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  • 1
    ISSN: 1573-4919
    Keywords: endothelin-1 ; ventricular cardiomyocytes ; contraction ; calcium ; heart failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Endothelin (ET-1) is found at elevated concentrations in the plasma of patients with heart failure and in animal models of cardiomyopathy. The peptide is a potent positive inotropic agent, the effects of which are mediated by increases in cytosolic Ca2+ in cardiomyocytes. The object of this study was to investigate at the cellular level, the actions of ET-1 on contractile function and on Ca2+ currents in heart-failed ventricular myocardium. Male New Zealand White rabbits (8 wks) were treated with twice weekly injections of epirubicin (4 mg/kg/wk, n=7) or with saline (n=7) for 6 wks, followed by a washout period of 2 wks. Ventricular cardiomyocytes were isolated from rabbit hearts using Langendorff perfusion with collagenase; contractile function was examined using a video microscopy method, and L-type Ca2+ currents were recorded using a whole-cell patch-clamp technique. ET-1 produced a concentration-dependent increase in contractile response (% increase from basal value) to a maximum at 1 nM ET-1 of 69 ± 11% (mean ± S.D.) in control cardiomyocytes and 33 ± 6% in heart-failed cells. However, there was no significant change in the EC50 obtained with ET-1 for healthy (0.31 ± 0.1 nM) and for failed cardiomyocytes (0.24 ± 0.1 nM). The effects of ET-1 on L-type Ca2+ channels were similar with a peak amplitude at 1 nM ET-1 of −3.26 ± 0.8 ⋬ in control cardiomyocytes and −3.32 ± 0.9 nA in heart-failed cells. The attenuation of the contractile response to ET-1 in heart-failed cells may reflect a desensitization of ET receptors as a consequence of elevated circulating levels of ET and was not reflected by alteration of transmembrane Ca2+ conductance. It is probable, therefore, that multiple signalling pathways are involved in the actions of ET on ventricular myocardium.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1619-1560
    Keywords: Heart rate variability ; Review ; Disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Non-invasive techniques for assessing heart rate variability can be used either diagnostically, as in identification of autonomic neuropathy associated with diabetes mellitus or tissue rejection following cardiac transplantation, or as a prognostic indicator in coronary artery disease. The methodology is based upon calculation of successive R—R intervals from an electrocardiogram, which can then be plotted as a frequency histogram (time domain analysis), undergo power spectral analysis to yield information in the frequency domain or be applied to chaos theory. In this review, several parameters are discussed which can be derived to quantify heart rate variability in the time and frequency domains; the latter providing information on autonomic balance. In the frequency domain up to three peaks may be observed, with the peak below 0.15 Hz being mediated by sympathetic and parasympathetic activity and peaks above 0.15 Hz being of vagal origin. The effects of different physiological and pathophysiological conditions on various indices of heart rate variability, and the use of heart rate variability analysis as a pharmacological method to assess the impact of drug therapy on sympathovagal balance are discussed.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-7241
    Keywords: hemodynamics ; calcium blockade ; angina
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A prospective, randomized study compared the effects of equivalent intravenous doses of three slow calciumchannel blockers (verapamil, diltiazem, and amlodipine) on rest and exercise haemodynamics in 30 ischemic heart disease patients. Following a stable control period during which rest and exercise (supine bicycle) hemodynamics were assessed, equivalent hypotensive doses of each compound were administered over 20 minutes and rest/exercise parameters were assessed 10 minutes later. At rest all agents similarly reduced systemic blood pressure; the fall in systemic vascular resistance and the increase in cardiac indices was ranked: amlodipine 〉 diltiazem 〉 verapamil. The heart rate increase for amlodopine differed from verapamil and diltiazem (+19.4% vs. +1.5% vs. −7%; p〈0.01). On exercise, similarly greater falls in the systemic vascular resistance index followed amlodipine, compared with verapamil and diltiazem (p〈0.05). Only amlodipine significantly reduced the exercise pulmonary artery occlusion pressure (PAOP). Exercise cardiac stroke volume improved after diltiazem and amlodipine. In terms of cardiac performance, both amlodipine and diltiazem produced an improvement, whereas verapamil depressed cardiac pumping activity. Thus, hemodynamic differences between slow-calcium-channel blocking drugs may be demonstrated in humans. These differences would be compatible with a predominant peripheral vascular site of action for amlodipine, in contrast with mixed cardiac and peripheral sites for diltiazem and verapamil.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1573-7241
    Keywords: elgodipine ; calcium channel antagonist ; coronary artery disease ; haemodynamics ; exercise ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Using an echo-Doppler method (Quantascope), the hemodynamic profile of the calcium channel antagonist elgodipine (64 μg/kg, iv) was investigated in 22 patients with angina pectoris at rest and during exercise. A placebo control was used. At rest, elgodipine significantly decreased systemic vascular resistance as well as systolic and diastolic blood pressure, while increasing cardiac output and stroke volume. During supine bicycle exercise at constant workload, elgodipine significantly increased cardiac output and stroke volume, and decreased the rate-pressure-product (double product); the exercise systolic blood pressure was decreased without change in the diastolic component. Elgodipine significantly reduced the incidence and severity (self-rated pain score) of exercise-induced anginal symptoms. Heart rate was not affected by elgodipine, either at rest or during exercise. In particular, no negative inotropy could be inferred from the echo-Doppler data. In the elgodipine plasma concentration profile (HPLC), three phases of elimination with half-life times of less than 1 hour, between 3 and 7 hours, and between 10 and 24 hours may be distinguished, indicating a “shallow” and a “deep” compartment. The hemodynamic data indicate an intermediate pharmacodynamic profile of elgodipine, lying between that of other dihydropyridines and that of compounds such as verapamil or diltiazem.
    Type of Medium: Electronic Resource
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