BACKGROUND: Surface cooling is frequently used in a number of conditions, especially traumatic, ischemic, burn, and neurologic injury to reduce the tissue damage. However, the protective mechanisms of cold therapy on traumatized tissues remain unclear. Tumor necrosis factor-alpha (TNF-alpha) is a fundamental mediator in inflammatory reactions and trauma-induced tissue injury. In the present study, we examined the microvascular response to TNF-alpha challenge and the effects of local cooling on the TNF-alpha-induced changes in the striated muscle of hamsters. METHODS: By the use of the dorsal skinfold chamber preparation and in vivo fluorescence microscopy in combination with computer-based image analysis, we determined TNF-alpha-induced leukocyte rolling and adhesion to microvascular endothelium, capillary perfusion, venular leakage, and cellular apoptosis with and without surface cooling. RESULTS: We found that topical administration of 2000 units TNF-alpha caused a progressive impairment of microvascular perfusion and increased leukocyte recruitment and vascular macromolecular leakage. Local cooling to 10 degrees C for 60 minutes markedly (P < .05) inhibited the TNF-alpha-induced capillary perfusion failure and leukocyte response and slightly attenuated the increase of microvascular permeability after 180 minutes of stimulation. Furthermore, it was observed that 24 hours of TNF-alpha stimulation increased the number of apoptotic cells (i.e., nuclear condensation and fragmentation) by 10-fold. This TNF-alpha-mediated effect was almost abolished by treatment with local hypothermia. CONCLUSION: These data suggest that the protective effect of surface cooling of traumatized tissue is due to its attenuation of the microvascular inflammatory response associated with the inhibition of the process of apoptosis.
BACKGROUND: Surface cooling is frequently used in a number of conditions, especially traumatic, ischemic, burn, and neurologic injury to reduce the tissue damage. However, the protective mechanisms of cold therapy on traumatized tissues remain unclear. Tumor necrosis factor-alpha (TNF-alpha) is a fundamental mediator in inflammatory reactions and trauma-induced tissue injury. In the present study, we examined the microvascular response to TNF-alpha challenge and the effects of local cooling on the TNF-alpha-induced changes in the striated muscle of hamsters. METHODS: By the use of the dorsal skinfold chamber preparation and in vivo fluorescence microscopy in combination with computer-based image analysis, we determined TNF-alpha-induced leukocyte rolling and adhesion to microvascular endothelium, capillary perfusion, venular leakage, and cellular apoptosis with and without surface cooling. RESULTS: We found that topical administration of 2000 units TNF-alpha caused a progressive impairment of microvascular perfusion and increased leukocyte recruitment and vascular macromolecular leakage. Local cooling to 10 degrees C for 60 minutes markedly (P < .05) inhibited the TNF-alpha-induced capillary perfusion failure and leukocyte response and slightly attenuated the increase of microvascular permeability after 180 minutes of stimulation. Furthermore, it was observed that 24 hours of TNF-alpha stimulation increased the number of apoptotic cells (i.e., nuclear condensation and fragmentation) by 10-fold. This TNF-alpha-mediated effect was almost abolished by treatment with local hypothermia. CONCLUSION: These data suggest that the protective effect of surface cooling of traumatized tissue is due to its attenuation of the microvascular inflammatory response associated with the inhibition of the process of apoptosis.