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Patients on hemodialysis (HD) have impaired exercise performance. Carnitine homeostasis is also abnormal in this population. As carnitine is an important cofactor for muscle energy metabolism, exercise performance and skeletal muscle carnitine metabolism were characterized in eight HD patients, and in five age-matched controls. Each patient underwent graded bicycle exercise testing to define maximal performance, and prolonged exercise at 70% of their peak work capacity. Muscle (vastus lateralis) total carnitine content (carnitine plus all acylcarnitines) at rest was lower in HD patients than in controls (2320 +/- 1190 vs. 3800 +/- 940 nmol/g, P less than 0.05). In patients on HD, muscle carnitine content was inversely correlated to time on HD (r = -0.74, P less than 0.05), and positively correlated to peak exercise performance (r = 0.77, P less than 0.05). In patients on HD, 8 +/- 7% of the muscle carnitine pool at rest was short-chain acylcarnitines (similar to the distribution in controls), but 32 +/- 5% of the plasma carnitine pool consisted of short-chain acylcarnitines. With high-intensity exercise in patients on HD, muscle short-chain acylcarnitine content increased from 130 +/- 130 to 1380 +/- 820 nmol/g (P less than 0.01). The change in muscle short-chain acylcarnitine content with exercise was correlated with the increase in muscle lactate content (r = 0.88, P less than 0.01). In summary, patients on HD had a lower muscle total carnitine content than control subjects which was correlated to exercise performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood levels of lipids and lipoproteins are prominent among the factors identified as contributing to the development of coronary artery disease. Studies have demonstrated that reduction of low density lipoprotein (LDL) levels lowers the risk of coronary events and retards the progression of atherosclerotic lesions. LDL receptors play a central role in the metabolism of LDL: they maintain cellular cholesterol homeostasis by effects on cholesterol synthesis, modulate the plasma level of lipoproteins by clearing LDL from the circulation and deliver cholesterol to the adrenal glands and gonads for steroid hormone synthesis and to the liver for bile acid synthesis. The 2 major strategies that have been developed so far to lower LDL levels involve the use of bile acid-binding resins, which bind cholesterol in the intestinal lumen, thereby leading to a decrease in intracellular cholesterol, which increases the rate of synthesis of LDL receptors and increases the rate of LDL clearance; and, more recently, the use of inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the key enzyme in the biosynthesis of cholesterol. Further studies are required to assess whether HMG-CoA reductase inhibitors, used alone or concomitantly with bile acid-binding resins, are safe and effective for long-term use in patients with elevated LDL levels.

The time course of metabolic and physiological adjustment to moderate iron deficiency anemia (MIDA, 8 g Hb/dl) and to severe iron deficiency anemia (SIDA, 4 g Hb/dl) was studied in adult, male Sprague-Dawley rats at 3, 7, 14, 30, 60, 90, 150, and 360 days, respectively. Our previous studies using the same rats used in the present study indicated that bone marrow iron was absent and plasma iron was significantly lower (p less than 0.001) in MIDA and SIDA relative to control. The following results with MIDA and SIDA rats are all expressed relative to control values. Red cell 2,3-diphosphoglycerate ranged from 45 to 146% greater in MIDA over the 360-day period and was 130% greater in SIDA at 30 days. Exhaustive run time consistently averaged 64 +/- 3% (SEM) less in MIDA over the time course and was further lowered to 18% in SIDA at 30 days. Heart rates of MIDA were elevated (p less than 0.05) at 180 days but lower (p less than 0.001) at 360 days in response to exercise. Resting heart rates of MIDA were the same at 180 and 360 days. Heart rates of SIDA were elevated (p less than 0.05) at rest and during exercise at 30 days. Organ weight/body weight changes indicated cardiomegaly in MIDA from 90 to 150 days which reverted to normal at 360 days; splenomegaly in MIDA from 90 to 360 days; and kidney atrophy in MIDA at 60 and 90 days which reverted to normal thereafter; in SIDA cardiomegaly and splenomegaly were present at 30 days. These results indicate that the onset and magnitude of physiological and metabolic adjustments occur in proportion to the severity of the anemia, and despite compensatory adjustments in parameters related to work performance, a new stable, lowered level of work tolerance is reached.

The purpose of this study was to assess cardiac adaptation to endurance training in rats. After 11 wk of progressive treadmill exercise (1 h/day), gastrocnemius cytochrome c oxidase activity was 38% higher (P less than 0.01) in the trained (n = 20) as compared to control (n = 20) rats. Cardiac Mg2+-stimulated myofibril ATPase activity (0.308 +/- 0.012 vs. 0.324 +/- 0.006 micrometer.mg-1.min-1) did not change nor was there any change in myofibril protein concentration (60.0 +/- 1.12 vs. 59.9 +/- 0.85 mg.g-1). The isolated left ventricular papillary muscle showed no significant change in time-to-peak tension (TPT) or half-relaxation time. Tension output, however, was significantly increased with training, 2.2 +/- 0.3 vs. 1.5 +/- 0.1 g.mm-2 (P less than 0.025). Furthermore, when the papillary preparations were perfused with 0.5 mM lanthanum (La3+) to displace membrane-bound Ca2+, the time course for tension decay was significantly prolonged in the trained muscles (P less than 0.001). We conclude that endurance running of this type does not necessarily increase myofibril ATPase activity or the time course of the isometric twitch of rat papillary muscle. However, tension output per unit area does increase and this appears to be due to a greater amount of Ca2+ being made available to the contractile apparatus.