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Biomedical subjects

D R Morel

Publications and source records attributed to D R Morel.

At least 19 recordsLinked to original sources
PubMed2003

Somato-sympathetic vasoconstriction to intranasal fluid administration with consecutive decrease in nasal nitric oxide.

AIM: Patients suffering from non-allergic chronic rhinosinusitis (NACRS) increasingly use intranasal saline sprays. They report better nasal comfort. METHODS: In order to better understand this phenomenon, we studied intranasal laser Doppler flowmetry (LDF) and nasal nitric oxide (NO) variations evoked by local administration of saline, histamine, N-acetylcysteine (NAC) and lidocaine at room temperature (22 degrees C). RESULTS: There was a significant (P < 0.05) 14 +/- 3.8% decrease in LDF signal after 30 s, which lasted for 60-90 s, for all the substances applied at 22 degrees C. This pharmaco-independent vasoconstriction was further studied in patients under general anaesthesia (GA), with saline at 37 degrees C and after intranasal adrenaline treatment. While GA did not influence the vasoconstriction, saline at 37 degrees C and adrenaline pre-treatment abolished it. Nasal NO is influenced by vasoconstriction. Therefore we investigated, whether the observed vasoconstriction also changes nasal NO. A significant (P < 0.001) 8.03 +/- 0.59% decrease in nasal NO was recorded 60 s after administration of all the substances, and under GA after 22 degrees C saline application. This NO decrease was absent after intranasal adrenaline pre-treatment. An additional experiment tested the effect of nose blowing on nasal NO concentration. We registered an NO decrease with a similar pattern than observed with the other substances. CONCLUSIONS: Intranasal fluid nebulization at 22 degrees C induces a sympathetic mediated, transient vasoconstrictor reflex response. This somato-sympathetic vasoconstriction induces a decrease in nasal NO. Both could be related to the subjective comfort experienced by NACRS patients using intranasal saline sprays.

Acetylcysteine↗
PubMed2003

Hemodynamics induced after acute reduction of proximal thoracic aorta compliance.

OBJECTIVE: to investigate the affect of reduced aortic compliance on cardiovascular hemodynamics. MATERIALS AND METHOD: fourteen Yucatan miniature swine were divided into two equal groups, a Sham Operated Group and a Banding Group. A Teflon prosthesis was wrapped around the aortic arc in order to limit proximal aortic compliance (Banding Group). Data were recorded operatively (after implantation of a pressure sensor and a flow probe in the ascending aorta), after banding (only in the Banding Group) and at 2 days postoperatively. RESULTS: after banding, compliance decreased by 52 +/- 13% ((-)X +/- SEM) (p < 0.01) while systolic and pulse pressure increased by 37 +/- 8% (p < 0.05) and 87 +/- 31% (p < 0.01), respectively. Diastolic pressure, mean blood pressure, cardiac output and systemic vascular resistance did not change significantly. Aortic characteristic impedance increased nearly 2.5 times. Amplitudes of forward and reflected pressure waves (derived from the aortic pressure wave) increased by 96 +/- 41% and 174 +/- 46%, respectively (p < 0.05), while the time delay between the two decreased by 36 +/- 7% (p < 0.05). CONCLUSIONS: about half of the total arterial compliance is located in the proximal thoracic aorta. Arterial reconstruction of the proximal aorta with a non-compliant graft results in a significant decrease in systemic arterial compliance, which in turn increases systolic and pulse pressure. The development of more compliant prosthesis, which matches the host artery compliance, is expected to reduce the hemodynamic changes induced after their implantation.

Animals↗
PubMed2001

Modulatory effect of two novel CGRP receptor antagonists on nasal vasodilatatory responses to exogenous CGRP, capsaicin, bradykinin and histamine in anaesthetised pigs.

Calcitonin gene-related peptide (CGRP) is a 37-amino acid peptide and potent vasodilatator agent located in sensory C fibres. Several functional studies suggest that CGRP could be involved in the vasodilatation of different vascular beds during neurogenic inflammation. We have studied, in pentobarbital anaesthetised pigs, the antagonistic effect of local intra-arterial (i.a.) pretreatment with the analogues CGRP 8-37, [D31, P34, F35]CGRP 27-37 and [N31, P34, F35]CGRP 27-37 on the vasodilatation of the nasal vascular bed induced by exogenous CGRP, capsaicin, bradykinin (BK) and histamine. The attenuating effect of CGRP 8-37 analogue on exogenous CGRP-induced vasodilatation, previously described in other in vivo animal models, was confirmed in the pig nasal mucosa. It also interfered with BK-and, to a lesser extent, with capsaicin-and histamine-induced decrease in vascular resistance. CGRP 27-37 analogues reduced the duration of CGRP-, capsaicin- and BK-induced vasodilatation by more than 50%. Peak values of vasodilatation were attenuated by more than 25% overall. Attenuation of histamine-induced decrease in vascular resistance was less pronounced. It is concluded that CGRP 27-37 analogues antagonise the action of exogenous CGRP, capsaicin, BK and histamine by attenuating their vasodilatation effect, both in intensity and duration. These results strongly suggest that BK- and histamine-induced vasodilatation is partly mediated by CGRP. CGRP 8-37 and 27-37 appear to be potential contributors to the study of CGRP and its physiological role in neurogenic inflammation. In addition, they may have putative therapeutic applications in the treatment of rhinitic patients suffering from chronic nasal obstruction.

Anesthesia↗
PubMed2001

Protective effects of volatile agents against methacholine-induced bronchoconstriction in rats.

BACKGROUND: The protective properties of common volatile agents against generalized lung constriction have previously been addressed only via estimations of parameters that combine airway and tissue mechanics. Their effectiveness in preventing airway constriction have not been compared systematically. Therefore, the authors investigated the abilities of halothane, isoflurane, sevoflurane, and desflurane to provide protection against airway constriction induced by methacholine. METHODS: Low-frequency pulmonary impedance data were collected in open-chest rats under baseline conditions and during three consecutive intravenous infusions of methacholine (32 microg x kg(-1) x min(-1)) while the animals were anesthetized with intravenous pentobarbital (control group). Methacholine challenges were performed in four other groups of rats, first during intravenous anesthesia and then repeated during the inhalation of halothane, isoflurane, sevoflurane, or desflurane at concentrations of 1 and 2 minimum alveolar concentration (MAC). Airway resistance and inertance, parenchymal damping, and elastance were estimated from the impedance data by model fitting. RESULTS: The methacholine-induced increases in airway resistance during intravenous pentobarbital anesthesia (204 +/- 53%) were markedly and significantly (P < 0.005) reduced by 1-MAC doses of halothane (80 +/- 48%), isoflurane (112 +/- 59%), sevoflurane (68 +/- 34%), and desflurane (96 +/- 34%), with no significant difference between the gases applied. Increasing the concentration to 2 MAC did not lead to any significant further protection against the increase in airway resistance. CONCLUSIONS: These data demonstrate that isoflurane, sevoflurane, and desflurane are as effective as the widely accepted halothane in protecting against methacholine-induced airway constriction.

Anesthetics, Inhalation↗
PubMed2001

Effects of abdominal Co2 insufflation on renal and hepatic blood flows during acute hemorrhage in anesthetized pigs.

OBJECTIVE: To evaluate the consequences of laparoscopy during hemorrhage, we studied the respiratory, renal, and hepatic blood flow changes induced by abdominal Co2 insufflation during severe hemorrhage in anesthetized pigs. DESIGN: Prospective animal study. SETTING: University research laboratory. SUBJECTS: Anesthetized and ventilated pigs (n = 18). INTERVENTIONS: The right carotid artery was cannulated to measure mean arterial pressure. A pulmonary artery catheter was inserted to measure mean pulmonary arterial pressure and cardiac output. After a midline abdominal incision, three flow probes were positioned around the portal vein, the hepatic artery, and the renal artery to measure portal vein blood flow, hepatic artery blood flow, and renal blood flow. To induce hemorrhage, blood was withdrawn until mean arterial pressure reached 50 mm Hg. Laparoscopy was mimicked by insufflating Co2 until intra-abdominal pressure reached approximately 15 mm Hg. Measurements were collected during hemorrhage, Co2 abdominal insufflation, and the combination of both interventions. MEASUREMENTS AND MAIN RESULTS: Severe pulmonary hypertension and hypercapnic acidosis occurred during abdominal Co2 insufflation. However, the abdominal Co2 insufflation did not aggravate the cardiac output and total hepatic blood flow changes induced by acute hemorrhage, whereas the combination of hemorrhage and abdominal Co2 insufflation markedly altered renal blood flow. CONCLUSIONS: These results suggest that renal function must be monitored carefully when performing laparoscopy in trauma patients. In contrast, hepatic perfusion seems well preserved.

Analysis of Variance↗
PubMed2000

Matrix metalloproteinases correlate with alveolar-capillary permeability alteration in lung ischemia-reperfusion injury.

BACKGROUND: Matrix metalloproteinases (MMPs) are able to degrade the endothelial basal lamina and increase vascular permeability. METHODS: In a porcine model of isolated-reperfused lung, we studied the alveolar-capillary permeability and the zymographic expression of MMP-9 and MMP-2 in the bronchoalveolar lavage fluid of lungs submitted ex vivo to ischemia in three preservation solutions [modified Euro-Collins (EC), low-potassium-dextran, modified-blood]. Twenty-two pigs were randomly divided into three groups according to the preservation solution used. One lung of each pig was rapidly reperfused and analyzed (control lung) although the other lung was reperfused and analyzed after 8 hr of ischemia (ischemic lung). RESULTS: Alveolar-capillary permeability, evaluated by the transferrin leak index, was increased after 8 hr of ischemia compared with controls in the three groups, but was significantly higher in the modified EC group. In the EC group, after 8 hr of ischemia, both proMMP-9 and MMP-9 increased significantly (8.8- and 22-fold, respectively) compared with controls and this increase correlated with the transferrin leak index. Neither proMMP-9 nor MMP-9 increased with the other two preservation solutions. The MMP-2 increase after ischemia was smaller and was also restricted to the EC group. CONCLUSION: MMP expression is enhanced during lung ischemia-reperfusion, especially in the presence of EC and this phenomenon correlates with the alteration of alveolar-capillary permeability.

Animals↗
PubMed2000

Hepatic haemodynamic changes following inhibition of endothelium-derived relaxing and hyperpolarising factors in anaesthetised miniature pigs.

The influence of endothelium-dependent vasodilatation in regulating the hepatic circulation has been investigated by intraportal infusion of inhibitors of either endothelium-derived relaxing factor (NG-nitro-L-arginine-methyl-ester [L-NAME]) or of endothelium-derived hyperpolarising factor (ATP-dependent K(+)-channel inhibitor, glybenclamide) in barbiturate anaesthetised miniature pigs. Intraportal infusion of acetylcholine (5.5 micrograms kg-1 min-1 over 2 min) produced a selective 3-fold increase in hepatic artery and coeliac trunk blood flow, while mesenteric, portal, systemic, and pulmonary vascular beds remained unchanged. Intraportal L-NAME or glybenclamide did not reduce the hepatic artery and coeliac trunk flows but increased systemic and mesenteric vascular resistances. The acetylcholine-induced hepatic artery vasodilatation was partially blocked by 59%, 76% and 66% by L-NAME, at 30, 100, and 300 mg/kg respectively. Glybenclamide pretreatment up to 3 mg/kg did not modify acetylcholine-induced vasodilatation of the hepatic artery and coeliac trunk. Furthermore, prior cyclooxygenase inhibition did not alter the hepatic vascular response to acetylcholine. These results suggest that, in contrast to what is observed in large vessels, the hepatic vascular tree may not be entirely regulated by nitric oxide under basal conditions, but nitric oxide is released readily upon stimulation with acetylcholine, a response that is largely but incompletely blocked by L-NAME pretreatment. Neither basal vascular tone nor acetylcholine-induced vasorelaxation are mediated by the opening of glybenclamide-sensitive K+ channels in the hepatic circulation in pigs.

Acetylcholine↗
PubMed2000

Cardiovascular responses to anesthetic induction in patients chronically treated with angiotensin-converting enzyme inhibitors.

PURPOSE: To investigate the effects of chronic ACE inhibition on cardiac neural function following induction of general anesthesia in patients with underlying coronary artery disease. METHOD: In a prospective case-control study, heart rate variability (HRV) and baroreflex control were compared preoperatively and 30 min after anesthesia induction in patients receiving, or not, ACEI (n=16, control group and n=16, ACEI group). All patients had normal cardiac function and anesthesia consisted of a fixed dose regimen of fentanyl and midazolam. Anesthesia-related hypotension was defined by systolic blood pressure < 90 mmHg. Spectral density of HRV was calculated for low frequency and high frequency bands (LF, from 0.05 to 0.15 Hz and HF, from > 0.15 to 0.6 Hz). Baroreflex sensitivity was estimated after blood pressure changes induced by injections of phenylephrine (PHE) and nitroglycerin (NTG). RESULTS: The HRV parameters and baroreflex sensitivity were not different between groups, during the awake and anesthesia periods. Anesthesia produced similar reduction in total HRV in the Control and ACEI groups (-93 +/- 28% vs -89 +/- 32%), and in baroreflex sensitivity during NTG (-64 +/- 21% vs -54 +/- 17%) or PHE tests (-74 +/- 25% vs -72 +/- 22%). Anesthesia-related hypotension occurred in nine patients in the ACEI group (vs two controls). Although the hypertensive response to phenylephrine was greater after anesthesia in both groups, the sensitivity to phenylephrine was attenuated in those patients experiencing hypotension in the ACEI group. CONCLUSIONS: Chronic preoperative treatment with ACEIs does not influence cardiac autonomic regulation and anesthetic-induced hypotensive episodes are mainly attributed to decreased alpha-adrenergic vasoconstrictive response.

Aged↗
PubMed2000

Postoperative fatal intestinal necrosis after enalapril treatment in a patient with rheumatoid arthritis.

The inappropriate use of antihypertensive medications may cause hypotensive responses associated with organ failure. We describe a patient who developed nonocclusive splanchnic ischemia leading to death following the administration of enalapril to treat postoperative hypertension. The mechanisms and consequences of refractory hypotension induced by angiotensin-converting enzyme inhibitors are discussed.

Aged↗
PubMed2000

Aprotinin does not impair renal haemodynamics and function after cardiac surgery.

Patients undergoing cardiac surgery with moderate hypothermic cardiopulmonary bypass (CPB) were allocated randomly to receive either saline (control group, n = 29) or a high-dose regimen of aprotinin (aprotinin group, n = 28). In both groups, CPB was associated with similar and transient increases in effective renal plasma flow (+54% in controls and +48% in aprotinin-treated patients) and in fractional excretion of sodium and potassium, but glomerular filtration rate remained unchanged. Plasma and urinary ratios of 6-keto-PGF1 alpha to thromboxane B2 (TxB2) increased significantly, indicating systemic and renal release of vasodilatory prostaglandins. Osmolar clearance correlated with urinary excretion of cyclic GMP (r = 0.79 and 0.86 in the control and aprotinin groups, respectively) and 6-keto-PGF1 alpha (r = 0.63 and 0.69 in the control and aprotinin groups, respectively). Compared with preoperative values, plasma atrial natriuretic peptide increased after weaning from CPB (+71% and +93% in the control and aprotinin groups, respectively). Aprotinin had no apparent adverse effect on renal function and it did not alter mechanisms involving prostanoids and atrial natriuretic peptide during cardiac surgery.

6-Ketoprostaglandin F1 alpha↗
PubMed2000

Spontaneous high systemic oxygen delivery increases survival rate in awake sheep during sustained endotoxemia.

OBJECTIVE: To study the natural evolution of systemic oxygen delivery (Do2) and oxygen consumption (Vo2) in sheep infused with low or high doses of endotoxin. DESIGN: Prospective, controlled experimental study. SETTING: Animal research laboratory at a medical university. SUBJECTS: Twenty-nine chronically instrumented awake sheep (25-35 kg). INTERVENTIONS: Awake animals were continuously infused with saline (n = 8) or two doses of Escherichia coli endotoxin (20 or 40 ng/kg/min; n = 21) for 72 hrs. No attempt was made to increase Do2, but respiratory failure was treated by mechanical ventilation and metabolic acidosis was corrected. MEASUREMENTS AND MAIN RESULTS: The mortality rate was 25% in the group infused with the low dose and 89% in the group infused with the high dose of endotoxin. During the first 12 hrs of endotoxemia, both surviving (S group; n = 10) and nonsurviving (NS group; n = 11) sheep developed similar pulmonary hypertension, left ventricular failure, and hypotension with low systemic vascular resistance. However, S sheep had less interstitial lung edema (pulmonary lymph protein clearance at 8 hrs was 13+/-3 mL/hr vs. 27+/-6 mL/hr in the NS group and 4+/-1 mL/hr in the control group). During this early phase of endotoxemia, Do2, Vo2, and oxygen extraction ratio did not change significantly in any group. After this phase, animals that ultimately survived had a persistent hyperdynamic syndrome with high cardiac output and hypotension. In this group, the Do2 increase was greater than the Do2 measured in controls and remained steady up to 48 hrs after the start of the endotoxin infusion. Because systemic Vo2 did not change significantly, oxygen extraction ratio decreased progressively to values less than those measured in controls. In contrast, animals that ultimately died had a hypotensive and normokinetic syndrome associated with pulmonary hypertension, persistent depressed left ventricular function, hypothermia, and a progressive deterioration of gas exchange. Systemic Do2 was not significantly different from that in the control group. In contrast, Vo2 decreased progressively to values significantly lower than those measured in controls and remained low until death. CONCLUSIONS: Our results indicate that in the absence of treatment such as fluid challenge or inotropic drugs in sheep infused with endotoxin, the occurrence of spontaneous hyperdynamic syndrome and high Do2 improves the survival rate.

Acidosis↗
PubMed2000

Human pharmacokinetics and safety evaluation of SonoVue, a new contrast agent for ultrasound imaging.

RATIONALE AND OBJECTIVES: To assess in humans the pharmacokinetics of SonoVue, a new echo contrast agent based on stabilized sulfur hexafluoride (SF6) microbubbles and to provide additional safety and tolerability information on the compound. METHODS: The blood kinetics and pulmonary elimination of SF6 after intravenous bolus injection of two dosage levels (0.03 and 0.3 mL/kg) of SonoVue were evaluated in 12 healthy subjects (7 men, 5 women). In addition, safety and tolerability were evaluated by monitoring vital signs, adverse effects, discomfort, and physical examination and laboratory parameters associated with the SonoVue injection. RESULTS: The blood kinetics of SF6 was not dose dependent. SF6 was rapidly removed from the blood by the pulmonary route, with 40% to 50% of the injected dose eliminated within the first minute after administration and 80% to 90% eliminated by 11 minutes after administration; the elimination was similar in men and women and independent of dose. Both dosages were well tolerated. No adverse effects were observed immediately or during the 24-hour follow-up period. CONCLUSIONS: SonoVue was shown to be rapidly removed from the blood. The route of SF6 elimination was by means of the lungs in the expired air. SonoVue appeared to be safe and well tolerated in healthy subjects.

Adult↗
PubMed1999

Effect of transient ischemia on the expression of glucose transporters GLUT-1 and GLUT-4 in rat myocardium.

A number of observations indicate that myocardial glucose utilization is increased late during post-ischemic reperfusion. The present study was designed to examine whether transient ischemia elicits altered expression of glucose transporters GLUT-1 and GLUT-4. In rats, the left anterior descending coronary artery was occluded for 20 min followed by reperfusion for 1, 3 or 7 days. Regional myocardial uptake and phosphorylation of glucose was determined based on myocardial accumulation of 2-deoxy-D-[2, 6-3H]glucose-6-phosphate. In hearts from fasted rats, after 3 days of reperfusion, myocardial uptake and phosphorylation of glucose was 48% higher in the reperfused region compared to a remote control region. No regional difference in myocardial glucose uptake and phosphorylation was detectable in hearts from fed rats. After 1 day of reperfusion, expression of myocardial glucose transporter GLUT-1 mRNA was increased to 195+/-24% (mean+/-SEM) of the value measured in the remote region and the expression of GLUT-4 mRNA was decreased to 58+/-7%. After 3 days of reperfusion both mRNA and protein of GLUT-1 were higher in the reperfused region, averaging 133+/-23% and 249+/-36%, respectively. The corresponding values for GLUT-4 mRNA and protein were 77+/-7% and 62+/-6%, respectively. The results indicate that a short period of ischemia alters the expression of glucose transporter isoforms GLUT-1 and GLUT-4. Observed changes may be involved in the mechanisms underlying late changes of substrate metabolism during reperfusion.

Acute Disease↗
PubMed1999

Chronic angiotensin converting inhibition does not influence renal hemodynamic and function during cardiac surgery.

PURPOSE: Treatment with angiotensin-converting enzyme (ACE) inhibitors affects the autoregulation of renal blood flow and glomerular filtration and provides renal protective effects. The purpose of this case-control study was to investigate the effects of chronic ACE inhibition on perioperative renal hemodynamics and function. METHOD: We prospectively studied renal function in two groups of patients, chronically treated or not, with ACE inhibitors (ACEI and control; n = 16, in each group) who underwent elective cardiac surgery under hypothermic cardiopulmonary bypass. Glomerular filtration rate, effective renal plasma flow, osmolar clearance and fractional excretion of sodium and potassium were determined before, during and after CPB. Additional measurements included plasma atrial natriuretic factor (ANF) as well as plasma and urinary cyclic GMP (cGMP), thromboxane B2 (TxB2) and 6-keto-PGF1. RESULTS: Renal functional and hemodynamic variables did not differ between the two groups, at any period. Cardiopulmonary bypass induced increases in urinary flow, osmolar clearance and fractional excretion of sodium and potassium in both groups. Plasma and urinary ratio of 6-keto-PGF to TxB2 increased markedly and reflected a predominant systemic and renal release of vasodilatory prostaglandins. Intraoperatively, ANF was higher in ACEIs than in control patients. CONCLUSIONS: Long term treatment with ACE inhibitors does not influence the perioperative changes in renal hemodynamics and function. During cardiopulmonary bypass, a transient impairment in solute reabsorption is associated with renal release of vasodilatory mediators (nitric oxide and prostacyclin).

Aged↗
PubMed1999

Influence of TASP-V, a novel neuropeptide Y (NPY) Y2 agonist, on nasal and bronchial responses evoked by histamine in anaesthetized pigs and in humans.

1. In nine anaesthetized pigs we have studied the influence of intranasal or intrabronchial pretreatment with TASP-V, a neuropeptide Y (NPY) Y2 agonist formed by the attachment of NPY 21-36 to a template-assembled synthetic peptide (TASP), on the functional responses to subsequent intranasal or intrabronchial histamine challenge. 2. In a parallel study, subjective and objective nasal airway resistance (NAR) increase following intranasal histamine challenge was evaluated in 11 healthy volunteers after TASP-V or placebo pretreatment. 3. In pigs, increase in sphenopalatine blood flow induced by histamine dihydrochloride nasal spray (0.25 mg kg(-1) in 3 ml of saline) was significantly reduced by 65% (P<0.05) following intranasal pretreatment with 10 microg kg(-1) of TASP-V. Bronchoconstriction induced by histamine dihydrochloride nebulization (0.5 mg kg(-1) in 3 ml of saline) was significantly attenuated by 25 and 55% following aerosolized pretreatment with TASP-V analogue at 10 and 20 microg kg(-1), respectively. 4. In healthy volunteers, objective increase in NAR and reduction in nasal minimal cross section area (MCSA) induced by intranasal spray of histamine dihydrochloride (15 microg kg(-1) in 200 microl of saline) were significantly attenuated by 50% following local pretreatment with 1.275 microg kg(-1) of TASP-V when compared with saline. 5. It is concluded that intranasal or intrabronchial pretreatment with TASP-V reduced nasal obstruction and bronchoconstriction evoked by histamine challenge in the pig. In healthy human volunteers, this agent attenuated NAR increase and MCSA reduction induced by intranasal application of histamine.

Adult↗
PubMed1999

Beneficial effects of leukocyte-depleted blood and low-potassium dextran solutions on microvascular permeability in preserved porcine lung.

Modified Euro-Collins (EC) solution, a crystalloid intracellular-type solution, has been commonly used for pulmonary preservation. Several experimental studies have shown the advantages of using extracellular colloid-based solutions. The aim of this study was to compare the quality of preservation of two extracellular colloid solutions, leukocyte-depleted blood (BL) and low-potassium dextran (LPD) solutions, with that of EC solution. Lungs of 22 domestic pigs were flushed and preserved with EC (n = 8), BL (n = 7), or LPD (n = 7) solution. After harvesting, one of the lungs was reperfused immediately in an ex vivo circuit (control lungs), whereas the contralateral lung was reperfused after 8 h of cold (4 degrees C) storage (preserved lungs). Besides the lung function parameters (gas exchange, pulmonary hemodynamics and mechanics), the permeability of the endothelial-epithelial barrier was assessed by determining the transferrin leak index (TLI) using a double radioisotopic method, by measuring the alveolar/arterial protein concentration ratio, and by analyzing histopathologic changes. The functional quality (oxygenation, airway resistance, dynamic compliance [CL, dyn]) of both BL and LPD lungs was slightly but significantly superior to that of EC lungs. However, pulmonary vascular resistance was lower in BL-preserved than in EC- or LPD-preserved lungs. The TLI was increased in EC control and preserved lungs, whereas it was low in BL and LPD control lungs and did not increase after preservation. The alveolar/arterial protein concentration ratio was not different between control groups, but was increased fourfold in EC-preserved compared with BL- or LPD-preserved lungs. Finally, EC-preserved lungs presented a weight gain about twice that of BL- and LPD-preserved lungs. Morphologic analysis confirmed these results, because in the EC-preserved lungs, rupture of alveolar septa and severe alveolar edema and hemorrhage were observed, whereas BL- and LPD-preserved lungs showed a relatively well-preserved structure. The results demonstrate that both BL and LPD flush solutions preserve the endothelial-epithelial barrier better than does EC solution. Although the quality of preservation is similar, pulmonary vascular resistance is higher in LPD-preserved than in BL-preserved lungs.

Animals↗
PubMed1998

Effects of fenoldopam on systemic and splanchnic haemodynamics and oxygen delivery/consumption relationship during hyperdynamic ovine endotoxaemia.

OBJECTIVE: To evaluate the use of a selective dopamine-1 agonist (fenoldopam) to provide selective splanchnic vasodilatation during sustained hypotensive endotoxaemia in sheep. DESIGN: Randomised, controlled, experimental study. SETTING: Animal research laboratory. SUBJECTS: 12 adult instrumented, midazolam-sedated sheep. INTERVENTIONS: The animals were randomised to receive a 20-min continuous infusion of dopamine (10 microg x kg(-1) x min(-1), fenoldopam (10 microg x kg(-1) x min(-1) and noradrenaline (1 microg x kg(-1) x min(-1)) under control conditions and 12 h after endotoxaemia was induced by a continuous infusion of Escherichia coli endotoxin producing a stable hyperdynamic state simulating human septic shock. This drug dosage was selected to produce a 25-30% increase in cardiac output by all three drugs during control conditions. MEASUREMENTS AND RESULTS: Systemic and splanchnic haemodynamic data were continuously obtained and systemic and splanchnic oxygen delivery (DO2) and consumption (VO2) were calculated. Hyperdynamic hypotensive endotoxaemia did not modify the splanchnic and renal reduction in DO2 and the vasoconstrictive reactivity to noradrenaline observed during control conditions. In contrast, endotoxaemia abolished the fenoldopam and dopamine-induced increase in splanchnic DO2 (especially in the coeliac trunk) observed during control conditions. CONCLUSIONS: During sustained hyperdynamic endotoxaemia, the dopaminergic-induced selective increase in coeliac trunk blood flow is abolished, most probably because of an already maximally vasodilated splanchnic circulation which prevented dopamine or fenoldopam to vasodilate this area further. Contrary to common belief, selective dopamine-1 agonist administration under these conditions may therefore not be beneficial to the splanchnic organs, though it improves whole body DO2 and VO2.

Animals↗