A prospective, randomized, double-blind, crossover study to compare the efficacy and safety of chronic nifedipine therapy with that of isosorbide dinitrate and their combination in the treatment of chronic congestive heart failure.

Elkayam, Uri; Amin, Jay; Mehra, Anilkumar; Vasquez, Janet; Weber, Laura; Rahimtoola, Shahbudin H.

doi:10.1161/01.cir.82.6.1954

Cited by 307 publications

(74 citation statements)

References 45 publications

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“…The drug had neither a beneficial nor deteriorating effect despite the improvement in exercise performance and LV function, as reported previously in the V-HeFT II trial in patients with chronic heart failure (79). Chronic nifedipine (which has strong peripheral vasodilating effects) therapy caused a higher incidence of clinical deterioration and worsening of heart failure (80,81). The DEFIANT-I study (Doppler Flow and Echocardiography in Functional Cardiac Insufficiency: Assessment of Nisoldipine Therapy) was a double-blind randomized study of the effects of the DHP nisoldipine on LV size and function after acute myocardial infarction.…”

Section: Ca 2+ Channel Antagonists and Ca 2+ -Binding Domainsmentioning

confidence: 99%

The L-type calcium channel in the heart: the beat goes on

Bódi¹

2005

Journal of Clinical Investigation

251

213

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Sydney Ringer would be overwhelmed today by the implications of his simple experiment performed over 120 years ago showing that the heart would not beat in the absence of Ca 2+ . Fascination with the role of Ca 2+ has proliferated into all aspects of our understanding of normal cardiac function and the progression of heart disease, including induction of cardiac hypertrophy, heart failure, and sudden death. This review examines the role of Ca 2+ and the L-type voltage-dependent Ca 2+ channels in cardiac disease.When Sydney Ringer (1) discovered the vital role of Ca 2+ in the heart, investigations took a leap forward and have continued unabated (2). Austrian scientist Otto Loewi, best known for his work on autonomic transmitters and discovery of "chemical vagusstoff," recognized the connection between digitalis and Ca 2+ in [1917][1918]. Although he always believed that Ca 2+ was the key to understanding life's processes, the Nobel Prize in Physiology and Medicine was awarded to Loewi and Sir Henry Hallett Dale in 1936 for their studies on neurotransmitters.Ca 2+ is the link in excitation-contraction (EC) coupling (Figure 1), which starts during the upstroke of the action potential (AP) and causes the opening of the L-type voltage-dependent Ca 2+ channel (L-VDCC). Interest in high-voltage-activated L-VDCCs began with biochemical and continued with molecular characterizations, culminating in the cloning of the pore-forming α 1 subunit and the auxiliary channel subunit α 2 /δ from rabbit skeletal muscle (3)(4)(5). Although the L-VDCC subunits are most abundant in fast skeletal transverse tubules, Ca 2+ influx is not required for contraction in skeletal muscle, unlike cardiac muscle, which requires Ca 2+ entry with each beat and triggers Ca 2+ release from the sarcoplasmic reticulum (SR) via Ca 2+ -release channels, e.g., ryanodine receptor 2 (RyR2). This amplifying process, termed Ca 2+ -induced Ca 2+ release (CICR) by A. Fabiato, causes a rapid increase in intracellular Ca 2+ concentration ([Ca 2+ ] i ) (from ∼100 nM to ∼1 µM) to a level required for optimal binding of Ca 2+ to troponin C and induction of contraction (2). There is a close correlation between activation of the L-type Ca 2+ current (I Ca,L ) and cardiac contraction. Contraction is followed by Ca 2+ release from troponin C and its reuptake by the SR via activation of the SR Ca 2+ -ATPase 2a (SERCA2a) Ca 2+ pump in addition to extrusion across the sarcolemma via the Na + /Ca 2+

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Section: Ca 2+ Channel Antagonists and Ca 2+ -Binding Domainsmentioning

confidence: 99%

The L-type calcium channel in the heart: the beat goes on

Bódi¹

2005

Journal of Clinical Investigation

251

213

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“…[1][2][3] The mechanism of these effects may be a negative inotropic action, particularly if there is some abrogation of the reflex sympathetic actions caused by these drugs due to the disappearance of sympathetic nerve endings in the heart as a part of the heart failure process. 4 In contrast to these views, amlodipine has been reported in the PRAISE-1 trial to have a substantial beneficial effect in a subgroup of patients with dilated cardiomyopathy who underwent posthoc analysis.…”

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confidence: 99%

Amlodipine Releases Nitric Oxide From Canine Coronary Microvessels

1998

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Background-Recent studies suggest that amlodipine may reduce mortality in patients with heart failure, especially those with dilated cardiomyopathy. In general, drugs that release NO, such as organic nitrates and ACE inhibitors, have been shown to be of substantial benefit in the treatment of heart failure. Methods and Results-We hypothesized that a portion of the beneficial actions of amlodipine may involve the release or action of NO. Coronary microvessels were isolated from the heart of normal dogs and incubated with increasing doses of the calcium channel blockers nifedipine, diltiazem, and amlodipine or the ACE inhibitors enalaprilat and ramiprilat. Neither nifedipine nor diltiazem increased nitrite production at any dose studied. In marked contrast, amlodipine caused a dose-dependent increase in nitrite production from 74Ϯ5 to 130Ϯ8 pmol/mg (by 85Ϯ21%,10 Ϫ5 mol/L, PϽ.05) that was similar in magnitude to that of either of the ACE inhibitors. Amlodipine also increased nitrite production in large coronary arteries and in aorta. N -Nitro-L-arginine methyl ester, HOE-140, and dichloroisocoumarin essentially abolished the increase in nitrite production, indicating that (1) nitrite production reflected NO formation, (2) nitrite production was dependent on stimulation of the kinin 2 receptor, and (3) nitrite production is most likely secondary to the formation of local kinins. Conclusions-Thus, unlike nifedipine and diltiazem, amlodipine releases NO from blood vessels. (Circulation.1998;97:576-580.)

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“…Results of study with long-acting dihydropyridines also showed disparities among the hemodynamic variables evaluated [16][17][18][19][20] . the authors were unable to categorically define the effects of calcium antagonists on exercise capacity and on the functional class of the patients with heart failure [21][22][23][24][25][26] (table I).…”

Section: Clinical Resultsmentioning

confidence: 99%