THERMAL PRECONDITIONING BEFORE RAT ARTERIAL BALLOON INJURY - LIMITATION OF INJURY AND SUSTAINED REDUCTION OF INTIMAL THICKENING

Heat shock proteins (HSPs) are a family of highly conserved proteins, essential to cell survival, that are induced during times of physiolog ical stress. These proteins, when induced, can provide tolerance to su bsequent injury. Several studies have documented that HSPs play an imp ortant role in the response of vascular cells to injury or stress. Whe ther the vasculature itself can be effectively preconditioned before a rterial injury is unknown. Vascular HSP induction by whole-body hypert hermia (WBH) was evaluated with regard to its effects on the vascular response to balloon injury. WBH treatment of Sprague-Dawley rats (colo nic temperatures of 41 to 42 degrees C for 15 minutes) resulted in max imal arterial HSP expression within 8 to 12 hours. Rats (male, 300 g, n=59) were randomly assigned to undergo either WBH or no treatment 8 h ours before standard carotid balloon injury. At 14 (n=26) and 90 (n=21 ) days after balloon injury, histomorphometric analysis revealed a sig nificant limitation of intimal accumulation ill preconditioned arterie s as compared to controls (intimal/medial area ratios+/-SEM: 14 days. 0.57+/-0.07 versus 0.86+/-0.08, P=0.01; 90 days, 0.78+/-0.12 versus 1. 19+/-0.14, P<0.05). The menial cell proliferation index at 4 days (n=1 2) was significantly reduced in the treated group as well (3.6+/-0.9% versus 7.2+/-1.3%, P<0.05). Conversely, the mean total cell number in the media of heated arteries was higher (393+/-20 venus 328+/-17, P<0. 05). Vascular preconditioning with brief WBH induces a heat shock resp onse in the arterial wall that is associated with a significant and su stained reduction in intimal accumulation. This effect appears to be d ue in part to preservation of medial cell integrity and limitation of the proliferative response. These results suggest that thermal precond itioning of vascular tissue may be an effective strategy to improve lo ng-term results after revascularization procedures.