Mechanism of skeletal muscle underperfusion in a dog model of low-output heart failure

Abstract

To investigate the mechanism responsible for underperfusion of working skeletal muscle in heart failure, we measured systemic and femoral bed hemodynamics during treadmill exercise and gracilis muscle resistance during contraction frequencies of 1-9 Hz in 8 dogs ventricularly paced at 260 beats/min for 3 wk to induce heart failure (HF) and in 9 control dogs. At peak treadmill exercise (4 mph, 10%), HF dogs had reduced cardiac outputs (control: 297 +/- 42 vs. HF: 212 +/- 16 ml X min-1 X kg-1) and femoral bed flows (control: 352 +/- 112 vs. HF: 229 +/- 95 ml/min) and elevated arterial lactates [control: 1.7 +/- 0.7 vs. HF: 4.1 +/- 0.7 mM (all P less than 0.04)], consistent with skeletal muscle underperfusion. This muscle underperfusion was associated with reduced mean arteriovenous pressure gradients [control: 119 +/- 12 vs. HF: 91 +/- 9 mmHg (P less than 0.001)] but with normal systemic vascular [control: 21 +/- 6 vs. HF: 23 +/- 5 U (P = NS)] and femoral bed resistances [control: 3.5 +/- 1.6 vs. HF: 4.4 +/- 2.3 X 10(2) U (P = NS)]. Both groups also had similar gracilis muscle minimal resistance during exercise (control: 2.0 +/- 1.1 vs. HF: 1.9 +/- 0.9 X 10(3) U/100 g) and following maximal vasodilation (control: 2.0 +/- 1.0 vs. HF: 2.1 +/- 1.0 X 10(3) U/100 g). These results suggest that 1) short-term rapid ventricular pacing in the dog produces a model of low output HF resembling HF in humans, and 2) skeletal muscle underperfusion in this model is due to a reduced muscle arteriovenous pressure gradient and not to impaired skeletal muscle arteriolar vasodilation.