Bradykinin pretreatment improves ischemia tolerance of the rabbit heart by tyrosine kinase mediated pathways

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17 Scopus citations

Abstract

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°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 μM bradykinin-enriched KHB and cardioplegic arrest with 0.1 μM bradykinin-enriched StTCP. Seven others received 40 μM Genistein (Research Biochemicals, Natick, MA), a selective inhibitor of TK, added to both the 0.1-μM bradykinin-enriched KHB and 0.1-μM 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.

Original languageEnglish (US)
Pages (from-to)1567-1572
Number of pages6
JournalAnnals of Thoracic Surgery
Volume68
Issue number5
DOIs
StatePublished - Nov 1 1999
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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