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

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.

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.

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.

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.