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Biomedical subjects

E Vicaut

Publications and source records attributed to E Vicaut.

At least 109 records · Page 6Linked to original sources
PubMed1995

Duration of inhibition of local microvascular ACE in spontaneously hypertensive rats.

OBJECTIVE: To investigate in vivo the duration of inhibition of local angiotensin converting enzyme (ACE) in the microcirculation after a 2-week oral treatment by three different ACE inhibitors. DESIGN: The local renin-angiotensin system was studied in the microcirculation of cremaster muscle in spontaneously hypertensive rats treated by gavage with equihypotensive doses of trandolapril (0.6 mg/kg per day), enalapril (10 mg/kg per day) and perindopril (2 mg/kg per day) for 2 weeks. Intravital microscopy was used in an original preparation of cremaster isolated from its normal blood supply and externally perfused with physiological solution, allowing exclusion of the circulating converting enzyme. Local ACE activity was estimated by measuring vasoconstriction in response to 0.01 and 0.1 nmol/ml angiotensin I in the arterioles studied and classified as being of second, third and fourth order (mean diameters 58 +/- 6, 30 +/- 4 and 15 +/- 1 mu m for the three orders, respectively). RESULTS: No difference among the ACE inhibitors was found 3 h after the last dose. Conversely at 7, 24 and 48 h after the last dose, a significant difference was found among the ACE inhibitors, with ACE inhibitors being higher in rats treated with trandolapril than in the other two groups. In addition, a comparison with untreated spontaneously hypertensive rats showed that significant inhibition persisted 48 h after the last dose for trandolapril- and perindopril- but not enalapril-treated rats. CONCLUSION: Large differences exist between the duration of inhibition of the microvascular ACE in vivo. At that level of the vascular system, trandolapril appeared to provide the greatest duration of inhibition among the three ACE inhibitors tested.

Administration, Oral↗
PubMed1994

Dipyridamole-thallium scintigraphy and gated radionuclide angiography to assess cardiac risk before abdominal aortic surgery.

BACKGROUND: Because many patients with atherosclerotic disease of the abdominal aorta also have coronary artery disease, assessment of cardiac risk before abdominal aortic surgery has received much attention. Our prospective study was designed to identify predictors of cardiac risk in consecutive patients evaluated preoperatively with dipyridamole-thallium single-photon-emission computed tomography (SPECT) to assess myocardial perfusion and radionuclide angiography to measure left ventricular ejection fraction. METHODS: Clinical and scintigraphic data were collected prospectively during hospitalization in 457 consecutive patients undergoing elective abdominal aortic surgery. Adverse cardiac outcomes were predicted with multivariate analyses. RESULTS: Eighty-six patients (19 percent) had one or more of the following postoperative complications: prolonged myocardial ischemia (61 patients), myocardial infarction (22), congestive heart failure (20), and severe ventricular tachyarrhythmia (2). Twenty patients died postoperatively (4.4 percent), half of them from cardiac causes. Information about myocardial perfusion obtained from dipyridamole-thallium SPECT did not accurately predict adverse cardiac outcomes. The best correlates of cardiac complications were definite clinical evidence of coronary artery disease (odds ratio, 2.6; 95 percent confidence interval, 1.6 to 4.3) and age greater than 65 years (odds ratio, 2.3; 95 percent confidence interval, 1.4 to 3.6). Measurement of the ejection fraction was useful only in the prediction of left ventricular failure. Age greater than 65 years was the only predictor of death (odds ratio, 26.4; 95 percent confidence interval, 3.5 to 200.0). CONCLUSIONS: The presence of definite clinical evidence of coronary artery disease and older age were the most important preoperative predictors of an adverse cardiac outcome after abdominal aortic surgery. These results suggest that the routine use of dipyridamole-thallium SPECT and radionuclide angiography for screening before abdominal aortic surgery may not be justified.

Aged↗
PubMed1994

Amplification by phenylephrine and serotonin of coronary vasoconstriction induced by a high arterial blood oxygen tension.

OBJECTIVE: The aim was to investigate the effect on the coronary network of the interaction between high arterial blood oxygen tension (PaO2) and stimulation by the alpha adrenergic agonist phenylephrine or by serotonin in an isolated, blood perfused rabbit heart preparation. METHODS: Fresh pig erythrocytes in Krebs-Henseleit buffer were oxygenated to reach normal PaO2 [19.4(SEM 0.7) kPa] or high PaO2 [53.2(5.5) kPa]. Blood oxygen content was kept constant despite the higher PaO2, by slightly reducing the haemoglobin concentration from 9.3(0.2) to 8.8(0.2) g.100 ml-1 (p < 0.01). Coronary blood flow was kept constant throughout the study, so that the oxygen supply would not vary with the rise in PaO2. Increases in coronary resistance were therefore reflected by increased perfusion pressure. RESULTS: Switching from normal to high PaO2 induced coronary vasoconstriction, reflected by enhanced perfusion pressure of +21(5)%. After pretreatment with the alpha adrenergic agonist phenylephrine, perfusion of a high PaO2 solution increased coronary resistance by +35(7)% (p < 0.05), a value significantly higher than that found without phenylephrine. Oxygen consumption and myocardial performance did not vary throughout the study. To determine whether this amplification of the response was specifically due to alpha agonist stimulation or could be observed with other vasoactive agents, we applied the same protocol using serotonin instead of phenylephrine. Here again, coronary vasoconstriction rose in response to high PaO2 after serotonin infusion [+25(5)% versus +59(10)%]. CONCLUSIONS: The response of the coronary network to high PaO2 is amplified by pretreatment with the alpha adrenergic agonist phenylephrine or with serotonin, regardless of any changes in metabolic status.

Animals↗
PubMed1994

Effects of L-arginine and L-nitro-arginine treatment on blood pressure and cardiac output in a rabbit endotoxin shock model.

OBJECTIVE: To verify the effect of nitric oxide system modification during sepsis, not only in terms of pressure but also in terms of perfusion flow. DESIGN: Experimental, comparative study. SETTING: Laboratory of a university hospital. SUBJECTS: Twenty-six New Zealand male rabbits (2 to 2.5 kg body weight) were studied under anesthesia. INTERVENTIONS: Nitric oxide pathways were modified during shock-induced hypotension, using L-arginine (600 mg/kg) and L-nitro-arginine (7.5 mg/kg), which were infused 75 mins after endotoxin injection. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure (MAP) and cardiac output, as well as ascending aortic velocity, were measured and aortic conductance (aortic velocity/MAP in cm/sec/mm Hg) was calculated. Both L-arginine and L-nitro-arginine increased MAP to the pre-endotoxin level, but only L-arginine increased aortic velocity in association with a marked increase in aortic conductance (p < .001). L-nitro-arginine significantly (p < .05) decreased aortic velocity as compared with the control endotoxin group, with an intense vasoconstriction as shown by a significant (p < .001) decrease in aortic conductance. CONCLUSIONS: These results, along with the high mortality rate in the L-nitro-arginine treated group, challenge the hypothesis that nitric oxide release inhibition has a beneficial effect in septic shock.

Animals↗
PubMed1994

ACE in three tunicae of rat aorta: expression in smooth muscle and effect of renovascular hypertension.

Angiotensin I-converting enzyme (ACE) is known to be present at the surface of endothelial cells and also in the adventitia in large vessels. The presence of ACE in the vascular smooth muscle remains controversial. We microdissected segments of adventitia and media with or without endothelium from a region devoid of collateral arteries. The membrane-bound ACE activity in the media averaged 41% (pmol [glycine-1-14C]hippuryl-L-histidyl-L-leucine hydrolyzed.g tissue-1.min-1) of the values found in the whole aorta, whereas the adventitia contained only 6%. Immunoreactive ACE in media was characterized by Western blotting. ACE mRNAs were detected and characterized after polymerase chain amplification in isolated media. Angiotensin I and angiotensin II were equally able to contract medial rings, and the response to angiotensin I was blocked by enalaprilat. In aortas of two-kidney, one-clip hypertensive rats, there was an increase in ACE mRNA estimated by ribonuclease protection assay (P = 0.02) and in ACE activity at 15 days and 1 and 3 mo after clipping. This corresponded to a 1.5- to 2-fold increase in the ACE activity of both the media and the adventitia compared with sham-operated rats (P < or = 0.02). Thus ACE gene expression occurs in smooth muscle of rat aorta, which contains roughly the same amount of enzyme as the endothelium and readily converts angiotensin I to angiotensin II. ACE in the medial layer and the adventitia is upregulated in renovascular hypertension.

Animals↗
PubMed1994

Nitric oxide-independent response to acetylcholine by terminal arterioles in rat cremaster muscle.

The aim of the present study was to establish whether, in terminal arterioles from the rat cremaster, acetylcholine (ACh) elicits nitric oxide (NO)-independent dilation corresponding to the transient ACh-induced endothelium-dependent hyperpolarization described in arteries. For this purpose, the responses of terminal arterioles [mean diam 15.0 +/- 0.4 (SE) microns] were studied by intravital microscopy in rat cremaster muscle. During 15 min of superfusion by 10(-5) M ACh, the response was characterized by an initial maximal dilation (peak time < 3 min) followed by a more sustained dilation that slightly decreased with time. Inhibition of NO synthesis by 2 x 10(-4) M N omega-nitro-L-arginine (L-NNA) significantly reduced, but did not eliminate, both the peak and sustained responses. Simultaneous administration of 2 x 10(-4) M L-NNA and 2 x 10(-5) M mefenamic acid, an inhibitor of prostaglandin synthesis, did not induce a significantly different response from that observed with L-NNA alone. Procaine (10(-3) M), which is known to inhibit completely ACh-induced hyperpolarization in carotid artery, drastically reduced the initial part of the ACh-induced dilation but not the sustained response. Simultaneous administration of procaine and L-NNA almost completely inhibited the peak response to ACh. Similar results were obtained when L-NNA was combined with a superfusion bath containing 20 mM KCl, a concentration known to reduce hyperpolarization in arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1994

Role of nitric oxide and prostaglandins in the regulation of diaphragmatic arteriolar tone in the rat.

We evaluated by intravital microscopy in rats the relative importance of nitric oxide (NO) and prostaglandins in 1) the maintenance of basal diaphragmatic arteriolar tone and 2) the response of diaphragmatic arterioles to the endothelium-dependent vasodilator acetylcholine (ACh). One hundred two mechanically ventilated rats were studied. Separate applications of N omega-nitro-L-arginine (L-NNA) and mefenamic acid (MA), which are specific inhibitors of NO and prostaglandin synthesis, respectively, elicited a significant reduction in basal diaphragmatic arteriolar diameter. A dramatic potentiation of the effect of each inhibitor was observed when both agents were applied simultaneously. ACh application induced a significant and dose-dependent increase in arteriolar diameter that was not significantly modified by the separate application of L-NNA or MA. Conversely, the simultaneous administration of L-NNA and MA almost completely prevented ACh-induced arteriolar dilatation. Dilatation in response to sodium nitroprusside was not significantly modified in the presence of both inhibitors. These results suggest that NO and prostaglandins act in concert to regulate basal diaphragmatic arteriolar tone and to mediate diaphragmatic arteriolar response to ACh.

Acetylcholine↗
PubMed1994

Local renin-angiotensin system in the microcirculation of spontaneously hypertensive rats.

We studied the local renin-angiotensin system in the microcirculation of cremaster muscle in spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto (WKY) controls. We used intravital microscopy in an original preparation of cremaster isolated from its normal blood supply and externally perfused with physiological solution, thus allowing the exclusion of circulating converting enzyme, circulating renin, and circulating angiotensinogen. We classified arterioles studied as second-, third-, and fourth-order, with mean diameters, respectively, of 67 +/- 6, 35 +/- 2, and 17 +/- 1 microns in WKY controls and 61 +/- 5, 34 +/- 2, and 16 +/- 1 microns in SHR. No difference between WKY controls and SHR was found for arteriolar vasoconstrictions in response to topical administration of 0.01 to 1 nmol/mL angiotensin II. Conversely, in response to 0.01 to 1 nmol/mL angiotensin I, significantly more arteriolar vasoconstriction was found in SHR cremaster muscle. In both strains, responses to angiotensin I were significantly inhibited by 10 nmol/mL of the angiotensin-converting enzyme inhibitor lisinopril. When angiotensinogen-rich, renin-free plasma containing 2.3 nmol/mL angiotensinogen was administered, almost no vasoconstriction was found in WKY controls, but significant constrictions were observed in SHR (23 +/- 4%, 30 +/- 5%, and 41 +/- 4% for second-, third-, and fourth-order arterioles, respectively). In SHR, vasoconstriction in response to angiotensinogen-rich, renin-free plasma was dose dependent, was inhibited by lisinopril, and was not found 24 hours after bilateral nephrectomy. Topical administration of 1.2 micrograms/mL renin did not induce arteriolar vasoconstriction in either WKY or SHR cremaster muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensins↗
PubMed1994

[Pressure-independent improvement of aortic distensibility in hypertensive hemodialysed patients].

Hypertensive patients undergoing hemodialysis (HPH) have a marked impairment of their large artery distensibility and an increased cardiovascular morbidity. We investigated twelve HPH (8 males, 4 females, 53 +/- 12 years of age, +/- SD) following a single dose of an ACE inhibitor (quinapril 20 mg) comparatively to a placebo in a randomised cross over study over a week (H0 to H172). We measured repeatedly blood pressure and aortic distensibility (carotid-femoral pulse wave velocity, PWV). Statistical analysis was made through repeated measure ANOVA and repeated measure analysis of covariance because of the tight link between pressure and arterial function. Blood pressure decreased (SAP: p < 0.01, DAP: p < 0.001), and PWV was significantly improved independently of the pressure decrease. ACE inhibitor reduces blood pressure in these patients and improves large arterial function independently of the blood pressure changes.

Adult↗
PubMed1993

Criteria for anatomical compatibility of the total artificial heart: computerized three-dimensional modeling of the cardiovascular anatomy.

A quantitative study of cardiovascular anatomy was performed by obtaining three-dimensional reconstructions from regular computed tomography scan images in 15 patients, all candidates for heart transplantation. Volumetric estimates of the cardiovascular structures were obtained from these three-dimensional reconstructions using data directly related to total artificial heart (TAH) implantations. By using computerized three-dimensional modeling of these structures, reproducible measurements of the parameters defining the shape and the anatomical connections of the intrathoracic space available for TAH implantation could be derived. The results are intended to be used for both technical and clinical applications such as computer-assisted drawing of the pericardial cavity and the anatomical connections (useful for improving the design of TAH) and combined statistical calculations (multiple regressions, cluster algorithm) of the measurement results, which will then enable the best selection to be made among two or three TAH models for each patient.

Aortography↗
PubMed1993

Role of nitric oxide in effects of tumor necrosis factor-alpha on microcirculation in rat.

The involvement of nitric oxide (NO) in the effects of tumor necrosis factor-alpha (TNF-alpha) on the microcirculation was studied by in vivo microscopy in rat cremaster muscle. We examined second-, third-, and fourth-order arterioles with mean diameters under control conditions of 62.2, 37.4, and 16.9 microns, respectively. The vasodilation observed after topical administration of 100 ng/ml recombinant TNF-alpha (rTNF-alpha) was partly but significantly inhibited when NO synthesis was inhibited by 2 x 10(-4) M N omega-nitro-L-arginine (L-NNA). Almost complete inhibition of the acute vasodilatory effect of rTNF-alpha was found when both NO and prostaglandin synthesis were blocked by simultaneous administration of L-NNA and mefanamic acid. The effect of rTNF-alpha on vasoconstriction in response to norepinephrine (NE) was a dramatic reduction after 2 h of exposure to 1 ng/ml rTNF-alpha. Concomitant administration of 2 x 10(-4) M L-NNA prevented this hyporeactivity for second- and third-order, but not for fourth-order, arterioles. However, at 2 x 10(-3) M, L-NNA totally prevented the hyporeactivity to NE for all arteriolar orders. No changes in vasoconstriction to 70 mM KCl were observed either immediately after rTNF-alpha administration or after 2 h of exposure. We conclude that 1) the direct acute vasodilatory effect of rTNF-alpha on the microcirculation is mediated by both prostaglandins and NO, 2) long exposure to rTNF-alpha diminishes the response of the arterioles to NE but not to KCl, and 3) this effect is mediated by NO.

Animals↗
PubMed1993

Arteriolar constriction and local renin-angiotensin system in rat microcirculation.

Intravital microscopy was used in a preparation of rat cremaster muscle that was isolated from its normal blood supply and externally perfused with a physiological solution, thus allowing exclusion of circulating converting enzyme, renin, and angiotensinogen. The arterioles studied were classified as second-, third-, and fourth-order arterioles with mean diameters of 60.5, 29.9, and 14.8 microns, respectively. Topical administration of 1 nmol/mL angiotensin I or 1 nmol/mL tetradecapeptide renin substrate induced marked vasoconstrictions (i.e., 38.5%, 61.5%, and 90.1% and 25%, 34%, and 88% for second-, third-, and fourth-order arterioles with angiotensin I and tetradecapeptide renin substrate, respectively). The angiotensin converting enzyme inhibitor quinapril significantly inhibited the vasoconstrictions caused by either angiotensin I or tetradecapeptide renin substrate. Almost no vasoconstriction was found when angiotensinogen-rich renin-free plasma containing either 2.45 nmol/mL of angiotensinogen or 1.2 micrograms/mL renin was administered. Conversely, these two compounds induced significant constrictions in cremaster muscle preparations in which normal blood perfusion (and thus circulating renin and angiotensinogen) was left in place. We concluded that, in skeletal muscle, 1) the microvascular network is a very effective site of local angiotensin converting enzyme activity and consequently an important target site of angiotensin converting enzyme inhibitors; 2) the effects of tetradecapeptide renin substrate are very different from those of angiotensinogen from plasma and suggest that a large part of the effect of tetradecapeptide renin substrate was due to its nonspecific hydrolysis; and 3) at the microvascular level, circulating renin and angiotensinogen are more effective in inducing arteriolar constriction, in the presence of their substrate or associated enzyme, than local renin and angiotensinogen.

Angiotensin I↗
PubMed1993

Acute digitalis intoxication--is pacing still appropriate?

Over a six year period, 92 patients intoxicated with either digitoxin or digoxin were admitted to our ICU. Fifty-one patients were treated with cardiac pacing and/or Fab fragments, and the mortality rate was 13% (14 were intoxications with digoxin, 36 with digitoxin, 1 was mixed). Forty-five cases were suicide attempts; six were accidental overdosages. Since cardiac pacing may trigger fatal arrhythmia or delay the administration of Fab fragments, we conducted a retrospective study to determine whether fatal outcomes could be related either to cardiac pacing or to unsatisfactory use of immunotherapy. In our study, prevention of life-threatening arrhythmia failed in 8% of cases with Fab and in 23% with pacing. Though Fab tended to be more effective, this difference was not significant. In our study, the main obstacles to the success of Fab were pacing-induced arrhythmias and delayed or insufficient administration of Fab. Iatrogenic accidents of cardiac pacing were frequent (14/39, 36%) and often fatal (5/39, 13%). In contrast, immunotherapy was not associated with any serious adverse effects (0/28, 0%) and was safer than cardiac pacing (p < 0.05). In conclusion, during digitalis intoxication, the pacemaker has limited preventive and curative effects, is difficult to handle, and exposes patients to severe iatrogenic accidents. Fab fragments act as a powerful antidote and are safer and much easier to use than pacing. These results encourage us to prescribe Fab fragments as first-line therapy during acute digitalis intoxication.

Adult↗
PubMed1992

Efficacy and safety of quinapril in the elderly hypertensive patient.

The efficacy and safety of once-daily administration of the new angiotensin-converting enzyme inhibitor quinapril or quinapril plus hydrochlorothiazide (HCTZ) were assessed in 64 older (greater than 65 years) patients with mild to moderate hypertension in an uncontrolled, open-label study. Treatment was initiated with 20 mg of quinapril once daily and titrated upward to 40 mg of quinapril or 40 mg of quinapril combined with 25 mg of HCTZ according to efficacy. At the end of the 12-week active-treatment phase, 43 patients received 20 mg of quinapril once daily, 12 patients received 40 mg of quinapril once daily, and 4 patients received 40 mg of quinapril combined with 25 mg of HCTZ once daily. Of 48 patients evaluable for efficacy, the mean decrease from baseline in sitting diastolic blood pressure (DBP) was 12.8 mm Hg; 96% of the patients had a blood pressure reduction of greater than or equal to 10 mm Hg, and 98% had a sitting DBP of less than or equal to 90 mm Hg 20 to 28 hours after administration. The decrease in sitting DBP was significant after 1 week and continued for the entire study, as did corresponding changes in sitting systolic blood pressure. We conclude that quinapril administered once daily is well tolerated and effective for the treatment of mild to moderate hypertension in elderly patients.

Aged↗
PubMed1992

Hypertension and the microcirculation: a brief overview of experimental studies.

PURPOSE: To review experimental findings on the importance of the microcirculation in hypertension. RESULTS OF DATA ANALYSIS: A significant part of the increase in vascular resistance found in hypertension involves alterations in the arteriolar network. Changes in vascular reactivity and amplification of normal microvascular autoregulatory loops are among the mechanisms involved in these microvascular alterations. Depending on the organ and the type of hypertension, different types of changes have been observed, including (1) changes in resting arteriolar diameter and increased tone, either throughout the arteriolar network or localized to certain arteriolar segments; (2) temporary closure of a significant fraction of the terminal arteriolar bed; and (3) degenerative processes in terminal arterioles and capillaries inducing anatomical rarefaction of the microvessels. CONCLUSIONS: Microvascular changes are responsible for only a portion of the increased resistance but they are extremely important in the global understanding of the hypertensive process, as they are potentially responsible for tissue damage and may be related to the increased risk of organ failure in hypertension.

Animals↗
PubMed1992

Specific esponse to 5-HT2 agonists by arterioles linked to Meth A tumors in mice.

Using intravital microscopy, we compared the responses to serotonin [5-hydroxytryptamine (5-HT)] and to a specific 5-HT2 agonist [1-(2,5-dimethoxy-4-bromo-phenyl)-2-aminopropane (DOB)] by normal arterioles and by the host-modified arterioles feeding a Meth A tumor implanted into the flank of female BALB/c mice. Topical and intravenous administration of 5-HT (10(-6) to 10(-4) M and 0.01-10 micrograms) or DOB (5 x 10(-7) to 5 x 10(-5) M and 0.01-10 micrograms) induced arteriolar constriction, which was far more pronounced for the arterioles feeding the tumor. This larger degree of vasoconstriction in tumor-feeding vs. normal arterioles was not found with norepinephrine. We also compared tumor growth and the mouse life span in three groups of mice, which were given 1 mg of serotonin or 0.74 mg DOB or saline solution. 5-HT or DOB both reduced tumor growth drastically compared with the controls (P less than 0.001), and survival rates were significantly higher in the 5-HT or DOB-treated groups (P less than 0.001). We conclude that 5-HT2-serotoninergic agonists are of particular pharmacological interest, since their vasoconstrictive action on the microvasculature feeding the tumors is much greater than in normal tissue and may interfere with tumor growth.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗