Mitochondrial respiration following acute hypoxia in the perfused rat heart.

Mitochondria isolated from tissues of hypoxic animals have increased respiratory capacity (State 3 respiration) when assayed in vitro at ambient oxygen tensions. The present study utilized the isolated perfused rat heart to determine whether or not this change could be produced in the absence of the neural and hormonal changes that accompany hypoxia in vivo. Following 10-min single pass retrograde perfusion with normoxic Krebs-Henseleit buffer (PO2 greater than or equal to 600 mmHg), perfusion was continued for up to 15 min with either normoxic or hypoxic buffer (PO2 less than or equal to 150 mmHg). After 10 min of hypoxic perfusion State 3 respiration of the mitochondria from the hypoxic hearts was 13 to 15% higher (P less than or equal to 0.05) than that of normoxic hearts when assayed with either glutamate/malate or succinate as substrate but was unchanged when TMPD and ascorbate was the substrate. Succinate-supported State 4 respiration of the hypoxic mitochondria also showed a small (10%) but significant (P less than or equal to 0.05) increase. These changes were not abolished by preperfusing the heart with propranolol (10(-7), 10(-6), or 10(-5) M) indicating that the response was not attributable to release of local stores of catecholamines. Respiratory control and ADP/O ratios as well as contents of cytochrome c and aa3 of the mitochondria from the hypoxic hearts were similar to those of normoxic hearts indicating that the mitochondria remained intact and tightly coupled. We concluded that the hypoxia-induced increase in mitochondrial State 3 respiration, while independent of neural and hormonal influences from the body requires an intracellular event, since they cannot be reproduced by subjecting isolated mitochondria to hypoxia in vitro.