Nesiritide Enhances Myocardial Protection during the Revascularization of Acutely Ischemic Myocardium

Background: Nesiritide, a recombinant human B-type natriuretic peptide, has been used in conjunction with inotropic agents in the management of low cardiac output and pulmonary hypertension following cardiac surgery. However, its independent effects on intraoperative myocardial protection are unknown. This study was, therefore, undertaken to determine whether nesiritide alone could enhance myocardial protection when given intraoperatively in a porcine model simulating urgent coronary artery bypass graft surgery.

Results: Twenty pigs underwent occlusion of the second and third diagonal coronary arteries using snares for 90 minutes followed by 45 minutes of antegrade, cold blood cardioplegic arrest and 180 minutes of reperfusion on cardiopulmonary bypass during which the snares were released. Ten animals received an IV bolus of Nesiritide (2 mug per kg) at the initiation of coronary occlusion followed by a 0.01-mug/kg per min IV infusion during coronary occlusion, cardioplegic arrest, and reperfusion. Ten other animals underwent the same protocol without Nesiritide (placebo). Infarct size was assessed by the area of necrosis/area of risk using histochemical staining, endothelial function by the % change in coronary vasodilation using ring chamber methodology, and lung edema using % change in wet/dry weights. Nesiritide-treated animals had significantly decreased infarct size (23.44% 3.13 SD% vs. 37.95%+/- 1.05%; p < 0.003), better preservation of endothelial function (70.1%+/- 12.3% vs. 38.9%+/- 10.3%; p < 0.001), and less lung edema (3.39%+/- 2.13% vs. 4.72 +/- 1.14%; p = 0.23).

Conclusions: In a porcine model of acute coronary occlusion simulating urgent CABG surgery, the intraoperative infusion of nesiritide limits myocardial injury.