Bradykinin pretreatment improves ischemia tolerance of the rabbit heart by tyrosine kinase mediated pathways.
BACKGROUND
Depressed myocardial performance is an important clinical problem after open-heart surgery. We hypothesized that: (1) pretreating the heart with bradykinin improves postischemic performance, and (2) bradykinin activates protein tyrosine kinase (TK).


METHODS
Twenty-seven adult rabbit hearts underwent retrograde perfusion with Krebs-Henseleit buffer (KHB) followed by 50 min 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 microM bradykinin-enriched KHB and cardioplegic arrest with 0.1 microM bradykinin-enriched StTCP. Seven others received 40 microM Genistein (Research Biochemicals, Natick, MA), a selective inhibitor of TK, added to both the 0.1-microM bradykinin-enriched KHB and 0.1-microM bradykinin-enriched StTCP solutions.


RESULTS
Bradykinin pretreatment significantly improved postischemic myocardial performance and coronary flow (CF) compared with control (left ventricular developed pressure: 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). Inhibition of TK with Genistein prevented this improvement in myocardial function, resulting in recovery equivalent to untreated controls.


CONCLUSIONS
Bradykinin pretreatment may be an important new strategy for improving myocardial protection during heart surgery. The molecular mechanism of action may be similar to those activated by ischemic preconditioning.
Feng
J
J
The Children's Hospital of Buffalo, and Department of Surgery, The State University of New York at Buffalo, 14222, USA.
Rosenkranz
E R
ER
D000818:Animals; D001639:Bicarbonates; D001920:Bradykinin / Q000494:pharmacology*; D002122:Calcium Chloride; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D003971:Diastole / Q000187:drug effects / Q000502:physiology; D006324:Heart Arrest, Induced; D019157:Ischemic Preconditioning, Myocardial; D008274:Magnesium; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D017202:Myocardial Ischemia / Q000503:physiopathology*; D011189:Potassium Chloride; D011292:Premedication; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011817:Rabbits; D012965:Sodium Chloride; D013599:Systole / Q000187:drug effects / Q000502:physiology; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
D001639:Bicarbonates; C041711:St. Thomas' Hospital cardioplegic solution; D012965:Sodium Chloride; D011189:Potassium Chloride; D011505:Protein-Tyrosine Kinases; D008274:Magnesium; D002122:Calcium Chloride; D001920:Bradykinin