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Biomedical subjects

E Vicaut

Publications and source records attributed to E Vicaut.

At least 91 records · Page 5Linked to original sources
PubMed1997

Risk factors for acute postoperative renal failure in thoracic or thoracoabdominal aortic surgery: a prospective study.

UNLABELLED: Acute postoperative renal failure is a common complication of thoracic aorta, thoracoabdominal aorta, or aortic arch surgery. To identify variables associated with acute postoperative renal failure, we prospectively studied 475 consecutive patients undergoing thoracoabdominal aortic surgery over a 12-yr period, including those requiring emergent surgery. One hundred twenty-one (25%) patients developed acute postoperative renal failure, and 39 (8%) required hemodialysis. Using multivariate analysis, acute postoperative renal failure was significantly associated with the following variables: age >50 yr (odds ratio [OR] 2.90 [95% confidence interval 1.52-5.53]), preoperative serum creatinine >120 micromol/L (OR 2.76 [1.70-4.48]), duration of left kidney ischemia >30 min (OR 2.01 [1.27-3.17]), packed red cells administration >5 units (OR 2.04 [1.24-3.37]), and Cell-Saver administration >5 units (OR 2.31 [1.34-1.96]). Reimplantation of visceral, renal arteries and the Adamkievicz artery; duration of visceral, spinal, and right kidney ischemia; requirement for fresh frozen plasma; administration of aprotinin; extracorporeal circulation; and procedures with circulatory arrest and profound hypothermia were not predictive of postoperative renal failure. In addition, age >50 yr (OR 5.59 [1.31-23.91]), requirement for packed red blood cells >5 unit (OR 3.91 [1.58-9.67]), and preoperative serum creatinine concentration >120 micromol/L (OR 2.26 [1.13-4.53]) were independent factors for acute renal failure requiring hemodialysis. In conclusion, acute renal failure is often observed after thoracic aortic surgery. Numerous predictive factors must be considered when evaluating the etiology of this complication. IMPLICATIONS: Acute postoperative renal insufficiency is a common complication of thoracic aortic surgery. This study found that age >50 yr, preoperative renal dysfunction, duration of renal ischemia, and amount of blood transfusion are significant predictors of this complication.

Acute Kidney Injury↗
PubMed1997

Mechanisms of coronary vasoconstriction induced by high arterial oxygen tension.

In isolated rabbit hearts perfused with suspension of red blood cells, we investigated the role of the endothelium and of several substances in the coronary vasoconstriction induced by a high arterial blood oxygen tension (PaO2). Red blood cells in Krebs-Henseleit buffer were oxygenated to obtain control and high-PaO2 perfusates. Arterial oxygen content was kept constant in both perfusates by reducing hemoglobin concentration in the high-PaO2 perfusate. Coronary blood flow was kept constant so that oxygen supply would not vary with the rise in PaO2. Increases in perfusion pressure therefore reflected increased coronary resistance. The high PaO2-induced coronary vasoconstriction was not affected by administration of indomethacin, nordihydroguaiaretic acid, NG-nitro-L-arginine, or superoxide dismutase and catalase but was abolished after endothelium damage or by cromakalim. These results demonstrate that 1) the endothelium contributes to the high PaO2-induced coronary vasoconstriction; 2) this effect is independent of cyclooxygenase or lipoxygenase products, nitric oxide, or free radicals; and 3) the closure of ATP-sensitive K+ channels mediates this vasoconstriction.

Adenosine Triphosphate↗
PubMed1997

Value of C-reactive protein in the detection of bacterial contamination at the time of presentation in drug-induced aspiration pneumonia.

STUDY OBJECTIVES: To compare the plasma concentration of C-reactive protein (CRP) with traditional markers for diagnosis of bacterial pneumonia in patients with suspected aspiration. DESIGN: Prospective, nonrandomized, controlled study of consecutive hospital admissions. SETTING: Toxicology ICU in a university hospital. PATIENTS OR PARTICIPANTS: Acutely poisoned comatose patients admitted to the hospital with suspicion of aspiration pneumonia. INTERVENTIONS: Distal protected catheter sampling per fiberoptic bronchoscopy and bacteriologic culture were employed as a standard to detect the bacterial component of suspected aspiration pneumonia. Plasma CRP concentrations, temperature, and WBC count were measured on hospital day 1. MEASUREMENTS AND RESULTS: Sixty-six patients were evaluated. Thirty-two had bacterial contamination by positive culture (> or =10(3) cfu/mL). Multiple receiver-operating characteristic (ROC) curves were used to compare each parameter for detection of infection secondary to aspiration. The ROC curve of CRP concentrations showed that a CRP >75 mg/L is associated with bacterial contamination with a sensitivity of 87%, specificity of 76%, positive predictive value of 78%, and negative predictive value of 87%. ROC curves of temperature and WBC count demonstrated poor diagnostic value of these markers in indicating the bacterial component of suspected aspiration pneumonia. CONCLUSIONS: Early measurement of CRP is useful for the diagnosis of aerobic bacterial content of aspiration pneumonia and perhaps in determining the need for invasive bacteriologic sampling. Temperature and WBC count are poor indicators of bacterial infection of aspiration pneumonia in poisoned patients.

Adult↗
PubMed1996

Therapeutic trial of diazepam versus placebo in acute chloroquine intoxications of moderate gravity.

OBJECTIVE: Acute chloroquine intoxication is responsible for a membrane-stabilising effect which results in electrocardiographic (ECG) and hemodynamic disturbances. Diazepam is used in acute chloroquine intoxication on the basis of clinical and experimental observations, but its utility alone, in man, remains unproven. The goal of this study was to verify whether diazepam alone has an effect on the membrane-stabilising effect observed in moderately severe chloroquine intoxications. DESIGN: Prospective, multi-center, double-blind, placebo-controlled study. SETTING: Prehospital mobile intensive care units (Paris) and hospital intensive care units (paris and Dakar). PATIENTS AND PARTICIPANTS: Adults with moderately severe intoxication defined as: a suspected ingested dose of 2 or more but less than 4 g, systolic blood pressure (SBP) higher than 80 mmHg, QRS duration less than 0.12 s and the absence of dysrhythmia at inclusion. INTERVENTIONS: Patients received either a loading dose of 0.5 mg/kg diazepam followed by an infusion of 1 mg/kg over 24 h or an equivalent volume of placebo. MEASUREMENTS AND RESULTS: Outcome was measured by serial assessments of SBP, ECG (QRS and QT segments) and clinical deterioration. There were no significant differences observed in the initial or serial ECG or SBP measurements. There were no deaths and no patient had to be removed from the study due to clinical deterioration. CONCLUSIONS: Diazepam, at the dose studied, does not appear to reverse the chloroquine-induced membrane-stabilising effect in acute moderately severe chloroquine intoxication. Supportive intensive care of these intoxications appears to be all that is necessary.

Acute Disease↗
PubMed1996

[Mechanisms of water exchanges: the Starling equation].

This review considers the main mathematical models used in the understanding of transvascular fluid exchanges and oedema formation. Models by Starling, Kedem-Katchalsky and Wiederhielm are briefly described. The main factors which determine the value of the physical parameters involved in these models are the osmotic and interstitial pressures in plasma and tissue. With regard to the regulation of interstitial osmotic pressure, the importance of the presence of mucopolysaccharidic gel in the interstitial compartment creating an exclusion volume for proteins diffusing from plasma is underlined, as well as the importance of lymphatic flow, a parameter neglected in several models of transcapillary exchanges. Consequences of variations in venous hydrostatic pressure, plasma oncotic pressure, endothelial permeability are discussed using the described models. In case of changes combining an increase in venous pressure and permeability and a decrease in plasma oncotic pressure, the importance of correcting venous pressure relatively to protein supply is discussed.

Blood Proteins↗
PubMed1996

Empiric use of flumazenil in comatose patients: limited applicability of criteria to define low risk.

STUDY OBJECTIVE: To develop clinical rules for the safe and effective use of flumazenil in suspected benzodiazepine overdose. METHODS: We assembled a retrospective series of 35 consecutive comatose patients admitted between October 1992 and July 1993 to a toxicologic ICU with the presumptive diagnosis of drug overdose. These patients were divided into two groups. Group A (low-risk) patients had a clinical picture compatible with uncomplicated benzodiazepine intoxication (calm, without abnormalities in pulse or blood pressure, lateralizing signs, hypertonia, hyperreflexia, or myoclonus) in the absence of predefined electrocardiographic or clinical signs of tricyclic antidepressant or other proconvulsant overdose, and absence of an available history of long-term benzodiazepine treatment or an underlying seizure disorder. Group B ("non-low risk") comprised all other patients. Efficacy of flumazenil was categorized as complete awakening (with normal level of alertness), partial awakening, or no change in alertness level. The safety of flumazenil was defined on the basis of the absence of seizures or death. RESULTS: In group A (n=4), flumazenil was associated with complete awakening in three patients and partial awakening in one. No seizures were observed. In group B (n=31), flumazenil was associated with complete awakening in 4 patients, partial awakening in 5, and no response in 22. In group B, five seizures occurred. CONCLUSION: Comatose patients with clinical or ECG criteria thought to contraindicate the use of flumazenil have a reasonably high risk of seizures after administration of this drug. Low-risk patients may be able to receive flumazenil safely, but they may be only a small portion of comatose patients with suspected overdose.

Adolescent↗
PubMed1996

Role of prostaglandins and nitric oxide on halothane-induced arteriolar dilatation in rat diaphragm.

The effects of anaesthetics on the microcirculation of the diaphragm are incompletely understood. Therefore, we assessed by in vivo intravital microscopy in rats the action of halothane on diaphragmatic arteriolar diameter and the role of nitric oxide and prostaglandins on halothane-induced diaphragmatic arteriolar diameter. We studied 54 rats anaesthetized with thiopentone. Dose-response curves to topically applied Krebs' solution saturated with halothane at increasing concentrations of 0%, 1%, 3% and 5% were carried out in the presence of an inhibitor of nitric oxide synthesis (N omega-nitro-L-arginine (LNA), 300 mumol litre-1) or inhibitors of prostaglandin synthesis (mefenamic acid 20 mumol litre-1 or indomethacin 20 mol litre-1) or in the absence of any inhibitor. We found dose-dependent arteriolar dilatation which was abolished by mefenamic acid and indomethacin. In contrast, the effect of halothane was not modified by LNA. These data demonstrated that halothane-induced arteriolar dilatation in the diaphragm of the rat was mediated by prostaglandins but not by nitric oxide.

Anesthetics, Inhalation↗
PubMed1996

Antihypertensive effects and arterial haemodynamic alterations during angiotensin converting enzyme inhibition.

OBJECTIVE: To assess the respective roles of the anti-hypertensive and blood pressure-independent effects of angiotensin converting enzyme (ACE) inhibition in the changed arterial haemodynamics observed in hypertensive patients with end-stage renal disease (ESRD) treated by haemodialysis. DESIGN AND METHODS: Twelve hypertensive patients with ESRD were included in a double-blind, cross-over study comparing a single 20 mg dose of the ACE inhibitor quinapril versus placebo. Two study periods each of 172 h duration were separated by a 2-week placebo period. Repeated measurements of the following parameters were performed: brachial artery systolic blood pressure (SBP); diastolic blood pressure and mean blood pressure (using a mercury sphygmomanometer); carotid artery SBP and pulse pressure (by applanation tonometry); aortic stiffness (by pulse wave velocity); and the effect of arterial wave reflections in the common carotid artery (the augmentation index, by applanation tonometry). A radioimmunoassay was used to determine plasma angiotensin II levels. Quinaprilat pharmacokinetics were studied using a specific assay. Two-way (time-treatment) analysis of variance for repeated measures, analysis of covariance for two within-factors and a covariate changing with the level of the factor time (pressures measured at each time) and baseline values of the studied parameter as a second covariate were used for statistical analysis. RESULTS: Quinapril treatment induced a long-lasting decrease in arterial wave reflections, which was still observable 172 h after quinapril administration and still present after removing the effect of the decrease in blood pressure. The effect on wave reflections was associated with a more pronounced and sustained decrease in carotid SBP and pulse pressure than that in brachial SBP and pulse pressure. Quinapril administration also induced a long-lasting decrease in aortic pulse wave velocity, but this effect was entirely dependent on parallel changes in blood pressure. Arterial haemodynamic changes were not related to plasma angiotensin II or quinaprilat levels. CONCLUSIONS: The results of this controlled study indicate that, in ESRD patients, ACE inhibition results in a long-lasting, blood pressure-independent decrease in arterial wave reflections. The consequence of this was a decrease in pulsatile pressure load in the central arteries with increased aortic distensibility. The increased aortic distensibility resulted from the decrease in blood pressure. The observed arterial haemodynamic alterations suggest that ACE inhibition induced alterations in arterial wave reflections in the distal parts of the arterial tree.

Adult↗
PubMed1996

Differences between cytokine effects in the microcirculation of the rat.

We studied by in vivo microscopy in rat cremaster muscle the acute and delayed effects of short exposure to tumor necrosis factor (TNF), interleukin (IL)-1 beta, and IL-6 on basal tone and vascular reactivity of second- to fourth-order arterioles (A2-A4). A 20-min exposure to recombinant human (rh) TNF (0.1-10 ng/ml) induced a significant arteriolar vasodilation, but no significant changes in basal tone were found after exposure to the same doses of IL-1 beta. In contrast, the same exposure to IL-6 (0.1-10 ng/ml) induced a significant dose-dependent vasoconstriction (i.e., 8, 15, and 21% at 10 ng/ml in A2-A4 arterioles, respectively). This vasoconstriction was inhibited by the thromboxane A2 receptor antagonist SQ-29548. We did not find any significant effect of rhTNF or IL-6 on vascular reactivity to norepinephrine immediately after exposure to these two cytokines or 100 min after the end of the exposure. Contrastingly, a large dose-dependent decrease in reactivity to norepinephrine was found immediately after exposure to IL-1 beta and still persisted 100 min after the end of the exposure. Such a decrease was not found for the vasoconstriction in response to KCl. We conclude that, at the microvascular level, large differences exist between the three cytokines generally considered to mediate the harmful cardiovascular effects in sepsis. 1) TNF but not IL-1 beta is responsible for a vasodilatory effect, whereas the effect of IL-6 is a thromboxane A2-mediated vasoconstriction. 2) Short exposure to IL-1 beta but not to rhTNF or IL-6 diminishes the response of the arterioles to norepinephrine but not to KCl.

Animals↗
PubMed1996

Effects of tumor necrosis factor and interleukin-1 on the constriction induced by angiotensin II in rat aorta.

To better understand the different steps in the changes occurring in vascular reactivity during sepsis, we studied the effects of a short exposure to tumor necrosis factor (TNF) and interleukin-1 (IL-1) on the contraction in response to angiotensin II (ANG II). The contraction elicited by ANG II was studied by using standard isometric tension techniques in aortic rings exposed for 1 h to 25 ng/ml TNF or to 5 or 20 ng/ml IL-1. This contraction was not significantly changed by TNF but was 109 +/- 23 and 190 +/- 38% greater than in control rings after 5 and 20 ng/ml IL-1, respectively. Because the contraction induced by ANG II is modulated by the simultaneous release of prostaglandins, we tested the hypothesis that IL-1 interferes with this modulation. We found that the IL-1-induced increase in contraction in response to ANG II was completely inhibited by 10(-5) M of the cyclooxygenase inhibitor indomethacin and also by 10(-5) M of the prostaglandin H2/thromboxane A2-receptor antagonist SQ-29548. Note, however, that in rings exposed to IL-1 the contraction in response to the thromboxane A2-receptor agonist U-46619 was not significantly different from the contraction in unexposed rings. Furthermore, no loss was observed in either the vasodilator response to 10(-9)-10(-4) M of the endothelium-dependent-receptor agonist acetylcholine or in the receptor-independent contraction induced by 60 mM K+. We conclude that short exposure to IL-1, but not to TNF, produces a specific increase in the vasoconstrictor response to ANG II via mechanisms mediated by prostaglandin H2/thromboxane A2. This increase might result from an IL-1-induced shift in favor of constrictor prostanoids in the balance of the dilator/constrictor prostanoids, the release of which is associated with stimulation by ANG II.

Acetylcholine↗
PubMed1996

Assessment of gastric mucosal perfusion during simulated hypovolemia in healthy volunteers.

We described here an original device for laser Doppler (LD) flowmetry measurements of gastric mucosal perfusion, which was used here in healthy volunteers. A modified nasogastric tube containing the LD probe was inserted. Aspiration via a catheter, fixed in parallel to the probe, held the probe against the gastric wall. This new device was used to assess gastric mucosal perfusion in seven volunteers during simulated hypovolemia induced by lower body negative pressure (LBNP) application. The LBNP consisted of three successive levels of depression (-10, -20, and -30 mm Hg). Although mean arterial pressure remained unchanged during negative pressure application, there was a significant decrease in cardiac output (transthoracic electrical impedance) at each stage of LBNP. In contrast, gastric mucosal perfusion decreased significantly only at higher level of sympathetic stimulation corresponding to unloading of both cardiopulmonary and arterial baroreflexes (-30 mm Hg). It may be hypothetized that local vascular mechanisms exist to maintain gastric mucosal perfusion during moderate sympathetic stimulation induced by selective unloading of cardiopulmonary receptors. In the healthy volunteers studied, we found that LD flowmetry is a valuable tool to evaluate gastric mucosal perfusion when the probe is maintained in a constant position by the technique described here.

Adult↗
PubMed1995

Hypokalaemia related to acute chloroquine ingestion.

Large doses of chloroquine can cause poisoning. Our aim was to determine the possible relation between the plasma potassium concentration on admission with the severity of acute chloroquine poisoning and to assess the mechanism of chloroquine-induced hypokalaemia. We conducted a retrospective study of 191 consecutive cases. The main data included the occurrence of vomiting before admission, plasma, and urinary potassium concentration at admission, whole blood chloroquine concentration on admission, haemodynamic parameters and ECG, administration of catecholamines and outcome. Mean blood chloroquine level was 20.1 mumol/L (SD 14.3) (therapeutic level < or = 6 mumol/L). Mean plasma potassium concentration was 3.0 mmol/L (0.8) and was lower in the subjects who died than in those who survived (p = 0.0003). Plasma potassium varied directly with the systolic blood pressure and inversely with the QRS and QT. Plasma potassium varied inversely with the blood chloroquine (p = 0.0001; tau = -0.42). Acute chloroquine intoxication is responsible for a hypokalaemia which correlates with the gravity of the intoxication and may be due to a transport-dependent mechanism. Plasma potassium concentrations should be carefully observed, particularly among patients who also receive catecholamine infusions. We should keep in mind, however, that overzealous repletion invokes the risk of subsequent hyperkalaemia and thus should be avoided.

Acute Disease↗
PubMed1995

Fibrinogen after coronary angioplasty as a risk factor for restenosis.

BACKGROUND: Fibrinogen is a risk factor for cardiovascular disease and is related to the severity of coronary atherosclerosis. Its role in restenosis after coronary angioplasty remains unknown. Although platelets and thrombosis contribute to the pathogenesis of restenosis, few clinical data are available concerning the relations between restenosis and proteins of the coagulation and fibrinolytic systems. METHODS AND RESULTS: In 107 consecutive patients undergoing coronary angioplasty, we measured plasma levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), von Willebrand factor, and fibrinogen before and immediately after angioplasty and at a 6-month follow-up. The individual changes of intraluminal diameter were measured by quantitative coronary angiography, and patients were classified according to four definitions of restenosis: (1) a final stenosis > 50%, (2) a loss of minimal luminal diameter during the follow-up period greater than the measurement variability in our laboratory (> 0.52 mm), (3) a loss of at least 50% of the gain in luminal diameter achieved by angioplasty, and (4) the combination of definitions 1 and 2. The relations between coagulation variables and each definition of restenosis were assessed univariately; then with the clinical variables included, the relations were analyzed multivariately. Angiographic follow-up was obtained in 92% of patients with a primary success of angioplasty. Global restenosis rates were 38%, 43%, 48%, and 30% for definitions 1 through 4, respectively. Plasma levels of t-PA antigen and PAI-1 antigen were not associated with any of the four definitions of restenosis. Multivariate analysis demonstrated that von Willebrand factor measured immediately after angioplasty predicted restenosis according to definitions 2 and 3. Fibrinogen measured within 6 months of follow-up was significantly increased in all restenosis groups of the four definitions. Patients with a fibrinogen concentration > 3.5 g/L at follow-up had higher restenosis rates than patients with a concentration < 3.5 g/L: 55% versus 22% (P = .001), 68% versus 31% (P = .002), 63% versus 37% (P = .01), and 74% versus 26% (P = .002) for definitions 1 through 4, respectively. The loss index was lower (P = .003) and the net gain higher (P = .03) in patients with a fibrinogen level < 3.5 g/L. There was a significant correlation between fibrinogen level and angiographic loss index (r = .41; P < .0001). Multivariate analysis confirmed that the fibrinogen level predicted restenosis with all definitions. CONCLUSIONS: An independent relation exists between von Willebrand factor measured immediately after angioplasty and restenosis defined by the degree of intraluminal renarrowing. An elevated fibrinogen level during follow-up is a strong biochemical predictor of restenosis. Therefore, fibrinogen should be considered at least as an independent marker of restenosis and perhaps as a common risk factor for both spontaneous coronary atherosclerosis and postangioplasty restenosis, which is an accelerated form of atherosclerosis.

Angioplasty, Balloon, Coronary↗
PubMed1995

Dose-response curves of inhaled nitric oxide with and without intravenous almitrine in nitric oxide-responding patients with acute respiratory distress syndrome.

BACKGROUND: Inhaled nitric oxide, a selective pulmonary vasodilator, in combination with intravenous almitrine, a selective pulmonary vasoconstrictor, markedly improves arterial oxygenation in 50-60% of patients with acute lung injury. The goal of this study was to assess dose response of inhaled nitric oxide with and without almitrine in patients with acute respiratory distress syndrome responding to nitric oxide. METHODS: Six critically ill patients (aged 44 +/- 7 yr) were studied during early stage of their acute respiratory failure (Murray score: 2.6 +/- 0.1). All responded to 15 parts per million (ppm) of inhaled nitric oxide by an increase in Pao2 of at least 40 mmHg at FIo2 1. Hemodynamic and respiratory parameters were recorded continuously from pulmonary artery and systemic catheters. Inspiratory, expiratory, and mean intratracheal nitric oxide concentrations were monitored continuously using a fast response time chemiluminescence apparatus (NOX 4000, Sérès, Aix-en-provence, France). On day 1, 6 inspiratory concentrations of nitric oxide were randomly administered: 0.15, 0.45, 1.5, 4.5, 15, and 45 ppm to determine the dose response of inhaled nitric oxide on Pao2, pulmonary shunt, mean pulmonary artery pressure, and pulmonary vascular resistance index. On day 2, a continuous intravenous infusion of almitrine at a dose of 16 micrograms.kg-1.min-1 was administered and dose response to inhaled nitrix oxide was repeated according to the same protocol as during day 1. A constant FIo2 of 0.85 was used throughout the study. RESULTS: Nitric oxide induced a dose-dependent increase in Pao2 for inspiratory nitric oxide concentrations ranging between 0.15 and 1.5 ppm. Almitrine increased Pao2/FIo2 from 161 +/- 30 to 251 +/- 45 mmHg (P < 0.001) and pulmonary vascular resistance index from 455 +/- 185 to 527 +/- 176 dyn.s.cm-5.m2 (P < 0.05), and decreased pulmonary shunt (Qs/QT) from 35 +/- 2 to 33 +/- 3% (P < 0.001). During almitrine combined with nitric oxide, a dose-dependent increase in Pao2 was observed for inspiratory nitric oxide concentrations ranging between 0.15 and 1.5 ppm. Almitrine plus nitric oxide 1.5 ppm increased Pao2/FIo2 from 161 +/- 30 to 355 +/- 36 mmHg (P < 0.001), decreased Qs/QT from 35 +/- 2 to 24 +/- 2% (P < 0.001), pulmonary vascular resistance index from 455 +/- 185 to 385 +/- 138 dyn.s.cm-5.m2 (P < 0.05), and mean pulmonary artery pressure from 31 +/- 4 to 28 +/- 4 mmHg (P < 0.001). CONCLUSIONS: In 6 patients with early acute respiratory distress syndrome and highly responsive to inhaled nitrix oxide, the administration of intravenous almitrine at a concentration of 16 micrograms.kg-1.min-1 induced an additional increase in Pao2. Dose response of nitric oxide was not changed by the administration of almitrine and a plateau effect was observed at inspiratory nitric oxide concentrations of 1.5 ppm.

Administration, Inhalation↗
PubMed1995

Leukocyte adherence in an ischemic muscle perfused by a collateral circulation.

Leukocyte adherence was studied in an original experiment that allowed study of the microcirculation in an ischemic muscle perfused by a collateral circulation. In this model, the artery feeding the cremaster muscle was ligated. Then the muscle homolateral to the ligation and its contralateral muscle were both studied by intra-vital-microscopy at 4 h, 1, 3, 7, and 21 days after the ligation. Rats were treated or not with 20 mg/kg/day pentoxifylline (PTX) i.m. In untreated rats, we found that both short-lasting and long-lasting leukocyte adherence was largely increased in the postcapillary venules of the ischemic muscle but not in its contralateral control. This dramatic increase was not limited to the hours immediately after the arterial ligation but was also found up to 3 weeks after the ligation when blood flow was almost restored to normal. This suggested that when muscle blood flow was chronically reduced, some changes promoting leukocyte adherence may occur in the endothelium. In rats treated with PTX, we found very effective inhibition of leukocyte adherence.

Animals↗
PubMed1995

Short exposure to endotoxin increases the constriction induced by angiotensin II in rat aorta.

The contraction elicited by angiotensin II (ANG II) was studied by using standard isometric tension techniques in aortic rings exposed for 1 h to 1 or 10 micrograms/ml Escherichia coli lipopolysaccharide endotoxin (LPS). This contraction was 18 and 71% greater for the two doses of LPS, respectively, than in unexposed control rings. In endothelium-denuded rings, the LPS-induced increase in contraction in response to ANG II was completely abolished. Because the contraction induced by ANG II is modulated by the simultaneous release of prostaglandins, we tested the hypothesis that LPS interferes with this modulation. We found that the LPS-induced increase in contraction to ANG II was inhibited in the presence of the cyclooxygenase inhibitor indomethacin (10(-5) M) or the prostaglandin H2/thromboxane A2-receptor antagonist SQ-29548 (2 x 10(-7) M). Conversely, the LPS-induced increase in contraction in response to ANG II was not inhibited by the presence of dexamethasone (10(-6) M), which inhibits new protein synthesis. In addition, there was no loss of vasodilator response to the endothelium-dependent receptor agonist acetylcholine (10(-8)-10(-4) M) or in the constrictor responses to norepinephrine (10(-9)-10(-5) M) and KCl (20-100 mM). We conclude that short exposure to LPS produces a specific increase in the constrictor response to ANG II via mechanisms mediated by prostaglandin H2/thromboxane A2. This effect could be a LPS-induced shift in favor of constrictor prostanoids in the balance of dilator/constrictor prostanoids, the release of which is associated with stimulation by ANG II.

Acetylcholine↗
PubMed1995

Opposite effects of red blood cell aggregation on resistance to blood flow.

We summarized the results of two series of independent experiments recently published by our group which studied the consequences of changes in red blood cell (RBC) aggregation on resistance to blood flow in vivo. The first series compared in vivo apparent viscosity in isolated hearts perfused by either normo-aggregating or non-aggregating RBC suspension. We showed that a moderate degree of RBC aggregation induces a significant decrease in apparent relative viscosity of a suspension of RBC when compared to a non-aggregating RBC suspension. The second series studied the effects of normo vs. hyperaggregation in muscle microvascular network. We showed that hyperaggregation of RBC is responsible for a decrease in arteriolar blood flow velocity and for a decrease in density of perfused capillaries. This latter induces an additional increase in the resistance to blood flow and may also have important deleterious consequences for tissue oxygenation. From these two series of experiments, we concluded that RBC aggregation can have two opposite effects on in vivo viscosity and tissue perfusion. A moderate level of RBC aggregation reduces in vivo viscosity whereas a high level of aggregation increases this viscosity and the resistance to blood flow. We believe that the normo-aggregating state is approximately an equilibrium point between these two tendencies. Consequently, RBC hyperaggregation induced either by acute pathological states, or by use of hyperaggregating plasma substitutes or by biological disturbances which increase RBC aggregation, such as high fibrinogen may have important deleterious consequences for tissue perfusion and tissue oxygenation.

Animals↗