Effect of myocardial reperfusion on the release of nitric oxide after regional ischemia: an experimental model of beating-heart surgery

Abstract

Off-pump coronary artery bypass surgery is increasing in popularity worldwide. However, very little is known about the effect of regional myocardial ischemia-reperfusion on nitric oxide release. In an animal model mimicking off-pump bypass, male Sprague-Dawley rats (350-450 g) were mechanically ventilated under general anesthesia. After left lateral thoracotomy, the animals underwent occlusion of either the left anterior descending artery (for 3, 5, 75, 10, 12.5, 15, or 20 minutes) or the circumflex artery (for 5, 10, or 15 minutes). Twenty-four hours after reperfusion, heart tissue was stained for determination of the area at risk and the infarcted area. Blood samples obtained before ischemia, 10 minutes after reperfusion, and 24 hours after reperfusion were analyzed for plasma concentrations of nitric oxide. After occlusion of the left anterior descending artery, the size of the infarcted area increased dramatically as the duration of occlusion increased, and was significantly larger after 12.5, 15, or 20 minutes of occlusion than after 3 minutes. After occlusion of the circumflex artery, the size of the infarcted area increased steadily and was significantly larger after 15 minutes of occlusion than after 5 minutes. There was no significant correlation between the duration of coronary occlusion and the plasma concentration of nitric oxide: 10 minutes after reperfusion, this concentration was significantly lower than that before ischemia, but it was twice the baseline level 24 hours after reperfusion. We concluded that the duration of regional ischemia did not affect the plasma concentration of nitric oxide in the systemic circulation.

Fig. 1 The IF/AR in the LAD occlusion group. IF/AR = infarcted area divided by the area at risk (%); LAD = left anterior descending artery *P <0.01 compared with results after 3 min of ischemia; P <0.05 compared with results after 5 min of ischemia **P <0.0001 compared with results after 3, 5, 7.5, 10, and 12.5 min of ischemia

Fig. 2 The IF/AR in the Cx occlusion group. IF/AR = infarcted area divided by the area at risk (%); Cx = circumflex artery *P <0.001 compared with results after 5 min of ischemia; P <0.05 compared with results after 10 min of ischemia

Fig. 3 Correlation between the duration of coronary artery occlusion and the plasma concentration of nitric oxide (NO): A) before ischemia, B) 10 minutes after reperfusion, and C) 24 hours after reperfusion. There was no statistically significant correlation between the duration of coronary artery occlusion and the plasma concentration of NO at any time-point of sampling.

Fig. 4 Time course of the plasma concentration of nitric oxide (NO). Samples from the control rats were not included. *P <0.05 compared with concentration before ischemia **P <0.0001 compared with concentration before ischemia and 10 min after reperfusion