Peripheral Adaptations in Trained Aged Rats With Femoral Artery Stenosis

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Abstract

The development and functional significance of exercise-induced peripheral adaptations were evaluated in aged animals with peripheral arterial insufficiency. Fisher 344 male rats (21 months old) were subjected to bilateral stenosis of the femoral arteries sufficient to limit active hyperemia but not to impair resting blood flow. Beginning the third day after stenosis, animals were (1) exercised by walking (n=12) on a treadmill at 20 m/min at 15% inclination, twice a day, 5 days per week, or (2) limited to cage activity (n=10). Exercise tolerance improved from ≈5 to ≈35 minutes (P<.001) over the 8 weeks of the training program but increased only marginally to =8 minutes for the sedentary group. An isolated hind limb preparation perfused at equivalent blood flows (≈1 ml · min−1 · g−1 with an arterial blood oxygen content of ≈ 20 vol%) was used to assess the functional and metabolic impact of muscle-specific adaptations during sequential contraction periods at 4, 8,15, 30, 45, 60, 75, and 90 tetani per minute. An initially similar force development of ≈10 N/g was better maintained (P<.001) by the trained group. The peak oxygen consumption attained by the trained group of 5.68±0.34 μmol · min−1 · g−1 was greater (P<.01) than that of the sedentary group (4.34±0.29 μmol · min−1 · g−1). This was due to a greater oxygen extraction, since oxygen delivery was the same (≈ 10 μmol · min−1 · g−1) to muscles of both groups. The improved muscle performance and greater oxygen extraction of trained muscle is attributed to an enriched capillary network (5.70±0.10 versus 4.68±0.11 capillary contacts per fiber, P<.001) and a 25% to 100% greater mitochondrial capacity (citrate synthase activity, P<.001) of the fibers. Thus, aged animals with peripheral arterial insufficiency are capable of developing training-induced adaptations that serve to improve muscle performance, even if blood flow is not improved. Similar activity-related adaptations in elderly patients with intermittent claudication could contribute to an improved exercise tolerance.

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