These results suggest that impaired muscle metabolism associated with early metabolic limitation determines exercise capacity during maximal systemic exercise in patients with CHF. There was a significant correlation between muscle metabolic capacity during systemic and local exercise in patients with CHF.

Acute systemic hypoxia causes significant increases in human skeletal muscle sympathetic nerve activity (MSNA), heart rate and ventilation. This phenomenon is thought to be primarily mediated by excitation of peripheral chemoreceptors sensing a fall in arterial free oxygen partial pressure (Pa,O2). We directly tested the role of Pa,O2 on MSNA (peroneal microneurography), heart rate, ventilation and leg haemodynamics (n = 7-8) at rest and during rhythmic handgrip exercise by using carbon monoxide (CO) to mimic the effect of systemic hypoxia on arterial oxyhaemoglobin (approximately 20 % lower O2Hba), while normalising or increasing Pa,O2 (range 40-620 mmHg). The four experimental conditions were: (1) normoxia (Pa,O2 approximately 110 mmHg; carboxyhaemoglobin (COHb) approximately 2 %); (2) hypoxia (Pa,O2 approximately 40 mmHg; COHb approximately 2 %); (3) CO + normoxia (Pa,O2 approximately 110 mmHg; COHb approximately 23 %); and (4) CO + hyperoxia (Pa,O2 approximately 620 mmHg; COHb ~24 %). Acute hypoxia augmented sympathetic burst frequency, integrated MSNA, heart rate and ventilation compared to normoxia over the entire protocol (7-13 bursts min-1, 100-118 %, 13-17 beats min-1, 2-4 l min-1, respectively, P < 0.05). The major new findings were: (1) CO + normoxia and CO + hyperoxia also elevated MSNA compared to normoxia (63-144 % increase in integrated MSNA; P < 0.05) but they did not increase heart rate (62-67 beats min-1) or ventilation (6.5-6.8 l min-1), and (2) despite the 4-fold elevation in MSNA with hypoxaemia and exercise, resting leg blood flow, vascular conductance and O2 uptake remained unchanged. In conclusion, the present results suggest that increases in MSNA with CO are not mediated by activation of the chemoreflex, whereas hypoxia-induced tachycardia and hyperventilation are mediated by activation of the chemoreflex in response to the decline in Pa,O2. Our findings also suggest that Pa,O2 is not an obligatory signal involved in the enhanced MSNA with reduced blood oxygenation.

Objective-To estimate muscle metabolism and oxygen delivery to skeletal muscle in patients with chronic heart failure. Methods-13 patients with chronic heart failure and 15 controls performed calf plantar flexion for six minutes at a constant workload of 50% of one repetition maximum. During recovery from exercise, skeletal muscle content of oxygenated haemoglobin (oxy-Hb) and the level of phosphocreatine (PCr) were measured by near-infrared spectroscopy and 31 P-magnetic resonance spectroscopy, respectively. Results-The mean (SD) time constants of PCr and oxy-Hb during recovery from exercise were significantly greater in patients with chronic heart failure than in normal subjects ( PCr: 76.3 (30.2) s v 36.5 (5.8) s; oxy-Hb: 48.3 (7.3) s v 30.1 (7.7) s; p < 0.01). Both time constants were similar in normal subjects, while the PCr was significantly greater than the oxy-Hb in patients with chronic heart failure. Conclusions-The slower recovery of PCr compared with oxy-Hb in patients with chronic heart failure indicates that haemoglobin resaturation is not a major rate limiting factor of PCr resynthesis. It is suggested that muscle metabolic recovery may depend more on oxygen utilisation than on haemoglobin resaturation or oxygen delivery in patients with chronic heart failure. (Heart 2000;83:161-166) Keywords: near-infrared spectroscopy; 31 P-magnetic resonance spectroscopy; chronic heart failure; exercise tolerance Studies have shown that the degree of exercise intolerance in patients with chronic heart failure is not significantly correlated with the extent of the central haemodynamic disturbance.1 2 This means that exercise capacity is not limited only by haemodynamics but also by peripheral abnormality. Studies using phosphorus-31 nuclear magnetic resonance spectroscopy ( 31 P-MRS) have shown that peripheral muscle metabolic abnormalities during exercise are important contributors to exercise intolerance in patients with chronic heart failure.3-8 Recent studies using nearinfrared spectroscopy (NIRS) to evaluate skeletal muscle oxygen kinetics have shown that peripheral muscle oxygenation is impaired during systemic exercise in patients with chronic heart failure.9 10 Both muscle metabolism and muscle oxygen kinetics are important determinants of exercise capacity and these factors have been separately evaluated in patients with chronic heart failure. In normal subjects, only a few studies have assessed both muscle metabolism and oxygen kinetics. McCully et al simultaneously measured oxygenated haemoglobin (oxy-Hb) and phosphocreatine (PCr) recovery after submaximal exercise in normal subjects using NIRS and 31 P-MRS respectively, and found that the time constants of these indices were similar.11 They suggested that oxy-Hb recovery is rate limiting for ATP synthesis, evaluated as the rate of PCr recovery after submaximal exercise. In patients with chronic heart failure, both skeletal muscle metabolism and oxygen delivery are impaired and these abnormalities are potential contributors to exercise into...