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Biomedical subjects

Michel Slama

Publications and source records attributed to Michel Slama.

At least 19 recordsLinked to original sources
PubMed2006

A randomized comparison of high clopidogrel loading doses in patients with non-ST-segment elevation acute coronary syndromes: the ALBION (Assessment of the Best Loading Dose of Clopidogrel to Blunt Platelet Activation, Inflammation and Ongoing Necrosis) trial.

OBJECTIVES: We sought to compare the antiplatelet effects of three clopidogrel loading doses (LDs). BACKGROUND: Administration of a 300-mg clopidogrel LD is beneficial in situations requiring rapid platelet inhibition. Whether higher LDs can provide further benefits remains unknown. METHODS: Patients (n = 103) with non-ST-segment elevation acute coronary syndromes were randomized to receive a 300-mg, 600-mg, or 900-mg clopidogrel LD, given on top of other standard therapy (including acetylsalicylic acid). The main outcome measure was inhibition of adenosine diphosphate-induced inhibition of platelet aggregation (IPA); inhibition of platelet activation, inflammatory markers, troponin I release, and major adverse cardiac events also were evaluated; all measures were blindly evaluated. RESULTS: Compared with the 300-mg LD, greater doses were associated with significantly greater platelet inhibition, with dose-effect relationships observed for onset of action, maximal plateau, 24-h areas under the curves of IPA, and rates of low IPA (<10% at 6 h), using 20 micromol/l major adverse cardiac events. A significant dose-response was also observed for the vasodilator-stimulated phosphoprotein index, a measure of P2Y(12) receptor inhibition. Similar but nonsignificant trends were observed for troponin release and major adverse cardiac events. Bleeding rates were similar in each group. CONCLUSIONS: In low-to-moderate risk patients with non-ST-elevation acute coronary syndromes, clopidogrel LDs >300 mg provide a faster onset of action, a higher IPA plateau, and greater reductions in platelet activation during the first 24 h. A 900-mg LD may induce a greater antiplatelet effect than 600 mg, when compared with the standard 300-mg regimen. These findings require further clinical confirmation.

Acute Disease↗
PubMed2006

Echocardiographic measurement of ventricular function.

PURPOSE OF REVIEW: We review new findings concerning ventricular function in patients in intensive care units with shock or unexplained respiratory distress syndrome analyzed using echocardiography. RECENT FINDINGS: Bedside echocardiography is not only an imaging technique but should be considered as a hemodynamic method. Left-ventricular systolic function can be assessed in daily clinical practice by measuring shortening fraction, fraction area change and ejection fraction. But these indices are dependent on load conditions. Index of myocardial performance can be also used. Rate of left-ventricular pressure increase may be measured from mitral regurgitation. Other indices such a maximal elastance and preload-adjusted maximal power were developed to evaluate myocardial systolic function but are not still used in clinical practice in patients in intensive care. Cardiac output measurement can be calculated easily from aortic annulus diameter and the velocity time integral of aortic blood flow. To complete the assessment of ventricular function, left-ventricular diastolic function and pressure as well as right ventricular size, septal movement and right pressures should be analyzed. SUMMARY: Using echocardiography the intensivist can examine both the mechanism and the cause of shock or pulmonary edema. It is time to increase the use of this technique in intensive care units.

Atrial Function, Right↗
PubMed2006

Hypertension in the intensive care unit.

PURPOSE OF REVIEW: The severity of hypertensive crises is determined by the presence of target organ damage rather than the level of blood pressure. Hypertensive urgencies with no signs of organ dysfunction can therefore be distinguished from hypertensive emergencies in which the presence of severe end-organ damage requires prompt therapy. Hypertensive emergencies include acute aortic dissection, hypertensive encephalopathy, acute myocardial ischaemia, severe pulmonary oedema, eclampsia, and acute renal failure. RECENT DEVELOPMENTS: Malignant hypertension is a severe form of hypertensive emergency demanding special consideration because of the risks of permanent blindness and renal failure. Catecholamine excess and postoperative hypertension may also sometimes require urgent treatment. The management of patients with hypertensive emergencies must be ensured in an intensive care unit, and must include the parenteral administration of antihypertensive drugs and accurate blood pressure monitoring. SUMMARY: Except for acute aortic dissection, the recommended goals of treatment are a reduction of mean arterial pressure by no more than 20% during the first few hours, because an abrupt fall in blood pressure in patients with preexisting hypertension may induce severe ischaemic injury in major organs as a result of the chronic adaptation of autoregulation mechanisms. Hypertension in the context of acute stroke should be treated only rarely and cautiously because of the presence of impaired autoregulation.

Acute Disease↗
PubMed2005

Validation of echocardiographic and Doppler indexes of left ventricular relaxation in adult hypertensive and normotensive rats.

This study was performed to validate echocardiographic and Doppler techniques for the assessment of left ventricular (LV) diastolic function in spontaneously hypertensive rats (SHR) and normotensive Wistar rats. In 11 Wistar rats and 20 SHR, we compared 51 sets of invasive and Doppler LV diastolic indexes. Noninvasive indexes of LV relaxation were related to the minimal rate of pressure decline (-dP/dt(min)), particularly isovolumic relaxation time (IVRT), the Tei index, the early velocity of the mitral annulus (E(m)) using Doppler tissue imaging, and early mitral flow propagation velocity using M-mode color (r = 0.28-0.56 and P < 0.05-0.0001). When the role of systolic load was considered, the correlation between Doppler indexes of LV diastolic function and relaxation rate [(-dP/dt(min))/LV systolic pressure] improved (r = 0.48-0.86 and P = 0.004-0.0001, respectively). Similarly, Doppler indexes of LV diastolic function and the time constant of isovolumic LV relaxation (tau) correlated well (r = 0.50-0.84 and P = 0.0002-0.0001, respectively). In addition, eight SHR and eight Wistar rats were compared; their LV end-diastolic diameters were similar, whereas the SHR LV mass was greater. Furthermore, IVRT and Tei index were significantly higher and E(m) was lower in SHR. Moreover, tau was higher in SHR, demonstrating impaired LV relaxation. In conclusion, LV relaxation can be assessed reliably using echocardiographic and Doppler techniques, and, using these indexes, impaired relaxation was demonstrated in SHR.

Animals↗
PubMed2004

Cardiac structural and functional responses to salt loading in SHR.

Increased dietary salt intake induces cardiac fibrosis in the spontaneously hypertensive rat (SHR), yet little information details its effects on left ventricular (LV) function. Additionally, young normotensive rats are more sensitive to the trophic effect of dietary sodium than older rats. Thus cardiac responses to salt loading were evaluated at two ages in the SHR; LV collagen content was also examined. SHR (8 or 20 wk of age) were given an 8% salt diet; their age-matched controls received standard chow. Echocardiographic indexes, arterial pressure, and LV hydroxyproline concentration were measured at 16 and 52 wk in the younger and older SHR groups, respectively. In most SHR, salt excess increased arterial pressure, LV mass, and hydroxyproline concentration and impaired LV relaxation manifested by prolonged isovolumic relaxation time, decreased early and atrial filling velocity ratio (V(E)/V(A)), and slower propagation velocity of E wave (V(P)). LV systolic function remained normal. However, one-quarter of the young salt-loaded SHR developed cardiac failure with systolic and diastolic dysfunction associated with greater LV mass and ventricular fibrosis. They also had lower arterial pressure, decreased fractional shortening, and a restrictive pattern of mitral flow. Moreover, the shorter deceleration time of the E wave and increased V(E)/V(P), an index of LV filling pressure, indicated increased LV stiffness in these rats. These findings demonstrated that sodium sensitivity in SHR is manifested not only by further pressure elevation but also by significant LV functional impairment that most likely is related to enhanced ventricular fibrosis. Moreover, the SHR are more susceptible to cardiac damage when high dietary salt is introduced earlier in life.

Aging↗
PubMed2004

Monitoring of respiratory variations of aortic blood flow velocity using esophageal Doppler.

OBJECTIVE: The purpose of this study was to determine whether monitoring of respiratory changes in aortic blood flow velocity, recorded by esophageal Doppler, could be used to detect changes in volume depletion. DESIGN: Animal study. ANIMALS AND INTERVENTIONS: After general anesthesia and tracheotomy, ten New Zealand female rabbits, weighing 4-4.5 kg were studied under mechanical ventilation at a fixed tidal volume; during this time 5-ml blood samples were withdrawn (in increments up to a total of 30 ml) and then retransfused. MEASUREMENTS AND RESULTS: At each step, systolic (SBP), diastolic (DBP), pulse (PP) pressures and maximum descending aortic blood flow (V) were recorded. Respiratory changes of V (DeltaV), SBP (DeltaSBP) and PP (DeltaPP) were calculated as the difference of maximal and minimal values divided by their respective means and expressed as a percentage. The amount of blood withdrawn correlated negatively with SBP, DBP, PP and V and positively with DeltaSBP, DeltaPP and DeltaV. Among these parameters, DeltaV correlated best with the amount of blood withdrawn ( r=0.89, p<0.001) and it was the most accurate index of volume depletion. CONCLUSION: Monitoring of the respiratory variation in V, calculated by esophageal Doppler technique, seems to be a highly accurate index of blood volume depletion and restitution.

Analysis of Variance↗
PubMed2004

DECOPI (DEsobstruction COronaire en Post-Infarctus): a randomized multi-centre trial of occluded artery angioplasty after acute myocardial infarction.

AIM: To determine whether late recanalization of an occluded infarct artery after acute myocardial infarction is beneficial. METHODS AND RESULTS: Two hundred and twelve patients with a first Q-wave myocardial infarction (MI) and an occluded infarct vessel were enrolled. After coronary and left ventricular contrast angiography, patients were randomized to percutaneous revascularization (PTCA, n=109), carried out 2-15 days after symptom onset or medical therapy (n=103). The primary endpoint was a composite of cardiac death, non-fatal MI, or ventricular tachyarrhythmia. The majority had single-vessel disease and less than one-third had involvement of the left anterior descending artery. The use of pharmacological therapy was high in both groups. At six months, left ventricular ejection fraction was 5% higher in the invasive compared with the medical group (P=0.013) and more patients had a patent artery (82.8% vs 34.2%, P<0.0001). Restenosis was seen in 49.4% of patients in the PTCA group. At a mean of 34 months of follow-up, the occurrence of the primary endpoint was similar in the medical and PTCA groups (8.7% vs 7.3% respectively, P=0.68), but the overall costs were higher for PTCA. The secondary endpoint combining the primary endpoint with admission for heart failure was also similar between groups (12.6% vs 10.1% in the medical and PTCA groups, respectively, P=0.56). CONCLUSIONS: Systematic late PTCA of the infarct vessel was associated with a higher left ventricular ejection fraction at six months, no difference in clinical outcomes, and higher costs than medical therapy. These results must be interpreted with caution given the small size and low risk of the population.

Adult↗
PubMed2004

The value of a completely automatic ECG gated blood pool SPECT processing method for the estimation of global systolic left ventricular function.

OBJECTIVES: Electrocardiographically gated blood pool SPECT (GBPS) is an interesting method for measuring left ventricular (LV) ejection fraction (LVEF) and volume. Recently, the availability of completely automatic GBPS processing software has been reported. We aimed to evaluate its reliability in measuring global LV systolic function. In addition, using the same population, we compared its reliability to that of three previously reported methods for processing GBPS. METHODS: We studied the performances of the new GBPS system for the evaluation of LVEFs and volumes in 29 patients. The LVEF provided by the planar equilibrium radionuclide angiography (planarLAO) and LV volumes provided by radiological LV contrast angiography (X-rays) were used as 'gold standards'. RESULTS: The new GBPS system failed in one patient. It shows good reproducibility for the measurement of both LVEF and volume. LVEF provided by this system is moderately correlated to planarLAO (r = 0.62; P < 0.001). The new GBPS constantly overestimates LVEF (P < 0.05). Results for LV volumes are moderately correlated to those obtained by X-ray investigation (r = 0.7; P < 0.001) but are significantly lower (P < 0.0001). There is a linear correlation between the average and the paired absolute difference for LV volumes (r = 0.52, P = 0.0001). CONCLUSIONS: The new, completely automatic, GBPS processing software is an interesting, moderately reliable method for measuring LVEF and volume. The performance of the method is lower than that previously reported for the same population for the other three GBPS processing methods.

Algorithms↗
PubMed2003

Long-term left ventricular echocardiographic follow-up of SHR and WKY rats: effects of hypertension and age.

Long-term follow-up of left ventricular (LV) function using echocardiography has not been reported and, in this study, was carried out in normotensive (WKY) rats and spontaneously hypertensive rats (SHR). In 10 WKY rats and SHR, LV diastolic and systolic diameter (LVEDD and LVSD), shortening fraction (SF), and weight (LVW) were determined at 8, 15, 20, 35, and 80 wk of age. The ratio of early to late mitral flow and mitral annulus velocity (VE/VA and Em/Am), isovolumic relaxation time (IVRT), deceleration time of the E wave (DTE), Tei index, and mitral flow propagation velocity (Vp) were measured. No difference in LVEDD was found between SHR and WKY rats; however, LVEDD was increased at 80 wk in both strains. SF decreased slightly in old WKY rats. LVW progressively increased from 20 to 80 wk in both strains and was greater in SHR. VE/VA and Em/Am decreased at 80 wk in WKY rats. LV relaxation (IVRT, Tei index, and Vp) was progressively impaired in SHR compared with WKY rats. LV compliance (DTE) was altered in old SHR. Echocardiography permitted a long follow-up of LV function in SHR and WKY rats. Ventricular relaxation was impaired early in the life of SHR and progressed with aging. Furthermore, LV compliance was altered, but systolic function remained unchanged, in old SHR. In contrast, relaxation and SF were only slightly altered in old WKY rats, suggesting that pressure-related changes in LV function were the dominant features in the SHR.

Aging↗
PubMed2003

Comparison of effects on markers of blood cell activation of enoxaparin, dalteparin, and unfractionated heparin in patients with unstable angina pectoris or non-ST-segment elevation acute myocardial infarction (the ARMADA study).

The low-molecular-weight heparins (LMWHs) enoxaparin and dalteparin have shown superior and equivalent efficacy, respectively, over unfractionated heparin (UFH) in patients with unstable angina pectoris (UAP) or non-ST-segment elevation myocardial infarction (NSTEMI). This study aimed to identify markers of blood cell activation that are independent predictors of outcomes at 1 month and to compare the effects of enoxaparin, dalteparin, and UFH on any such markers. In this multicenter, prospective, open-label study, 141 patients with UAP or NSTEMI were randomized to treatment for 48 to 120 hours with enoxaparin (n = 46), dalteparin (n = 48), or UFH (n = 47). Blood samples were taken at the time of randomization and after > or =48 hours of treatment but before catheterization. Multivariate analysis identified increased plasma levels of von Willebrand factor (vWF) and decreased platelet levels of glycoprotein Ib/IX complexes as independent predictors of 1-month adverse outcome (a composite of death, myocardial infarction, and recurrent ischemia). vWF release was strongly related to and may have been released by inflammation as measured by C-reactive protein. Both LMWHs reduced the release of vWF in plasma (as well as C-reactive protein) compared with UFH. Enoxaparin had a more favorable effect on glycoprotein Ib/IX complexes than either dalteparin or UFH. The incidence of the composite clinical efficacy end point was: 13% (enoxaparin), 19% (dalteparin), and 28% (UFH). vWF and its receptor glycoprotein Ib/IX play a key role in acute coronary syndromes. vWF is linked to inflammation and, like glycoprotein Ib/IX, is affected more favorably by the LWMHs than by UFH.

Angina, Unstable↗
PubMed2003

Comparative value of ECG-gated blood pool SPET and ECG-gated myocardial perfusion SPET in the assessment of global systolic left ventricular function.

Both electrocardiographically (ECG) gated blood pool SPET (GBPS) and ECG-gated myocardial perfusion SPET (GSPET) are currently used for the measurement of global systolic left ventricular (LV) function. In this study, we aimed to compare the value of GSPET and GBPS for this purpose. The population included 65 patients who underwent rest thallium-201 GSPET imaging at 15 min after (201)Tl injection followed by planar (planar(RNA)) and GBPS equilibrium radionuclide angiography immediately after 4-h redistribution myocardial perfusion SPET imaging. Thirty-five patients also underwent LV conventional contrast angiography (X-rays). LV ejection fraction (EF) and LV volume [end-diastolic (EDV) and end-systolic (ESV) volumes] were calculated with GBPS and GSPET and compared with the gold standard methods (planar(RNA) LVEF and X-ray based calculation of LV volume). For both LVEF and LV volume, the inter-observer variability was lower with GBPS than with GSPET. GBPS LVEF was higher than planar(RNA) (P<0.01) and GSPET LVEF (P<0.01). Planar(RNA) LVEF showed a slightly better correlation with GBPS LVEF than with GSPET LVEF: r=0.87 and r=0.83 respectively. GSPET LV volume was lower than that obtained using X-rays and GBPS (P<0.01 for both). LV volume calculated using X-rays showed a slightly better correlation with GBPS LV volume than with GSPET LV volume: r=0.88 and r=0.83 respectively. On stepwise regression analysis, the accuracy of GSPET for the measurement of LVEF and LV volume was correlated with a number of factors, including planar(RNA) LVEF, signal to noise ratio, LV volume calculated using X-rays, summed rest score and acquisition scan distance (i.e. the radius of rotation). The accuracy of GBPS for the measurement of LVEF and LV volume was correlated only with the signal level, the signal to noise ratio and the acquisition scan distance. Both GSPET and GBPS provide reliable estimation of global systolic LV function. The better reliability of GBPS and in particular its lower sensitivity to different variables as compared with GSPET favours its use when precise assessment of global systolic LV function is clinically indicated.

Adult↗
PubMed2003

Omapatrilat induces profound renal vasodilation but does not affect coronary hemodynamics.

BACKGROUND: Omapatrilat has potent enzymatic inhibitory effects on the angiotensin-converting enzyme and neutral endopeptidase. The prolonged effects of this inhibition on systemic and regional hemodynamics, cardiovascular mass, and hydroxyproline concentration in spontaneously hypertensive rats were studied. The contribution of endogenous bradykinin on the cardiovascular actions of omapatrilat in this genetic model of hypertension was also investigated. METHODS AND RESULTS: Systemic and regional hemodynamics (radionuclide-labeled microspheres), left and right ventricular and aortic masses, and hydroxyproline concentration were determined in 35-week-old spontaneously hypertensive rats after 12 weeks of treatment with omapatrilat (40 mg/kg/day), with and without the bradykinin receptor antagonist icatibant (500 microg/kg/day). Omapatrilat decreased mean arterial pressure, reducing total peripheral resistance as well as decreased left ventricular and aortic mass indices. It also induced a profound renovasodilation associated with a decrease renal vascular resistance that markedly increased renal blood flow. Coronary hemodynamics and left ventricular hydroxyproline concentration remained unaltered. Concomitant blockade of bradykinin receptors partially attenuated the hypotensive effect of omapatrilat and its effect on aortic mass; and icatibant did not influence the renovasodilation. CONCLUSION: Omapatrilat produced profoundly beneficial effects on systemic and renal hemodynamics, as well as on left ventricular and aortic masses, without any effect on coronary hemodynamics. These effects of omapatrilat on arterial pressure and aortic mass, but not on renal hemodynamics and left ventricular mass, may have been at least partially mediated through the action of bradykinin.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2003

Performance of OSEM and depth-dependent resolution recovery algorithms for the evaluation of global left ventricular function in 201Tl gated myocardial perfusion SPECT.

UNLABELLED: It is unknown whether the use of ordered-subsets expectation maximization (OSEM) and depth-dependent resolution recovery (RR) will increase the accuracy of (201)Tl electrocardiogram-gated SPECT (GSPECT) for the measurement of global left ventricular (LV) function. METHODS: Fifty-six patients having both rest (201)Tl GSPECT and planar equilibrium radionuclide angiography (planar(RNA)) on the same day were studied. Twenty-nine patients also had LV conventional contrast angiography (Rx). LV ejection fraction (LVEF), end-diastolic volume (EDV), and end-systolic volume (ESV) were calculated with the quantitative gated SPECT software (QGS) using 4 different processing methods: filtered backprojection (FBP), OSEM, RR + FBP, and RR + OSEM. LVEF calculated with planar(RNA) and LV EDV and ESV calculated with Rx were considered gold standards. LVEF and volumes provided with the GSPECT methods were compared with the gold standard methods. RESULTS: LVEF calculated with GSPECT methods (FBP, OSEM, RR + FBP, and RR + OSEM) were similar (not statistically significant) and correlated well with planar(RNA). On Bland-Altman analysis, the mean +/- SD of absolute difference in LVEF with GSPECT FBP, OSEM, RR + FBP, and RR + OSEM methods versus planar(RNA) were similar, with relatively large limits of agreement. LV volumes calculated with the 4 GSPECT methods were significantly lower but correlated well with Rx LV volumes. LV volumes calculated with FBP and OSEM were lower than those calculated with RR + FBP and RR + OSEM (P < 0.01). On Bland-Altman analysis, the mean +/- SD of absolute difference in LV volumes with FBP, OSEM, RR + FBP, and RR + OSEM versus Rx was, respectively, 56 +/- 45 mL (P < 0.01 vs. the other 3 methods), 57 +/- 45 mL (P < 0.01 vs. the other 3 methods), 43 +/- 48 mL, and 46 +/- 47 mL, with correspondingly large limits of agreement. The variance of random error did not differ between FBP, OSEM, RR + FBP, and RR + OSEM for either LVEF or volumes. CONCLUSION: OSEM and FBP presented similar accuracy for LVEF and volume measured with the QGS software. Their combination with depth-dependent RR provided similar LVEF but more accurate LV volumes.

Algorithms↗
PubMed2002

Echocardiographic measurement of cardiac output in rats.

The systematic evaluation of different transthoracic echocardiographic (TTE) methods to determine cardiac output (CO) and the effect of changes in intravascular volume on echocardiographically determined indexes of cardiovascular structure in the rat has not been documented. With the use of 11 Wistar rats, simultaneous echocardiographic and thermodilution measurements of CO were compared at baseline and after blood withdrawal or transfusion at 43 different levels of intravascular volume and using 10 different echocardiographic approaches. The best correlation (r = 0.93; P < 0.0001), least bias (-3 ml/min), and best precision (16 ml/min) between thermodilution and echocardiographic methods were obtained at the level of aortic annulus using pulsed Doppler. In conclusion, CO could be accurately assessed in rats using TTE and pulsed Doppler at the level of the aortic annulus. This annulus was demonstrated to remain stable, but pulmonary annulus, thoracic aorta, mitral valve, and left ventricular diameters were found to be more modifiable during volumic changes.

Animals↗
PubMed2002

Respiratory variations of aortic VTI: a new index of hypovolemia and fluid responsiveness.

In 12 mechanically ventilated and anesthetized rabbits, we investigated whether the magnitude of respiratory changes in the aortic velocity time integral (VTI(Ao)), recorded by transthoracic echocardiography (TTE) during a stepwise blood withdrawal and restitution, could be used as a reliable indicator of volume depletion and responsiveness. At each step, left and right ventricular dimensions and the aortic diameter and VTI(Ao) were recorded to calculate stroke volume (SV) and cardiac output (CO). Respiratory changes of VTI(Ao) (maximal - minimal values divided by their respective means) were calculated. The amount of blood withdrawal correlated negatively with left and right ventricular diastolic diameters, VTI(Ao), SV, and CO and correlated directly with respiratory changes of VTI(Ao). Respiratory VTI(Ao) variations (but not other parameters) at the last blood withdrawal step was also correlated with changes in SV after blood restitution (r = 0.83, P < 0.001). In conclusion, respiratory variations in VTI(Ao) using TTE appear to be a sensitive index of blood volume depletion and restitution. This dynamic parameter predicted fluid responsiveness more reliably than static markers of cardiac preload.

Animals↗