Bradykinin pretreatment improves ischemia tolerance of the rabbit heart by tyrosine kinase mediated pathways Jun Feng, MD, PhD, Eliot R Rosenkranz, MD

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Presentation transcript:

Bradykinin pretreatment improves ischemia tolerance of the rabbit heart by tyrosine kinase mediated pathways Jun Feng, MD, PhD, Eliot R Rosenkranz, MD The Annals of Thoracic Surgery Volume 68, Issue 5, Pages 1567-1572 (November 1999) DOI: 10.1016/S0003-4975(99)01041-3

Fig 1 Experimental protocol. Group 1 hearts received no pretreatment before arrest with St Thomas’ cardioplegia solution (StTCP). Group 2 hearts were pretreated with bradykinin (BK) before arrest with StTCP supplemented with BK. Group 3 hearts were pretreated with Genistein (Gen) and BK pretreatment before arrest with StTCP supplemented with both BK and Gen. (Hatched bars = ischemic period; KHB = Krebs-Henseleit Buffer.) The Annals of Thoracic Surgery 1999 68, 1567-1572DOI: (10.1016/S0003-4975(99)01041-3)

Fig 2 Recovery of left ventricular developed pressure (LVDP). Bradykinin slightly increased LVDP during pretreatment and significantly improved recovery throughout the period of reperfusion. Genistein completely blocked the salutary effect of bradykinin pretreatment. Data points represent the mean ± the standard error of the mean. (BK = Bradykinin; Gen = Genistein.) The Annals of Thoracic Surgery 1999 68, 1567-1572DOI: (10.1016/S0003-4975(99)01041-3)

Fig 3 Recovery of left ventricular contractility (+dP/dt). Bradykinin pretreatment significantly improved the recovery of contractility compared with control hearts. Genistein prevented this recovery. Data points represent the mean ± the standard error of the mean. (BK = Bradykinin; Gen = Genistein.) The Annals of Thoracic Surgery 1999 68, 1567-1572DOI: (10.1016/S0003-4975(99)01041-3)

Fig 4 Recovery of left ventricular end diastolic pressure (LVEDP). LVEDP rose significantly in all hearts during ischemia and declined during reperfusion. LVEDP was significantly lower throughout reperfusion in Bradykinin-pretreated hearts. Genistein prevented this recovery. Data points represent the mean ± the standard error of the mean. (BK = Bradykinin; Gen = Genistein.) The Annals of Thoracic Surgery 1999 68, 1567-1572DOI: (10.1016/S0003-4975(99)01041-3)

Fig 5 Recovery of left ventricular compliance (−dP/dt). Bradykinin pretreatment significantly improved the recovery of compliance compared with control hearts. Genistein prevented this recovery. Data points represent the mean ± the standard error of the mean. (BK = Bradykinin; Gen = Genistein.) The Annals of Thoracic Surgery 1999 68, 1567-1572DOI: (10.1016/S0003-4975(99)01041-3)

Fig 6 Recovery of coronary flow (CF). Bradykinin increased CF during pretreatment and significantly improved its recovery throughout the period of reperfusion. Genistein completely blocked the salutary effect of bradykinin pretreatment. Data points represent the mean ± the standard error of the mean. (BK = Bradykinin; Gen = Genistein.) The Annals of Thoracic Surgery 1999 68, 1567-1572DOI: (10.1016/S0003-4975(99)01041-3)

Fig 7 Proposed molecular mechanisms involved in bradykinin pretreatment. Solid arrows refer to pathways requiring protein tyrosine kinase (TK) activation. Dashed arrows refer to alternative pathways involving protein kinase C (PKC). (Perpendicular lines = inhibition; MAP kinase = p38MAP kinase; KATP = ATP-sensitive potassium channel.) The Annals of Thoracic Surgery 1999 68, 1567-1572DOI: (10.1016/S0003-4975(99)01041-3)