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 post-ischemic 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 degrees C 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 microMol/L bradykinin-enriched KHB and cardioplegic arrest with 0.1 microMol/L bradykinin-enriched StTCP. Six other hearts received 0.1 microMol/L HOE 140, a selective B2 receptor antagonist, added to both the 0.1 microMol/L bradykinin-enriched KHB and 0.1 microMol/L bradykinin-enriched StTCP solutions. Finally, six other hearts received 100 microMol/L of N-omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, added to both the 0.1 microMol/L bradykinin-enriched KHB and 0.1 microMol/L bradykinin-enriched StTCP solutions.


RESULTS
Bradykinin pretreatment significantly improved postischemic performance and coronary flow (CF) compared with control (LVDP: 53 +/- 5* vs 27 +/- 4 mm Hg; +dP/dtmax: 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.
Feng
J
J
Daughtry Family Department of Surgery, University of Miami School of Medicine, Florida, USA.
Li
H
H
Rosenkranz
E R
ER
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D019157:Ischemic Preconditioning, Myocardial; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009569:Nitric Oxide / Q000502:physiology*; D011292:Premedication; D011817:Rabbits
D009569:Nitric Oxide; D001920:Bradykinin