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Biomedical subjects

Michel Carrier

Publications and source records attributed to Michel Carrier.

At least 19 recordsLinked to original sources
PubMed2007

Effect of intravenous N-acetylcysteine on outcomes after coronary artery bypass surgery: a randomized, double-blind, placebo-controlled clinical trial.

OBJECTIVE: N-acetylcysteine, a potent anti-inflammatory and antioxidant agent, is known to decrease the production of reactive oxygen species after cardiac surgery. The objective of this study was to evaluate the effects of intravenous N-acetylcysteine on clinical and biochemical outcomes after coronary artery bypass surgery with cardiopulmonary bypass. METHODS: One hundred patients (mean age 60.5 years, range 43-78 years, 89% male) undergoing coronary artery bypass grafting at the Montreal Heart Institute were randomized to receive either N-acetylcysteine (600 mg orally the day before and the morning of the operation, a bolus of 150 mg/kg of intravenous N-acetylcysteine before skin incision, followed by perfusion at 12.5 mg x kg(-1) x h(-1) over 24 hours; n = 50) or placebo (n = 50). The patients and clinical team were blinded to group assignments. Preoperative characteristics were similar between the two groups. Postoperative clinical data (death, myocardial infarction, low-output syndromes, arrhythmias, bleeding, transfusion requirements, and intensive care unit and hospital lengths of stay) and biochemical markers (creatine kinase MB, troponin T, creatinine, hemoglobin, and platelet levels) were evaluated serially over 4 days. RESULTS: Clinical outcomes were not significantly different between the two groups with regard to the incidence of death, myocardial infarction, bleeding, transfusion requirements, intubation time, and hospital length of stay. No differences were found in postoperative biochemical markers (troponin T, creatine kinase MB, creatinine, hemoglobin, and platelets) between the groups. No differences were observed between the groups in interleukin-6 production (P = not significant). CONCLUSIONS: Prophylactic use of N-acetylcysteine in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass does not lead to improvement in clinical results or biochemical markers. Further strategies to decrease reperfusion injury should be devised.

Acetylcysteine↗
PubMed2006

Alterations in the endothelial G-protein coupled receptor pathway in epicardial arteries and subendocardial arterioles in compensated left ventricular hypertrophy.

The present study was designed to compare alterations of endothelium-dependent vasorelaxation in coronary epicardial arteries and subendocardial arterioles occurring in left ventricular hypertrophy (LVH) secondary to 60 days of aortic banding in a porcine model. Development of LVH was documented by echocardiogram and the endothelial function of subendocardial and epicardial vessels was studied by constructing concentration-response curves in a pressure myograph and standard organ chambers, respectively. 5-HT induced relaxations were reduced (p<0.05) in both vessel types isolated from pigs with LVH. Dilations of subendocardial arterioles and epicardial vessels to UK14304 were depressed by LVH. In the presence of Nomega-nitro-L-arginine (L-NNA), EDHF solely accounts for BK-induced relaxations; it fully compensates for the loss of NO in arterioles, but only partially in epicardial arteries isolated from LVH swine. Endothelium-independent relaxations induced by SNP were not altered in both vessel types from the LVH group. In a porcine model of LVH secondary to 60 days of aortic banding, the associated coronary endothelial dysfunction preferentially involves Gi-protein mediated relaxations in arterioles and arteries but also affects Gq-protein mediated relaxations in epicardial coronary arteries.

Animals↗
PubMed2006

Effect of tetrahydrobiopterin on selective endothelial dysfunction of epicardial porcine coronary arteries induced by cardiopulmonary bypass.

BACKGROUND: We hypothesized that cardiopulmonary bypass induces a selective alteration of the coronary arterial endothelial cell signal transduction which could be explained by a state of depletion and/or decreased activity of endogenous tetrahydrobiopterin (BH(4)). The aim of this study was to assess the effects of cardiopulmonary bypass and BH(4) on the endothelial function of epicardial coronary arteries in a swine model of cardiopulmonary bypass. METHODS: Swine underwent 90 min of cardiopulmonary bypass alone (N=19) or in association with a brief cardioplegic arrest with (N = 6) or without (N = 5) in vivo BH(4) administration, followed by a 60-min period following weaning from cardiopulmonary bypass and were compared to a control group (N = 7). Endothelium-dependent relaxations of epicardial coronary artery rings were studied using standard organ chamber experiments in the presence or absence of in vitro BH(4) or superoxide dismutase (SOD) and catalase. RESULTS: Cardiopulmonary bypass caused a statistically significant reduction of endothelium-dependent relaxations to serotonin (p < 0.0001), bradykinin (p < 0.001), UK14304 (p < 0.0001) and calcium ionophore (p < 0.01) in epicardial porcine coronary arteries. In vitro and in vivo BH(4) supplementation improved endothelium-dependent relaxations to serotonin and bradykinin, which were left unchanged by SOD-catalase administration. Cardiopulmonary bypass was associated with a decrease in nitric oxide availability (p = 0.002) and increased oxidative stress (p < 0.001), which were both restored by in vivo BH(4) administration (p < 0.001). CONCLUSION: Treatment with BH(4) improves the endothelial dysfunction of porcine epicardial coronary arteries, restores nitric oxide availability and reduces the oxidative stress associated with cardiopulmonary bypass.

Animals↗
PubMed2006

Importance of relative pulmonary hypertension in cardiac surgery: the mean systemic-to-pulmonary artery pressure ratio.

OBJECTIVE: To determine the importance of the mean arterial pressure-to-mean pulmonary artery pressure ratio (MAP/MPAP) in cardiac surgical patients. DESIGN: Retrospective and prospective studies (3 groups). SETTING: Tertiary care hospital. PARTICIPANTS: Cardiac surgical patients (1,557). INTERVENTION: Retrospective analysis (group 1), induction of general anesthesia (group 2), and transesophageal Doppler echocardiography (group 3). MEASUREMENTS AND MAIN RESULTS: In group 1 (n = 1,439), demographic, hemodynamic, and other perioperative variables were collected with follow-up until hospital discharge. The primary outcome was a composite index of hemodynamic complications that included death, resuscitated cardiac arrest, use of vasopressive drugs for >24 hours postoperatively, or the use of an intra-aortic balloon pump that was not present preoperatively. In group 2 (n = 34), the effect of general anesthesia on the MAP/MPAP ratio was studied, and Doppler echocardiography was used to evaluate diastolic profiles in group 3 (n = 74). In group 1, a total of 302 patients experienced hemodynamic complications (21%). The MAP/MPAP ratio was significantly lower in the patients who developed complications (3.3 +/- 1.3 v 4.0 +/- 1.4, p < 0.0001). Multiple stepwise logistic regression analysis showed the MAP/MPAP ratio to be an independent predictor of hemodynamic complications (p < 0.0001). In group 2, the induction of anesthesia decreased both MAP and MPAP, but the ratio remain unchanged (p = 0.242). In group 3, patients with moderate-to-severe diastolic dysfunction (DD) had a lower ratio (3.5 +/- 0.9 v 4.0 +/- 1.1 compared with those with normal-to-mild DD, p = 0.07). CONCLUSION: The MAP/MPAP ratio is a useful hemodynamic variable in cardiac surgery. It can be used to predict hemodynamic complications after cardiac surgery, is not influenced by the induction of anesthesia, and tends to correlate with the severity of left ventricular diastolic profiles.

Aged↗
PubMed2006

Left and right ventricular diastolic dysfunction as predictors of difficult separation from cardiopulmonary bypass.

PURPOSE: As the evaluation of diastolic function can be complex in the setting of a busy cardiac operating room, its assessment may benefit from an algorithmic approach using transesophageal echocardiography. We developed a diagnostic algorithm which was then applied in a series of cardiac surgery patients to determine whether moderate to severe left ventricular diastolic dysfunction (LVDD) and right ventricular diastolic dysfunction (RVDD) can predict difficult separation from cardiopulmonary bypass (DSB). METHODS: An algorithm using pulsed-wave Doppler interrogation of the mitral and tricuspid valve, the pulmonary and hepatic venous flow, and tissue Doppler interrogation of the mitral and tricuspid annulus was developed. The study was divided in two phases involving two groups of patients undergoing cardiac surgery. In phase I, echocardiographic evaluations of patients (n = 74) were used to test the reproducibility of the algorithm and to evaluate inter-observer variability using Cohen's kappa values which were calculated in three specific periods. In phase II, the algorithm was applied to a second group of patients (validation group, n = 179) to explore its prognostic significance. The primary end-point in phase II was DSB. RESULTS: In phase I, the kappa coefficients for LVDD and RVDD algorithms were 0.77 and 0.82, respectively. In phase II, moderate or severe degrees of LVDD were observed in 29 patients (16%) and moderate to severe RVDD was observed in 18 patients (10%) before cardiac surgery. Both moderate and severe LVDD (P = 0.017) and RVDD (P = 0.049) before surgery were observed more frequently in patients with DSB. CONCLUSION: Moderate and severe LVDD and RVDD can be identified with very good reproducibility, and both degrees of diastolic dysfunction are associated with DSB.

Aged↗
PubMed2006

Invited commentary.

Explore the source record for details and available documents.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2006

Pexelizumab reduces death and myocardial infarction in higher risk cardiac surgical patients.

BACKGROUND: Morbidity and mortality after coronary artery bypass graft surgery are directly related to specific preoperative risk factors. We assessed the influence of preoperative risk factors on the effect of pexelizumab, a C5 complement inhibitor, to reduce postoperative morbidity and mortality in this post hoc analysis of the Pexelizumab for Reduction in Myocardial Infarction and MOrtality in Coronary Artery Bypass Graft surgery (PRIMO-CABG) trial, a phase III double-blind, placebo-controlled study of 3,099 patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass. METHODS: The composite endpoint of death or myocardial infarction or both through postoperative day 30 was examined in subpopulations of patients with pre-specified risk factors, which included diabetes mellitus, prior coronary artery bypass graft, urgent intervention, female sex, history of neurologic event, history of congestive heart failure, and two or more previous myocardial infarctions or a recent myocardial infarction. Stratified post hoc analyses were also performed on patients presenting with two or more and three or more of those risk factors. RESULTS: Pexelizumab significantly reduced the incidence of the composite endpoint of death or myocardial infarction through postoperative day 30 by 28% in patients with two or more risk factors (p = 0.004) and 44% in patients with three or more risk factors (p < 0.001). CONCLUSIONS: The C5 complement inhibitor, pexelizumab, reduced morbidity and mortality among high-risk patients undergoing coronary artery bypass grafting with cardiopulmonary bypass.

Antibodies, Monoclonal↗
PubMed2006

Effect of pexelizumab in coronary artery bypass graft surgery with extended aortic cross-clamp time.

BACKGROUND: Prolonged cross-clamp time during cardiac surgery increases the risk of postoperative mortality and myocardial injury. This subanalysis from the pexelizumab for reduction of infarction and mortality in coronary artery bypass grafting surgery (PRIMO-CABG) trial, a phase III double-blind, placebo-controlled study of 3,099 patients undergoing on-pump coronary artery bypass graft surgery with or without valve surgery, assessed the impact of pexelizumab, an investigational C5 complement inhibitor, on postoperative outcomes after prolonged aortic cross-clamp time. METHODS: The composite endpoint of death or myocardial infarction through postoperative day 30 and death alone through days 30, 90, and 180 were examined in subpopulations of patients across different cross-clamp times. RESULTS: After prolonged cross-clamping (> or = 90 minutes), death, or myocardial infarction through day 30 and death through days 30, 90, and 180 were significantly increased in the intent-to-treat population and were even higher in patients with two or more prespecified risk factors, compared with all patients cross-clamped less than 90 minutes. Pexelizumab significantly reduced the incidence of death or myocardial infarction through day 30, and significantly reduced the incidence of mortality through day 180, in patients with two or more risk factors that required prolonged cross-clamp time. Pexelizumab also significantly reduced perioperative myocardial injury in all patients requiring prolonged cross-clamp time. CONCLUSIONS: In this retrospective, subgroup analysis, pexelizumab reduced postoperative morbidity and myocardial injury in patients with multiple risk factors who underwent prolonged cross-clamp time during coronary artery bypass surgery. The clinical benefit of pexelizumab may be related to the effect of complement inhibition in the presence of potential ischemic-reperfusion injury associated with prolonged aortic cross-clamp time.

Antibodies, Monoclonal↗
PubMed2006

Randomized controlled trial of pericardial blood processing with a cell-saving device on neurologic markers in elderly patients undergoing coronary artery bypass graft surgery.

BACKGROUND: Processing of pericardial shed blood with a cell-saving device was claimed to prevent lipid microembolization and to protect from neurocognitive dysfunction after cardiopulmonary bypass. The present study tested the hypothesis that processing of pericardial shed blood with a cell-saving device during cardiopulmonary bypass would significantly decrease serum levels of protein S100B, and improve brain oxygen saturation and neurologic outcome, all markers of brain injury in elderly patients. METHODS: Forty patients, 65 years of age and older, undergoing coronary artery bypass graft with cardiopulmonary bypass, were prospectively randomly assigned to processing of pericardial shed blood with a cell-saving device or to conventional use of a standard closed venous reservoir where cardiotomy blood was collected and reinfused through the arterial circuit (control group). Serum in S100B was measured 30 minutes, 4 hours, 24 hours, and 48 hours after surgery. Near-infrared spectroscopy monitoring was performed during the procedure and the National Institutes of Health stroke scale was measured before surgery and at the time of discharge of the hospital. RESULTS: Patients in the cell-saving device group averaged 72 +/- 3 years of age and underwent 3.1 +/- 0.7 coronary artery grafts with a mean of 62 +/- 20 minutes of cardiopulmonary bypass time. Patients in the control group averaged 75 +/- 4 years of age (p = 0.03) and underwent 3.3 +/- 0.6 coronary artery grafts (p = 0.49) with a mean of 75 +/- 25 minutes of cardiopulmonary bypass time (p = 0.12). The quantity of blood administered from the cell-saving device averaged 281 +/- 162 mL per patient. Serum protein S100B levels averaged 0.06 +/- 0.03 before surgery and 0.51 +/- 0.23 microg/L 30 minutes after surgery in the cell-saving device patients compared with 0.076 +/- 0.04 before surgery (p = 0.32) and 1.48 +/- 0.66 (p < 0.0001) in the control patients. The near-infrared spectroscopy baseline mean value of left and right cortical region was 58% +/- 12% and 55% +/- 7% in the cell-saving device group versus 59% +/- 7% and 53% +/- 6% in the control group (p = 0.67 and 0.36), and no difference occurred over time in each group. The National Institutes of Health stroke score before and after surgery was similar in the two groups. There was one cerebrovascular complication in the control group (1 of 20, 5%) after surgery. CONCLUSIONS: The difference between the two groups occurred 30 minutes after surgery, at which time serum levels of protein S100B were significantly higher in the control group compared with cell-saving device patients. Although use of the cell-saving device was not associated with higher brain oxygen saturation nor changes in the National Institutes of Health stroke score, it is associated with lesser release of nonspecific markers of brain injury in elderly patients.

Aged↗
PubMed2006

Dynamic quantitative echocardiographic evaluation of mitral regurgitation in the operating department.

Hemodynamic modifications induced by general anesthesia could lead to underestimation of mitral regurgitation (MR) severity in the operating department and potentially serious consequences. The intraoperative severity of MR was prospectively compared with the preoperative baseline evaluation using dynamic quantitative transesophageal echocardiography in 25 patients who were stable with MR 2/4 or greater undergoing coronary bypass, mitral valve operation, or both. Significant changes in the severity of MR using transesophageal echocardiographic criteria occurred after the induction of general anesthesia and with phenylephrine. Quantitative transesophageal echocardiographic evaluation of MR using effective orifice area and vena contracta, and the use of phenylephrine challenge, were useful to avoid underestimating MR severity in the operating department.

Adolescent↗
PubMed2006

Biventricular diastolic filling patterns after coronary artery bypass graft surgery.

OBJECTIVE: We sought to study the evolution of biventricular filling properties after coronary artery bypass grafting. BACKGROUND: The evolution of diastolic function as defined with newer echocardiographic modalities after coronary artery bypass grafting surgery is unknown in patients with preoperative left ventricular diastolic dysfunction. METHODS: Transthoracic echocardiography was performed preoperatively and 48 hours and 6 months after coronary artery bypass grafting in 49 patients (randomized to milrinone [n = 25]) or placebo [n = 24]) with preoperative left ventricular diastolic dysfunction classified according to published criteria. Mild right ventricular diastolic dysfunction was defined as the ratio of early to atrial filling velocity of less than 1 in transtricuspid flow or the velocity of reversed atrial flow of greater than 50% of that of systolic flow in hepatic venous flow or the ratio of tricuspid annulus velocity during early and atrial filling of less than 1 if both the ratio of early to atrial filling velocity and the ratio of systolic to diastolic velocity was greater than 1 in hepatic venous flow. Moderate right ventricular diastolic dysfunction was diagnosed when there was a ratio of early to atrial filling velocity of greater than 1 with a ratio of systolic to diastolic velocity of less than 1. Severe right ventricular diastolic dysfunction was defined as a ratio of early to atrial filling velocity of greater than 1 associated with reversed systolic wave in hepatic venous flow. RESULTS: Moderate and severe left ventricular diastolic dysfunction increased from preoperatively to 48 hours after coronary artery bypass grafting from 8.2% to 53.7% and from 2.0% to 9.7%, respectively (P < .0001, 48 hours vs preoperatively for both), and the patterns at 6 months were similar to those observed preoperatively. Similar evolution over time was found for right ventricular diastolic dysfunction. CONCLUSIONS: In patients with preoperative left ventricular diastolic dysfunction, biventricular filling patterns are impaired initially but return to preoperative status 6 months after coronary artery bypass grafting.

Aged↗
PubMed2006

Prevalence, characteristics, and predictors of chronic nonanginal postoperative pain after a cardiac operation: a cross-sectional study.

OBJECTIVE: This study was designed to assess the prevalence, characteristics, effect, and predictors of chronic postoperative pain 1 to 3 years after cardiac surgery. METHODS: Seven hundred thirty-six patients who underwent coronary artery bypass surgery, valve replacement, or both between 1999 and 2002 were mailed questionnaires (response rate, 79% [n = 579]; 564 questionnaires were analyzed), and their hospital records were reviewed. RESULTS: Nonanginal chronic postoperative pain affected 23% of patients. Eighty percent of them had pain 1 or more days per week. The worst and usual pain intensities during the week preceding the survey reached moderate to severe levels (> or =4/10) in more than half of the patients. Thirty-one percent of the patients with chronic postoperative pain had taken analgesic pain medication during that week. During the same period, pain interfered significantly (> or =4/10) with various aspects of patients' daily life (eg, general activity level: 39.1%, sleep: 36.7%). When patients with and without chronic postoperative pain were compared, the former group had significantly higher levels of anxiety and depression, and they perceived their health-related quality of life as more compromised. Multivariate logistic regression analysis revealed that greater analgesic needs in the first few days postoperatively were associated with an increased risk of chronic postoperative pain. The only other significant factor was the time elapsed from surgical intervention to survey: the longer it was, the less likely the patients were to report chronic postoperative pain. CONCLUSION: The prevalence, severity, and effect of chronic postoperative pain after cardiac surgery should not be underestimated. Longitudinal prospective studies are needed to further evaluate risk factors, including inadequate postoperative pain relief in the acute period.

Adult↗
PubMed2006

Temporary coronary artery occlusion during off-pump coronary artery bypass grafting with the new poloxamer P407 does not cause endothelial dysfunction in epicardial coronary arteries.

OBJECTIVE: The aim of this study was to assess the efficacy of the novel reversible thermosensitive gel poloxamer 407 for occlusion of the coronary vessel necessary for minimally invasive operations and its effects on coronary endothelium. METHODS: Domestic swine were submitted to occlusion of the left anterior descending or right coronary artery using the poloxamer. The left and right internal thoracic arteries were used as grafts to perform coronary artery bypasses. Animals were humanely killed after 3 hours of perfusion (acute; n = 8) or 3 days (subacute; n = 6). The vascular reactivity of coronary artery was evaluated in response to serotonin and bradykinin. Histologic studies were performed to analyze cardiomyocyte necrosis and endothelial coverage. RESULTS: The gel led to an occlusion of 7.8 +/- 2.2 minutes. Concentration-response curves of occluded coronary segments showed no difference of endothelium-dependent relaxations in both operated groups (P < .05 vs control). Histologic studies demonstrated the absence of cardiomyocyte necrosis after coronary artery occlusion in the acute group; a small infarct zone was detected in 1 animal in the subacute group, resulting from an occlusion of the first diagonal branch. The endothelial layer coverage was preserved in both groups. CONCLUSION: The poloxamer 407 represents a promising technique for obtaining hemostasis at the site of anastomosis during construction of bypasses during beating heart coronary artery surgery, without damage to the endothelium or ischemic consequence.

Anastomosis, Surgical↗
PubMed2006

Role of probucol on endothelial dysfunction of epicardial coronary arteries associated with left ventricular hypertrophy.

The lipid-lowering agent probucol may be efficacious, through its antioxidant properties, to limit and reverse the vascular endothelial dysfunction associated with left ventricular hypertrophy (LVH). LVH was induced by performing an aortic banding (AB) on swine, except for controls (group 1). The untreated AB group received a placebo (group 2) whereas the treated groups received probucol (1000 mg/d orally); the third group began its treatment on the day of the banding (for 60 d), the fourth began on day 30 and the fifth on day 60 after AB (both for 30 d). Hypertrophy was assessed by echocardiography and histology. Coronary vascular reactivity was evaluated in organ chambers and endothelial function by quantification of NO2/NO3 and cyclic guanosine-3',5'-monophosphate. To assess oxidative stress, hydroperoxides and angiotensin II levels as well as superoxide dismutase activity were evaluated. After treatment with probucol, a significant decrease in left ventricle/body weight ratio was observed compared with the untreated group. Dose-response curves of the probucol groups showed an improvement in endothelium-dependent relaxations, associated with increased nitric oxide bioavailability and decreased angiotensin II and hydroperoxide levels. In conclusion, the antioxidant probucol limited the development and induced the regression of LVH and the associated coronary endothelial dysfunction.

Angiotensin II↗