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J Surg Res. 2008 Dec;150(2):286-92. doi: 10.1016/j.jss.2007.12.772. Epub 2008 Jan 16.

Vascular endothelial growth factor improves myocardial functional recovery following ischemia/reperfusion injury.

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1
Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA.

Abstract

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.

PMID:
18619619
DOI:
10.1016/j.jss.2007.12.772
[Indexed for MEDLINE]
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