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  • 1
    ISSN: 1435-1803
    Keywords: atrial natriuretic peptide ; heart failure ; regionalblood flow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To characterize the systemic and regional vascular effects of atrial natriuretic peptide (ANP) in chronic heart failure, central hemodynamics, regional blood flow and plasma ANP levels were determined in a rat model of myocardial infarction and failure and in sham-operated animals. Measurements were made in the conscious state before and after intravenous rANP [99-126] (8 μg bolus followed by continuous infusion of 1.0 μg/kg/min). With this protocol, ANP significantly decreased cardiac output, right atrial, left ventricular enddiastolic and arterial pressures and there were increases in heart rate, systemic and intestinal vascular resistances in sham animals. Renal blood flow per gram of tissue was unchanged with ANP, but when expressed as a percentage of cardiac output, increased significantly, indicating a preferential renal vasodilatory effect of ANP. In rats with infarction and failure, this dose did not alter cardiac output or arterial pressure, but decreased right atrial and left ventricular blood flow. Although significantly reduced as compared to the control group, renal blood flow was not improved with ANP in the heart failure group. ANP plasma levels of the heart failure group were elevated at baseline (p〈0.01), and increased 5–10 times after infusion of rANP. Thus, in rats with chronic heart failure, the renal vascular effects of ANP are blunted, which may, in part, explain the failure of ANP to restore the altered volume homeostasis in heart failure despite elevated ANP plasma levels. However, the effects on venous return were preserved which, in turn, improved cardiac performance via a reduction of preload.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Basic research in cardiology 91 (1996), S. 17-22 
    ISSN: 1435-1803
    Keywords: Excitation-contraction coupling ; heart failure ; force-frequency relation ; calcium cycling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Myocardial function, intracellular calcium and levels of calcium cycling proteins were analyzed in failing and nonfailing human myocardium. Myocardial function was evaluated by the isometric force-frequency relation, and intracellular calcium was studied by aequorin light emission. When stimulation frequency was increased above 30 min−1, there was a continuous increase in isometric tension development in the nonfailing myocardium. In contrast, in failing myocardium, frequency potentiation of contractile force was blunted or inverse. As a consequence, at higher rates of stimulation, twitch tension was reduced significantly in failing compared to nonfailing human myocardium. Aequorin measurements indicated that the contractile deficit in the failing myocardium at higher rates of stimulation is associated with decreased free intracellular calcium concentration. Western blot analysis indicated that in the failing myocardium protein levels of SR-Ca2+-ATPase are significantly reduced and protein levels of Na+−Ca2+-exchanger are significantly increased. Levels of phospholamban are slightly reduced in the failing myocardium, and ryanodine receptor and calsequestrin protein levels are unchanged. There was a close positive correlation between the protein levels of SR-Ca2+-ATPase and frequency potentiation of contractile force. From these data, we conclude that in failing compared to nonfailing human myocardium 1) force-frequency relation is blunted or inverse. 2) Frequency-dependence of contractile force is closely correlated with frequency-dependence of intracellular calcium cycling. 3) Protein levels of SR-Ca2+-ATPase may determine frequency-dependence of sarcoplasmic reticulum calcium release. 4) Calcium elimination by an increased number of Na+−Ca2+-exchanger molecules may be a compensatory mechanism to prevent diastolic calcium accumulation in failing myocardium with a reduced number of SR calcium pumps.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Basic research in cardiology 92 (1997), S. 87-93 
    ISSN: 1435-1803
    Keywords: Calcium ; heart failure ; sarcoplasmic reticulum ; geneexpression ; human myocardium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There is accumulating evidence that disturbed calcium homeostasis may play a key role in the pathophysiology of human heart failure. Because disturbed calcium handling could result from altered protein expression, levels of calcium handling proteins were quantitated by Western Blot analysis in failing and nonfailing human myocardium from hearts with endstage failing dilated or ischemic cardiomyopathy. Protein levels of the sarcoplasmic reticulum calcium release channel (ryanodine receptor) and of calcium storage proteins (calsequestrin and calreticulin) were similar in failing and nonfailing human myocardium. However, proteins involved in calcium removal from the cytosol were significantly altered in the failing human heart: 1) SR-Ca2+-ATPase, relevant for removal of calcium from the cytosol into the lumen of the sarcoplasmic reticulum, was decreased; 2) phospholamban, which inhibits the SR-Ca2+-ATPase in the basal unphosphorylated state, was slightly decreased; 3) the ratio of SR-Ca2+-ATPase to phospholamban was decreased; 4) the sarcolemmal Na+−Ca2+-exchanger, relevant for transsarcolemmal calcium extrusion was increased in the failing hearts. In summary, altered levels of proteins involved in calcium removal from the cytosol suggest an increase in transsarcolemmal calcium elimination relative to sarcoplasmic reticulum calcium removal. These findings support the concept that reduced function of the sarcoplasmic reticulum to accumulate calcium may reflect a major defect in excitationcontraction coupling in human heart failure.
    Type of Medium: Electronic Resource
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