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Biomedical subjects

E Pussard

Publications and source records attributed to E Pussard.

At least 37 records · Page 2Linked to original sources
PubMed1994

[Relationships between plasma concentrations of endothelin and the severity of liver cirrhosis].

OBJECTIVES: Results of studies on plasma endothelin concentrations in patients with cirrhosis are conflicting. Moreover, the relationships between plasma endothelin concentrations and the severity of cirrhosis have not yet been studied. The aim of this study was to measure plasma endothelin concentrations in controls and in patients with cirrhosis. In addition, this study examined the relationships between plasma endothelin concentrations, and the severity of liver disease, splanchnic and systemic hemodynamics. METHODS: Plasma endothelin concentrations (in the hepatic vein and the right atria), hepatic venous pressures, arterial pressure, cardiac output, pulmonary pressures and plasma concentrations of sodium and creatinine were measured in 7 controls and 28 patients with cirrhosis. RESULTS: Plasma endothelin concentrations in the hepatic vein and the right atria were significantly higher in patients with cirrhosis (18.9 +/- 2.9 and 20.2 +/- 3.1 pg/mL, respectively) than in controls (6.1 +/- 1.1 and 7.2 +/- 1.1 pg/mL, respectively). In these patients, hepatic venous plasma endothelin concentrations were significantly correlated with Pugh's score (r = 0.49), hepatic venous pressure gradient (r = -0.44), and plasma sodium concentrations (r = -0.46). No significant correlation was found between plasma endothelin concentrations and systemic hemodynamics. CONCLUSION: Plasma endothelin concentrations are increased in patients with cirrhosis. Moreover, this increase is more marked in patients with severe liver disease than in patients with no or moderate impairment of liver function.

Blood Chemical Analysis↗
PubMed1993

Comparison of the hemodynamic effects of hydroxocobalamin and cobalt edetate at equipotent cyanide antidotal doses in conscious dogs.

OBJECTIVES: The hemodynamic effects of two cyanide antidotes, hydroxocobalamin and cobalt edetate were compared. DESIGN: This experimental study was performed in chronically instrumented conscious dogs and at equipotent cyanide antidotal doses (hydroxocobalamin 70 mg.kg-1; cobalt edetate 10.5 mg.kg-1). RESULTS: Peak plasma cobalt concentrations did not differ in the two groups (412 +/- 183 vs 400 +/- 160 mumol.l-1). Hydroxocobalamin induced a slight increase in mean arterial pressure (+17 +/- 9%, p < 0.05) and systemic resistance (+19 +/- 15%, p < 0.05). In contrast, cobalt edetate induced an increase in heart rate (+78 +/- 33%, p < 0.05), in cardiac output (+63 +/- 39%, p < 0.05), and in maximum rise of left ventricular pressure (+33 +/- 15%, p < 0.05), did not modify mean arterial pressure, and decreased systemic resistance (-36 +/- 15%, p < 0.05). These hemodynamic effects were associated with an increase in plasma catecholamine concentrations (epinephrine: 2524 +/- 3025 vs. 58 +/- 37 pg.ml-1, p < 0.05; norepinephrine: 1106 +/- 609 vs. 343 +/- 146 pg.ml-1, p < 0.05), which in contrast remained unchanged after hydroxocobalamin administration. Cobalt edetate also induced an increase in blood glucose concentrations (9.9 +/- 1.9 vs. 6.1 +/- 1.2 mmol.l-1, p < 0.05) and a moderate metabolic acidosis, whereas hydroxocobalamin did not. After adrenergic (alpha 1, beta) and cholinergic receptor blockade, cobalt edetate did not modify heart rate and various indices of cardiac function, suggesting that it has no direct cardiac effects. CONCLUSION: Considering its lack of hemodynamically relevant effects, these results indicate that hydroxocobalamin is potentially a safer cyanide antidote than cobalt edetate.

Animals↗
PubMed1993

Efficacy of intramuscular amopyroquin for treatment of Plasmodium falciparum malaria in the Gabon Republic.

The efficacy of a 12-mg/kg (of body weight) intramuscular amopyroquin (ApQ) regimen (two successive 6-mg/kg injections at a 24-h interval), previously established from kinetic studies on healthy volunteers and multicenter studies on patients with malaria, was investigated in 152 patients (children and adults) in Gabon with Plasmodium falciparum malaria. All children in the present study (ages, 1 to 14 years) showed higher degrees of parasitemia and temperatures and lower hematocrit values than did adults at the time of admission. No major side effects in the patients were observed. On day 7, all patients were apyretic; clearance of parasites was obtained in 143 of 152 patients (94%); a low level of parasitemia was observed in nine patients, all of whom were children (6%). In vitro chemosusceptibility tests carried out on P. falciparum isolates from patients demonstrated 51% of resistance to chloroquine (Cq). A correlation was found between the in vitro chemosusceptibilities to Cq and ApQ, but no relationship between the in vitro activity and the in vivo efficacy of ApQ could be found. Concentrations of ApQ in blood assayed by high-performance liquid chromatography on day 2 did not differ significantly between the groups in whom therapy was a success or a failure, although the mean ApQ concentration in blood for the group that failed therapy was 31% lower. Concentrations greater than 100 nmol of self-prescribed Cq and amodiaquine per liter, which were assayed simultaneously with ApQ, were observed in 78 patients (51%). They did not correlate with degrees of parasitemia compared with ApQ alone, which did. Successful treatment by day 7 was obtained in 69 of 74 patients (93%) who had no other 4-aminoquinolines in their blood. The results of the present study show that an ApQ regimen of 12 mg/kg over 2 days may be an alternative for the treatment of Cq-resistant malaria, at least in adult patients, in the field.

Adolescent↗
PubMed1993

Cardiopulmonary and carotid baroreflex control of splanchnic and forearm circulations.

The objective was to determine whether a rise in carotid sinus transmural pressure by neck suction (NS) would counteract vasoconstriction secondary to inhibition of discharge of arterial and cardiopulmonary baroreceptors by simultaneous lower body negative pressure (LBNP). NS alone was applied to seven normal human subjects at -40 mmHg for 400-600 ms at each heartbeat during a 6-min period. NS reduced mean arterial pressure (MAP) from 94 +/- 6 to 86 +/- 9 mmHg and heart rate (HR) from 64 +/- 5 to 60 +/- 4.7 beats/min but did not affect vascular resistance in the splanchnic region (flow by constant infusion of indocyanine green; assumed constant extraction) or in the forearm (venous occlusion plethysmography). The same NS stimulus was applied during 23 min of continuous LBNP at -40 mmHg. LBNP alone before NS significantly reduced central venous pressure (CVP) from 5 +/- 0.3 to 1 +/- 0.5 mmHg and raised splanchnic (+34%) and forearm (+70%) vascular resistances and HR (from 64 to 74 beats/min) without reducing MAP. NS plus LBNP reduced MAP from 103 +/- 8 to 95 +/- 6 mmHg and HR from 74 +/- 6 to 67 +/- 5 beats/min without changing CVP but did not alter vascular resistances, which remained elevated and constant throughout LBNP before and after NS. Increments in plasma concentrations of renin (240%), aldosterone (70%), epinephrine (112%), and norepinephrine (46%) accompanied LBNP and NS; a separate influence of NS was not discernible. We conclude that vasoconstriction in response to combined cardiopulmonary and aortic inhibition is not overpowered by carotid sinus stimulation.

Adult↗
PubMed1992

Beneficial effects of trandolapril on experimentally induced congestive heart failure in rats.

Angiotensin-converting enzyme (ACE) inhibitors have been shown to prolong life expectancy in patients with congestive heart failure. In order to determine the relative contributions of the different factors involved in this beneficial effect, we investigated in an experimental model of postinfarction cardiac insufficiency in the rat over a 9-12-month period (1) the kinetics of the development of the hemodynamic, biologic, and morphologic alterations that accompany heart failure, and (2) the kinetics of the effects of a new, long-acting ACE inhibitor, trandolapril. Following induction of infarction, systolic blood pressure, left ventricular dP/dt, and end-diastolic pressure were immediately decreased, decreased, and increased, respectively, and these modifications persisted throughout the study. Cardiac index, on the other hand, was only initially and transiently decreased. Cardiac remodeling (left ventricular dilation, myocardial hypertrophy, and fibrosis) occurred as early as 7 days after infarction and worsened throughout the study. Plasma atrial natriuretic factor (ANF) and urinary cyclic guanosine monophosphate (cGMP) were also increased. In this model, a 1-year oral treatment with trandolapril resulted in early hemodynamic and biologic beneficial effects (reductions in pre- and afterload, increase in cardiac index, and decrease in plasma ANF), and in a delayed reversal of the infarction-induced cardiac morphologic alterations. Hence, the trandolapril-induced increase in survival rate is due initially to the drug's hemodynamic effects and over the long-term to both its hemodynamic and cardiac morphologic (limitation of remodeling) effects.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

Evidence for normal nitric oxide-mediated vasodilator tone in conscious rats with cirrhosis.

Because it has been hypothesized that the hyperkinetic circulation in portal hypertension is the result of increased synthesis of nitric oxide, we compared the hemodynamic effects of nitric oxide synthesis--specific agonist (L-arginine) and antagonist between normal and cirrhotic conscious rats. The dose-response curves showed that L-arginine significantly decreased arterial pressure and increased heart rate. These changes started at the 200 mg/kg dose and were similar in both groups of rats. In both groups of rats NG-monomethyl-L-arginine (25 mg/kg) significantly decreased cardiac output by 35%. In cirrhotic rats, NG-monomethyl-L-arginine decreased portal pressure from 15.3 +/- 0.9 mm Hg to 13.6 +/- 0.7 mm Hg and portal tributary blood flow from 7.8 +/- 0.7 ml.min-1.100 gm-1 to 5.9 +/- 0.7 ml.min-1.100 gm-1; it significantly increased portal territory vascular resistance from 950 +/- 108 dyn.sec.cm-5.100 gm-1 x 10(3) to 1,579 +/- 258 dyn.sec.cm-5.100 gm-1 x 10(3). In normal rats, portal tributary blood flow decreased similarly, by 27%, and portal territory vascular resistance increased by 55%. In neither group was hepatic arterial blood flow altered. Before and after NG-monomethyl-L-arginine administration, arterial cyclic GMP concentrations were not significantly different between normal and cirrhotic rats. In conclusion, this study shows evidence of a normal role for nitric oxide-mediated vasodilatation in rats with cirrhosis and that inhibition of nitric oxide synthesis reduces portal hypertension. These results did not support the hypothesis that nitric oxide synthesis is increased in cirrhosis.

Animals↗
PubMed1992

Hemodynamic, neurohumoral, and metabolic responses to amino acid infusion in patients with cirrhosis.

In patients with cirrhosis the renal response to amino acid infusion is controversial. In addition, the renal and systemic metabolic effects of amino acids are unknown. Therefore, the present study examined the effects of amino acids on renal hemodynamics, renal and systemic oxygen (O2) consumption, and hormones in patients with cirrhosis. Twelve patients received an 8% amino acid solution for 30 minutes at a rate providing 250 mg of amino acids/kg body wt. Renal blood flow increased by 45% (P less than 0.05) and the glomerular filtration rate by only 9% (P greater than 0.05). Renal vascular resistance decreased by 23% (P less than 0.05), and renal perfusion pressure did not change significantly. Renal and systemic O2 consumption and pulmonary artery plasma glucagon level significantly increased. There were no significant changes in plasma osmolality, plasma volume, and plasma atrial natriuretic peptide concentrations. In conclusion, the results show that amino acid-induced renal vasodilation caused hyperperfusion but not renal hyperfiltration in patients with cirrhosis. In addition, renal hyperemia was associated with renal and systemic hypermetabolism.

Amino Acids↗
PubMed1992

Hemodynamic and sympathetic responses to human atrial natriuretic peptide infusion in patients with cirrhosis.

To determine the potential usefulness of atrial natriuretic peptide (ANP) in patients with cirrhosis, we examined the effects of the infusion of a low dose of alpha-human ANP (alpha hANP, 25 ng.kg-1.min-1 for 30 min) on renal, splanchnic, systemic hemodynamics and sympathetic outflow in eight patients. Pulmonary arterial plasma ANP concentrations increased from 59 +/- 9 to 328 +/- 41 pg/ml (mean +/- S.E., p less than 0.05). Mean values of glomerular filtration rate and renal plasma flow were not significantly changed. Individual renal plasma flow responses differed from one patient to another. Renal plasma flow increased in two patients, decreased in three and did not change in the other patients. Renal plasma flow changes were correlated with basal renal plasma flow values (r = -0.938, p less than 0.05) but not with arterial pressure changes or renal vein plasma norepinephrine concentration changes. Azygos blood flow increased from 0.43 +/- 0.10 to 0.63 +/- 0.13 l/min (p less than 0.05) and the hepatic-venous pressure gradient decreased from 19.9 +/- 1.5 to 17.5 +/- 2.9 mmHg in post-infusion (p less than 0.05). Mean arterial pressure decreased significantly by 18% and cardiac output by 12%. Systemic vascular resistance and pulmonary arterial plasma norepinephrine concentrations were not significantly modified. Thus, in patients with cirrhosis, alpha hANP appears to have a direct vasodilating action on renal arterioles when basal renal vascular tone is high. In addition, although alpha hANP might exert a portal hypotensive action, alpha hANP induced arterial hypotension as a result of both low cardiac output and a lack of increased sympathetic vascular tone. The arterial hypotensive action may, thus, limit the therapeutic use of low doses of alpha hANP in cirrhotic patients.

Aldosterone↗
PubMed1992

Systemic and regional hemodynamic effects of zabicipril in healthy volunteers.

The effects of two oral doses of zabicipril, a new angiotensin converting enzyme inhibitor, on systemic (arterial pressure, heart rate, and cardiac output) hemodynamic parameters and regional (brachial, carotid and femoral arteries' diameters and flows) hemodynamic parameters and on biologic (plasma-converting enzyme and renin activities, catecholamines, and atrial natriuretic factor) parameters were noninvasively investigated and compared with those of a placebo in a double-blind crossover study performed in six healthy male volunteers. Although it did not affect the systemic hemodynamic parameters, zabicipril induced a strong peripheral vasodilation, significantly reducing brachial, carotid, and femoral resistances and increasing the corresponding blood flows from 3 or 4 1/2 hours to 9 hours. This vasodilation affected only the arterioles, not the large arteries, and resulted in a redistribution of cardiac output toward the three regional vascular beds. Zabicipril induced an early, potent, and long-lasting converting enzyme inhibition. Furthermore, zabicipril did not affect plasma catecholamines and atrial natriuretic factor.

Analysis of Variance↗
PubMed1992

Amiodarone decreases cardiac beta-adrenoceptors through an antagonistic effect on 3,5,3' triiodothyronine.

Because surprising similarities exist between the cardiac effects of amiodarone and those observed during hypothyroidism, we tested three different mechanisms of action in rats to determine whether amiodarone might act by inducing a tissular hypothyroidism: (a) a decrease in thyroid secretion, (b) an inhibiting effect on the conversion of thyroxine (T4) to 3,5,3' triiodothyronine (T3), and (c) a direct antagonistic effect on the cellular action of T3. Five groups of rats, treated orally for 7 or 13 days, were studied: I, control (0.5 ml saline for 7 or 13 days, n = 14); II, amiodarone (50 mg/kg for 7 days, n = 5); III, iopanoic acid (100 mg/kg for 13 days, n = 7); IV, control + T3 (0.5 ml saline for 13 days and 0.5 mg/kg T3 for the last 6 days, n = 5); V, amiodarone + T3 (amiodarone 50 mg/kg for 13 days and 0.5 mg/kg T3 for the last 6 days, n = 5). Cardiac beta-adrenoceptor density (CBARD) and heart rate (HR) were the two endpoint parameters investigated. Thyroid status was evaluated by serum thyrotropin (TSH), T4, T3, rT3 concentrations and liver type I 5'-deiodinase (5'D-I) activity. Amiodarone (group II) decreased CBARD (-22%, p less than 0.05) without altering thyroid secretion and T3 serum level, whereas 5'D-I was strongly inhibited (-90%, p less than 0.01). Iopanoic acid had no effect on CBARD and HR, but deeply inhibited 5'D-I.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiodarone↗
PubMed1992

Flosequinan does not affect systemic and regional vascular responses to simulated orthostatic stress in healthy volunteers.

1. The effects of a single oral dose (100 mg) of flosequinan on systemic and regional (forearm, splanchnic and renal) vascular responses to simulated orthostatic stress (lower body negative pressure, LBNP) were investigated in nine healthy male volunteers, in a double-blind, placebo-controlled crossover study. 2. Forty-five minutes after its administration and before LBNP, flosequinan induced a significant decrease in total peripheral and in forearm vascular resistances without any concomitant change in arterial pressure, in heart rate and in the investigated biological parameters (plasma catecholamines, arginine vasopressin and renin activity). 3. After flosequinan and placebo, LBNP induced similar decreases in central venous pressure at all levels of LBNP (-10, -20 and -40 mm Hg) and in pulse pressure at LBNP -40 mm Hg. LBNP-induced increase in forearm vascular resistance was significantly more marked after flosequinan than after placebo at all levels of LBNP, and this was also true for splanchnic vascular resistance but at LBNP -40 mm Hg only. However, inasmuch as the basal values of these two parameters before LBNP were lower after flosequinan than after placebo, their final values after LBNP -40 mm Hg were similar. Finally, LBNP-induced changes in renal vascular resistance, glomerular filtration rate and filtration fraction as well as in plasma catecholamines, arginine vasopressin and renin activity were similar after flosequinan and placebo at all levels of LBNP. 4. Flosequinan affected neither reflex control of heart rate (phenylephrine test) nor non-specific vasoconstrictor responses (cold pressor test). (ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

[Correlations between plasma concentrations of atrial natriuretic factor and right ventricular function in patients with severe cardiac failure].

The atrial natriuretic factor (ANF) is secreted by the atria in mild and moderate cardiac failure but, during the evolution of the cardiac failure, the ventricles are also recruited and secrete ANF. In order to investigate the relation between plasma ANF and Doppler echocardiographic parameters of severe cardiac failure, the concentrations were measured simultaneously in 20 patients with NYHA Class III and IV cardiac failure (10 due to ischaemic and 10 due to primary dilated cardiomyopathy) despite optimal medical treatment including an angiotensin converting enzyme inhibitor. Overall, there was a weak negative correlation between the plasma ANF concentrations and the decrease in right ventricular surface area (r = -0.58, p less than 0.005, n = 20 patients). This relation was highly significant in ischaemic cardiomyopathy (r = -0.81, p less than 0.002, n = 10 patients) and not significant in primary dilated cardiomyopathy (r = -0.29, NS, n = 10 patients). No relationship was observed between plasma ANF and other echocardiographic parameters (atrial surface area, right and left ventricular dimensions, left ventricular ejection fraction and mass) or with Doppler aortic indices (acceleration, maximum and mean velocities, aortic velocity-time integrals). However, plasma ANF was related to the velocity of mitral regurgitant jets (r = -0.70, p less than 0.01) which is dependent on left ventricular pump function. These results show that plasma ANF concentrations are only related to right ventricular systolic function and the velocity of mitral regurgitation in patients with severe cardiac failure.

Adult↗
PubMed1992

Baroreflex control of regional vascular resistances during simulated orthostatism.

Orthostatic stress or moderate hypovolemia was simulated in 10 healthy volunteers by the lower body negative pressure technique (LBNP at -10, -20 and -40 mm Hg). LBNP induced a progressive and parallel decrease in central venous pressure and cardiac output but mean arterial pressure remained unchanged regardless of the LBNP level. Heart rate and pulse pressure were only significantly increased and decreased at LBNP -40 mm Hg, respectively, indicating that cardiopulmonary baroreflexes were selectively deactivated up to LBNP -20 mm Hg, whereas both cardiopulmonary and arterial baroreflexes were deactivated at LBNP -40 mm Hg. The LBNP-induced increase in total peripheral resistance was heterogeneously distributed within the body. Forearm vasoconstriction occurred at low levels of LBNP and was exclusively related to an increase in sympathetic tone. Splanchnic vasoconstriction also occurred at low levels of LBNP, but was related to activation in sympathetic and renin-angiotensin systems. Renal vasoconstriction occurred mainly at high levels of LBNP (-40 mm Hg), but glomerular filtration rate and filtration fraction increased at low levels of LBNP (-10 mm Hg). Thus, if renal vascular resistance is not of major importance for the control of blood pressure during orthostatism or moderate hypovolemia, neurohumoral mechanisms triggered through deactivation of cardiopulmonary receptors play a key role in the maintenance of intrarenal homeostasis associated with reduction in cardiac filling pressure.

Adult↗
PubMed1991

Clearance of atrial natriuretic peptide in patients with cirrhosis. Role of liver failure.

In non-cirrhotic patients, splanchnic, renal and pulmonary vascular beds are involved in the plasma clearance for atrial natriuretic peptide (ANP). In patients with cirrhosis, endogenous plasma ANP clearance by these vascular beds has not been systematically studied. In addition, the influence of the severity of liver failure on plasma ANP clearance is not known. Thus, in this study we determined plasma ANP clearance by splanchnic, renal and pulmonary circulations using both arteriovenous differences in plasma ANP concentrations and organ plasma flow in 11 patients with cirrhosis. The role of forearm circulation in plasma ANP extraction was also studied. Splanchnic plasma ANP extraction was 29 +/- 7% (mean +/- S.E.) and splanchnic plasma ANP clearance was 404 +/- 130 ml/min (n = 7). Renal plasma ANP extraction and clearance were 32 +/- 8% and 191 +/- 57 ml/min, respectively. Forearm plasma ANP extraction was 11 +/- 4%. Pulmonary plasma ANP extraction and clearance were 8 +/- 5% and 312 +/- 272 ml/min, respectively. A significant negative correlation was found between logarithm of serum bilirubin concentration, on one hand, and splanchnic and forearm plasma ANP extraction, on the other. A significant negative correlation was found between Pugh's score, on one hand, and renal plasma ANP extraction and clearance, on the other. No significant correlation was found between the severity of liver failure and pulmonary plasma ANP extraction and clearance. As a result, we conclude that in cirrhotic patients splanchnic, renal, forearm and pulmonary vascular beds are involved in plasma ANP extraction and clearance. Plasma ANP extraction and/or clearance may be attenuated in the splanchnic, renal and forearm circulations due to liver failure.

Atrial Natriuretic Factor↗
PubMed1991

[Effects of lidocaine on arterial and venous circulation of limbs in man].

The effects of intravenous lidocaine on limb arteries and veins were investigated in a placebo-controlled study. Seven young healthy volunteers, 23 to 28-years-old, were included. Electrocardiogram, arterial pressure and arm and leg blood flows were recorded continuously. Systolic and diastolic blood pressures were measured in the left arm by finger photoplethysmography. Limb blood flow and the limb venous system were studied by venous occlusive plethysmography. The venous parameters studied were venous tone, lowest closing pressure, venous volume at 30 mmHg, and venous distensibility. After an initial bolus of 1.5 mg.kg-1 lidocaine had been given, 30, and then 60, micrograms.kg-1.min-1 were given for one hour each. Plasma noradrenaline and serum lidocaine titres were measured before giving the lidocaine, and at the end of each one hour period. Placebo consisted in a two hour infusion of 0.25 ml.min-1 normal saline. Lidocaine titres were 1.64 +/- 0.40 microgram.ml-1 after one hour, and 2.55 +/- 0.69 microgram.ml-1 after two hours. Lidocaine increased vascular resistances in both the forearm (+81% to +93%) and the calf (+38% to +57%). There was a concomitant increase in mean arterial blood pressure (+21% to +28%) without any change in heart rate. There was a significant dose-dependent increase in plasma noradrenaline levels during the second period of the lidocaine infusion with respect to the preinfusion period and the same period during the placebo infusion. Venous capacitance measured before any infusion had been started was greater in the leg than in the arm.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Arterial vasodilating profile and biological effects of pinacidil in healthy volunteers.

1. The effects of pinacidil (25 mg, sustained release formulation) a) on systemic (arterial pressure, cardiac output) and regional (brachial and carotid arteries' diameters and flows) haemodynamics (pulsed Doppler techniques), b) on sympathetic (plasma noradrenaline) and renin-angiotensin (plasma renin activity) systems, and c) on atrial natriuretic factor have been investigated and compared with those of a placebo during the 12 h period following oral administration in a randomized, double-blind and cross-over study performed in six healthy volunteers. Simultaneously, the plasma levels of pinacidil and of its active metabolite, pinacidil N-oxide, were determined. 2. As compared with placebo, pinacidil decreased systemic vascular resistance and arterial blood pressure but cardiac output was not modified. 3. Pinacidil significantly increased brachial and carotid arteries' diameters (by 7 and 8% respectively) and flows (by 60 and 17% respectively) and decreased forearm vascular resistance (by 43%). Thus, pinacidil dilates both large and small arteries, increases large vessels' compliance and redistributes blood flow towards the muscular vascular bed. These effects peaked at 4 h and their duration at the brachial level was 8 h. 4. Pinacidil administration resulted in a stimulation of both sympathetic (increases in heart rate and plasma noradrenaline) and renin-angiotensin systems, and induced a transient increase in atrial natriuretic factor. 5. The duration of pinacidil haemodynamic effects at the brachial level is consistent with the pharmacokinetic data which show that pinacidil and pinacidil N-oxide plasma levels almost plateaued between 3 and 8, and 2 and 8 h respectively after oral administration of the sustained release formulation used.

Adult↗
PubMed1991

Amiodarone: influence of the route of administration on thyroid status and cardiac beta-adrenoceptors in the rat.

The influence of 2 different routes of amiodarone (AMIO) administration, oral gavage (OG) and subcutaneous injection (SC), on the density of cardiac beta-adrenoceptors (Bmax), hepatic type I 5' iodothyronine deiodinase (5' DI) and thyroid hormone serum concentrations was studied. Compared with respective control values, AMIO treatment (50 mg/kg per day, 7 days) via both OG and SC routes significantly lowered Bmax (OG: 14.6 +/- 1.92 vs 18.2 +/- 1.03 fmol/mg and SC: 16.6 +/- 2.34 vs 19.1 +/- 2.05 fmol/mg) and 5' DI activity (from 409 to 85 and 340 to 47 fmol I-/mg per min, respectively). The SC route induced a fall in thyroid secretion and a generalized hypothyroidism (decreased serum FT4 and FT3, inhibition of body weight gain. The OG route did not modify thyroid secretion. These results demonstrated that the effects on cardiac beta-receptor density in the SC group might be due to the generalized hypothyroidism and that AMIO produced its specific cardiac effects only after oral route medication, suggesting that the oral route is the best choice for studying AMIO cardiac effects on beta-receptor density.

Administration, Oral↗