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Biomedical subjects

R Naeije

Publications and source records attributed to R Naeije.

At least 73 records · Page 4Linked to original sources
PubMed1995

Effects of dexfenfluramine on hypoxic pulmonary vasoconstriction and embolic pulmonary hypertension in dogs.

There has been suggestion of a possible relationship between the intake of the appetite suppressant dexfenfluramine and the development of primary pulmonary hypertension. We investigated the pulmonary vascular effects of acute intravenous dexfenfluramine in pentobarbital-anesthetized dogs ventilated in hyperoxia (fraction of inspired oxygen, FIO2, 0.4) and either challenged with a FIO2 of 0.1 to induce hypoxic pulmonary hypertension (n = 20) or given autologous blood clots to induce embolic pulmonary hypertension (n = 6). Pulmonary vascular tone was evaluated by multipoint (mean pulmonary artery pressure [Ppa] - pulmonary artery occluded pressure [Ppao])/cardiac output (Q) plots. Hypoxia increased Ppa - Ppao over the entire range of Q studied, from 1.5 to 4.0 L/min/m2, in 12 dogs (responders) and had no significant effect on (Ppa - Ppao)/Q plots in 8 other dogs (nonresponders). Dexfenfluramine did not affect (Ppa - Ppao)/Q plots in 6 responders but shifted (Ppa - Ppao)/Q plots to higher pressures in hypoxia in 6 nonresponders (p < 0.001). Dexfenfluramine had no effect on (Ppa - Ppao)/Q plots in the 6 dogs with embolic pulmonary hypertension. Because dexfenfluramine has serotoninergic properties, we compared the effects of ketanserin, a serotonin (5-hydroxytryptamine, 5-HT) S2 receptor antagonist, on naturally present versus dexfenfluramine-restored hypoxic pulmonary vasoconstriction. Ketanserin did not affect hyperoxic or hypoxic pulmonary vascular tone, neither in 6 responders nor in 2 nonresponders with dexfenfluramine-restored hypoxic vasoconstriction. We conclude that dexfenfluramine restores hypoxic pulmonary vasoconstriction in dogs with weak or absent hypoxic pressor response and that this effect is unlikely to be mediated by activation of 5-HT S2 receptors.

Animals↗
PubMed1994

Effects of endogenous nitric oxide on pulmonary vascular tone in intact dogs.

The interaction between inspiratory fraction of O2 (FIO2) and endogenous nitric oxide (NO) regulation of pulmonary vascular tone was examined in intact anesthetized dogs. Stimulus (FIO2 of 1, 0.4, 0.21, 0.12, and 0.1)-response (changes in pulmonary artery pressure minus pulmonary artery occlusion pressure) curves were constructed with cardiac output kept constant (by opening a femoral arteriovenous bypass or inflating an inferior vena cava balloon catheter), before and after administration of compounds acting at different levels of the L-arginine-NO pathway, NG-nitro-L-arginine (L-NNA, 10 mg/kg iv, n = 16), a NO synthase inhibitor, and methylene blue (8 mg/kg iv, n = 16), a guanylate cyclase inhibitor. L-NNA and methylene blue did not influence pulmonary vascular tone in hyperoxic and in normoxic conditions, but they increased it during hypoxia, thus enhancing the vasopressor response to hypoxia (from 4.5 +/- 0.9 to 10.4 +/- 1.2 mmHg and from 4.2 +/- 0.8 to 9 +/- 1.5 mmHg, respectively, both P < 0.01). Hypoxic pulmonary vasoconstriction was augmented in dogs with a baseline hypoxic response ("responders") and restored in dogs without hypoxic response ("nonresponders"). These results suggest that endogenous NO does not influence hyperoxic and normoxic pulmonary vascular tone, but that it inhibits hypoxic pulmonary vasoconstriction in intact anesthetized dogs.

Animals↗
PubMed1994

Increased left atrial pressure inhibits hypoxic pulmonary vasoconstriction.

An increase in left atrial pressure (Pla) has been reported to either inhibit or not affect hypoxic pulmonary vasoconstriction in intact dogs. We investigated mean pulmonary arterial pressure (Ppa)-flow (Q) relationships at low and high fixed Pla and Ppa-Pla relationships at fixed Q in piglets, which are known to present with a stronger hypoxic pulmonary pressor response than dogs. Seven piglets were anesthetized; equipped with balloon catheters in inferior vena cava and left atrium to control Q and Pla, respectively; and ventilated alternatively in hyperoxia [fractional concn of O2 in inspired air (FIO2) 0.4] and hypoxia (FIO2 0.12). In all experimental conditions, Ppa-Q plots were best described by a linear approximation with extrapolated pressure intercepts (Pi) not different from Pla. Hypoxia increased slope but not Pi of Ppa-Q plots. An increase in Pla from 8 to 17 mmHg induced a parallel shift of Ppa-Q plots to higher Ppa in hyperoxia but did not affect Ppa-Q plots in hypoxia. In hyperoxia, an increase in Pla at constant Q induced an approximately equal increase in Ppa, whereas in hypoxia there was no effect. The hypoxia-induced increase in Ppa was blunted by increased Pla at all levels of Q studied. We conclude that in anesthetized piglets at fixed Pla hypoxia increases the slope of Ppa-Q plots without affecting Pi and an increase in Pla inhibits hypoxic pulmonary vasoconstriction. The results suggest that no closing pressure higher than normal Pla contributes to hyperoxic or hypoxic Ppa in the intact porcine pulmonary circulation.

Animals↗
PubMed1994

Stimulus-response curve of hypoxic pulmonary vasoconstriction in intact dogs: effects of ASA.

Hypoxic pulmonary vasoconstriction (HPV) has been reported to decrease during severe hypoxia in isolated lungs, but it remains unknown whether this decrease occurs in the intact animal and how it is affected by cyclooxygenase inhibition. We investigated the HPV stimulus-response relationship in eight pentobarbital sodium-anesthetized intact dogs with a naturally occurring response to hypoxia ("responders"). The pulmonary arterial minus wedge pressure difference (Ppa-Ppw) was measured at 11 inspired O2 fraction (FIO2) values between 0.40 and 0.04 while ventilation, cardiac output, and acid-base status were kept constant. Ppa-Ppw increased by 8 +/- 1 mmHg between FIO2 of 0.40 and 0.10 (alveolar PO2 of approximately 40 Torr) and decreased by 3 +/- 1 mmHg between FIO2 of 0.10 and 0.04. To assess the effects of cyclooxygenase inhibition, similar stimulus-response curves were obtained after administration of 20 mg/kg of acetylsalicylic acid (ASA) in 16 more dogs selected as either nonresponders or responders to hypoxia. ASA restored HPV in nonresponders and enhanced HPV in responders, with the difference between Ppa-Ppw at FIO2 of 0.10 and 0.40 increasing from 1 +/- 1 to 8 +/- 1 mmHg (P < 0.001) and from 7 +/- 1 to 10 +/- 1 mmHg (P < 0.05), respectively. In both groups, the shape of the stimulus-response curve after ASA was comparable to that of spontaneous HPV, with a maximum at FIO2 of 0.10 and a significant decrease at lower FIO2. We conclude that severe hypoxia attenuates HPV in the intact animal and that ASA restores or enhances HPV by affecting the magnitude of the hypoxic response and not the sensitivity to hypoxia.

Acid-Base Equilibrium↗
PubMed1994

Effects of a chronic aortopulmonary shunt on pulmonary hemodynamics in piglets.

Systemic-to-pulmonary shunting in growing pigs has been proposed as an experimental model of high-flow pulmonary hypertension associated with congenital heart defects. We investigated multipoint pulmonary arterial pressure (Ppa) vs. cardiac output (Q) plots and pulmonary vascular impedance spectra in 13 piglets aged approximately 4 mo and ventilated alternatively in hyperoxia (inspired O2 fraction 0.4) and in hypoxia (inspired O2 fraction 0.12). The measurements were done 8 wk after either an anastomosis between the thoracic aorta and the pulmonary trunk (n = 7 piglets) or a sham operation (n = 6). Cardiac output was altered by a manipulation of venous return. In the sham-operated piglets, hypoxia increased Ppa by an average of 12 mmHg over the entire range of Q studied, from 60 to 120 ml/kg, and increased both 0 Hz (Z0) and characteristic (Zc) pulmonary vascular impedance. In the shunted piglets compared with the sham-operated piglets in hyperoxia, Ppa was increased by an average of 5-6 mmHg at all levels of Q studied, from 60 to 120 ml/kg (P < 0.01), and Zc was also increased (P < 0.01), whereas Z0 was unchanged. In the shunted piglets, hypoxia increased Ppa at all levels of Q studied only to an average of 3 mmHg, and neither Z0 nor Zc was altered by hypoxia. We conclude that an aortopulmonary shunt of 2-mo duration in growing pigs increases both pulmonary vascular resistance and impedance and is associated with a blunting of pulmonary vascular reactivity to hypoxia.

Animals↗
PubMed1994

Nature of pulmonary hypertension in congestive heart failure. Effects of cardiac transplantation.

Pulmonary hypertension associated with congestive heart failure carries a risk of right ventricular failure after cardiac transplantation. Few data, however, are available on the hemodynamic behavior of the pulmonary circulation in these patients. We therefore studied mean pulmonary artery pressure minus left atrial pressure (estimated by pulmonary artery occluded pressure) versus cardiac output relationships in 20 patients with congestive heart failure evaluated for orthotopic cardiac transplantation, and we repeated this study either within the first 3 days postoperatively (n = 10) or 1 month postoperatively (n = 11). Cardiac output was increased by physical exercise or (in the early postoperative period) by an infusion of dobutamine. Reversibility of pulmonary hypertension was tested by an infusion of prostaglandin E1. At preoperative evaluation, the extrapolated pressure intercept of pulmonary vascular pressure:flow plots was negative in 10 of the patients, suggesting active exercise-induced pulmonary vasoconstriction. In the other 10 patients, the extrapolated pressure intercept was positive, suggesting that an increased closing pressure contributed to pulmonary hypertension. However, transplantation was constantly associated with proportional decreases of pulmonary artery pressure and left atrial pressure. On the other hand, pulmonary vascular pressure:flow plots were displaced to equal or lower pressures and to higher flows by prostaglandin E1 before as well as after transplantation. We conclude that in patients with congestive heart failure evaluated for cardiac transplantation, an increased pulmonary venous pressure more than a reversible increase in closing pressure determines the severity of pulmonary hypertension.

Adolescent↗
PubMed1993

Systemic and renal haemodynamic effects of angiotensin converting enzyme inhibition by zabicipril in young and in old normal men.

Zabicipril is a recently introduced angiotensin converting enzyme (ACE) inhibitor, which has been observed in experimental animals to increase diuresis, natriuresis, glomerular filtration rate (GFR) and renal plasma flow (RPF). We have investigated the acute effects of zabicipril on systemic and renal haemodynamics in two groups of 8 sodium-replete normal men, aged 23 to 30 y and 65 to 74 y. Zabicipril 0.5 mg, 1 mg or 2.5 mg and a placebo were administered orally, at one week intervals, in a random order and in a double blind fashion. Haemodynamic measurements were performed at base line and every hour for 4 hours after intake of drug or placebo. Cardiac output (Q) was measured by Doppler echography, and RPF and GFR by the constant infusion technique using I123 iodohippurate and Cr51 EDTA, respectively. In the young men zabicipril did not affect Q, heart rate (HR), systemic arterial pressure (AP) or GFR, but it did increase RPF at the 4th hour after the highest dose (from 540 to 653 ml.min-1.m-2). In the old men zabicipril had similar actions, but the effect of the highest dose on RPF (from 355 to 415 ml.min-1.m-2) was less marked than in the young men. In the young and old men the inhibition of ACE peaked at about of 90% or more from the 2th to the 4th hour after the highest dose of zabicipril. We conclude that, in normal men, zabicipril increases the renal fraction of cardiac output in the absence of a concomitant change in systemic haemodynamics. This specific effect of zabicipril on the kidney may be less important with advancing age.

Adult↗
PubMed1993

Relationship of middle cerebral artery blood flow velocity to intensity during dynamic exercise in normal subjects.

Cerebral blood flow has been reported to increase during dynamic exercise, but whether this occurs in proportion to the intensity remains unsettled. We measured middle cerebral artery blood flow velocity (vm) by transcranial Doppler ultrasound in 14 healthy young adults, at rest and during dynamic exercise performed on a cycle ergometer at a intensity progressively increasing, by 50 W every 4 min until exhaustion. Arterial blood pressure, heart rate, end-tidal, partial pressure of carbon dioxide (PETCO2), oxygen uptake (VO2) and carbon dioxide output were determined at exercise intensity. Mean vM increased from 53 (SEM 2) cm.s-1 at rest to a maximum of 75 (SEM 4) cm.s-1 at 57% of the maximal attained VO2 (VO2max), and thereafter progressively decreased to 59 (SEM 4) cm.s-1 at VO2max. The respiratory exchange ratio (R) was 0.97 (SEM 0.01) at 57% of VO2max and 1.10 (SEM 0.01) at VO2max. The PETCO2 increased from 5.9 (SEM 0.2) kPa at rest to 7.4 (SEM 0.2) kPa at 57% of VO2max, and thereafter decreased to 5.9 (SEM 0.2) kPa at VO2max. Mean arterial pressure increased from 98 (SEM 1) mmHg (13.1 kPa) at rest to 116 (SEM 1) mmHg (15.5 kPa) at 90% of VO2max, and decreased slightly to 108 (SEM 1) mmHg (14.4 kPa) at VO2max. In all the subjects, the maximal value of vm was recorded at the highest attained exercise intensity below the anaerobic threshold (defined by R greater than 1). We concluded that cerebral blood flow as evaluated by middle cerebral artery flow velocity increased during dynamic exercise as a function of exercise intensity below the anaerobic threshold.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Is nitric oxide released in oleic acid lung injury?

Inhibitors of endothelium-derived nitric oxide synthesis or activity have been reported to enhance hypoxic vasoconstriction in isolated lung preparations. We hypothesized that methylene blue, a guanylate cyclase inhibitor, and N omega-nitro-L-arginine, a nitric oxide synthase inhibitor, would increase pulmonary vascular tone and improve gas exchange in anesthetized and ventilated (inspired O2 fraction 0.4) dogs with oleic acid (OA) lung injury. Mean pulmonary arterial pressure-(Ppa) flow (Q) relationships (generated by a manipulation of venous return, which was increased by opening a femoral arteriovenous bypass or decreased by inflating an inferior vena cava balloon) and gas exchange (evaluated by arterial blood gases and SF6 intrapulmonary shunt determinations) were investigated before and after OA (0.06 ml/kg i.v.) and again after solvent (n = 8), methylene blue (8 mg/kg i.v., n = 10), or N omega-nitro-L-arginine (40 mg/kg i.v., n = 8) in a randomized order. OA administration induced pulmonary hypertension, decreased arterial PO2, and increased intrapulmonary shunt. After OA, solvent had no effect on pulmonary hemodynamics and gas exchange. Both methylene blue and N omega-nitro-L-arginine further increased Ppa at all levels of Q. Only methylene blue, however, improved gas exchange after OA (arterial PO2 from 71 +/- 6 to 89 +/- 12 Torr and intrapulmonary shunt from 44 +/- 6 to 34 +/- 6%, both P < 0.02). These results suggest that nitric oxide is released during OA lung injury and modulates pulmonary hypertension. Whether nitric oxide impairs the regulation of gas exchange in OA lung injury remains uncertain, however.

Amino Acid Oxidoreductases↗
PubMed1993

Embolus size affects gas exchange in canine autologous blood clot pulmonary embolism.

Embolic pulmonary hypertension is associated with alterations in gas exchange of variable severity, which we hypothesized to be related to embolus size. We therefore examined the effects of different-size autologous blood clot embolization on pulmonary arterial pressure-cardiac output relationships (Ppa/Q) and on the distribution of ventilation-perfusion ratios (VA/Q) in 18 intact anesthetized and ventilated (inspired fraction of O2 0.4) dogs. Multipoint Ppa/Q plots were generated by a manipulation of venous return before and 60 min after sufficient amounts of small (1 mm, n = 6 dogs), medium (5 mm, n = 6 dogs), or large (10 mm, n = 6 dogs) clots to increase Ppa to 50 mmHg. The distribution of VA/Q was determined by the multiple inert gas elimination technique at the same intermediate Q in each of these experimental conditions. All three sizes of emboli resulted in an 82-92% mean angiographic pulmonary vascular obstruction and increased both the extrapolated pressure intercepts and the slopes of the linear Ppa/Q plots. Gas exchange was altered the most after large clots, which were associated with lower arterial pH, higher physiological and inert gas dead spaces, higher dispersion of ventilation, and also lower mean VA/Q of perfusion distributions. In contrast, inert gas dead space was decreased after small clots. We conclude that, in autologous blood clot embolic pulmonary hypertension, Ppa/Q characteristics are unaffected by embolus size but that gas exchange is affected differently, mainly in high-VA/Q regions and most often after the largest clots.

Angiography↗
PubMed1993

Mechanisms of improved arterial oxygenation after peripheral chemoreceptor stimulation during hypoxic exercise.

Almitrine, a peripheral chemoreceptor agonist, has been reported to increase arterial O2 saturation (SaO2) without changing minute ventilation (VE) during hypoxic exercise (Giesbrecht et al. J. Appl. Physiol. 70: 1770-1774, 1991). To explain this finding, we studied pulmonary hemodynamics (right heart catheterization) and gas exchange (multiple inert gas elimination technique) in six healthy volunteers at rest and during heavy exercise in normobaric normoxia (fractional concentration of O2 in inspired air 0.21) or hypoxia (fractional concentration of O2 in inspired air 0.125), before and after 75 mg of almitrine taken orally. During normoxic exercise, at a mean O2 uptake (VO2) of 4.0 l/min, almitrine increased arterial PO2 (PaO2) (P < 0.05), SaO2 (P < 0.01), and VE (P < 0.05) and decreased arterial PCO2 (P < 0.01), without affecting pulmonary hemodynamics or ventilation-perfusion distributions. During hypoxic exercise, at a mean VO2 of 3.0 l/min, almitrine increased SaO2 (P < 0.01) and VE (P < 0.01) and decreased arterial PCO2 (P < 0.05), with no effect on PaO2 or on ventilation-perfusion distributions and with a slight pulmonary vasoconstriction (P < 0.01). Almitrine during hypoxia did not affect cardiac output or calculated O2 diffusing capacity, but it did increase the slope of the VE/VO2 relationship (P < 0.01). We conclude that during hypoxic exercise, a pharmacological stimulation of the peripheral chemoreceptors improves SaO2 but not PaO2 by means of increased ventilation and an associated leftward shift of the oxyhemoglobin dissociation curve.

Adult↗
PubMed1993

Pulmonary vascular impedance vs. resistance in hypoxic and hyperoxic dogs: effects of propofol and isoflurane.

The pulmonary vascular effects of inhaled anesthetics have been reported variably. We compared the effects of intravenous anesthesia (propofol) and inhalational anesthesia (isoflurane) on multipoint mean [pulmonary arterial pressure (Ppa)-pulmonary arterial occluded pressure (PpaO)]/cardiac output (Q) plots and on pulmonary vascular impedance (PVZ) spectra in eight dogs alternatively ventilated in hyperoxia [inspired O2 fraction (FIO2) 0.4] and in hypoxia (FIO2 0.1). Q was altered by a manipulation of venous return. During propofol, hypoxia increased (Ppa-PpaO) by an average of 2-3 mmHg over the entire range of Q studied, from 1 to 2.5 l.min-1 x m-2. This hypoxic pulmonary vasoconstriction (HPV) was associated with insignificant changes in PVZ. Decreasing Q in hypoxia and hyperoxia did not affect PVZ. Compared with propofol, isoflurane decreased (Ppa-PpaO) by an average of 2-5 mmHg at all levels of Q studied in both hypoxia and hyperoxia but did not affect HPV. During isoflurane anesthesia, 0 Hz PVZ was lower (P < 0.01) in hypoxia, but otherwise the PVZ spectrum was not different from that recorded during propofol anesthesia. We conclude that, in dogs, 1 degree general anesthesia with isoflurane alone decreases pulmonary vascular tone without inhibition of HPV and that 2 degrees pressure/Q plots in the time domain are more sensitive than those in the frequency domain to subtle hemodynamic changes induced by hypoxia or isoflurane at the periphery of the pulmonary vasculature.

Anesthesia↗
PubMed1993

Medical treatment of pulmonary hypertension in acute lung disease.

A moderate pulmonary hypertension is a hallmark of experimental, as well as clinical, acute lung injury. Pulmonary hypertension in acute lung injury, appears to be caused primarily by a partially reversible increase in extra-alveolar vascular closing pressure, the latter being modulated by vasodilating products of the cyclooxygenase pathway of arachidonic acid metabolism, as well as by an endogenous release of nitric oxide. Gas exchange in acute lung injury is improved by increased pulmonary vascular tone. However it is also improved by inhaled nitric oxide, which increases perfusion to the better aerated lung areas. Whether pharmacological interventions aimed at the prevention of right ventricular failure in acute lung injury improve right ventriculo-vascular coupling sufficiently to exert a favourable influence on outcome, remains to be shown.

Animals↗
PubMed1992

Pulmonary circulation in hypoxia.

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. However, in the absence of high altitude pulmonary edema (HAPE) or chronic mountain sickness, a right heart failure that would be the human counterpart of brisket disease described in cattle, apparently never occurs. In adult patients with HAPE, reported mean pulmonary artery pressures (Ppa) measured during a right heart catheterization range from 22 to 63 mmHg with an average of 39 mmHg. Recent echo-Doppler estimates of systolic Ppa in patients with a HAPE are at an average of 53 mmHg, only moderately higher than in healthy subjects exposed to comparable normobaric or hypobaric hypoxia. Subjects with a previous HAPE often present with an enhanced pulmonary vascular reactivity to hypoxia compared to controls when tested at sea level, but the overlap is great. Non invasive echo-Doppler pulmonary hemodynamic studies at sea level have not been reported to reliably discriminate subjects susceptible to HAPE.

Altitude Sickness↗
PubMed1992

Stimulus-response curves for hypoxic pulmonary vasoconstriction in piglets.

OBJECTIVE: The aim was to characterise stimulus-response curves for hypoxic pulmonary vasoconstriction and to observe the effects of drugs reputed to enhance it: aspirin (a cyclo-oxygenase inhibitor), and doxapram (a peripheral chemoreceptor agonist). METHODS: Mean pulmonary artery pressure (Ppa) versus fraction of inspired O2 (FIO2) relationships were studied in 18 intact anaesthetised piglets, before and after the intravenous administration, in random order, of either physiological saline, 1 g aspirin, or 20 mg.kg-1 doxapram. Cardiac output (Q) was kept constant, to avoid passive Q dependent changes in Ppa. RESULTS: A progressive decrease in FIO2 from 100% to 12% was associated with an average increase in Ppa from 19 to 38 mm Hg (p < 0.001). When FIO2 was further decreased to 8%, Ppa decreased to 32 mm Hg (p < 0.01). This stimulus-response curve was unaffected by saline, but displaced in a non-PO2-dependent manner to higher Ppa by doxapram and by aspirin. CONCLUSIONS: The pulmonary vascular response to inspiratory hypoxia in intact anaesthetised piglets is biphasic, with a maximum at an FIO2 of 12%. Neither aspirin nor doxapram affect the shape of this stimulus-response curve, and in particular do not prevent low FIO2 associated inhibition of hypoxic pulmonary vasoconstriction.

Animals↗