BACKGROUND: Vascular endothelial growth factor (VEGF) is a central growth and survival factor for both the endothelium and the myocardium. Recent evidence also suggests that VEGF may play a critical role in stem-cell-mediated paracrine cardioprotection. However, the acute effect of exogenous VEGF on myocardium after ischemia, indeed whether isolated VEGF alone may be a clinically useful therapeutic modality, remains unknown. We hypothesize that infusion of exogenous VEGF immediately prior to ischemia will improve myocardial functional recovery. MATERIALS AND METHODS: Adult male Sprague Dawley rat hearts were isolated and perfused via Langendorff model. All hearts were subject to 15-min equilibration, 25-min warm global ischemia, and 40-min reperfusion. Experimental hearts received a VEGF infusion of 3 x physiological (13 nM, n = 4), 5x physiological (20 nM, n = 4), or 10x physiological (40 nM, n = 5) immediately prior to ischemia. Controls (n = 5) were infused with perfusate vehicle. Functional indices (left ventricular developed pressure), end diastolic pressure, +/-dP/dt were continuously recorded. RESULTS: End diastolic pressure (mmHg) was elevated in response to ischemia/reperfusion. However, hearts infused with 10x VEGF demonstrated significantly (P < 0.05, analysis of variance and Bonferroni's) decreased end diastolic pressure throughout reperfusion compared to control (49.82 +/- 10.35 mmHg versus 80.73 +/- 6.08 mmHg at end reperfusion). 10x VEGF-treated hearts also exhibited significantly (P < 0.05, analysis of variance and Bonferroni's) greater recovery of left ventricular developed pressure (69.97 +/- 9.69% versus 39.74 +/- 7.01% of equilibration), +dP/dt, and -dP/dt at end reperfusion. However, neither 3 x nor 5x VEGF improved recovery after ischemia. VEGF also did not influence coronary flow after ischemia. CONCLUSION: This is the first demonstration that exogenous VEGF administration acutely improves myocardial functional recovery after ischemia. These findings may help elucidate the role of VEGF in acute stem-cell-mediated paracrine effects and suggests that isolated VEGF may be of therapeutic value.
BACKGROUND:Vascular endothelial growth factor (VEGF) is a central growth and survival factor for both the endothelium and the myocardium. Recent evidence also suggests that VEGF may play a critical role in stem-cell-mediated paracrine cardioprotection. However, the acute effect of exogenous VEGF on myocardium after ischemia, indeed whether isolated VEGF alone may be a clinically useful therapeutic modality, remains unknown. We hypothesize that infusion of exogenous VEGF immediately prior to ischemia will improve myocardial functional recovery. MATERIALS AND METHODS: Adult male Sprague Dawley rat hearts were isolated and perfused via Langendorff model. All hearts were subject to 15-min equilibration, 25-min warm global ischemia, and 40-min reperfusion. Experimental hearts received a VEGF infusion of 3 x physiological (13 nM, n = 4), 5x physiological (20 nM, n = 4), or 10x physiological (40 nM, n = 5) immediately prior to ischemia. Controls (n = 5) were infused with perfusate vehicle. Functional indices (left ventricular developed pressure), end diastolic pressure, +/-dP/dt were continuously recorded. RESULTS: End diastolic pressure (mmHg) was elevated in response to ischemia/reperfusion. However, hearts infused with 10x VEGF demonstrated significantly (P < 0.05, analysis of variance and Bonferroni's) decreased end diastolic pressure throughout reperfusion compared to control (49.82 +/- 10.35 mmHg versus 80.73 +/- 6.08 mmHg at end reperfusion). 10x VEGF-treated hearts also exhibited significantly (P < 0.05, analysis of variance and Bonferroni's) greater recovery of left ventricular developed pressure (69.97 +/- 9.69% versus 39.74 +/- 7.01% of equilibration), +dP/dt, and -dP/dt at end reperfusion. However, neither 3 x nor 5x VEGF improved recovery after ischemia. VEGF also did not influence coronary flow after ischemia. CONCLUSION: This is the first demonstration that exogenous VEGF administration acutely improves myocardial functional recovery after ischemia. These findings may help elucidate the role of VEGF in acute stem-cell-mediated paracrine effects and suggests that isolated VEGF may be of therapeutic value.
Authors: Aaron M Abarbanell; Yue Wang; Jeremy L Herrmann; Brent R Weil; Jeffrey A Poynter; Mariuxi C Manukyan; Daniel R Meldrum Journal: Am J Physiol Heart Circ Physiol Date: 2010-02-19 Impact factor: 4.733
Authors: Troy A Markel; Yue Wang; Jeremy L Herrmann; Paul R Crisostomo; Meijing Wang; Nathan M Novotny; Christine M Herring; Jiangning Tan; Tim Lahm; Daniel R Meldrum Journal: Am J Physiol Heart Circ Physiol Date: 2008-10-10 Impact factor: 4.733
Authors: Troy A Markel; Paul R Crisostomo; Maiuxi C Manukyan; Dalia Al-Azzawi; Christine M Herring; Tim Lahm; Nathan M Novotny; Daniel R Meldrum Journal: J Surg Res Date: 2008-04-28 Impact factor: 2.192
Authors: Jeremy L Herrmann; Aaron M Abarbanell; Brent R Weil; Mariuxi C Manukyan; Jeffrey A Poynter; Benjamin J Brewster; Yue Wang; Daniel R Meldrum Journal: J Surg Res Date: 2010-06-16 Impact factor: 2.192
Authors: Robert M Osipov; Michael P Robich; Jun Feng; Richard T Clements; Yuhong Liu; Hilary P Glazer; John Wagstaff; Cesario Bianchi; Frank W Sellke Journal: J Appl Physiol (1985) Date: 2009-04-16
Authors: Xiaomei Niu; Mehdi Nouraie; Andrew Campbell; Sohail Rana; Caterina P Minniti; Craig Sable; Deepika Darbari; Niti Dham; N Scott Reading; Josef T Prchal; Gregory J Kato; Mark T Gladwin; Oswaldo L Castro; Victor R Gordeuk Journal: PLoS One Date: 2009-11-23 Impact factor: 3.240