SKELETAL-MUSCLE LACTATE ACCUMULATION AND CREATINE-PHOSPHATE DEPLETIONDURING HEAVY EXERCISE IN CONGESTIVE-HEART-FAILURE - CAUSE OF LIMITED EXERCISE CAPACITY

Objective To study the mechanisms of limited exercise capacity and ske letal muscle energy production in male patients with congestive heart failure. Design Muscle biopsy study. Patients Skeletal muscle metaboli c response to maximal bicycle exercise was studied in 10 patients with chronic congestive heart failure (ejection fraction 0.22 +/- 0.05; pe ak oxygen consumption, Vo(2) 15.1+/-4.9 ml.min(-1).kg(-1)) and in nine healthy subjects (peak Vo(2) 33.5 +/- 6.7 ml.min(-1).kg(-1)). Activit ies of skeletal muscle enzymes were measured from the vastus lateralis muscle of 48 patients (ejection fraction 0.24+/-0.06, peak Vo(2) 17.4 +/- 5.4 ml.min(-1).kg(-1)) and 36 healthy subjects (peak Vo(2) 38.3 /- 8.4 ml.min(-1).kg(-1)). Results Although blood lactate levels were lower in patients than in healthy subjects (2.2 +/- 0.3 vs 5.2 +/- 0.6 mmol.l(-1); P<0.001) at peak exercise (96 +/- 11 W for patients and 2 73 +/- 14 W for controls), skeletal muscle lactate was similarly eleva ted (25.6+/-3.2 vs 22.7 +/- 2.7 mmol.kg(-1)) and creatine phosphate wa s equally depressed (P<0.02) to low levels (7.0 +/- 1.9 vs 6.7 +/- 0.9 mmol.kg(-1)). The muscle ATP decreased by 21% (P<0.05) and 8% (P<0.01 ) in the patients and controls, respectively. Activities of rate limit ing enzymes of the citric acid cycle (alpha-ketoglutarate dehydrogenas e) and oxidation of free fatty acids (carnitine palmitoyltransferase I I) were 48% and 21% lower than in controls, but the mean phosphofructo kinase activity was unchanged in congestive heart failure. Conclusions It seems that the main limiting factor of exercise performance during heavy exercise is the same in congestive heart failure and healthy su bjects, a high rate of skeletal muscle lactate accumulation and high-e nergy phosphate depletion. In congestive heart failure, the low activi ty of aerobic enzymes is likely to impair energy production and lead t o lactate acidosis at low workloads.