Abstract
Introduction:
The genotype associated with an inducible response to dynamic exercise is different from the genotype associated with the intrinsic capacity for aerobic exercise. The inducible response is an established component of rehab protocols after ischemic events, but the influence of the intrinsic capacity for exercise on the vascular response to active exercise following ischemic injury is unknown.
Hypothesis:
Reduced intrinsic aerobic exercise capacity will limit the early (2 week) inducible vascular response to active exercise after hind limb ischemia.
Methods:
Hind limb ischemic injury was created by unilateral femoral artery occlusion in previously established rat strains for high and low aerobic capacity phenotypes (HCR and LCR, Female, 40 weeks, n = 16 each). Beginning 3 days after the occlusion, 8 animals in each cohort began a 10 day, progressively increasing treadmill running protocol. Remaining animals served as sedentary post-ischemic controls. 14 days after occlusion, all animals were euthanized. Skeletal muscle was harvested from both hind limbs. Samples from the non-occluded contralateral hind limb were used as internal controls. All samples were stored in OCT at -80°C until processed for histologic assessment of capillarization (Rosenblatt staining).
Results:
LCR animals were about 80g heavier while HCRs had about 500% greater intrinsic running capacity (both p < 0.01). HCRs showed 26% better preservation of muscle fiber area in the post-ischemic limb, but LCRs increased fiber area with exercise at least 2 fold more with active exercise (p < 0.05). HCRs showed a greater increase (80%) in capillary density and perfusion exchange ratio (40%) in response to exercise. PCR for multiple angiogenic genes showed expression levels that were consistently higher in the LCRs, consistent with increased ongoing ischemic stress.
Conclusions:
Decreased baseline capillarization in the LCRs predisposed them to greater tissue loss following occlusion. The increased burden of exercise on the remaining fibers increased muscle growth in LCRs, but vasculogenic responses were delayed, despite stronger gene induction. Combining occlusion with exercise after occlusion in LCRs appeared to overwhelm the early angiogenic remodeling response.