Direct measurement of skeletal muscle fatigue in patients with chronic heart failure

Skeletal muscle function was measured as force production and fatigue in both the quadriceps (a large locomotive muscle) and adductor pollicis (a small intrinsic hand muscle) in five healthy volunteers, five patients with mild chronic heart failure, and five patients with severe chronic heart failure. The quadriceps of patients with chronic heart failure had a reduced muscle cross sectional area, a reduced maximum isometric force production, and an increased tendency to fatigue. Isometric force production and fatigue of the adductor pollicis, however, were not significantly different between the three groups under control conditions. But during circulatory occlusion fatigue in the adductor pollicis increased more in the patients with severe chronic heart failure. These differing findings in quadriceps and adductor pollicis suggest that skeletal muscle atrophy and reduced isometric force production are not a necessary consequence of chronic heart failure per se, because they were only present in the large locomotive muscle. The normal values for muscle fatigue observed in adductor pollicis in patients with chronic heart failure imply that skeletal muscle blood flow must increase normally during muscle activation when only a small muscle mass is used. These results are not compatible with the concept of a generalised impairment of normal vasodilatation within active skeletal muscle. In contrast, activation of a large muscle, such as quadriceps, results in the rapid onset of fatigue in patients with severe chronic heart failure. This fatigue may be related to the inability of the cardiovascular system to provide the required blood flow for the activation of a large muscle mass. The finding of a relatively greater increase in fatigue of adductor pollicis during circulatory occlusion in patients with severe chronic heart failure supports the hypnosis of an intrinsic abnormality of skeletal muscle in these patients.     

Comparison of rabbit coronary arterial relaxation induced by acetylcholine and lemakalim: activation of ATP sensitive potassium channels.

STUDY OBJECTIVE--The purpose was to assess the role of ATP sensitive potassium channels (KATP) in endothelium dependent vasodilatation induced by acetylcholine, or endothelium independent vasodilatation induced by lemakalim in rabbit coronary arteries. DESIGN--The effect of glibenclamide, a specific inhibitor of KATP, on coronary artery relaxation induced by acetylcholine or lemakalim was investigated. The relaxing effectiveness of acetylcholine and lemakalim on coronary arteries precontracted with KCl (K+) or prostaglandin F2 alpha (PGF2 alpha) was compared. EXPERIMENTAL MATERIALS--Left epicardial coronary arteries from male New Zealand white rabbits (2.5-3.0 kg), killed by an overdose of pentobarbitone, were dissected free of connective tissue. Rings suspended in organ baths for the measurement of isometric tension. MEASUREMENTS AND MAIN RESULTS--K+ (30 mmol.litre-1) and PGF2 alpha (3 mumols.litre-1) caused comparable contraction (p greater than 0.05) in endothelium intact or endothelium denuded coronary arterial rings. Acetylcholine induced relaxation was greater in endothelium intact rings precontracted with PGF2 alpha than with K+ and was abolished by the removal of endothelium. Relaxations induced by acetylcholine (0.1 and 0.3 mumol.litre-1) were reduced from 82(SEM 2.7)% and 93(2.8)% to 71(2.4)% and 82(2.7)% (p less than 0.05), and to 63(3.2)% and 79(4.5)% (p less than 0.05 or less than 0.01) by glibenclamide (3 and 10 mumols.litre-1) respectively in PGF2 alpha precontracted rings; and also attenuated (p less than 0.05 or less than 0.01) in K+ precontracted rings. Lemakalim induced relaxation was greater in endothelium denuded rings precontracted with PGF2 alpha than with K+, and was markedly reduced by glibenclamide (p less than 0.01). CONCLUSIONS--These results suggest that activation of KATP may partially be involved in endothelium dependent relaxation induced by acetylcholine in rabbit coronary arteries. Lemakalim-induced endothelium independent relaxation results mainly from activation of KATP.     

Anaemia of chronic disease in chronic heart failure: the emerging evidence.

Elucidating disease pathogenesis constitutes an important aimof scientific endeavour, being critical for the identificationof novel therapeutic strategies for the alleviation of suffering.Nowhere has this been more apparent than in chronic heart failure(CHF), where impressive survival benefits have been achievedas a long-term consequence of mechanistic studies into the roleof neurohormonal activation in disease progression.¹ Therefore,given this magnitude of potential benefit, illuminating themechanisms that drive adverse phenomena in CHF remains an agendaof substantial importance. Anaemia is a prevalent and adverse comorbidity in CHF, but littleis known about its origins. Over the past 5 years, a plethoraof studies have suggested that not only is anaemia more commonin CHF than could be accounted for by age and other demographiccharacteristics,     

Regional blood flow, muscle strength and skeletal muscle histology in severe congestive heart failure

Regional blood flow to exercising skeletal muscle is reduced in patients who have undergone treatment for severe congestive heart failure, and is a key factor determining the limitation of exercise capacity. Recent studies have shown that the histology, contractile function and biochemistry of skeletal muscle are also abnormal. The mechanisms for both the reduced blood flow and the intrinsic abnormality of skeletal muscle are unknown. The interpretation of experimental data is complicated by different etiologies of heart failure, drug treatment, exercise protocols, the limitations of methods for the measurement of blood flow and metabolism in intact humans, and by the selection of particular groups of muscles for study that may not reflect changes in other muscles in the body.     

氯沙坦心衰生存研究（ELITE Ⅱ）：氯沙坦和卡托普利对心衰相关预后和症状的作用比较氯沙坦心衰生存研究（ELITE Ⅱ）：氯沙坦和卡托普利对心衰相关预后和症状的作用比较

背景：利用血管紧张素转换酶抑制剂阻断肾素-血管紧张素系统可以改善心衰（HF）患者的预后和症状。在ELITEⅡ研究中，比较了氯沙坦和卡托普利对心衰患者死亡率、发病率以及功能状态方面的作用。方法和结果：总共3152例年龄≥60岁、NYHA心功能分级为Ⅱ-Ⅳ级、射血分数≤40％的HF患者入选研究，接受氯沙坦50mg1次／d或卡托普利50mg3次／d。判断预后的指标包括：全因或HF相关的死亡、住院和停止治疗；NYHA分级的变化；生活质量（QoL）。各治疗组问HF相关预后无显著性差异。两组的NYHA分级得到了相似的改善（P〈0．01）。观察1856例患者的QoL发现，1343例患者至少存活1年以上；两组中1年存活者的QoL均得到了改善（与基线相比，P〈0．001）。