Paradoxical Arteriole Constriction Compromises Cytosolic and Mitochondrial Oxygen Delivery in the Isolated Saline-Perfused Heart.

The isolated saline-perfused heart is utilized extensively to study cardiac physiology. Previous isolated heart studies demonstrated lower tissue oxygenation than in vivo based on myoglobin oxygenation and mitochondria redox state. These data, consistent with small anoxic regions, suggest that the homeostatic balance between work and oxygen delivery is impaired. We hypothesized these anoxic regions are caused by inadequate local perfusion due to a paradoxical arteriole constriction (PAC) generated by a disrupted vasoregulatory network. We tested this hypothesis by applying two exogenous vasodilatory agents, adenosine and cromakalim, to relax vascular tone in an isolated, saline-perfused, working rabbit heart. Oxygenation was monitored using differential optical transmission spectroscopy and full spectral fitting. Increases in coronary flow over control with adenosine (27 ± 4 mL/min) or cromakalim (44 ± 4 mL/min) were associated with proportional spectral changes indicative of myoglobin oxygenation and cytochrome oxidase (COX) oxidation consistent with a decrease in tissue anoxia. Quantitatively, adenosine decreased deoxymyoglobin optical density across the wall by .053 ± .008 OD while the reduced form of COX was decreased by .039 ± .005 OD. Cromakalim was more potent decreasing deoxymyoglobin and reduction level of COX by .070 ± .019 OD and .062 ± .019 OD, respectively. These effects were not species specific as Langendorff perfused mouse hearts treated with adenosine demonstrated similar changes. These data are consistent with PAC as a major source of regional anoxia during saline heart perfusion. We suggest that the vasoregulatory network is disrupted by the washout of interstitial vasoactive metabolites, in vitro.