Myoglobin supported oxygen consumption in isolated rat hearts under dysoxic conditions

Abstract

Oxygen consumption was assessed in contracting, isolated rat hearts subjected to Langendorff perfusion. Initially, hearts were perfused with Krebs-Henseleit bicarbonate medium (KHB). Some hearts were treated with a 10 min pulse of medium containing 0.05 m m phenylhydrazine to oxidize approximately 78% of myoglobin to a state incapable of binding oxygen. Stepwise reduction in input P o 2 resulted in a decline in oxygen consumption (MO 2) in control and treated hearts. Phenylhydrazine treatment had no effect upon MO 2 in hearts perfused with medium having a P o 2 of about 585 mmHg or higher. However, at an input P o 2 of approximately 370 mmHg, MO 2 was decreased to 60% of the level at an input P o 2 of 710 mmHg in untreated hearts and significantly lower to 32% of initial level in myoglobin blocked hearts. In subsequent experiments, hearts were perfused with KHB containing human red blood cells (RBCs) to elevate the oxygen content of the perfusate. The addition of RBCs to medium having a P o 2 of ≈ 140 mmHg resulted in enhancement of MO 2 and maintenance of performance. But the preparations were considered to be dysoxic since MO 2 with RBCs in the medium was lower than under perfusion with KHB. This should however not detract from the utility of the model in elucidating myoglobin function under oxygen limiting conditions. At an input P o 2 of 140 mmHg hearts treated with phenylhydrazine to impede myoglobin function had a significantly lower MO 2 and viability than untreated hearts. The difference was even more emphatic at an input P o 2 of 40 mmHg where untreated hearts survived for at least 45 min but all myoglobin blocked hearts failed within 7 min. These studies support the contention that myoglobin plays a critical role in oxygen consumption by the intact mammalian heart under conditions which are considered to be dysoxic.