Changes in levels of proteases, protease inhibitors, and inflammatory markers have been correlated with wound healing. These findings further support the idea that inflammatory dysregulation and a persistent inflammatory state leads to failure of wound healing in the acute setting. These findings highlight potential targets for the development of a biological assay to individualize management of complex soft-tissue wounds, based on patient physiology and response, that would be applicable to not only military trauma but also civilian trauma. Ultimately, this would result in earlier wound closure, reduction in the number of operating room trips, and reduced health care costs.

We investigated effects of bolus administration of corticotropin-releasing factor (CRF) on parameters of cardiac activity in isolated working rat hearts. Effects at a dose of 5 micrograms of CRF were compared in hearts perfused with Krebs-Henseleit solution, norepinephrine (NE, 10(-9) M), propranolol (3 x 10(-6) M), NG-nitro-L-arginine (L-NNA, 3 x 10(-5) M), or indomethacin (3 x 10(-5) M). CRF increased coronary flow for > 30 min (P < 0.01) with maximum increases of 31.7%, suggesting a prolonged vasodilatory action of the peptide. CRF, in addition, induced transient (lasting < 10 min) increases in maximum aortic pressure and oxygen consumption (P < 0.01), suggesting an inotropic action of the peptide. Perfusions of NE and propranolol did not change the cardiac response to CRF. L-NNA, inhibiting release of endothelium-derived relaxant factor (EDRF), and indomethacin diminished the vasodilatory response to CRF, as indicated by significantly shortened increases in coronary flow after CRF (P < 0.05). Indomethacin also enhanced peak increases in maximum aortic pressure after CRF (P < 0.01). The data confirm direct effects of CRF on cardiac activity. They also suggest that the mediation of coronary vasodilation by CRF involves the endothelial release of prostacyclin and EDRF.