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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review paper deals with recent data concerning the physiopathology of chronic heart failure. Broadly speaking, the cause of chronic heart failure is arterial hypertension and/or coronary disease. Myocardial hypertrophy is only one example of biological adjustment to the environment, and chronic heart failure, an adaptation disease, indicates its limits. Diastolic dysfunction includes 3 elements. Relaxation is slowed down by a decrease in density of Ca(2+)-ATPase in the sarcoplasmic reticulum and by a fall in Na+/Ca2+ exchange activity. The decline of tissue compliance is mainly explained by probably hormonal changes in collagen. Changes in isomyosins account for abnormalities of atrial contraction. At the beginning of mechanical overload, the fall in systolic function enables the heart to produce a normal tension. The determinant element is slowing down of intracellular calcium movements. Enlarged hearts generate arrhythmias. The origin is probably the presence of unstable calcium homeostasis.
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PMID:[Chronic heart failure: biological bases of myocardial function]. 131 2

Na+/K(+)-ATPase of the cell membrane is considered to be closely related to the pathology of various diseases including hypertension and heart failure. The activity of this enzyme in the erythrocyte membrane has been determined in earlier reports by the assay of inorganic phosphate generated from the substrate ATP or radioimmunoassay after binding 3H ouabain to the erythrocyte membrane, using a large volume of blood samples. However, as neither method was appropriate for wide routine use, we developed a method to assay this enzyme in a small volume (10 ml) of fresh human blood samples with re-evaluation of conditions for the inorganic phosphate assay. In this method, the coefficient value (CV) of membrane protein amount and the NA+/K(+)-ATPase activity were 2.2% and 2.5% respectively, indicating sufficient precision of the assay. Moreover, in 97 subjects without abnormalities in blood biochemical tests (77 males and 20 females) aged 35-59 years, the enzyme activity showed no differences according to age or sex, ranging from 0.217 to 0.071 mumols Pi/mg/hr with a mean of 0.130.
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PMID:[Determination of human erythrocyte membrane Na+/K(+)-ATPase activity in small volume of blood sample]. 131 73

Circulating concentrations of human atrial natriuretic peptide (hANP) are elevated in patients with heart failure; however, the natriuretic effect of hANP is blunted in these patients. In this study, the relationship between urinary cGMP, the second messenger for the natriuretic effect of hANP in vivo, and endogenous hANP was examined in six patients with heart failure and four normal subjects. In addition, right heart catheterization for the determination of central hemodynamics was performed in the heart failure patients. The heart failure patients were in New York Heart Association Classes II to IV and were receiving no medications at the time of the study. Supine plasma hANP and urinary cGMP concentrations were determined on two occasions in each subject, as were right and left atrial pressures in the heart failure patients. At the time of study, the patients were in positive sodium balance, and control subjects were in normal sodium balance. Plasma hANP and urinary cGMP excretion rates were elevated in heart failure patients as compared with those in controls: hANP, 139.0 +/- 42.0 versus 22.0 +/- 6.1 pg/mL (P less than 0.05); urinary cGMP, 1.14 +/- 0.31 versus 0.35 +/- 0.05 nmol/min (P less than 0.05). In heart failure patients, right atrial pressure correlated positively with plasma hANP (r = 0.96; P less than 0.01) and urinary cGMP concentrations (r = 0.93; P less than 0.05) and the excretion rate (r = 0.92; P less than 0.05). Moreover, plasma hANP was strongly correlated with urinary cGMP concentration (r = 0.91; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Atrial natriuretic peptide and urinary cyclic guanosine monophosphate in patients with chronic heart failure. 132 37

We investigated whether cardiac hypertrophy induced by volume loading influences baroreflex sensitivity. Aortic insufficiency (AI) was induced in male Wistar rats by graded disruption of the aortic valve, which, after 2 weeks, resulted in a 30% increase in heart/body weight or left-ventricular/body weight ratio compared with control animals. Baroreflex sensitivity was assessed in conscious animals by measuring the heart rate (HR) responses to the changes in mean arterial pressure (MAP) induced by phenylephrine and nitroprusside sodium at 2 weeks. The slopes of the HR vs MAP plots obtained with phenylephrine and nitroprusside decreased significantly with increasing heart weight/body weight ratio (correlation coefficient r = 0.625 and 0.526, respectively). In isolated right atria from AI animals baseline rate was higher, and the isoproterenol effect on sinus rate was significantly smaller than in atria from control animals, indicating a dysfunction of the beta-adrenoceptor pathway. The data show that baroreflex dysfunction associated with a down-regulation of the beta-adrenoceptor pathway of the sinus node develops simultaneously with volume overload-induced hypertrophy in the absence of overt heart failure.
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PMID:Baroreflex and beta-adrenoceptor function are diminished in rat cardiac hypertrophy due to volume overload. 132 73

1. The present studies compared the renal and hypotensive response to (a) exogenous atrial natriuretic peptide (ANP) (99-126), (b) an endopeptidase-24.11 inhibitor (candoxatrilat) and (c) an antagonist of ANP clearance receptors (SC 46542) in conscious rats. 2. Infusion of low-dose-ANP (100 ng kg-1 min-1) produced a gradual increase in urinary sodium and guanosine 3':5'-cyclic monophosphate (cyclic GMP) excretion without significant change in glomerular filtration rate (GFR) or fractional lithium clearance (FeLi). There was a significant fall in blood pressure. 3. Infusion of high-dose ANP (300 ng kg-1 min-1) produced a brisk, 3 fold increase in urinary sodium and cyclic GMP excretion along with a rise in GFR, but had no significant effect on FeLi compared to the control group. The renal response was accompanied by a pronounced fall in blood pressure. 4. Candoxatrilat or SC 46542, alone, had no significant effect on sodium excretion compared to control animals. Both compounds enhanced the natriuretic and cyclic GMP responses to a low-dose ANP infusion (100 ng kg-1 min-1) to levels similar to, or greater than, those observed with the high-dose ANP (300 ng kg-1 min-1). However, unlike high-dose ANP, these renal effects were not accompanied by a significant change in GFR and neither compound potentiated the hypotensive effect of the low-dose ANP infusion. Only candoxatrilat when given with ANP produced a marked rise in FeLi.5. Similarly, combined administration of candoxatrilat and SC 46542 (without exogenous ANP) induced an increase in sodium and cyclic GMP excretion comparable to high-dose ANP but did so without a significant increase in GFR and with a significantly smaller fall in blood pressure. Interestingly, there was no increase in FeLi with the combination of the two compounds, suggesting that the major contribution to sodium excretion came from SC 46542.6. Both candoxatrilat and SC 46542 increased sodium and cyclic GMP excretion in the rat A-V fistula model of heart failure, a model hyporesponsive to infusions of ANP, without significant change in blood pressure.7. These data show that candoxatrilat and SC 46542 do not simply reproduce the effects of an ANP infusion but preferentially enhance the natriuretic response to ANP. Inhibition of E-24.11 may potentiate a tubule action of ANP while the renal mechanism of action of the C-ANP receptor ligand needs further study. Both manipulations are of potential value in the management of heart failure.
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PMID:Response to atrial natriuretic peptide, endopeptidase 24.11 inhibitor and C-ANP receptor ligand in the rat. 133 Jan 65

We have investigated whether binding parameters and subtypes of glomerular, papillary, and vascular atrial natriuretic factor (ANF) receptors differ in rats with moderate high-output heart failure [aortocaval (AC) shunt] from their sham-operated controls. Body weight was lower and relative heart weight was higher in the AC shunt group than in the control group. Plasma renin activity (PRA) was also greater in AC shunt rats. Plasma COOH- and NH2-terminal ANF levels were higher in AC shunt animals than in their control counterparts. Total atrial ANF content was elevated in both the right and left atria of the AC shunt group. Glomerular and papillary ANF receptor density (Bmax) and ANF receptor affinity (Kd) were similar in both AC shunt and control rats. Vascular ANF receptor density and affinity were lower in AC shunt (Bmax = 65 +/- 13 fmol.mg protein; Kd = 467 +/- 52 pM) than in control rats (Bmax = 188 +/- 34 fmol.mg protein; Kd = 278 +/- 11 pM). Irreversible cross-linking of 125I-labeled ANF followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions and radioautography demonstrated that both high- and low-molecular weight receptors were unchanged in glomerular membranes and downregulated in vascular membranes from AC shunt animals. However, guanosine 3',5'-cyclic monophosphate (cGMP) production by the isolated glomeruli of AC shunt rats was lower than that of controls. We conclude that in the presence of elevated plasma ANF levels, glomerular, papillary, and vascular ANF receptors may be regulated differently.
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PMID:Divergent regulation of atrial natriuretic factor receptors in high-output heart failure. 133 15

20R 14 beta-amino 3 beta-rhamnosyl 5 beta-pregnan 20 beta-ol (LND 623, CAS 90520-42-6) was investigated and compared to digoxin in anesthetized dogs. The hemodynamic profiles showed: a) a pure positive inotropic action of LND-623; b) its potency was four-fold higher than that of digoxin and more marked in heart failure; c) its duration of action was maintained for at least 6 h. The onset and reversal of the inotropic effects of a single dose (3.3 nmol.kg-1.min-1) were faster with LND-623 than those of digoxin. This reversal is consistent with the faster dissociation profile observed at the level of the high affinity cardiac Na+,K(+)-ATPase receptor form. The advantage of LND-623 over digoxin resides in its larger therapeutic index (ratio of arrhythmogenic to inotropic responses) in anesthetized dogs with propranolol-induced heart failure. This index was 6 for LND-623 and 2 for digoxin.
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PMID:Efficacy and safety of the novel Na+,K(+)-ATPase inhibitor 20R 14 beta-amino 3 beta-rhamnosyl 5 beta-pregnan 20 beta-ol in a dog model of heart failure. 133 48

To define the renal effects of atrial natriuretic peptide (ANP) in heart failure, we studied rats with heart failure after coronary artery ligation. The rats received either captopril (2 milligrams drinking water) or placebo for 4 weeks. Glomerular filtration rate, renal plasma flow, filtration fraction, urine volume, urinary sodium excretion and the percent fractional excretion of sodium were measured before and after an infusion of ANP (0.3 microgram/kg/min). To determine whether changes in ANP receptor binding and responsiveness occur in heart failure and after captopril treatment, we performed radioreceptor binding studies and measured guanylate cyclase activity. Atrial natriuretic peptide in sham-operated rats decreased mean arterial pressure from 118 +/- 5 to 95 +/- 5 mm Hg (P less than .001), increased urine volume from 0.06 +/- 0.02 to 0.16 +/- 0.05 ml/min/kg (P less than .05), urinary sodium excretion, 14.2 +/- 3.1 to 41.4 +/- 8.9 mu eq/min/kg (P less than .02), filtration fraction from 0.30 +/- 0.03 to 0.40 +/- 0.4 (P less than .05), and the percent fractional excretion of sodium from 0.84 +/- 0.19 to 2.85 +/- 0.61 (P less than .02). Atrial natriuretic peptide in untreated rats with heart failure produced no significant systemic or renal hemodynamic effects. In rats with heart failure treated with captopril, ANP decreased mean arterial pressure from 93 +/- 4 to 86 +/- 4 mm Hg (P less than .05) and increased hematocrit from 50 +/- 2 to 52 +/- 1 (P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Captopril and ANP: changes in renal hemodynamics, glomerular-ANP receptors and guanylate cyclase activity in rats with heart failure. 134 64

The major risk factor associated with the appearance of adverse cardiovascular events and outcome attributable to cardiovascular disease is left ventricular hypertrophy (LVH). Why this should be so resides not in the increase in myocardial mass per se, but in the disruption of myocardial structure. An abnormal accumulation of fibrillar collagen within the adventitia of intramyocardial coronary arteries and neighboring interstitial spaces represents such a distortion in structure. Furthermore, this fibrosis disrupts the electrical and mechanical behavior of the hypertrophied myocardium. Mechanisms responsible for fibrillar collagen accumulation have been examined in intact animals and cultured cardiac fibroblasts. In vivo studies indicate that myocardial fibrosis is associated with the presence of chronic mineralocorticoid excess, relative to sodium intake and excretion, not hemodynamic workload. Accordingly, fibrosis can appear in both the hypertensive, hypertrophied and nonhypertensive, nonhypertrophied ventricles. In both primary and secondary hyperaldosteronism it was possible to prevent myocardial fibrosis with an aldosterone receptor antagonist, while in unilateral renal ischemia angiotensin converting enzyme (ACE) inhibition was similarly cardioprotective. A regression in fibrous tissue and normalization of diastolic stiffness has also been possible using ACE inhibition, bringing forward the concept of cardioreparation and the notion that heart failure due to fibrosis may be reversible. In vitro studies indicate that effector hormones of the renin-angiotensin-aldosterone system stimulate fibroblast collagen synthesis. Aldosterone, in pathophysiologic concentrations, and angiotensin II, in much larger concentrations, each enhance collagen synthesis without altering the mitogenic potential of these cells. Thus, elevations in circulating aldosterone and angiotensin II, relative to sodium intake, have the potential to not only alter sodium homeostasis and vascular tonicity, but also the structure of cardiovascular tissue. Thus, myocardial fibrosis represents a structural basis for pathologic hypertrophy and ultimately accounts for the appearance of adverse cardiovascular events and outcomes.
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PMID:Pathologic hypertrophy with fibrosis: the structural basis for myocardial failure. 136 63

The Na+/Ca2+ exchanger plays important roles in Ca2+ handling in many excitable cells. In particular, the Na+/Ca2+ exchanger is expressed at high levels in the cardiac sarcolemma and is the dominant mechanism of Ca2+ extrusion from the cells. In addition, the exchanger has been suggested to play key roles in digitalis action and in postischemic reperfusion injury of cardiac myocytes. We report here the isolation and characterization of the cDNA encoding the human cardiac Na+/Ca2+ exchanger. Twelve overlapping clones corresponding to 5.6 kilobases of the exchanger cDNA sequence were isolated from 5 x 10(5) phage plaques screened. The sequence predicted a 973-amino acid polypeptide with a putative leader peptide, 11 potential membrane-spanning regions, and one large putative cytoplasmic loop between the fifth and sixth transmembrane helices. When RNA was synthesized in vitro from the cloned cDNA and injected into Xenopus oocytes, it induced expression of Na+/Ca2+ exchange activity at high levels, confirming that this clone encodes the functional Na+/Ca2+ exchanger. Southern blot analysis indicated that the cardiac exchanger gene exists as a single copy in the human genome, although existence of other related genes cannot be ruled out. Northern blot and S1 mapping analyses revealed that the cardiac type exchanger mRNA is expressed most abundantly in the heart and next in the brain. The cardiac-type exchanger mRNA was also expressed in the retina and in skeletal and smooth muscles at very low levels. The levels of mRNA encoding the exchanger were significantly lower in fetal hearts than in adult hearts but were unchanged in the myocardium from patients with end-stage heart failure.
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PMID:Molecular cloning and characterization of the human cardiac Na+/Ca2+ exchanger cDNA. 137 13


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