who observed greater increases in interstitial adenosine concentrations in isovolumically beating hearts than in empty beating hearts when both underwent similar coronary blood flow reductions. Moreover, these authors observed excellent inverse correlations between the myocardial oxygen supply-demand balance and interstitial adenosine concentrations (26). Therefore, it is likely that, in the present study, impaired coronary vasodilation after K channels.…”

“…The present findings suggest that, when adenosine concentrations are relatively low, e.g., under resting conditions, the K ϩ ATP channel blocking (vasoconstrictor) effects of glibenclamide predominate over the K ϩ ATP channel activating (vasodilator) actions of adenosine. It is possible that, when exercise in the presence of glibenclamide causes further deterioration of the myocardial oxygen supplydemand balance, adenosine concentrations increase to levels that can effectively compete with glibenclamide, resulting in activation of the channels and coronary vasodilation (26,30).…”

Functional properties and responses to ischaemia‐reperfusion in Langendorff perfused mouse heart

“…7 demonstrate that a more consistent relation exists between functional recovery and ischaemic duration in the isovolumic versus the unloaded apicobasally contracting model. In the apiscobasal model, metabolic rate is only 65 YO of that for isovolumically contracting hearts (Table l), in agreement with the greater cost of isovolumic work (Headrick et al 1991). Ischaemic contracture was less pronounced and coronary reflow was greater in the apicobasal model, probably due to reduced vascular compression.…”

“…2000). We predicted greater tolerance to ischaemia in the apicobasal model, due to reduced metabolic rate or 'demand' in unloaded hearts (Headrick et al 1991), reduced contracture and vascular compression. It seems paradoxical that ventricular function recovered to a lesser extent in the apicobasal model (Figs 4, 6 and 7) despite reduced enzyme and purine efflux (both 5&60%0 of values for isovolumic hearts).…”