Thermal preconditioning prior to arterial balloon injury: Limitation of injury and sustained reduction of intimal thickening

Heat shock proteins (HSP) are a family of highly conserved proteins, essential to cell survival. These proteins, when induced, can provide tolerance to subsequent injury. Whole body hyperthermia (WBH) was evaluated with regard to preconditioning the vasculature before balloon injury to limit damage and reduce neointima formation. WBH (41°-42° for 15 min.) treatment of Sprague-Dawley rats resulted in maximal HSP expression at 8-12 hours. Rats were randomized to either WBH or not, 8 hours prior to carotid balloon injury. At 14 (n=26) and 90 (n=21) days following balloon injury, histomorphometric analysis revealed a significant limitation of intimai thickening in preconditioned arteries as compared to controls (intima/media area ratios +/-SEM; 14 days: 0.57+/-0.072 vs 0.86+/-0.081, P=0.01; 90 days: 0.78+/-0.12 vs 1.18+/-0.135 P<0.05). The medial cell proliferation index at 4 days (n=12) was also significantly reduced in the treatment group: (3.6+/-0.9% vs 7.2+/-1.3% P<0.05). Conversely, the mean cell number in the media of heated arteries was higher (393+/-20 vs 328+/-17 P<0.05. We conclude that vascular preconditioning with brief WBH induces a heat shock response in the arterial wall that is associated with a significant and sustained reduction in intimai thickening. This effect appears to be due in part to preservation of medial cell integrity and limitation of the proliferative response. This suggests that thermal preconditioning of vascular tissue may be an effective strategy to improve long term results after revascularization procedures.