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Biomedical subjects

D Bichet

Publications and source records attributed to D Bichet.

At least 37 records · Page 2Linked to original sources
PubMed1991

Activation of neurohumoral systems following acute myocardial infarction.

Previous studies have indicated that patients with an acute myocardial infarction have marked activation of all neurohumoral systems on admission to the hospital. This activation begins to subside within the first 72 hours so that by 7-10 days, all plasma neurohormones have returned to normal. The only documented exceptions were found to occur in patients with left ventricular dysfunction and overt heart failure, where both plasma renin activity and atrial natriuretic peptide were increased, and in patients with left ventricular dysfunction but no overt heart failure, where only atrial natriuretic peptide was increased. Although these studies suggest that neurohumoral activation rarely occurs at the time of hospital discharge, they were small and may have missed an important subgroup of patients with persistent neurohumoral activation. In the Survival and Ventricular Enlargement (SAVE) study, 522 patients had plasma neurohumoral levels measured at a mean of 12 days postinfarction. All SAVE patients had left ventricular dysfunction (left ventricular ejection fraction less than or equal to 40%), but no overt heart failure. In this group of patients, all neurohumoral levels (plasma renin activity, norepinephrine, arginine vasopressin, and atrial natriuretic peptide) were found to be increased compared with age-matched control subjects. These results indicate that, in fact, a subgroup of patients without overt heart failure has persistent neurohumoral activation at the time of hospital discharge postinfarction, and that this activation involves several neurohumoral systems. Since patients with persistent neurohumoral activation postinfarction are likely those most at risk of developing complications and the ones most likely to benefit from pharmacologic interventions blunting the effects of neurohumoral activation, measurement of predischarge neurohumoral levels may be useful.

Humans↗
PubMed1991

Pharmacokinetics of oral diltiazem and five of its metabolites in patients with chronic renal failure.

The pharmacokinetics of oral diltiazem were studied in 10 patients with chronic renal failure not requiring dialysis and in five healthy volunteers after a single dose of 120 mg. We found that patients with chronic renal failure had lower amounts of unchanged diltiazem and of its main metabolite (MA) in urine and a trend to have slightly higher values of plasma concentration. Since the terminal elimination phase is not affected by chronic renal failure we conclude that this trend is probably the result of alterations in the volume of distribution of diltiazem in these patients.

Administration, Oral↗
PubMed1991

Pharmacokinetics of intravenous diltiazem and five of its metabolites in patients with chronic renal failure and in healthy volunteers.

The pharmacokinetics of diltiazem were studied in seven patients with chronic renal failure (CRF) not requiring dialysis and in three healthy volunteers after a rapid i.v. infusion of 20 mg. Mean plasma concentrations at the end of infusion were 3.15 times higher in patients with CRF than in healthy volunteers. From 0.5 to 12 h post-infusion, the difference remained between 25 per cent and 73 per cent. Mean AUC0-infinity was statistically greater in patients than in volunteers while mean V area, CLtot, and CLren were statistically lower. The t1/2 alpha and t1/2 beta values were not significantly (p greater than 0.05) different between patients and volunteers. Renal excretion was statistically more important in volunteers (6.6 per cent of the dose) than in patients (1.2 per cent of the dose). We therefore conclude that CRF does not influence t1/2 beta of diltiazem but it interferes with the extent and possibly the rate of its extravascular distribution. That could result in transient high plasma concentrations after rapid i.v. infusion.

Adult↗
PubMed1990

Sustained beneficial effect of a seventy-two hour intravenous infusion of nitroglycerin in patients with severe chronic congestive heart failure.

To determine whether a 72-hour infusion of nitroglycerin produces hemodynamic improvement in patients with severe congestive heart failure and to assess the contributing role of various possible causes of hemodynamic tolerance to nitroglycerin, 19 patients received an infusion of nitroglycerin 1.5 micrograms/kg/min for 72 hours. In a subgroup of patients (n = 10), there was an increase in stroke work index and a decrease in ventricular filling pressures throughout the infusion and even after it was discontinued. Tolerance to the hemodynamic effects of nitroglycerin was partially reversed 8 hours after the infusion was stopped. Neurohumoral changes occurred but appeared to play only a minor role in the development of nitroglycerin tolerance. However, hematocrit fell 9 +/- 5%, which suggests that an increased intravascular volume contributed to tolerance. In summary: (1) a 72-hour infusion of nitroglycerin improves ventricular function in some patients with severe heart failure; (2) volume shifts from the extravascular to the intravascular compartments may, at least in part, be responsible for nitroglycerin tolerance; and (3) reflex neurohumoral activation may also play a small role in nitrate tolerance.

Administration, Sublingual↗
PubMed1990

Effect of water intake on the progression of chronic renal failure in the 5/6 nephrectomized rat.

This study tests the possible influence of the urinary concentrating process and/or of vasopressin (AVP) on the progression of early chronic renal failure (CRF). Male Sprague-Dawley rats were submitted to 5/6 nephrectomy and were offered water ad libitum throughout the study. In addition, half of the rats (high water intake, HWI) received their food mixed with a water-rich agar gel. The other rats (normal water intake, NWI) ate the same amount of food plus agar in the usual dry powder form. This resulted in doubling the daily water ingestion in HWI. Renal function was studied for 10 wk and kidney morphology assessed thereafter. Increased water intake in HWI reduced solute-free water reabsorption and urine osmolality about threefold to 12 +/- 1 ml/day and 390 +/- 9 mosmol/kgH2O, respectively (week 5 as example). Hematocrit, plasma sodium, and plasma creatinine concentration were unchanged. The progressive increases in urinary protein excretion and in systolic blood pressure observed in this model of CRF were significantly slowed in HWI compared with NWI (at week 5, 8.6 +/- 1.8 vs. 23.1 +/- 6.2 mg protein/day and 142 +/- 8 vs. 167 +/- 10 mmHg, respectively). Remnant kidney weight per unit body weight was 21% lower in HWI than in NWI (P less than 0.02). Incidence of glomerulosclerosis was also reduced and was correlated with kidney weight (P less than 0.01). AVP plasma level (PAVP) and plasma renin activity (PRA) were measured in additional rats. PAVP was about twofold higher (P less than 0.05) and PRA twofold lower (P less than 0.001) in rats with 5/6 nephrectomy than in control rats with two kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗
PubMed1990

Captopril does not prevent nitroglycerin tolerance in heart failure.

Tolerance to the continuous intravenous infusion of nitroglycerin is thought to be largely the result of a decrease in vascular responsiveness, possibly due to intra-smooth muscle sulfhydryl group depletion. Another mechanism proposed to contribute to tolerance is nitroglycerin-induced reflex neurohumoral activation resulting in vasoconstriction and sodium and water retention. It has been proposed that the sulfhydryl group-containing angiotensin converting enzyme (ACE) inhibitor captopril may be useful in preventing tolerance to nitroglycerin by repleting sulfhydryl groups and by decreasing reflex neurohumoral activation. However, by decreasing renal perfusion pressure, the combination of captopril and nitrates could also lead to renal dysfunction. The objectives of this study were to determine whether captopril prevented or significantly reduced hemodynamic tolerance to a 72 h infusion of nitroglycerin, and to determine whether the combination of nitroglycerin and captopril caused deterioration of renal function. Nineteen patients with congestive heart failure received nitroglycerin (1.5 micrograms/kg/min) alone (n = 11) or in combination with oral captopril (63 +/- 8 mg/day) (n = 8). In both groups, partial hemodynamic tolerance developed within the first 24 h of nitroglycerin infusion. Nitroglycerin therapy, with or without captopril, did not affect plasma adrenaline, noradrenaline, aldosterone or arginine vasopressin. However, plasma renin activity increased and atrial natriuretic peptide decreased in both groups, these changes being significant after 1 h of infusion but gradually returning towards baseline, in both groups, over the next 71 h. The nitroglycerin infusion did not alter body weight, urine output, creatinine clearance or fractional sodium excretion in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Osmoregulation of vasopressin secretion and thirst during the estrous cycle of pigs.

The influence of the reproductive cycle on ingestive behaviors, osmotically induced fluid intake, and peripheral blood levels of several hormones involved in fluid electrolyte balance was investigated in young adult female pigs. Food, water, and salt intakes and plasma aldosterone levels were significantly lower during estrus compared with the luteal and follicular phases, whereas plasma sodium (PNa) was higher. Plasma renin activity and lysine vasopressin (LVP) levels did not vary with the cycle. Regression analyses of the relationship between plasma LVP and PNa in unanesthetized, unstressed animals infused for 2 h with intravenous 5% NaCl revealed no significant differences in terms of the osmotic threshold and sensitivity of LVP release at different stages of the reproductive cycle. In contrast, when osmotic loading was carried out with continuous access to water, the osmotic threshold for drinking was found to be significantly higher and the rate of drinking lower during estrus. The results indicate that in the adult female pig the stage of the reproductive cycle has an influence on ingestive behaviors and the osmoregulation of thirst. Osmoregulation of vasopressin secretion, on the other hand, appears to be independent of the estrous cycle in this species.

Animals↗
PubMed1989

Plasma atriopeptin during exercise in dogs under beta-blockade.

The purpose of this study was to describe plasma atriopeptin concentrations at rest and in response to moderate treadmill exercise (10 min, 4 km/h, 26% slope) performed with or without nonspecific beta-adrenergic blockade (1 mg/kg iv propranolol) in 10 mongrel dogs [19 +/- 2 (SE) kg]. A small (20%) but significant (P less than 0.05) increase in plasma atriopeptin concentration was observed from rest (43 +/- 5 pg/ml) to exercise (52 +/- 6 pg/ml) without beta-blockade. Propranolol significantly reduced heart rate at rest (89 +/- 7 vs. 104 +/- 7 beats/min) and during exercise (96 +/- 10 vs. 176 +/- 11 beats/min), and this was associated with a larger increase in plasma atriopeptin concentration during exercise (rest 46 +/- 6 pg/ml; exercise 171 +/- 22 pg/ml). Exercise under beta-blockade is associated with an increased preload of the heart. These results further support the hypothesis that atriopeptin release during exercise is under the control of atrial stretch. The higher plasma atriopeptin concentration observed during exercise under beta-blockade may contribute to the reduction of the response of plasma renin activity (1.0 +/- 0.1 vs. 3.0 +/- 0.6 ng.ml-1.h-1) and aldosterone concentration (87 +/- 36 vs. 138 +/- 25 pg/ml). Vasopressin concentration was lower at rest and during exercise under propranolol (3.5 +/- 1.3 vs. 4.9 +/- 0.9 and 6.1 +/- 2.2 vs. 9.9 +/- 1.5 pg/ml, respectively), which might reflect a dissociation between activity of the renin-angiotensin system and vasopressin release.

Adrenergic beta-Antagonists↗
PubMed1988

Atrial natriuretic peptide in congestive heart failure: postural changes and reset with chronic captopril therapy.

The response of atrial natriuretic peptide (ANP) to standing and the acute and chronic administration of the vasodilator, captopril, were examined in 15 patients with chronic congestive heart failure. In the supine position, ANP was increased (361 +/- 202 pg/ml); however, only a loose correlation existed between atrial pressures and ANP (right atrial vs ANP, r = 0.03, p = N.S., and pulmonary capillary wedge pressures vs ANP, r = 0.4, p = N.S.). Standing and acute captopril therapy decreased atrial pressures and ANP but did not significantly improve the correlation between atrial pressures and ANP. With chronic captopril therapy, atrial pressures remained decreased; however, ANP had returned to control values (370 +/- 254 pg/ml vs 361 +/- 202 pg/ml) and failed to decrease with standing (370 +/- 259 pg/ml lying vs 351 +/- 194 pg/ml standing). These changes in ANP (with chronic captopril therapy) persisted even once the hemodynamic effects of captopril had dissipated (3 hours post dose). This study indicates that in patients with severe chronic congestive heart failure (1) only a poor correlation exists between ANP and atrial pressures and (2) with chronic captopril therapy ANP increases to higher levels for a given atrial pressure and fails to decrease with standing despite a decrease in atrial pressures.

Atrial Function↗
PubMed1988

Neurohumoral and hemodynamic changes in congestive heart failure: lack of correlation and evidence of compensatory mechanisms.

The objective of this study was to assess the hemodynamic and neurohumoral (plasma renin activity, aldosterone, epinephrine, norepinephrine, vasopressin, and atrial natriuretic peptide) determinants of systemic vascular resistance in 35 patients with stable congestive heart failure. In the supine position, although activation of the various neurohumoral systems tended to occur in the same patients, there was little correlation between activation of any of the neurohumoral systems, as reflected by circulating levels, and systemic vascular resistance. There was also little correlation between changes in circulating neurohormones and changes in either mean arterial pressure or systemic vascular resistance in the standing position. Acutely reducing the activity of the renin-angiotensin system with the use of captopril did not improve the correlation between other neurohumoral and hemodynamic variables. In fact there was no correlation between the effects of acute captopril therapy and baseline renin values. These results support the concept that activation of one or another vasoconstrictor neurohumoral system varies from patient to patient and that the effects of their activation are tempered by activation of parallel vasodilator systems and by attenuation of neurohormone release and effector organ response.

Adaptation, Physiological↗
PubMed1988

Effect of induced ventricular tachycardia on atrial natriuretic peptide in humans.

The effects of induced sustained ventricular tachycardia on the release of plasma-immunoreactive atrial natriuretic peptide were evaluated in 11 adult patients undergoing diagnostic electrophysiologic study. Plasma concentrations of atrial natriuretic peptide withdrawn from the right atrium before and during sustained ventricular tachycardia (mean tachycardia cycle length 320 +/- 68 ms, duration greater than 30 s) were determined by radioimmunoassay. Hemodynamic measurements included phasic femoral artery blood pressure and mean right atrial blood pressure before and during ventricular tachycardia. During ventricular tachycardia, atrial natriuretic peptide increased from 93 +/- 49 pg/ml to 234 +/- 195 pg/ml (p less than 0.05), systolic arterial blood pressure decreased from 120 +/- 16 to 70 +/- 23 mm Hg (p less than 0.001), diastolic arterial blood pressure decreased from 63 +/- 8 to 51 +/- 16 mm Hg (p = NS) and mean right atrial blood pressure increased from 3 +/- 1 to 8 +/- 5 mm Hg (p less than 0.02). In six patients, all hemodynamic variables and the atrial natriuretic peptide were measured during repeated stimulation protocols to investigate the effect of ventricular stimulation for ventricular tachycardia induction on atrial natriuretic factor release. Compared with the values obtained during sinus rhythm, there was no significant increase in atrial natriuretic factor during ventricular stimulation at a cycle length of 600 ms (45 +/- 20 versus 52 +/- 21 pg/ml) or at a cycle length of 400 ms (45 +/- 20 versus 57 +/- 18 pg/ml). No significant linear relation could be found among the changes in mean right atrial pressure, systolic arterial blood pressure and the increase in atrial natriuretic peptide.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Plasma AVP and renal concentrating defect in chloride depletion metabolic alkalosis.

These studies were undertaken to determine the effect of chronic chloride depletion metabolic alkalosis (Cl-DEP-MALK) on water intake, plasma arginine vasopressin (AVP) levels, and renal concentrating ability. Cl-DEP-MALK was induced by feeding a chloride-free diet to rats subjected to gastric drainage and to dogs treated with furosemide. All of the animals developed a urine concentrating defect, polydipsia, and a persistent reduction in plasma osmolality. However, AVP release was not suppressed. The results of osmotic loading experiments in dogs analyzed using either linear or log-linear models have shown that chronic Cl-DEP-MALK significantly alters the relation between plasma osmolality and plasma AVP. In the classic linear analysis the results suggest that Cl-DEP-MALK reduces the plasma osmolality at which plasma AVP can be detected, i.e., reduced "threshold," and increases the slope of the plasma osmolality-to-plasma AVP relation nearly twofold, i.e., increased "sensitivity." Finally, we provide evidence that the concentrating defect is not related to high water turnover or deficient endogenous AVP and is therefore nephrogenic.

Alkalosis↗
PubMed1987

Chronic renal and neurohumoral effects of the calcium entry blocker nisoldipine in patients with congestive heart failure.

Nisoldipine, a calcium entry blocker, was given to 10 patients with congestive heart failure. During a 2 month follow-up period, 7 of the 10 patients were readmitted with pulmonary edema; daily furosemide doses were increased (128 +/- 87 to 192 +/- 135 mg/day, p less than 0.01), and plasma creatinine increased (1.5 +/- 0.5 to 1.8 +/- 0.6 mg/dl, p less than 0.05) (all values mean +/- SD). Despite this unfavorable clinical course, nisoldipine caused some beneficial chronic (1 month) hemodynamic effects. It decreased systemic vascular resistance (from 1,781 +/- 229 to 1,306 +/- 345 dynes X s X cm-5, p less than 0.01), decreased mean arterial pressure (from 88 +/- 0 to 74 +/- 4 mm Hg, p less than 0.001) and increased stroke volume index (from 27 +/- 6 to 33 +/- 9 ml/min per m2, p less than 0.02). Heart rate, pulmonary capillary wedge pressure and stroke work index did not change. However, nisoldipine's chronic renal and neurohumoral effects were not as favorable. These were assessed during a 5 hour water load (15 ml/kg body weight of 5% dextrose in water) and compared with the effects of a water load before therapy. Nisoldipine did not change creatinine clearance or sodium excretion, but decreased water excretion (from 58 +/- 35 to 46 +/- 40% of water load in 5 hours). Over this 5 hour study, mean plasma vasopressin was also higher with nisoldipine (1.9 +/- 2.3 versus 2.7 +/- 3.2 pg/ml, p less than 0.05), but mean plasma aldosterone was lower (67 +/- 31 to 47 +/- 27 mg/dl, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Body Water↗
PubMed1986

Neuroendocrine factors mediating polydipsia induced by dietary Na, Cl, and K depletion.

We investigated whether the increased intake of water during dietary electrolyte depletion is related to activation of the renin-angiotensin system. Young adult male rats were fed a low Na-, Cl-, K-free (low-salt) diet for 2 wk during which measurements were made of daily water intake and urine volume, plasma osmolality (Posm) and electrolytes, and plasma renin activity (PRA) and angiotensin I (ANG I) concentration. Water intake and urine output increased on day 3 of the low-salt diet, reached a maximum on day 4, and remained elevated, paralleling the time course of increases in PRA and ANG I plasma concentrations. Posm was normal after 2 days on the low-salt, although it was significantly lower by day 11. Renal concentrating ability was not different from controls after 6 days, but was significantly reduced after 11 days of treatment. Electrolytic lesions of the subfornical organ (SFO) abolished the low-salt diet-induced polydipsia, but had no effect on the diet-induced increases in PRA and plasma ANG I concentration. These data demonstrate that polydipsia induced by feeding a low-salt diet can develop in the presence of a normal or reduced Posm and precedes the development of a renal concentrating defect. The primary polydipsia is associated with elevated PRA and ANG I and appears to be mediated by angiotensin receptors in the SFO.

Animals↗
PubMed1986

Differential long-term intrarenal and neurohormonal effects of captopril and prazosin in patients with chronic congestive heart failure: importance of initial plasma renin activity.

Fifty patients with congestive heart failure received, by infusion, 15 ml/kg body weight water load, and systemic hemodynamic, renal function, and neurohumoral parameters values were measured before, 2 days, and 1 month after randomly allocating patients to prazosin or captopril therapy. Both prazosin and captopril caused similar and persistent hemodynamic changes, but important differences existed between their renal and neurohumoral effects. After 1 month of continuous therapy, captopril increased creatinine clearance from 71 to 84 ml/min/1.73(2) (p less than .05), increased the water load excreted in 5 hr from 50% to 71% (p less than .005), and increased 5 hr sodium excreted from 6.8 to 14.7 meq (p less than .005), Captopril also caused a decrease in plasma norepinephrine from 568 to 448 pg/ml (p less than .005), in plasma epinephrine from 94 to 73 pg/ml (p less than .05), and in plasma aldosterone from 57 to 28 ng/dl (p less than .005), without changing plasma vasopressin. These beneficial effects were greater after 1 month of therapy than after 2 days. The only beneficial effect of prazosin was to increase water excretion from 49% to 59% (p less than .05). The long-term response to captopril was similar in patients with higher (greater than 2.5 ng/ml/hr) and lower renin levels. However, in patients with lower renin levels, prazosin decreased pulmonary capillary wedge pressure (24.8 to 21.8 mm Hg, p less than .05), decreased plasma arginine vasopressin (1.16 to 0.75 pg/ml, p less than .05), increased water excretion (62% to 85%, p less than .005), and decreased plasma epinephrine (81 to 46 pg/ml, p less than .05), while in patients with higher renin levels none of these beneficial effects were noted. We conclude that captopril produces long-term beneficial renal and neurohumoral effects that prazosin does not despite similar hemodynamic changes with the two drugs, that these effects are at least partially dependent on the initial neurohumoral and hemodynamic status of the patient, and that through hemodynamic improvement vasodilators may chronically interrupt vasopressin overstimulation.

Captopril↗
PubMed1986

Syndrome of inappropriate antidiuresis in the absence of arginine vasopressin.

The syndrome of inappropriate antidiuresis (SIAD) is usually associated with inappropriately elevated plasma arginine vasopressin (AVP) concentrations. We describe herein a patient with a macroprolactinoma who had symptomatic hyponatremia due to SIAD. Although the patient had excessive thirst, severe plasma hypoosmolality, and hyperosmolar urine, no immunoassayable AVP could be detected. During long term treatment with bromocriptine, there was gradual shrinkage of the prolactinoma coincident with improvement in the ability to excrete a water load and normalization of the thirst threshold. At this point, plasma immunoactive AVP was measurable during a hypertonic saline infusion for the first time. By high pressure liquid chromatographic analysis, this immunoactive substance coeluted with AVP. These studies suggest that the SIAD in this patient was due to the production of an antidiuretic substance distinct from AVP in association with his prolactinoma.

Adult↗
PubMed1986

Sodium and water excretion abnormalities in congestive heart failure. Determinant factors and clinical implications.

The renal hemodynamic and neurohumoral determinants of sodium and water excretion abnormalities were studied in 66 patients with severe chronic congestive heart failure. Abnormalities were not closely related to any one variable but were the result of the convergence of a number of determinants. The most important determinants for sodium excretion were activation of the renin-angiotensin system and ventricular function; and the most important for water excretion were plasma vasopressin, plasma norepinephrine, and renal and ventricular functions. In a subgroup of patients, neurohumoral overactivation led to severe sodium and water excretion abnormalities and to increased furosemide requirements. A 17-month follow-up of all 66 patients showed a less favorable clinical course for this subgroup even when compared with hemodynamically matched patients.

Aged↗