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21.
Comparison of rabbit coronary arterial relaxation induced by acetylcholine and lemakalim: activation of ATP sensitive potassium channels. 总被引:1,自引:0,他引:1
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. 相似文献
22.
Darlington O Okonko Dirk J Van Veldhuisen Philip A Poole-Wilson Stefan D Anker 《European heart journal》2005,26(21):2213-2214
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, 相似文献
23.
Regional blood flow, muscle strength and skeletal muscle histology in severe congestive heart failure 总被引:2,自引:0,他引:2
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. 相似文献
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Heart failure in a district general hospital: are target doses of beta-blockers realistic? 总被引:2,自引:0,他引:2
Mehta PA McDonagh S Poole-Wilson PA Grocott-Mason R Dubrey SW 《QJM : monthly journal of the Association of Physicians》2004,97(3):133-139
BACKGROUND: Carvedilol therapy reduces mortality in patients with chronic heart failure. Multi-centre studies suggest a low first dose failure rate and high levels of tolerability to carvedilol. Little is known, however, concerning the eligibility and tolerance to treatment with carvedilol within a district general hospital setting. Aim: To evaluate the eligibility and tolerance of patients with heart failure to carvedilol within a district general hospital. DESIGN: Prospective clinical audit analysis. METHODS: We assessed 100 heart failure patients eligibility to commence carvedilol therapy. In those who satisfied clinical criteria, we evaluated first dose failure rate, target dose achievement, reasons for intolerance, heart rate and blood pressure reduction and resource requirements over a six-month period. RESULTS: Of 100 patients, 16% had contra-indications to commence carvedilol and 22% were receiving a beta-blocker as part of their existing heart failure therapy. Although 62% satisfied eligibility criteria, 1% refused therapy, thus 61% were initiated on carvedilol. The first dose failure rate was 11.5% and 6.6% of patients achieved 'target dose'. Mean heart rate and systolic blood pressure reductions were 15 (SE 1.2)bpm and 17 (SE 1.7) mmHg, respectively. Resource requirements included 155 hours of work-time for a trained heart failure specialist nurse and doctor. CONCLUSIONS: In the general setting, eligible patients appear to display a high first dose failure rate, poor tolerance to higher doses and achievement of a 'target dose' of carvedilol. Responses to adrenergic blockade were similar to previously published data, irrespective of the final tolerated dose, suggesting that the concept of achieving a 'target dose' may not be clinically useful. Guidelines and treatment protocols for heart failure should reflect not only what is considered gold standard, but also what is practical in general hospitals. 相似文献
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Ponikowski P Francis DP Piepoli MF Davies LC Chua TP Davos CH Florea V Banasiak W Poole-Wilson PA Coats AJ Anker SD 《Circulation》2001,103(7):967-972