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× physiological (13 nm, n = 4), 5× physiological (20 nm, n = 4), or 10× 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 10× 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). 10× 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× nor 5× 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.
- stem cell paracrine
ASJC Scopus subject areas