The angiogenic stimulators VEGF and naltrexone induce development of veins and arteries in a proportional manner. In contrast, the angiogenic inhibitors OGF and retinoic acid demonstrated a greater inhibitory effect on arterial as compared with venous angiogenesis. Such differential effects on angiogenesis may be important in both defining mechanisms of action and designing therapeutic interventions.

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Mitochondrial dynamics are altered in favor of mitochondrial fission during MI/R. Mitochondrial fission is associated with shortening of mitochondria, decreased ATP production, and increased reactive oxygen species during MI/R, and is thought to promote cardiomyocyte loss. Therefore, inhibition of mitochondrial fission may be a new strategy to salvage injured cardiac myocytes and limit infarct size. To test this hypothesis, the cardioprotective effects of a novel mitochondrial fission inhibitor, P110 (MW=2427 g/mol), a cell permeable peptide, that selectively inhibits the interaction between dynamin related protein 1 and fission protein 1, were determined in isolated perfused rat hearts subjected to I (30 min)/R (45 min). P110 (1 µM) given for 10 min before ischemia and for 20 min post‐reperfusion, significantly restored left ventricular developed pressure (LVDP) and the peak of the first derivative of left ventricular pressure (dP/dtmax) to 77 ± 9% and 58 ± 7% of baseline values at 45 min post‐reperfusion, respectively, as compared to control I/R hearts (both p<0.01, n=6). The LVDP and dP/dtmax of control I/R hearts (n=8) only recovered to 34 ± 8% and 29 ± 4% of baseline values at 45 min post‐reperfusion, respectively. P110 also significantly reduced infarct size to 20 ± 3% compared to 41 ± 4% in control I/R hearts (p<0.01). The preliminary results suggest that inhibition of mitochondrial fission during MI/R improves post‐reperfused cardiac contractile function and reduces infarct size.