Biomedical subjects

Pierre Fesler

Publications and source records attributed to Pierre Fesler.

18 recordsLinked to original sources

PubMed2006

Effects of sildenafil on hypoxic pulmonary vascular function in dogs.

Sildenafil has been shown to be an effective treatment of pulmonary arterial hypertension and is believed to present with pulmonary selectivity. This study was designed to determine the site of action of sildenafil compared with inhaled nitric oxide (NO) and intravenous sodium nitroprusside (SNP), known as selective and nonselective pulmonary vasodilators, respectively. Inhaled NO (40 ppm), and maximum tolerated doses of intravenous SNP and sildenafil, (5 microg x kg(-1) x min(-1) and 0.1 mg x kg(-1) x h(-1)), respectively, were administered to eight dogs ventilated in hypoxia. Pulmonary vascular resistance (PVR) was evaluated by pulmonary arterial pressure (Ppa) minus left atrial pressure (Pla) vs. flow curves, and partitioned into arterial and venous segments by the occlusion method. Right ventricular hydraulic load was defined by pulmonary arterial characteristic impedance (Zc) and elastance (Ea) calculations. Right ventricular arterial coupling was estimated by the ratio of end-systolic elastance (Ees) to Ea. Decreasing the inspired oxygen fraction from 0.4 to 0.1 increased Ppa - Pla at a standardized flow of 3 l x min(-1) x m(-2) from 6 +/- 1 to 18 +/- 1 mmHg (mean +/- SE). Ppa - Pla was decreased to 9 +/- 1 by inhaled NO, 14 +/- 1 by SNP, and 14 +/- 1 mmHg by sildenafil. The partition of PVR, Zc, Ea, and Ees/Ea was not affected by the three interventions. Inhaled NO did not affect systemic arterial pressure, which was similarly decreased by sildenafil and SNP, from 115 +/- 4 to 101 +/- 4 and 98 +/- 5 mmHg, respectively. We conclude that inhaled NO inhibits hypoxic pulmonary vasoconstriction more effectively than sildenafil or SNP, and sildenafil shows no more selectivity for the pulmonary circulation than SNP.

Administration, Inhalation↗

PubMed2006

[Management of renal hypertension].

Assessment of every hypertensive patient must include the search for kidney disease, i.e. elevated serum creatinine and proteinuria. Antihypertensive therapy may attenuate both the risk of progression toward renal failure and the cardiovascular risk associated with chronic kidney disease, albeit the cause or the consequence of hypertension. Any alteration in renal function will promote salt-sensitivity of blood pressure and increase the deleterious effects of salt intake on target organ damage. The goal of antihypertensive therapy in patients with chronic kidney disease is first to reduce systolic blood pressure below 130 mmHg. The second goal is to lower urinary protein excretion to less than 0.5 g per day. The presence of proteinuria calls for blockers of the renin-angiotensin system among antihypertensive drugs. Global risk management (i.e. fighting tobacco, obesity, dyslipemia) will reduce the renal as well as the cardiovascular risk.

Antihypertensive Agents↗

PubMed2006

Effects of levosimendan versus dobutamine on pressure load-induced right ventricular failure.

OBJECTIVE: A transient increase in pulmonary arterial (PA) pressure can persistently depress right ventricular (RV) contractility. We investigated the effects of dobutamine and levosimendan on RV-PA coupling in this model of RV failure. DESIGN: Prospective, controlled, randomized animal study. SETTING: University research laboratory. SUBJECTS: Fifteen anesthetized dogs. INTERVENTIONS: Transient (90-min) PA constriction to induce persistent RV failure. Random assignment to dobutamine 5 and 10 microg/kg/min or levosimendan 12 microg/kg for 10 mins followed by 0.1 and 0.2 microg/kg/min. MEASUREMENTS AND MAIN RESULTS: We measured PA distal resistance and proximal elastance by pressure-flow relationships and vascular impedance. We measured RV contractility by the end-systolic pressure-volume relationship (Ees), PA effective elastance by the end-diastolic to end-systolic relationship (Ea), and RV-PA coupling efficiency by the Ees/Ea ratio. PA constriction persistently increased PA resistance and elastance, increased Ea from 0.95 +/- 0.07 to 3.01 +/- 0.28 mm Hg/mL, decreased Ees from 1.17 +/- 0.09 to 0.58 +/- 0.07 mm Hg/mL, and decreased Ees/Ea from 1.26 +/- 0.09 to 0.22 +/- 0.03 (p < .05). Dobutamine did not affect pulmonary hemodynamics, markedly increased RV contractility, and improved RV-PA coupling. Levosimendan decreased PA resistance and elastance, increased RV contractility, and restored RV-PA coupling. Compared with dobutamine, levosimendan decreased RV afterload and therefore better restored RV-PA coupling at similar inotropic state. CONCLUSIONS: A transient increase in PA pressure persistently worsens PA hemodynamics, RV contractility, RV-PA coupling, and cardiac output. Levosimendan restores RV-PA coupling better than dobutamine because of similar inotropic effects and additional pulmonary vasodilatory effects.

Animals↗

PubMed2005

Prevention of pulmonary vascular remodeling and of decreased BMPR-2 expression by losartan therapy in shunt-induced pulmonary hypertension.

The renin-ANG system has been reported to be overexpressed in pulmonary arterial hypertension (PAH). We investigated the effects of ANG receptor-1 blockade by losartan on hemodynamics and signaling molecules in a piglet overflow model of early PAH. Twenty-six 3-wk-old piglets were randomized to placebo or losartan therapy (1 mg.kg(-1).day(-1)) after anastomosis of the inominate to the main pulmonary artery or after a sham operation. Three months later, the animals underwent a hemodynamic evaluation, followed by pulmonary tissue sampling for morphometry, immunohistochemistry, and real-time quantitative-PCR. Chronic systemic-to-pulmonary shunting increased the pulmonary vascular resistance from 2.5 +/- 0.2 to 6.2 +/- 0.3 mmHg.l(-1).min.m(-2) and arteriolar medial thickness from 13.6 to 25.4%. These changes were associated with increased expressions of ANG II and its type 1 (AT1) and type 2 (AT2) receptors, endothelin-1 (ET-1) and its type B receptor (ETB), and angiopoietin-1, together with decreased expressions of bone morphogeneic protein receptor-1A and -2 (BMPR-1A and BMPR-2, respectively) and unchanged expression of the receptor tyrosine kinase with immunoglobulin and EGF homology domains-2 (Tie 2). Pretreatment with losartan decreased shunt-induced pulmonary vascular resistance and medial thickness by 51% and 35%, respectively. Losartan therapy was associated with persistent overexpressions of ANG II, AT2, ET-1, ETB, and angiopoietin-1 and with a return to normal of the BMPR-2 expression. These results suggest that ANG II contributes to left-to-right, shunt-induced PAH.

Animals↗

PubMed2005

Subaortic obstruction and complete atrioventricular block in Behçet's disease.

Left ventricular outflow tract obstruction may be dynamic, most commonly associated with hypertrophic cardiomyopathy, and, uncommonly, by congenital anomalies such as discrete subaortic stenosis. We describe a patient with Behçet's disease, presenting with a systolic murmur, fever, and syncope, in whom a diagnosis of subaortic obstruction caused by a pseudo-aneurysm dissecting the interventricular septum and associated with a complete atrioventricular block was made.

Adult↗

PubMed2005

Relative glomerular hyperfiltration in primary aldosteronism.

Experimental and clinical data suggest that primary aldosteronism (PA) may be associated with cardiovascular hypertrophy and fibrosis, in part independent of the BP level. Whether PA may also result in specific deleterious effects on the kidneys was less studied. In 25 patients with tumoral PA, renal studies (urinary excretion of proteins, GFR, and effective renal plasma flow [ERPF], as clearances of technetium-labeled diethylene triaminopentaacetic acid and 131I-ortho iodohippurate, respectively) were performed both before and 6 mo after surgical cure. A control group consisting of patients with essential hypertension (EH) was studied before and after 6 mo of antihypertensive therapy. At baseline, PA and EH patients were similar with respect to demographic data, duration and level of hypertension, and GFR and ERPF. Urinary excretion of albumin and beta2 microglobulin were higher in PA than EH (88 +/- 26 versus 39 +/- 12 and 0.91 +/- 0.23 versus 0.26 +/- 0.19 mg/24 h, respectively; both P < 0.05). Adrenalectomy was followed by a decrease in arterial BP (by 28 +/- 3/13 +/- 2 mmHg), urinary excretion of albumin and beta2 microglobulin (by 48 +/- 19 and 0.53 +/- 0.21 mg/24 h, respectively), and GFR and ERPF (by 15 +/- 3 and 54 +/- 15 ml/min per 1.73 m(2), respectively). In EH, a similar decrease in pressure was associated with a decrease in albuminuria but no change in GFR or ERPF. In 17 of the 25 PA patients who received a 6-mo treatment of spironolactone, both GFR and ERPF decreased in parallel with BP, similar to what was observed after surgery. These data suggest that PA was associated with relative hyperfiltration, unmasked after suppression of aldosterone excess.

Adenoma↗

PubMed2005

Elevated pulse pressure is associated with low renal function in elderly patients with isolated systolic hypertension.

In the past decade, pulse pressure has emerged as a strong predictor of cardiovascular morbidity and mortality. During aging, elevation of pulse pressure is a consequence of stiffening of the arterial wall. The relationship between pulse pressure and the renal aging process was studied in a cohort of 212 patients with never-treated isolated systolic hypertension. Glomerular filtration rate and effective renal plasma flow were measured using constant infusion of technetium 99m (99mTc)-DTPA and 131I-ortho-iodohippurate, respectively, and timed urine collections. The relationship between pulse pressure and renal function was studied using a linear regression model in the total population and in 40 to 49, 50 to 59, and 60 years and older age categories. In the whole population, there was an inverse relationship between pulse pressure and glomerular filtration rate; however, this relation did not persist after adjustment for age. In fact, the inverse relationship between pulse pressure and glomerular filtration rate was only present in patients 60 years of age or older. This relationship in elderly patients remained after adjustment for age, gender, MAP, and cardiovascular risk factors (P=0.006). It is suggested that pulse pressure, a marker of arterial stiffening, may have a detrimental influence on the age-related decline in glomerular filtration rate, after 60 years of age in patients with never-treated isolated systolic hypertension.

Adult↗

PubMed2005

Estimation of renal function in subjects with normal serum creatinine levels: influence of age and body mass index.

BACKGROUND: The Cockcroft-Gault (CG) and simplified Modification of Diet in Renal Disease (MDRD) formulas are the most widely used estimates of renal function. The influence of age and body mass index (BMI) on the performance of these equations was analyzed in 850 subjects with serum creatinine levels less than 1.5 mg/dL (<133 micromol/L). METHODS: Glomerular filtration rate (GFR) was measured as urinary clearance of continuously infused technetium Tc 99m-labeled diethylene triaminopentaacetic acid. Performance was assessed as bias, precision, and accuracy. RESULTS: In the total population, the CG and MDRD calculations based on enzymatic measurement of serum creatinine (which is constantly less than that obtained by using the alkaline picrate [Jaffé] method) significantly underestimated GFR by 4.9 and 12.4 mL/min/1.73 m2 (0.08 and 0.21 mL/s/1.73 m2), respectively. In patients 65 years and older, underestimation by means of the CG formula was enhanced, whereas that by means of the MDRD formula was blunted, compared with the group younger than 65 years (-11.3 versus -3.7 mL/min/1.73 m2 [-0.19 versus -0.06 mL/s/1.73 m2] for CG and -3.7 versus -14.0 mL/min/1.73 m2 [-0.06 versus -0.23 mL/s/1.73 m2] for MDRD). GFR was underestimated to a large extent by means of the MDRD equation irrespective of BMI. Conversely, the underestimation by means of the CG formula found in lean people (-13.0 mL/min/1.73 m2 [-0.22 mL/s/1.73 m2]) was blunted in overweight people (BMI, 25 to 30 kg/m2) and reversed to overestimation (+10.1 mL/min/1.73 m2 [+0.17 mL/s/1.73 m2]) in obese subjects (BMI > 30 kg/m2). CONCLUSION: As suggested by estimations obtained using enzymatic serum creatinine measurement, the MDRD equation may be the estimation of choice in elderly patients, whereas the CG estimate is preferable in subjects younger than 65 years. Nevertheless, when obesity is present, no reliable estimation can be obtained by using the CG or MDRD formula.

Adolescent↗

PubMed2005

Determinants of cardiorenal damage progression in normotensive and never-treated hypertensive subjects.

BACKGROUND: In the present longitudinal study, we attempted to identify the determinants of cardiorenal damage progression in normotensive subjects (<140/90 mm Hg) and patients with never-treated essential hypertension. METHODS: Renal hemodynamics and function and cardiac morphology were evaluated by isotopic techniques and echocardiography at baseline and after a median follow-up period of 5.2 years (range 3 to 13) in 30 normotensive and 33 hypertensive subjects. RESULTS: The results are mean +/- SD. Among normotensive subjects at baseline, 50% became hypertensive during follow-up. In the whole population, multivariate analysis showed that age was the main determinant of the progression of systolic blood pressure. The yearly change in glomerular filtration rate (GFR) was exaggerated in hypertensive when compared to normotensive subjects at baseline (-1.22 +/- 2.71 vs. 0.12 +/- 2.08 mL/min/year, respectively) (P= 0.033). In the whole population, only baseline systolic blood pressure remained correlated to the change in GFR, independently of GFR at baseline (model r(2)= 0.44) (P < 0.0001). The observed increase in albuminuria was correlated with change in blood pressure only in hypertensive subjects at baseline. Left ventricular mass (LVM) progression was significant only in men and its determinants were basal plasma aldosterone, serum uric acid, and triglyceride and change in systolic blood pressure (r(2)= 0.71) (P < 0.0001). CONCLUSION: In a population of untreated subjects, baseline blood pressure as well as progression of blood pressure during follow-up are the main determinants of the decline in GFR, progression of albuminuria, and LVM.

Adolescent↗

PubMed2004

Signaling molecules in overcirculation-induced pulmonary hypertension in piglets: effects of sildenafil therapy.

BACKGROUND: The phosphodiesterase type-5 (PDE-5) inhibitor sildenafil has been reported to improve pulmonary arterial hypertension (PAH), but the mechanisms that account for this effect are incompletely understood. Severe pulmonary hypertension has been characterized by defects in a signaling pathway involving angiopoietin-1 and the bone morphogenetic receptor-2 (BMPR-2). We investigated the effects of sildenafil on hemodynamics and signaling molecules in a piglet overcirculation-induced model of early PAH. METHODS AND RESULTS: Thirty 3-week-old piglets were randomized to placebo or sildenafil therapy 0.75 mg/kg TID after anastomosis of the left subclavian artery to the pulmonary arterial trunk or after a sham operation. Three months later, the animals underwent a hemodynamic evaluation followed by pulmonary tissue sampling for morphometry, immunohistochemistry or radioimmunoassay, and real-time quantitative-polymerase chain reaction. Chronic systemic-to-pulmonary shunting increased pulmonary mRNA for angiopoietin-1, endothelin-1 (ET-1), angiotensin II, inducible nitric oxide synthase, vascular endothelial growth factor, and PDE-5. Pulmonary messenger RNA for BMPR-1A and BMPR-2 decreased. Pulmonary angiotensin II, ET-1, and vascular endothelial growth factor proteins increased. Pulmonary artery pressure increased from 20+/-2 to 33+/-1 mm Hg, and arteriolar medial thickness increased by 91%. The expressions of angiopoietin-1, ET-1, and angiotensin II were tightly correlated to pulmonary hypertension. Sildenafil prevented the increase in pulmonary artery pressure, limited the increase in medial thickness to 41%, and corrected associated biological perturbations except for the angiopoietin-1/BMPR-2 pathway, PDE-5, and angiotensin II. CONCLUSIONS: Sildenafil partially prevents overcirculation-induced PAH and associated changes in signaling molecules. Angiotensin II, PDE-5, and angiopoietin-1/BMPR-2 signaling may play a dominant role in the early stages of the disease.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed2004

Heterogeneity of cardiorenal characteristics in normotensive subjects.

Blood pressure is a marker of elevated risk for cardiovascular disease, even within the normotensive range. The present study evaluates cardiorenal modifications observed in normotensive (<140/90 mm Hg) subjects. Using World Health Organization-International Society of Hypertension definitions, 265 normotensive subjects were categorized as having optimal (n=73), normal (n=84), and high-normal (n=108) blood pressure. Renal hemodynamics and function and cardiac morphology were evaluated by isotopic clearance techniques and ultrasonography, respectively. Urinary albumin excretion was measured in 24-hour urine collections. Body mass index and 24-hour urinary sodium (estimate of sodium intake), as well as left ventricular mass index, relative wall thickness, and glomerular filtration rate and filtration fraction, progressively increased in the optimal to high-normal groups. In contrast, effective renal plasma flow remained constant. Albuminuria was similar in all groups. Of interest, the proportion of subjects with concentric pattern of cardiac geometry (relative wall thickness > or =0.44) increased from 7% in optimal to 13% and 20% in normal and high-normal groups, respectively (P<0.05). Within this normotensive range of blood pressure, left ventricular mass index and relative wall thickness but not albuminuria were linearly correlated to systolic blood pressure; however, no correlation with diastolic blood pressure was found. In conclusion, changes in cardiac geometry and renal hemodynamics (increase in glomerular filtration rate and filtration fraction, an approximate index of glomerular pressure) that could predispose to cardiovascular morbidity and renal risk are already present in normotensive subjects with blood pressure higher than 120/80 mm Hg.

Adolescent↗

PubMed2004

Isoflurane and desflurane impair right ventricular-pulmonary arterial coupling in dogs.

BACKGROUND: Halogenated anesthetics depress left ventricular function, but their effects on the right ventricle have been less well studied. Therefore, the authors studied the effects of isoflurane and desflurane on pulmonary arterial (PA) and right ventricular (RV) properties at baseline and in hypoxia. METHODS: Right ventricular and PA pressures were measured by micromanometer catheters, and PA flow was measured by an ultrasonic flow probe. PA mechanics were assessed by flow-pressure relations and by impedance spectra derived from flow and pressure waves. RV contractility was assessed by end-systolic elastance (Ees), RV afterload was assessed by effective PA elastance (Ea), and RV-PA coupling efficiency was assessed by the Ees:Ea ratio. Anesthetized dogs were randomly assigned to increasing concentrations (0.5, 1, and 1.5 times the minimum alveolar concentration) of isoflurane (n = 7) or desflurane (n = 7) in hyperoxia (fraction of inspired oxygen, 0.4) and hypoxia (fraction of inspired oxygen, 0.1). RESULTS: Isoflurane and desflurane had similar effects. During hyperoxia, both anesthetics increased PA resistance and characteristic impedance, increased Ea (isoflurane, from 0.82 to 1.44 mmHg/ml; desflurane, from 0.86 to 1.47 mmHg/ml), decreased Ees (isoflurane, from 1.09 to 0.66 mmHg/ml; desflurane, from 1.10 to 0.72 mmHg/ml), and decreased Ees:Ea (isoflurane, from 1.48 to 0.52; desflurane, from 1.52 to 0.54) in a dose-dependent manner (all P < 0.05). Hypoxia increased PA resistance, did not affect characteristic impedance, increased afterload, and increased contractility. During hypoxia, isoflurane and desflurane had similar ventricular effects as during hyperoxia. CONCLUSIONS: Isoflurane and desflurane markedly impair RV-PA coupling efficiency in dogs, during hyperoxia and hypoxia, both by increasing RV afterload and by decreasing RV contractility.

Anesthetics, Inhalation↗

PubMed2004

Dietary sodium and pulse pressure in normotensive and essential hypertensive subjects.

OBJECTIVES: To assess the influence of sodium intake on the two components of arterial blood pressure [mean blood pressure (MBP) and pulse pressure] and left ventricular mass (LVM) in normotensive subjects and never-treated hypertensive patients. METHODS: Blood pressure, LVM (M-mode echocardiography) and sodium excretion as an index of dietary sodium were measured in 459 males and 396 females, aged 14-93 years, with elevated (63% of population) or normal blood pressure. RESULTS: Because pulse pressure decreased with age up to approximately 40 years of age, and increased thereafter, analysis was undertaken separately in 438 young (age < or = 40 years) and 417 middle-aged to elderly subjects. Before age 40 years, only pulse pressure was independently and positively influenced by urinary sodium excretion. After age 40 years, MBP and LVM index but not pulse pressure were positively influenced by urinary sodium excretion. When men and women were analysed separately according to tertiles of urinary sodium excretion, pulse pressure adjusted for MBP and age increased from the first to the third tertile of urinary sodium excretion in males (P < 0.03), but not in females. CONCLUSIONS: The influence of sodium intake on pulse pressure was found in the younger subjects of both males and females and only in men older than 40 years.

Adolescent↗

PubMed2004

Effects of norepinephrine and dobutamine on pressure load-induced right ventricular failure.

OBJECTIVE: A transient increase in pulmonary arterial (PA) pressure can persistently depress right ventricular (RV) contractility. We investigated the effects norepinephrine and dobutamine on RV-PA coupling in this model of RV failure. DESIGN: Prospective, controlled, randomized animal study. SETTING: University research laboratory. SUBJECTS: Twenty-two anesthetized dogs. INTERVENTIONS: Animals underwent transient (90-min) PA constriction to induce persistent RV failure. They were randomly assigned to control, norepinephrine, or dobutamine group. Norepinephrine was administered at 0.1 and 0.5 microg x kg x min or dobutamine at 5 and 10 microg x kg x min. MEASUREMENTS AND MAIN RESULTS: We measured PA distal resistance and proximal elastance by pressure-flow relationships and vascular impedance. We also measured RV contractility by the end-systolic pressure-volume relationship (Ees), PA effective elastance by the end-diastolic to end-systolic relationship (Ea), and RV-PA coupling efficiency by the Ees/Ea ratio. The transient PA constriction persistently increased PA resistance and elastance, increased Ea from 0.8+/-0.1 to 2.7+/-0.3 mmHg/mL, decreased Ees from 1.1+/-0.1 to 0.5+/-0.1 mm Hg/mL, and decreased Ees/Ea from 1.2+/-0.1 to 0.2+/-0.1. Norepinephrine restored arterial pressure, increased RV contractility, and increased but did not normalize RV-PA coupling and cardiac output. Dobutamine restored arterial pressure, markedly increased RV contractility, and normalized RV-PA coupling and cardiac output. Compared with norepinephrine, dobutamine decreased PA resistance and elastance and increased RV contractility and RV-PA coupling. CONCLUSIONS: A transient increase in PA pressure persistently worsens PA hemodynamics, RV contractility, RV-PA coupling, and cardiac output. Dobutamine restores RV-PA coupling and cardiac output better than norepinephrine because of its more pronounced inotropic effect.

Animals↗

PubMed2003

Preoperative partitioning of pulmonary vascular resistance correlates with early outcome after thromboendarterectomy for chronic thromboembolic pulmonary hypertension.

BACKGROUND: Pulmonary thromboendarterectomy (PTE) is the preferred treatment for chronic thromboembolic pulmonary hypertension (CTEPH), but persistent pulmonary hypertension after PTE, as a result of either inaccessible distal thrombotic material or coexistent intrinsic small-vessel disease, remains a major determinant of poor outcome. Conventional preoperative evaluation is unreliable in identifying patients at risk for persistent pulmonary hypertension or predicting postoperative hemodynamic outcome. We postulated that pulmonary arterial occlusion pressure waveform analysis, a technique that has been used for partitioning pulmonary vascular resistance, might identify CTEPH patients with significant distal, small-vessel disease. METHODS AND RESULTS: Twenty-six patients underwent preoperative right heart catheterization before PTE. Pulmonary artery occlusion waveform recordings were performed in triplicate. Postoperative hemodynamics after PTE were compared with preoperative partitioning of pulmonary vascular resistance derived from the occlusion data. Preoperative assessment of upstream resistance (Rup) correlated with both postoperative total pulmonary resistance index (R2=0.79, P<0.001) and postoperative mean pulmonary artery pressure (R2=0.75, P<0.001). All 4 postoperative deaths occurred in patients with a preoperative Rup <60%. CONCLUSIONS: Pulmonary arterial occlusion pressure waveform analysis may identify CTEPH patients at risk for persistent pulmonary hypertension and poor outcome after PTE. Patients with CTEPH and Rup value <60% appear to be at highest risk.

Adult↗

PubMed2003

Hemodynamic effects of glibenclamide during endotoxemia: contrasting findings in vitro versus in vivo.

The final common pathway involved in the cardiovascular alterations of septic shock is incompletely defined. The opening of KATP channels is associated with vasorelaxation and alterations in cardiac contractility. This event may be triggered during septic shock by increased nitric oxide (NO) production, by a decreased intracellular content of ATP, or by a change in the transmembrane electrical potential. In the present study, we assessed the effects of glibenclamide, an agent that blocks the opening of KATP channels in vitro, on the contractile response of rat aortic rings to norepinephrine, and in vivo in anesthetized dogs, with or without exposure to Escherichia coli endotoxin. In vitro, glibenclamide decreased the contractile response to norepinephrine in the presence of endotoxin, provided that the endothelium was intact. In vivo, administration of 0.15 mg/kg increased systemic vascular resistance (SVR) in the absence of endotoxin only, and increased myocardial performance. A higher dose of 1 mg/kg increased SVR and decreased myocardial performance, both during endotoxic shock and in control conditions. Renal and mesenteric blood flows decreased, but the respective fractional flows were unchanged. Oxygen delivery decreased in both experimental conditions, but oxygen consumption decreased only in control conditions. The in vitro observations suggest that the opening of KATP channels is involved in the regulation of vascular tone during endotoxemia, via an endothelium-dependent mechanism. As different effects of glibenclamide were observed in vivo, the importance of the opening of KATP channels in endotoxic shock may be limited.

Animals↗

PubMed2003

Left ventricular remodeling and renal function in never-treated essential hypertension.

In the general population, renal function linearly declines with age; hypertension may accelerate this decline. Because concentric left ventricular (LV) hypertrophy is a strong marker of the severity of hypertension, the influence of LV geometry on the age-associated decline in renal function was assessed in 195 normotensive subjects and 645 patients with never-treated essential hypertension with an average duration of 30 mo. According to LV mass and relative wall thickness, hypertensive patients were divided into normal LV (NL, 48%), concentric remodeling (CR, 19%), and concentric (CH, 22%) and eccentric (EH, 11%) hypertrophy. GFR and effective renal plasma flow (ERPF) were estimated by isotopic clearance technique. GFR and ERPF were inversely correlated with age in normotensive and hypertensive subjects, and no marked influence of the BP level or the presence of LV hypertrophy was detected. However, the slope of the regression line of GFR versus age was accentuated (P < 0.01) in patients with CH or CR (slope values of -0.95 +/- 0.11, -0.86 +/- 0.14 ml/min per yr, respectively) when compared with patients with EH or NL (slope values of -0.58 +/- 0.16 and -0.58 +/- 0.08 ml/min per yr, respectively). No such results were obtained when creatinine clearance was considered. Urinary albumin excretion was higher in patients with concentric or eccentric LV hypertrophy than in patients with concentric LV remodeling or normal LV. These results demonstrate that in never-treated essential hypertension, the age-associated decline in GFR is markedly influenced by the concentric pattern of LV response to hypertension rather than the level of BP and/or the presence of LV hypertrophy.

Adolescent↗

PubMed2003

Pulmonary vascular effects of dobutamine in experimental pulmonary hypertension.

OBJECTIVE: To characterize the dose-related effects of dobutamine on pulmonary vascular tone and associated changes in right ventricular afterload in canine microembolic lung injury . DESIGN: Prospective, interventional study. SETTING: University laboratory. SUBJECTS: Ten anesthetized and ventilated dogs. INTERVENTIONS: Right heart catheterization for the measurement of pulmonary vascular resistance by multipoint mean pulmonary artery pressure (Ppa)/cardiac output (Q) plots, partitioning of pulmonary vascular resistance by the occlusion method, and determination of pulmonary arterial input impedance from spectral analysis of Ppa and Q waves, in ten anesthetized and ventilated dogs, before and after induction of acute microembolic lung injury, and without or with 5, 10, 15, and 20 microg.kg(-1).min(-1) dobutamine. MEASUREMENTS AND MAIN RESULTS: Microembolic pulmonary hypertension was associated with a shift of Ppa/Q plots to higher pressures, a slight decrease in the arterial component of pulmonary vascular resistance, a decrease in characteristic impedance, and an increase in the pulsatile component of right ventricular hydraulic load. At baseline, dobutamine had no effect on Ppa/Q plots at 5 and 10 microg.kg(-1).min(-1) but increased Ppa at 15 and 20 microg.kg(-1).min(-1). In microembolic pulmonary hypertension, the only effect of dobutamine on Ppa/Q plots was a decrease in Ppa at 20 microg.kg(-1).min(-1). Dobutamine had no effect on the partitioning of pulmonary vascular resistance or on pulmonary arterial input impedance spectrum. CONCLUSIONS: Dobutamine at doses up to 10 microg.kg(-1).min(-1) has no flow-independent effect on the normal or the acutely hypertensive pulmonary circulation. Higher doses may be constricting or dilating depending on preexisting tone.

Animals↗