Effects of Pentoxifylline on Exercising Skeletal Muscle Vascular Control in Rats with Chronic Heart Failure

Abstract

Purpose: Chronic heart failure (CHF) is hallmarked by cardiac and peripheral vasculature dysfunction which has been associated with elevations in tumor necrosis factor-α (TNF-α) and exercise intolerance. The pharmaceutical TNF-α synthesis suppressor pentoxifylline (PTX) reduces plasma [TNF-α] and improves left ventricular (LV) function in CHF rats, but the effects of PTX on skeletal muscle blood flow (BF) and vascular conductance (VC) during exercise are unknown. We tested the hypothesis that PTX would elevate skeletal muscle BF and VC at rest and during submaximal treadmill exercise in CHF rats and improve exercise tolerance and peak O₂ uptake.

Methods: CHF rats (coronary artery ligation) received i.p. injections of 30 mg·kg^-1·day^-1of PTX (CHF+PTX, n=13) or saline (CHF, n=8) for 21 days. BF was measured using radiolabeled microspheres at rest and during exercise (treadmill, 20 m/min^-1, 5% grade).

Results: Resting and exercising mean arterial pressures (MAP) were greater in CHF+PTX compared to CHF (i.e., closer to expected healthy values, both p<0.05). During exercise PTX increased total hindlimb BF (CHF: 83±9, CHF+PTX: 114±8 ml·min^-1·100g^-1, p<0.05) and VC (CHF: 0.75±0.08, CHF+PTX: 0.88±0.06 ml·min^-1·100g^-1·mmHg^-1, p<0.05). Furthermore, exercising BF was increased in 21 and VC in 11, of the 28 individual hindlimb muscles or muscle parts with no apparent fiber-type specificity.

Conclusions: PTX administration augments skeletal muscle BF and VC during locomotory exercise in CHF rats, but the lack of increased exercise tolerance or peak O₂ uptake suggest continued peripheral O₂ pathway dysfunction.