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Biomedical subjects

R J Cody

Publications and source records attributed to R J Cody.

At least 73 records · Page 4Linked to original sources
PubMed1990

Hemodynamic and renal effects of atrial natriuretic peptide in congestive heart failure.

The hemodynamic and renal effects of anaritide (human atrial natriuretic peptide 102-126), a synthetic analog of atrial natriuretic peptide, were evaluated in 35 patients with chronic New York Heart Association class II to IV heart failure. There were 32 men and 3 women, aged 33 to 75 (mean +/- standard error of the mean 56 +/- 2) years. In the first phase of the study, right-sided heart catheterization was performed, and anaritide was administered as 1-hour infusions. The rate of the infusion varied among patients from 0.03 to 0.3 micrograms/kg/min. In response to anaritide, there were decreases in mean systemic arterial (94 +/- 2 to 87 +/- 2 mm Hg), right atrial (10 +/- 1 to 8 +/- 1 mm Hg), mean pulmonary arterial (33 +/- 2 to 28 +/- 2 mm Hg) and pulmonary artery wedge (22 +/- 2 to 15 +/- 2 mm Hg) pressures (all p less than 0.05). Cardiac index increased (2.39 +/- 0.15 to 2.62 +/- 0.15 liters/min/m2, p less than 0.05) and heart rate was unchanged. Systemic vascular resistance decreased significantly, but pulmonary vascular resistance was unchanged. There were increases in urine volume (1.6 +/- 0.2 to 2.3 +/- 0.4 ml/min), sodium excretion (47 +/- 13 to 74 +/- 20 muEq/min) and fractional excretion of sodium (0.41 +/- 0.11 to 0.59 +/- 0.14%, all p less than 0.05), while potassium excretion and creatinine clearance did not change. In the second phase of the study, patients received 2-hour infusions of anaritide (0.03 to 0.6 micrograms/kg/min) and placebo with noninvasive monitoring.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Comparative accuracy of Doppler echocardiographic methods for clinical stroke volume determination.

Numerous Doppler echocardiographic methods to measure stroke volume have been proposed in experimental or clinical studies, but their relative accuracy in patients compared with an invasive reference standard remains uncertain. Accordingly, we compared Doppler with thermodilution stroke volume measurement in 18 hospitalized patients, 16 with an acute manifestation of coronary artery disease and two with chronic cardiomyopathies. Doppler time-velocity integrals were measured by darkest line (modal velocity) and the leading edge (maximal velocity) techniques at the aortic annular plane, the mitral orifice, and the mitral annular plane. Two-dimensional echocardiography was used to measure cross-sectional areas (M-mode-corrected at the mitral orifice). The combination of aortic annular cross-sectional area and the leading edge technique of measuring the time-velocity integral of blood flow at this site provided the most accurate measure of stroke volume (r = 0.87, p less than 0.0001, standard error of estimate = 11 cm3; mean difference from thermodilution = 2.8 ml +/- 8.9 ml, p = NS). It also resulted in the most accurate measurement of cardiac output (r = 0.88, p less than 0.0003; mean difference from thermodilution = 0.11 L/min +/- 0.69 L/min, p = NS). Other methods yielded values that correlated less closely and deviated systematically from thermodilution measurements. We therefore conclude that of the six common methods evaluated, the aortic annular leading edge method measures stroke volume with the best accuracy and is most suitable for clinical application.

Adult↗
PubMed1990

Atrial natriuretic factor in edematous disorders.

This article provides a brief overview of atrial natriuretic factor (ANF). Considered by many investigators to be the putative "third factor" governing sodium excretion, ANF is a peptide actively secreted by the heart, with multiple target organ effectors. As such, ANF represents the first clearly documented cardiac hormone.

Animals↗
PubMed1990

Role of the kidney in congestive heart failure. Relationship of cardiac index to kidney function.

Because of inappropriate signals from the volume-regulation system and a reduction in renal blood flow, the kidney is not able to prevent sodium and water retention in chronic congestive heart failure (CHF). A brief summary of normal renal function and renal involvement in CHF is given and a study of renal function in patients with moderate or severe chronic CHF is presented. To evaluate the impact of cardiac output reduction on the regulation of the glomerular filtration rate (GFR) in heart failure, GFR (inulin clearance), renal plasma flow [p-aminohippurate (PAH) clearance], invasive haemodynamics, blood volume, plasma renin and plasma catecholamines were measured in 34 patients with chronic CHF. The patients were divided into 3 groups according to their cardiac index (CI): CI greater than 2.0 L/min/m2 (group A), CI 1.5 to 2.0 L/min/m2 (group B), and CI less than 1.5 L/min/m2 (group C). Differences in the relationship between GFR, renal plasma flow and filtration fraction for the 3 groups emerged. Despite an intergroup reduction in the renal fraction of cardiac output and renal blood flow, GFR was similar in groups A and B (62 and 67 ml/min/1.73 m2, respectively), and was accompanied by a compensatory increase in filtration fraction, from 24% in group A to 35% in group B. Group C had a much lower GFR (38 ml/min/1.73 m2), however, the filtration fraction (28%) was intermediate in value between those of groups A and B. The differences in GFR were reflected by blood urea nitrogen levels but not by serum creatinine levels. The occurrence of a non-compensatory filtration fraction response in the patients with the greatest impairment of CI and renal blood flow suggests that GFR becomes dependent on afferent arteriolar flow in the most severe heart failure, despite stimulation of haemodynamic and hormonal pathways, which would normally increase efferent arteriolar tone. It is thus suggested that GFR becomes flow dependent in patients in the most severe stage of chronic CHF.

Adult↗
PubMed1990

Alpha-adrenergic component of the sympathetic nervous system in congestive heart failure.

The alpha-adrenergic component of the sympathetic nervous system plays a major role in the pathophysiology, clinical manifestations, and natural history of human congestive heart failure. While the augmentation of alpha-adrenergic tone (through the neuronal release of norepinephrine) is a valuable mechanism to maintain adequate systemic blood pressure and perfusion of vital organs in states of circulatory collapse, stimulation of alpha-adrenergic receptors produces detrimental hemodynamic effects in congestive heart failure. These undesirable effects result from alpha-mediated vasoconstriction and consist of excessive elevation of right and left ventricular filling pressures and pulmonary and systemic vascular resistances. The enhancement of alpha-adrenergic tone preferentially reduces blood flow to the hepatosplanchnic circulation. Many of the hemodynamic responses that are seen after activation of the renin-angiotensin system are related to the ability of angiotensin II to amplify the actions of the alpha-adrenergic system. Stimulation of myocardial alpha-adrenergic receptors in most species elicits a modest positive inotropic effect, but the presence and importance of this property in the human heart remains controversial. Chronic stimulation of myocardial alpha-adrenergic receptors may result in the hypertrophy of cardiomyocytes and may also contribute to the development of catecholamine-induced cardiomyopathy. Acute blockade of the heightened alpha-adrenergic tone in congestive heart failure (e.g., with first doses of prazosin) results in favorable hemodynamic effects, but repeated dosing leads to pharmacological tolerance. Consequently, the long-term administration of alpha-adrenergic blocking agents in human heart failure has not been accompanied by an improvement in clinical status, exercise capacity, or survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Ability of left ventricular stress-shortening relations, end-systolic stress/volume ratio and indirect indexes to detect severe contractile failure in ischemic or idiopathic dilated cardiomyopathy.

The ability of several proposed indirect and direct indexes of left ventricular LV) systolic performance and contractility to detect clinically important LV dysfunction was evaluated in 42 patients with refractory dilated cardiomyopathy studied with right-sided heart catheterization and M-mode echocardiography. Hemodynamic evaluation demonstrated elevated filling pressure (mean pulmonary artery wedge pressure 24 +/- 6 mm Hg) and depressed function (cardiac index 1.68 +/- 0.43 liters/min/m2). Echocardiographic LV end-diastolic dimension (7.3 +/- 1.0 cm), mass (182 +/- 60 gm/m2) and end-systolic stress (163 +/- 44 x 10(3) dynes/cm2) were increased whereas fractional shortening was depressed in all (mean 12 +/- 4%). During follow-up 88% of patients died at a median interval of 16 months after study. Indirect measurements of LV function (mitral E point-septal separation and the ratio of preejection period to LV ejection time) were abnormal in 100 and 88% of patients, respectively. Contractility was classified as depressed in 36 (86%) patients by the end-systolic stress volume index ratio and in 31 (74%) by the relation between fractional shortening and end-systolic stress. In contrast, the relation between end-systolic stress and velocity of circumferential shortening identified only 7 (17%) patients as having subnormal contractility and classified 9 (21%) as having supernormal contractility. Rate correction of velocity of circumferential shortening only modestly improved the ability of the relation to identify depressed contractility (abnormal in 16 patients or 38 percent).

Aged↗
PubMed1989

Renal and hormonal effects of phosphodiesterase III inhibition in congestive heart failure.

Evaluation of the impact of therapeutic interventions in congestive heart failure (CHF) with compounds such as the phosphodiesterase (PDE) III inhibitors must include the determination of regional blood flow and functional changes. Thus, whereas PDE III inhibitors produce a significant increase in cardiac output and reduction of systemic vascular resistance, it is necessary to understand their effects on the kidney and neurohormonal parameters. The evaluation of these effects must take into consideration both the baseline renal and neurohormonal abnormalities in CHF, and the cellular actions of PDE III inhibition, which include an increase in cyclic adenosine monophosphate and cytosolic calcium. In a group of 13 patients with CHF, milrinone therapy for 1 month did not increase renal blood flow or glomerular filtration rate, or favorably affect neurohormonal parameters. However, forearm blood flow increased proportionately with cardiac output. Therefore PDE III inhibition produces a preferential increase in skeletal muscle blood flow, which may be a relative shunting of blood from the kidney. Alternatively, PDE III inhibition may activate renal cellular mechanisms that offset the anticipated favorable response to the increase of cardiac output produced by milrinone.

Aldosterone↗
PubMed1989

Plasma atrial natriuretic factor in essential hypertension: relation to cardiac size, function and systemic hemodynamics.

To evaluate determinants of elevated plasma atrial natriuretic factor levels in patients with hypertension, immunoreactive plasma atrial natriuretic factor in 54 normal subjects and 40 untreated hypertensive patients was compared with echocardiographic measurements of cardiac size, function and systemic hemodynamics. In normal subjects, plasma atrial natriuretic factor was related to age, systolic blood pressure and left atrial and ventricular chamber sizes, but only age and ventricular size were independent predictors. In untreated hypertensive patients, atrial natriuretic factor was directly related to age, atrial size, systolic pressure, peripheral resistance and ventricular systolic performance; age, atrial size and peripheral resistance were independent predictors. Eight patients with elevated atrial natriuretic factor values (greater than 25 fmol/ml) were significantly (p less than 0.01) older and had greater atrial and ventricular size and higher systolic pressure and function than normal subjects or patients with normal natriuretic factor levels. Plasma atrial natriuretic factor was inversely related to peak diastolic filling rate in normal subjects (r = -0.59; p less than 0.001), whereas it was positively related to the proportional contribution of atrial systole to left ventricular filling in hypertensive patients (r = 0.77; p less than 0.001). These findings suggest that in normal subjects, impairment of ventricular relaxation with age may contribute to atrial natriuretic factor secretion by increasing left atrial afterload; the correlation with left ventricular size may reflect physiologic fluctuations in plasma volume. In patients with uncomplicated hypertension, left atrial enlargement and consequent stronger atrial contraction contributed to increased atrial natriuretic factor release, whereas no independent relation existed with left ventricular hypertrophy or systolic function. Because ventricular relaxation was normal and ventricular size and systolic performance were increased in hypertensive patients with high atrial natriuretic factor levels, the observed increase in left atrial size and atrial contribution to ventricular filling might reflect a primary increase in venous return in this subset of hypertensive patients.

Adult↗
PubMed1989

Reversal of a calcium-mediated vasoconstrictor component in patients with congestive heart failure.

The influx of calcium into vascular smooth muscle cells is a major determinant of vasoconstriction, yet this concept has not been explored in congestive heart failure (CHF). We therefore used an "isolated" forearm model to assess the direct effects of the inhibition of calcium influx into vascular smooth muscle in 11 patients who had CHF, with use of the soluble dihydropyridine, nicardipine. Nicardipine produced a dose-dependent increase of forearm blood flow and a reduction of resistance, without producing a systemic hemodynamic effect. Patients with the lowest baseline forearm blood flow levels had the greatest percentage increases in forearm blood flow (r = -0.729, p less than 0.01), and a favorable metabolic effect was documented by a reduction in oxygen extraction across the forearm. This study demonstrated the importance of vascular smooth muscle intracellular calcium as a determinant of vasoconstriction in patients who have CHF.

Calcium Channels↗
PubMed1989

Hemodynamic responses to converting enzyme inhibition in patients with renal disease.

We studied the effects of lisinopril on mean arterial blood pressure (MAP), plasma renin activity (PRA), and renal hemodynamics in nine patients with chronic renal disease and hypertension, before, and after three months of therapy. Lisinopril normalized blood pressure in five of nine patients (responders) and did not in the remaining four (nonresponders). PRA rose after lisinopril (4.8 +/- 2.6 ng/mL/h to 25 +/- 15 ng/mL/h, P less than 0.05) in responders, but not in nonresponders (2.0 +/- 1.4 ng/mL/h to 3.4 +/- 2.9 ng/mL/h). Glomerular filtration rate remained stable in both groups (responders: 43 +/- 11 mL/min to 43 +/- 22 mL/min; nonresponders: 39 +/- 25 mL/min to 32 +/- 21 mL/min). In the responders renal hemodynamics remained stable after lisinopril (renal plasma flow: 223 +/- 80 mL/min to 216 +/- 91 mL/min; filtration fraction: .20 +/- .04 to .20 +/- .05; renal vascular resistance: 386 +/- 179 to 326 +/- 209 units). In the nonresponders, renal plasma flow decreased (228 +/- 141 mL/min to 162 +/- 117 mL/min, P less than 0.005), filtration fraction increased (.19 +/- .08 to .24 +/- .12, P less than 0.05), and renal vascular resistance increased (695 +/- 747 to 1265 +/- 1574 units, P less than 0.05) after chronic lisinopril therapy. We conclude (1) there is a heterogeneous response to lisinopril in patients with chronic renal disease and hypertension, (2) lisinopril monotherapy may result in effective blood pressure control without renal hemodynamic compromise, and (3) an increase in PRA following converting enzyme inhibition may identify those in whom the circulating renin angiotensin system is participating in systemic hypertension and intrarenal hemodynamic changes.

Adult↗
PubMed1989

Neurohormonal influences in the pathogenesis of congestive heart failure.

Despite the interest in neurotransmitter and hormonal influences in heart failure in the last decade, the issues surrounding their contribution to the pathophysiology of congestive heart failure have become more complex. This must be considered in view of the pathway of hormonal stimulation and inhibition (Fig. 3) and the multiple steps where abnormal responses can interrupt these pathways. It is reasonable to state that the extent of neurotransmitter and hormonal activity in stage IV heart patients, treated with digoxin and diuretics, has been characterized. However, these observations cannot be extended to other stages of CHF, and assumptions cannot be made regarding either the untreated patient, or the nature of disease progression. Furthermore, there is insufficient information regarding the direct effect of these hormonal systems, with the exception of norepinephrine, on the myocardium. These issues must be the focus of future studies.

Atrial Natriuretic Factor↗
PubMed1989

Age-related hemodynamic, renal, and hormonal differences among patients with congestive heart failure.

The purpose of this study was to determine if there were characteristics that distinguish elderly patients with heart failure (greater than 65 years of age) from younger patients with heart failure. We studied 128 consecutively admitted patients with chronic congestive heart failure (CHF) under uniform conditions, with measurement of systemic hemodynamics, vasoactive hormones and sodium status, and renal function. Additional characterization included the hemodynamic response to gravitational stress (head-up tilt; n = 65), and renal blood flow and function by steady-state clearance techniques (n = 46). Compared with younger patients with CHF, there was a greater frequency of ischemic heart disease in the elderly patients with CHF. Within the CHF population there was an increase of systemic vascular resistance and a trend of decreased heart rate with aging. Heart rate responsiveness was attenuated during tilt according to age. Circulating norepinephrine increased with aging, but a clear-cut age-related effect was not observed for renin system activity or sodium status. Both serum urea nitrogen and serum creatinine increased with age. More detailed renal studies confirmed an age-related decrease of glomerular filtration rate and a noncompensatory filtration fraction, despite increasing renal vascular resistance. We conclude that elderly patients with CHF have relatively greater vasoconstriction (or decreased compliance) and blunted heart rate responsiveness associated with increased circulating norepinephrine. Furthermore, renal function in the elderly patient with CHF is markedly compromised. These findings are consistent with superimposition of an aging effect on the CHF process, which must be considered in evaluating the response to drug therapy and the outcome of multicenter CHF trials.

Adult↗
PubMed1988

Regulation of glomerular filtration rate in chronic congestive heart failure patients.

The purpose of this study was to identify the factor(s) that characterize impaired glomerular filtration rate (GFR) in congestive heart failure (CHF) patients. We studied 34 patients, measuring systemic hemodynamics, vasoactive hormones, and sodium and volume status. Renal plasma flow (para-aminohippurate) and GFR (inulin) were assessed by steady-state clearance techniques. Both linear and multiple regression analyses were performed. Impaired GFR was characterized by reduction of renal blood flow and renal fraction of cardiac output, and by an increase of renal vascular resistance. The correlation between GFR and filtration fraction (r = 0.492, P less than 0.003) indicated that individuals with greatest impairment of GFR had the lowest filtration fraction and increased overall renal vascular resistance, indicating dependence of GFR on afferent, rather than efferent vasoconstriction, under conditions of low renal perfusion. Mean vasoactive hormones and blood volume were increased, but without clear cut correlation with GFR. The greatest impairment of GFR was observed in elderly CHF patients, as renal blood flow and function demonstrated an age-dependent decline, in addition to the adverse effects of CHF. In a multiple regression model, renal blood flow and filtration fraction accounted for 69% and 25%, respectively, of the variability of GFR, with a co-linear influence of age. Thus, we have identified age-related, abnormal renal hemodynamic patterns in CHF, and the fragile nature of GFR in the elderly CHF population.

Adult↗