Biomedical subjects

M M Redfield

Publications and source records attributed to M M Redfield.

62 records · Page 4Linked to original sources

PubMed1992

Cardiac atrial natriuretic factor during evolution of congestive heart failure.

Congestive heart failure (CHF) is a pathophysiological condition associated with increased plasma levels of atrial natriuretic factor (ANF), a peptide hormone of cardiac origin that participates in the homeostatic control of intravascular volume and vascular tone. Atrial myocytes serve as the principal source of ANF under physiological conditions, although recent studies have demonstrated that ventricular myocardium may also synthesize ANF in models of CHF associated with ventricular hypertrophy. The current study was designed to investigate the roles of atrial and ventricular myocardium to synthesize, store, and release ANF during the evolution of tachycardia-induced CHF in the dog. The present study demonstrates a persistent elevation of plasma ANF during the evolution of CHF. In acute CHF (3 h), plasma ANF increased independent of cardiac ANF synthesis. In chronic CHF (15 and 30 days), plasma ANF is maintained by an increase in atrial synthesis and release of the peptide, without recruitment of ventricular ANF synthesis. The present study demonstrates that in acute CHF the increase in plasma ANF is regulated by release of stored peptide, and in chronic CHF the persistent elevation of plasma ANF is maintained by an increase in atrial synthesis of ANF.

Animals↗

PubMed1990

Atrial natriuretic factor inhibits hypertonic saline-mediated decreases in renal hemodynamics.

The present study in the anesthetized dogs was designed to test the hypothesis that atrial natriuretic factor (ANF) attenuates whole kidney tubuloglomerular feedback (TGF) mediated decreases in renal blood flow (RBF) and glomerular filtration rate (GFR) produced by hypertonic saline (HS). Secondly, as adenosine (AD) has been implicated as a metabolic mediator of TGF, we also hypothesized that ANF would antagonize the renal actions of AD. To test this hypothesis, RBF and GFR were assessed in response to hypertonic saline (HS, 16%, i.r.) or adenosine (AD, 0.1 mumol/min, i.r.) in the presence and absence of exogenous ANF (100 ng/kg/min, i.r.). ANF attenuated HS-mediated reductions in GFR (HS, -39.6 +/- 9.8 ml/min vs. HS + ANF, -14.3 +/- 4.5 ml/min, P less than 0.05) and in RBF (HS, -143 +/- 35 ml/min vs. HS + ANF, -5 +/- 22 ml/min, P less than 0.05). GFR was reduced by AD (-9.2 +/- 3.0 ml/min, P less than 0.05), but maintained by AD + ANF (-0.4 +/- 2.0 ml/min, NS). A transient adenosine-mediated vasoconstriction was attenuated by ANF (AD, -54.5 +/- 3.6 ml/min vs. AD + ANF, -3.7 +/- 3.1 ml/min, P less than 0.005). We conclude that ANF at pharmacologic concentrations attenuates at the whole kidney level hypertonic saline and adenosine-mediated reductions in RBF and GFR.

Adenosine↗

PubMed1989

Restoration of renal response to atrial natriuretic factor in experimental low-output heart failure.

The renal response to atrial natriuretic factor (ANF) has been shown to be blunted in several experimental models of acute and chronic congestive heart failure. The mechanism responsible for this blunted response has been postulated to be activation of the renin-angiotensin system with associated potent antinatriuretic effects and/or the reduction in renal perfusion pressure (RPP) characteristic of heart failure. The present study was designed to examine the relative role of these two factors in mediating the blunted response to ANF in a model of acute low output heart failure produced by thoracic inferior vena cava constriction (TIVCC) in the anesthetized dog. TIVCC was produced in five groups of dogs. In group 1, ANF was infused after TIVCC to document the blunted natriuretic response. In group 2, ANF was infused after TIVCC in the presence of blockade of intrarenal angiotensin II (ANG II) by the intrarenal infusion of saralasin (Sar) at a dose without systemic effects. In group 3, ANF was infused after TIVCC in the presence of restoration of RPP by infusion of ANG II at a dose titrated to restore RPP to the level present before TIVCC. In group 4, ANF was infused in the presence of restoration of RPP with ANG II and blockade of intrarenal ANG II with Sar. Group 5 served as an additional control group where the effect of ANG II and Sar in TIVCC was examined in the absence of ANF. Restoration of RPP but not blockade of intrarenal ANG II resulted in a restoration of the response of sodium excretion and glomerular filtration rate to ANF. ANG II plus Sar in the absence of ANF did not produce a natriuresis. We conclude that RPP, more than intrarenal ANG II, modulates the blunted renal response to ANF observed in this model of acute low-output heart failure.

Animals↗

PubMed1989

Failure of atrial natriuretic factor to increase with volume expansion in acute and chronic congestive heart failure in the dog.

It remains unclear whether the levels of atrial natriuretic factor (ANF) observed in chronic CHF are appropriate for the magnitude of elevations in atrial pressures. Specifically, it is not known whether acute increases in atrial pressure in CHF can result in further significant increases in circulating ANF. The present study was designed to test the hypothesis that in chronic CHF there is an attenuated relation between circulating ANF and atrial pressure such that the heart is unable to respond to further increases in atrial pressure with appropriate increases in ANF. Cardiovascular hemodynamics and plasma levels of ANF were measured at baseline and after rapid right ventricular pacing (RRVP) to produce acute (n = 10, 25 minutes RRVP) and chronic (n = 7, 14-16 days RRVP) CHF. Acute saline volume expansion was then performed in each group to determine the response of circulating ANF to acute increases in atrial pressure in both acute and chronic CHF. In chronic CHF, right atrial pressure was much higher than in acute CHF (8.5 +/- 0.9 vs. 3.4 +/- 1.3 mm Hg, p less than 0.05); however, circulating ANF was not greater in chronic as compared with acute CHF (385 +/- 73 vs. 500 +/- 89 pg/ml), which is consistent with an attenuated release of ANF in chronic CHF. In response to volume expansion, right atrial pressure increased in both acute (3.4 +/- 1.3 to 12.1 +/- 7 mm Hg) and chronic (8.5 +/- .9 to 13.3 +/- 1.0 mm Hg) CHF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Integrated cardiac, renal, and endocrine actions of endothelin.

Endothelin, a newly discovered endothelial-derived peptide, has been demonstrated in vitro to have potent vasocontractile properties and has been speculated to play a role in vivo in arterial pressure-volume homeostasis. The present studies in anesthetized dogs were designed to determine the action of endothelin on cardiovascular-renal and endocrine function in vivo as in acute arterial pressure-volume regulation. Intravenous infusion of endothelin (50 ng/kg per min) increases arterial pressure by increasing peripheral vascular resistance but in association with an increase in coronary vascular resistance and decreases in cardiac output. Renal blood flow and glomerular filtration rate were markedly reduced in association with a sustained reduction in sodium excretion and an increase in plasma renin activity. Atrial natriuretic factor, vasopressin, and aldosterone were also elevated. These results indicate that endothelin is a potent vasoconstrictor that elevates systemic blood pressure in association with marked decreases in cardiovascular and renal function. This peptide may function as a counterregulatory hormone to the effects of endothelial-derived vasodilator agent(s).

Animals↗

PubMedDate not supplied

Pulmonary venous velocity patterns in mitral stenosis.

Pulmonary venous (PV) velocities obtained by transthoracic echocardiography are used to assess diastolic function. The systolic/diastolic (S/D) PV velocity ratio is increased with impaired early diastolic filling and decreased with elevated mean left atrial pressure (LAP). Mitral stenosis (MS) is characterized by impaired filling and elevated LAP. We hypothesized that the S/D ratio would be increased in MS except in severe MS with high LAP, in which the S/D ratio would be decreased. Patients with isolated MS who underwent transthoracic echocardiography were studied. The PV S/D ratio was compared in mild (n = 18), moderate (n = 16), and severe (n = 7) MS. There was no characteristic PV pattern, with each category showing a wide range of S/D ratios (mild, S/D ratio = 1.42 +/- 0.56; moderate, S/D ratio = 1.19 +/- 0.59, and severe, S/D ratio = 1.33 +/- 0.53) (mean +/- SD). Furthermore, there was no relationship between the S/D ratio and any index of severity of MS. There is no characteristic PV velocity pattern in MS.

Atrial Function, Left↗

PubMedDate not supplied

Assessment of left ventricular end-diastolic pressure by Doppler echocardiography: contribution of duration of pulmonary venous versus mitral flow velocity curves at atrial contraction.

The difference in the durations of flow with atrial contraction (A duration) at the pulmonary veins and mitral valve has been reported to detect the presence of elevated left ventricular end-diastolic pressure. It is postulated that with left ventricular filling during atrial contraction, reduced ventricular compliance results in the transmission of increased pressure into the left atrium, resulting in prolongation of the pulmonary venous flow with atrial contraction. However, the relationship between ventricular compliance during atrial contraction and the pulmonary venous and mitral A durations and their difference have not been carefully examined. We performed recordings of left ventricular pressure and complete Doppler analysis of pulmonary venous and transmitral flow in 87 patients. Operant ventricular compliance at atrial contraction was estimated by measuring the increase in ventricular pressure with atrial contraction (left ventricular a wave) and by using a compliance index, which incorporated an estimate of flow into the ventricle with atrial contraction from the Doppler transmitral a wave. The difference in pulmonary venous and mitral A durations correlated well with left ventricular end-diastolic pressure (r = 0.73, p < 0.01) and the pulmonary venous reversal duration exceeding the duration of the mitral A velocity curve provided high sensitivity (82%) and specificity (92%) for the detection of an end-diastolic pressure of 20 mm Hg or greater. The pulmonary venous A duration increased with a moderate decrease in ventricular compliance but was not increased further in patients with a severe decrease in compliance. In contrast, mitral A duration was not different in patients with moderate reduction in compliance, but was shorter in patients with severe decreases in ventricular compliance. Pulmonary venous and mitral A durations are related to ventricular compliance and they change in an opposite and progressive manner. Their difference is a sensitive method for the detection of the elevated end-diastolic pressure associated with reduction in ventricular compliance.

Adult↗

PubMedDate not supplied

Augmented cardiac cardiotrophin-1 in experimental congestive heart failure.

BACKGROUND: Cardiotrophin-1 (CT-1) is a potent hypertrophic factor discovered by coupling expression cloning in a mouse embryonic stem cell-based model of cardiogenesis. METHODS AND RESULTS: The present study was designed to investigate the potential activation of atrial and ventricular CT-1 expression in pacing-induced experimental congestive heart failure (CHF) and its relationship to left ventricular hypertrophy by the method of Northern blot analysis and immunohistochemistry. We used a canine model of pacing-induced experimental CHF based on hemodynamic and neurohumoral characteristics that closely mimic human dilated cardiomyopathy. Northern blot analysis demonstrated that CT-1 gene expression was present in normal atrium and ventricle and was increased in CHF hearts. There was a positive correlation between ventricular CT-1 mRNA and left ventricular mass index. Immunohistochemistry revealed positive immunostaining in the atrial and ventricular cardiomyocytes from both normal and CHF hearts. CT-1 immunoreactivity was more intense in the atrium and ventricle from CHF hearts than in normal hearts. CONCLUSIONS: The present study demonstrates that both atrium and ventricle synthesize CT-1 and that cardiac production of CT-1 is augmented in a canine model of experimental CHF. This study also demonstrates that ventricular CT-1 mRNA correlates with left ventricular hypertrophy, suggesting that CT-1 plays an important role in the structural remodeling that characterizes CHF.

Animals↗