Real-Time Measurement of Nitric Oxide in Coronary Outflow during Transient Myocardial Ischemia and Reperfusion

To examine the kinetics and determinants of the production and release of nitric oxide (NO) from a heart during transient myocardial ischemia and reperfusion, we directly measured NO in the coronary efluent from isolated beating rat hearts during reperfusion following transient myocardial ischemia using a newly developed NO microelectrode. Isolated rat hearts were perfused with an oxygenated Krebs-Henseleit buffered solution and were subjected to one-minute or ten-minute global ischemia followed by reperfusion at 100 cmH2O. The time course of measured NO current during reperfusion showed a monophasic pattern in the case of one-minute ischemia but a biphasic pattern in the case of ten-minute ischemia. Immediately after the onset of reperfusion, coronary flow increased almost stepwise after one-minute ischemia and gradually after ten-minute ischemia. After one-minute ischemia? measured NO current first stayed at a relatively low level and then gradually increased (monophasic pattern). After ten-minute ischemia, following a transient peak, the measured NO current gradually increased (biphasic pattern). There was an excellent linear relationship between coronary flow rate and the calculated amount of NO during the second rise of NO release in the case often-minute ischemia. These data suggest that the time course of NO release from a heart during reperfusion is determined by the production of NO during ischemia, which is ischemic-duration dependent, and by the reperfusion-rate dependent mechanism.