O2 free radical-mediated myocardial and vascular dysfunction.

In the present investigation electrolysis of a physiological buffer solution for 2 min with a constant current (20 mA, DC stainless steel anode) was observed to generate free radicals, determined by a luminol assay. Rabbit isolated hearts perfused with physiological buffer subjected to electrolysis were observed to undergo an increase in coronary artery perfusion pressure (PP) and in left ventricular end-diastolic pressure (LVEDP), 80 +/- 4 and 52 +/- 7 mmHg, respectively. Immediately after electrolysis of the physiological buffer, the hearts were observed to accumulate and retain (8-fold) more 125I-labeled albumin than hearts perfused with normal buffer without electrolysis, indicating an increased vascular permeability. The free radical scavengers, dimethyl sulfoxide (DMSO) and catalase (CAT), provided significant protection of the hearts against the changes in PP, LVEDP, and vascular permeability. This study demonstrates that toxic oxygen species generated independently of circulating blood elements or enzymatic reactions can have a direct effect on the vasculature of an isolated heart leading to alterations in cardiac function. The protection afforded by the addition of DMSO or CAT to the perfusion system would suggest that the OH. radical and H2O2 were the reactive oxygen species involved in producing the observed vascular and cardiac effects.