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Biomedical subjects

R Naeije

Publications and source records attributed to R Naeije.

At least 55 records · Page 3Linked to original sources
PubMed1998

Partitioning of pulmonary vascular resistance in primary pulmonary hypertension.

OBJECTIVES: This study sought to determine the site of increased pulmonary vascular resistance (PVR) in primary pulmonary hypertension by standard bedside hemodynamic evaluation. BACKGROUND: The measurement of pulmonary vascular pressures at several levels of flow (Q) allows the discrimination between active and passive, flow-dependent changes in mean pulmonary artery pressure (Ppa), and may detect the presence of an increased pulmonary vascular closing pressure. The determination of a capillary pressure (Pc') from the analysis of a Ppa decay curve after balloon occlusion allows the partitioning of PVR in an arterial and a (capillary + venous) segment. These approaches have not been reported in primary pulmonary hypertension. METHODS: Ppa and Pc' were measured at baseline and after an increase in Q induced either by exercise or by an infusion of dobutamine, at a dosage up to 8 microg/kg body weight per min, in 11 patients with primary pulmonary hypertension. Reversibility of pulmonary hypertension was assessed by the inhalation of 20 ppm nitric oxide (NO), and, in 6 patients, by an infusion of prostacyclin. RESULTS: At baseline, Ppa was 52+/-3 mm Hg (mean value+/-SE), Q 2.2+/-0.2 liters/min per m2, and Pc' 29+/-3 mm Hg. Dobutamine did not affect Pc' and allowed the calculation of an averaged extrapolated pressure intercept of Ppa/Q plots of 34 mm Hg. Inhaled NO had no effect. Prostacyclin decreased Pc' and PVR. Exercise increased Pc' to 40+/-3 mm Hg but did not affect PVR. CONCLUSIONS: ns. These findings are compatible with a major increase of resistance and reactivity at the periphery of the pulmonary arterial tree.

Adrenergic beta-Antagonists↗
PubMed1998

Effects of pulmonary embolism on pulmonary vascular impedance in dogs and minipigs.

Pigs have been reported to present with a stronger pulmonary vascular reactivity than many other species, including dogs. We investigated the pulmonary vascular impedance response to autologous blood clot embolic pulmonary hypertension in anesthetized and ventilated minipigs (n = 6) and dogs (n = 6). Before embolization, minipigs, compared with dogs, presented with higher mean pulmonary arterial pressure (Ppa; by an average of 9 mmHg), a steeper slope of Ppa-flow (Q) relationships, and higher 0-Hz impedance (Z0) and first-harmonic impedance (Z1), without significant differences in characteristic impedance (Zc), and a lower ratio of pulsatile hydraulic power to total hydraulic power. Embolic pulmonary hypertension (mean Ppa: 40-55 mmHg) was associated with increased Z0 and Z1 in both species, but the minipigs had a steeper slope of Ppa/Q plots and an increased Zc. At identical Q and Ppa, minipigs still presented with higher Z1 and Zc and a lower ratio of pulsatile hydraulic power to total hydraulic power. The energy transmission ratio, defined as the hydraulic power in the measured waves divided by the hydraulic power in the forward waves, was better preserved after embolism in minipigs. No differences in wave reflection indexes were found before and after embolism. We conclude that minipigs, compared with dogs, present with a higher pulmonary vascular resistance and reactivity and adapt to embolic pulmonary hypertension by an increased Zc without earlier wave reflection. These differences allow for a reduced pulsatile component of hydraulic power and, therefore, a better energy transfer from the right ventricle to the pulmonary circulation.

Animals↗
PubMed1998

High incidence of primary pulmonary hypertension associated with appetite suppressants in Belgium.

Primary pulmonary hypertension is a rare, progressive and incurable disease, which has been associated with the intake of appetite suppressant drugs. The importance of this association was evaluated in Belgium while this country still had no restriction on the prescription of appetite suppressants. Thirty-five patients with primary pulmonary hypertension and 85 matched controls were recruited over 32 months (1992-1994) in Belgium. Exposure to appetite-suppressants was assessed on the basis of hospital records and standardized interview. Twenty-three of the patients had previously taken appetite suppressants, mainly fenfluramines, as compared with only 5 of the controls (66 versus 6%, p<0.0001). Five patients died before the interview, all of them had taken appetite suppressants. In 8 patients the diagnosis of primary pulmonary hypertension was uncertain, 5 of them had taken appetite suppressants. The patients who had been exposed to appetite suppressants tended to be on average more severely ill, and to have a shorter median delay between onset of symptoms and diagnosis. A policy of unrestricted prescription of appetite suppressants may lead to a high incidence of associated primary pulmonary hypertension. Intake of appetite suppressants may accelerate the progression of the disease.

Adult↗
PubMed1998

False-positive diagnosis of pulmonary hypertension by Doppler echocardiography.

A 37-yr-old female presented with a history of several months of exertional dyspnoea. A diagnosis of primary pulmonary hypertension was suspected on the basis of a negative extensive cardiorespiratory work-up with a systolic pulmonary artery pressure of 41-46 mmHg calculated from repeated measurement of the maximum velocity of tricuspid regurgitation jets at 2.8-3 m x s(-1) by continuous-wave Doppler echocardiography. However, a right heart catheterization with a high-fidelity transducer-tipped catheter revealed pulmonary artery pressures of 22/8 mmHg at rest, which remained within normal limits at exercise. This case indicates a possible misleading overestimation of pulmonary artery pressures from Doppler echocardiographic studies of tricuspid regurgitation.

Adult↗
PubMed1997

Sympathetic modulation of hypoxic pulmonary vasoconstriction in intact dogs.

BACKGROUND: The effects of the sympathetic nervous system on hypoxic pulmonary vasoconstriction (HPV) have been reported variably. We studied the effects of adrenergic receptor blockade and epidural blockade on HPV in 32 pentobarbital-anaesthetised intact dogs. METHODS: Pulmonary arterial flow-pressure relationships were determined in hyperoxia and hypoxia, at baseline and after alpha-blockade (phentolamine 2 mg/kg + 50 micrograms.kg-1.-1), beta-blockade (propranolol 2 mg/kg), alpha beta-blockade, epidural blockade (lignocaine 20 mg/kg), and alpha beta-plus epidural blockade. RESULTS: At reference flow of 3.5 1.min-1.m-2, the mean hypoxic response (hypoxia-induced increase in transpulmonary pressure gradient, each n = 8) changed from 6.0 +/- 0.9 to 3.5 +/- 1.0 mmHg after alpha-blockade, from 5.8 +/- 0.9 to 0.7 mmHg after beta-blockade, from 4.1 +/- 0.8 to 0.9 +/- 1.4 mmHg after alpha beta-blockade from 3.4 +/- 1.0 to 4.3 +/- 0.9 mmHg after epidural blockade (all P < 0.05), and was not affected by epidural blockade after alpha beta-blockade. CONCLUSIONS: In pentobarbital-anaesthetised dogs, (1) HPV is attenuated by alpha- and enhanced by beta-, alpha beta- and epidural blockade, and (2) epidural blockade has no significant adrenergic-unrelated effect on the pulmonary vasculature.

Adrenergic alpha-Antagonists↗
PubMed1997

Comparison of the effects of isoflurane with those of propofol on pulmonary vascular impedance in experimental embolic pulmonary hypertension.

Inhaled but not i.v. anaesthetics are reported to decrease pulmonary vascular resistance. The aim of this study was to compare the effects of isoflurane with those of propofol on the interaction between right ventricular (RV) function and the pulmonary vascular system in embolic pulmonary hypertension. Nine dogs received in random sequence propofol 18 mg kg-1 h-1 and 1.4% end-tidal isoflurane. Pulmonary haemodynamic state was evaluated by pulmonary arterial pressure/flow (PAP/Q) plots and pulmonary vascular impedance (PVZ) spectra. Right ventricular function was assessed by total hydraulic power (Wtot), ratio of oscillatory power (Wosc) to Wtot, and dP/dtmax. Measurements were obtained, with both anaesthetics, before and after pulmonary embolic hypertension induced by autologous blood clots. Embolism increased PAP, 0 Hz and low frequency input impedance, displaced first minimum of PAP/Q moduli and zero crossing of phase to higher frequencies, decreased characteristic impedance, decreased Wosc/Wtot without affecting Wtot, and increased dP/dtmax. Compared with propofol, isoflurane at baseline did not affect PAP/Q plots, PVZ or hydraulic power data, but decreased dP/dtmax. After embolism, isoflurane shifted PAP/Q plots to lower PAP without affecting PVZ, did not affect hydraulic power data and decreased dP/dtmax. We conclude that in canine embolic pulmonary hypertension, isoflurane compared with propofol impeded RV vascular coupling caused by decreased RV contractility, while after-load remained unchanged despite some decrease in pulmonary vascular tone.

Anesthetics, Inhalation↗
PubMed1997

Pulmonary circulation at high altitude.

Hypoxia constricts the pulmonary vessels. An increase in pulmonary vascular resistance is seen in normal subjects during hypoxic breathing at sea level, in acclimatized lowlanders and in high-altitude natives. Hypoxic pulmonary hypertension in all these circumstances is most generally moderate, except in high-altitude natives at exercise. Pulmonary hypertension may become severe during high-altitude pulmonary edema, during infantile or adult forms of subacute mountain sickness, and during chronic mountain sickness. Subacute and chronic mountain sickness may be associated with a right heart failure that would be the human counterpart of brisket disease described in cattle. Subjects susceptible to high-altitude pulmonary edema present with a slight increase in pulmonary vascular resistance at rest and at exercise, and often with an enhanced pulmonary vascular reactivity to hypoxia. However, compared to unselected controls, the overlap is great, so that noninvasive echo-Doppler studies of the pulmonary circulation at sea level are of little predictive value of tolerance to altitudes on an individual basis.

Acclimatization↗
PubMed1997

Site of pulmonary vasodilation by inhaled nitric oxide in microembolic lung injury.

We investigated the site of pulmonary vasodilation and associated effects on gas exchange in response to inhaled NO in acute microembolic lung injury. Pulmonary arterial (Ppa) and effective capillary (Pc') pressures versus cardiac output (Q) plots were generated in anesthetized dogs before and after, successively, (1) embolization with 100 microns glass beads, (2) administration of either a placebo (n = 5) or 80 ppm inhaled NO followed by cyclooxygenase inhibition by aspirin 1 g given intravenously and again 80 ppm inhaled NO (n = 8). Pc' was estimated from the pressure decay curve after pulmonary artery balloon occlusion. Embolism increased pulmonary vascular resistance, with a slight decrease in its precapillary component, from 77 to 66%. NO decreased Ppa at the highest levels of Q, and aspirin increased Ppa at all levels of Q. Neither NO nor aspirin affected Pc'/Q plots or pulmonary shunt. We conclude that pulmonary vascular resistance in microembolic lung injury increases at the periphery of the pulmonary arterial tree, with partial reversibility by inhaled NO and by endogenous products of the cyclooxygenase pathway upstream from the site of effective capillary resistance. Reduced pulmonary vascular tone does not improve gas exchange in this model of acute lung injury.

Animals↗
PubMed1996

Systemic vascular effects of isoflurane versus propofol anesthesia in dogs.

Vascular effects of general anesthesia are usually described by changes in vascular resistance, which assumes a linear pressure-flow relationship passing through the zero-flow zero-pressure point, and neglects the pulsatile properties of the circulation. We compared the systemic vascular effects of isoflurane versus propofol anesthesia by measurements of aortic pressure-flow relationships, systemic vascular impedance (SVZ), and pressure transfer function (PTF). Eight mechanically ventilated dogs received isoflurane 1.4% end-tidal and propofol 18 mg.kg-1.h-1 in a random sequence. During both periods, pressure-flow data and SVZ data were obtained at baseline and after stepwise reduction of the cardiac output by inflation of a balloon in the inferior vena cava. Instantaneous pressure and flow were measured at the aortic root using a micromanometer-tipped catheter and an ultrasonic flow probe. Compared to baseline, low flow decreased the aortic pressure and increased the resistance, characteristic impedance, and oscillatory/total work ratio. Compared with isoflurane, propofol resulted in higher aortic pressure, lower characteristic impedance, and lower oscillatory/total work ratio. Low-frequency PTF moduli decreased at low flow and increased with propofol. We conclude that, compared with isoflurane, propofol better preserves aortic pressure and increases aortic compliance, and thus improves the energy transmission from the left ventricle to the arterial system.

Anesthetics, Inhalation↗
PubMed1996

Hypoxic pulmonary vasoconstriction and gas exchange in acute canine pulmonary embolism.

Hypoxic pulmonary vasoconstriction (HPV) is inhibited in several models of acute lung injury. Whether HPV is preserved in pulmonary embolism is unknown. We investigated the effects of a reduction in the fraction of inspired O2 (FIO2) on pulmonary hemodynamics and gas exchange in anesthetized dogs before and after autologous blood clot pulmonary embolism. In a first group of 14 dogs, stimulus-response curves for HPV were constructed as pulmonary arterial pressure (Ppa) vs. FIO2 varied between 1.0 and 0.06 at a cardiac output (Q) kept constant at 3.5 l.min-1.m-2. Gas exchange was evaluated by using the multiple inert-gas elimination technique at FIO2 of 1.0, 0.4, and 0.1. Embolism decreased the relative magnitude of HPV, expressed as the gradient between Ppa and pulmonary arterial occluded pressure in hypoxia divided by (Ppa-pulmonary arterial occluded pressure) at FIO2 of 1.0, from 1.8 to 1.2 (P < 0.05). Retention minus excretion gradients for sulfur hexafluoride and ethane were increased by decreased FIO2 (P < 0.005 and P < 0.05, respectively) before but not after embolism. Hypoxia-induced deterioration in gas exchange before embolism was related to the amount of baseline very low ventilation-perfusion (VA/Q) ratios. Similar results were obtained in a second group of seven dogs with Q decreased to maintain Ppa at the same average value as before embolism. However, gas exchange was not affected by inspiratory hypoxia before as well as after embolism in this group, which presented with a lesser amount of baseline very low VA/Q. In both groups of dogs, increase in the FIO2 from 0.4 to 1.0 did not affect gas exchange. We conclude that 1) pulmonary embolism is associated with a partial inhibition of HPV, 2) HPV does not contribute to preserve gas exchange in pulmonary embolism, and 3) a strong HPV may deteriorate gas exchange in severe hypoxia in the presence of minor very low VA/Q inequality.

Animals↗
PubMed1996

Effects of hypoxic pulmonary vasoconstriction on pulmonary gas exchange.

Several reports have suggested that hypoxic pulmonary vasoconstriction (HPV) might result in deterioration of pulmonary gas exchange in severe hypoxia. We therefore investigated the effects of HPV on gas exchange in normal and diseased lungs. We incorporated a biphasic HPV stimulus-response curve observed in intact dogs (S. Brimioulle, and R. Lejeune, J.L. Vachièry, M. Delcroix, R. Hallemans, and R. Naeije, J. Appl. Physiol. 77: 476-480, 1994) into a 50-compartment lung model (J.B. West, Respir. Physiol. 7: 88-110, 1969) to control the amount of blood flow directed to each lung compartment according to the local hypoxic stimulus. The resulting model accurately reproduced the blood gas modifications caused by HPV changes in dogs with acute lung injury. In single lung units, HPV had a moderate protective effect on alveolar oxygenation, which was maximal at near-normal alveolar PO2 (75-80 Torr), mixed venous PO2 (35 Torr), and PO2 at which hemoglobin is 50% saturated (24 Torr). In simulated diseased lungs associated with 40-60 Torr arterial PO2, however, HPV increased arterial PO2 by 15-20 Torr. We conclude that HPV can improve arterial oxygenation substantially in respiratory failure.

Acidosis, Respiratory↗
PubMed1996

Effects of chronic dexfenfluramine treatment on pulmonary hemodynamics in dogs.

An epidemic of primary pulmonary hypertension occurred in Europe in the 1960s, after the introduction of the appetite suppressant aminorex. Recently, a cluster of cases of pulmonary hypertension was observed in France in relation to the intake of the appetite suppressant dexfenfluramine. We previously reported that intravenous dexfenfluramine enhances hypoxic pulmonary vasoconstriction in dogs. We therefore investigated the pulmonary hemodynamic effects of chronic oral intake of this drug. Twenty-four dogs with a strong (n = 12) and a weak hypoxic pulmonary vasoconstriction (n = 12) respectively were randomly allocated in a double blind manner to a twice daily oral intake of either a placebo or dexfenfluramine 1.5 mg/kg for 20 d. A strong hypoxic vasoconstriction was defined as a hypoxia-induced increase in pulmonary artery pressure by more than 3 mm Hg at a standardized cardiac output of 3 L/min/m2. Pulmonary hemodynamics were studied in hyperoxia (fraction of inspired O2 [F(I)O2] 0.4) and in hypoxia (F(I)O2 0.1) before and after treatment. Venous return was manipulated at post-treatment evaluation for isoflow comparisons of pulmonary vascular pressures. Dexfenfluramine had no effect on systemic hemodynamics or blood gases, but increased pulmonary vascular resistance from 155 +/- 17 to 192 +/- 14 dyne x s x cm(-5) in hyperoxia (mean +/- SE, p < 0.05) and from 237 +/- 27 to 293 +/- 47 dyne x s x cm(-5) in hypoxia (p < 0.01). Dexfenfluramine, and not placebo, increased the isoflow pulmonary vascular pressure gradient in hyperoxia and in hypoxia. This effect was unrelated to the magnitude of pretreatment hypoxic vasoconstriction. We conclude that the chronic intake of dexfenfluramine in dogs is associated with a moderate increase in pulmonary vascular resistance which is unrelated to pulmonary vasoreactivity to hypoxia.

Administration, Oral↗
PubMed1996

High-altitude pulmonary edema with primary pulmonary hypertension.

A 43-year-old woman had two episodes of lung edema at moderate altitudes. She had taken slimming pills containing fenfluramine hydrochloride and diethylpropion hydrochloride. At sea level, catheterization of the right side of the heart showed a mean pulmonary artery pressure of 16 mm Hg, which increased to 34 mm Hg with mild exercise in a supine position. An extensive workup failed to identify a cardiac or a pulmonary cause of pulmonary hypertension. This patient experienced mild primary pulmonary hypertension related to the intake of anorexigens, which was revealed by high-altitude pulmonary edema.

Adult↗
PubMed1995

Doppler assessment of hypoxic pulmonary vasoconstriction and susceptibility to high altitude pulmonary oedema.

BACKGROUND: Subjects with previous high altitude pulmonary oedema may have stronger than normal hypoxic pulmonary vasoconstriction. Susceptibility to high altitude pulmonary oedema may be detectable by echo Doppler assessment of the pulmonary vascular reactivity to breathing a hypoxic gas mixture at sea level. METHODS: The study included 20 healthy controls, seven subjects with a previous episode of high altitude pulmonary oedema, and nine who had successfully climbed to altitudes of 6000-8842 m during the 40th anniversary British expedition to Mount Everest. Echo Doppler measurements of pulmonary blood flow acceleration time (AT) and ejection time (ET), and of the peak velocity of the tricuspid regurgitation jet (TR), were obtained under normobaric conditions of normoxia (fraction of inspired oxygen, FIO2, 0.21), of hyperoxia (FIO2 1.0), and of hypoxia (FIO2 0.125). RESULTS: Hypoxia decreased AT/ET by mean (SE) 0.06 (0.01) in the control subjects, by 0.11 (0.01) in those susceptible to high altitude pulmonary oedema, and by 0.02 (0.02) in the successful high altitude climbers. Hypoxia increased TR in the three groups by 0.22 (0.06) (n = 14), 0.56 (0.13) (n = 5), and 0.18 (0.1) (n = 7) m/s, respectively. However, AT/ET and/or TR measurements outside the normal range, defined as mean +/- 2 SD of measurements obtained in the controls under hypoxia, were observed in only two of the subjects susceptible to high altitude pulmonary oedema and in five of the successful high altitude climbers. CONCLUSIONS: Pulmonary vascular reactivity to hypoxia is enhanced in subjects with previous high altitude pulmonary oedema and decreased in successful high altitude climbers. However, echo Doppler estimates of hypoxic pulmonary vaso-constriction at sea level cannot reliably identify subjects susceptible to high altitude pulmonary oedema or successful high altitude climbers from a normal control population.

Adult↗
PubMed1995

Starling resistor vs. distensible vessel models for embolic pulmonary hypertension.

We investigated whether the Starling resistor model (Mitzner et al. J. Appl. Physiol. 51: 1065-1071, 1981) or a distensible vessel model (Haworth et al. J. Appl. Physiol. 70: 15-26, 1991) best describes pulmonary vascular pressure-flow (Q) relationships in embolic pulmonary hypertension. Mean pulmonary arterial pressure (Ppa)-Q plots at constant left atrial pressure (Pla) and Ppa-Pla plots at constant Q were investigated in seven dogs before and after 500-micron glass bead pulmonary embolism. Embolization to a mean angiographic obstruction of 78% increased the slope and extrapolated pressure intercept (P(i)) of Ppa-Q plots and increased the inflection point of Ppa-Pla plots, above which an increase in Pla is transmitted to Ppa in a ratio of approximately 1:1. The Starling resistor and the distensible vessel model provided a reasonably good fit to the Ppa-Q and Ppa-Pla coordinates before and after embolism. However, contrary to the prediction of the Starling resistor model, no correlation was found between the inflection point of Ppa-Pla plots and P(i). We therefore conclude that an increased closing pressure is unlikely to contribute to embolic pulmonary hypertension.

Animals↗
PubMed1995

Pulmonary vascular impedance response to hypoxia in dogs and minipigs: effects of inhaled nitric oxide.

The pig has been reported to present with a stronger hypoxic pulmonary vasoconstriction (HPV) than many other species, including dogs. We investigated [pulmonary arterial pressure (Ppa)-pulmonary arterial occluded pressure (Ppao)] vs. pulmonary blood flow (Q) relationships and pulmonary vascular impedance (PVZ) spectra in nine minipigs and nine weight-matched dogs. The animals were anesthetized and ventilated in hyperoxia [inspired O2 fraction 0.4] or hypoxia (inspired O2 fraction 0.12). PVZ was computed from the Fourier series for Ppa and Q. In hyperoxia, the pigs had a higher Ppa (26 +/- 1 vs. 16 +/- 1 mmHg), a higher first-harmonic impedance (Z1), and a more negative low-frequency phase angle but no different characteristic impedance (Zc) compared with the dogs at the same Q. Hypoxia in the dogs increased (Ppa-Ppao) at all levels of Q studied by an average of 2 mmHg but did not affect Z1 or Zc. Hypoxia in the pigs increased (Ppa-Ppao) at all levels of Q by an average of 13 mmHg and increased Z1 and Zc. Inhaled NO (150 ppm) reversed the hypoxia-induced changes in (Ppa-Ppao)/Q plots and PVZ in the dogs and pigs. However, differences in (Ppa-Ppao)/Q plots and PVZ between the dogs and pigs in hyperoxia and hypoxia were not affected by inhaled NO. We conclude 1) that minipigs present with an elevated pulmonary vascular resistance and impedance in hypoxia more than in hyperoxia and 2) that baseline differences in pulmonary hemodynamics between dogs and minipigs are structural rather than functional.

Administration, Inhalation↗