Bradykinin protects the rabbit heart after cardioplegic ischemia via NO-dependent pathways

Background. Depressed myocardial performance is an important clinical problem after open heart surgery. We hypothesized pretreating with bradykinin would pharmacologically precondition the heart and improve postischemic performance, and induce myocardial preconditioning by activating nitric oxide synthase. Methods. Thirty-three rabbit hearts underwent retrograde perfusion with Krebs-Henseleit buffer (KHB) followed by 50 minutes of 37 degreesC cardioplegic ischemia with St. Thomas' cardioplegia solution (StTCP). Ten control hearts received no pretreatment. Ten bradykinin-pretreated hearts received a 10-minute infusion of 0.1 mu Mol/L bradykinin-enriched KHB and cardioplegic arrest with 0.1 mu Mol/L bradykinin-enriched StTCP. Six other hearts received 0.1 mu Mol/L HOE 140, a selective B2 receptor antagonist, added to both the 0.1 mu Mol/L bradykinin-enriched KHB and 0.1 mu Mol/L bradykinin-enriched StTCP solutions. Finally, six other hearts received 100 mu Mol/L of N-Omega -nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, added to both the 0.1 mu Mol/L bradykinin-enriched KHB and 0.1 mu Mol/L bradykinin-enriched StTCP solutions. Results. Bradykinin pretreatment significantly improved postischemic performance and coronary now (CF) compared with control (LVDP: 53 +/- 5* vs 27 +/- 4 mm Hg; +dP/dt(max): 1,025 +/- 93* vs 507 +/- 85 mm Hg/s; CF: 31 +/- 3* vs 22 +/- 2 mL/min; *p < 0.05). Both HOE 140 and L-NAME abolished bradykinin-induced protection, resulting in recovery equivalent to untreated controls. Conclusions. Bradykinin pretreatment improves recovery of ventricular and coronary vascular function via nitric oxide-dependent mechanisms. Pharmacologic preconditioning by bradykinin pretreatment may be an important new strategy for improving myocardial protection during heart surgery. (Ann Thorac Surg 2000;70:2119-24) (C) 2000 by The Society of Thoracic Surgeons.