Biomedical subjects
Louis P Perrault
Publications and source records attributed to Louis P Perrault.
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.
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.
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.
Successful explantation of a left ventricular assist device following acute fulminant myocarditis.
A left ventricular (LV) assist device was implanted in a 53-year-old woman in cardiogenic shock secondary to fulminant myocarditis. LV function recovered to normal after one week of support from an LV assist device. The device was explanted and the patient is showing a good outcome with a normalized LV function.
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.
Late iatrogenic coronary stenosis after selective intraoperative antegrade myocardial protection for stentless aortic valve replacement.
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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.
Temporary internal thoracic artery occlusion during off-pump coronary artery bypass grafting with the new poloxamer P407 does not cause endothelial dysfunction.
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Carbon dioxide embolism induced by endoscopic saphenous vein harvesting during coronary artery bypass grafting.
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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.
Inhaled milrinone: a new alternative in cardiac surgery?
The administration of milrinone through inhalation has been studied in only a few animal and human studies. Compared to the intravenous administration, inhaled milrinone has been shown to reduce pulmonary artery pressure without systemic hypotension. Therefore, this approach could represent an alternative to nitric oxide. This current state of knowledge of intravenous and inhaled milrinone is presented and summarized.
Fifteen years of clinical and echocardiographic follow up with the carbomedics heart valve.
BACKGROUND AND AIM OF THE STUDY: Mechanical prostheses are used in young patients, the CarboMedics valve having been the mechanical valve of choice of the present authors during the past 15 years. The study aim was to analyze long-term clinical and echocardiographic results obtained with CarboMedics mechanical valves. METHODS: A total of 2,953 patients underwent valve replacement with the CarboMedics valve between 1988 and 2004 at the Montreal Heart Institute. Patients were prospectively followed at the outpatient valve clinic. Subsequently, 1,004 patients underwent echocardiographic examinations during follow up. RESULTS: In total, 1,597 patients (mean age 57 +/- 12 years) underwent isolated aortic valve replacement (AVR), 1,043 patients (mean age 59 +/- 10 years) underwent isolated mitral valve replacement (MVR), and 313 patients (mean age 58 +/- 11 years) underwent AVR+MVR. The mean five-, 10- and 15-year actuarial survival rates were 83 +/- 1%, 70 +/- 2% and 62 +/- 3% in AVR patients, 76 +/- 1%, 59 +/- 2% and 40 +/- 14% in MVR patients, and 68 +/- 3%, 51 +/- 4% and 33 +/- 9% in AVR+MVR patients. The mean 15-year freedom from cerebral embolism, hemorrhage and reoperation was 95 +/- 1%, 97 +/- 1% and 95 +/- 1% in AVR patients, 92 +/- 1%, 97 +/- 1% and 93 +/- 1% in MVR patients, and 94 +/- 2%, 93 +/- 2% and 91 +/- 4% in AVR+MVR patients. AVR patients had a mean aortic gradient of 29 +/- 14, 20 +/- 8, 18 +/- 7, 16 +/- 7, 12 +/- 5 and 11 +/- 5 mmHg with 19, 21, 23, 25, 27 and 29 mm prostheses, respectively (p = 0.001). MVR patients had a mean mitral gradient of 5.3 +/- 3, 4.9 +/- 2.2, 4.6 +/- 2, 4.4 +/- 2.9 and 4.9 +/- 1.8 mmHg with 25, 27, 29, 31 and 33 mm prostheses, respectively (p = 0.63). CONCLUSION: Patient survival and valve-related complications were satisfactory at 15 years after valve replacement with the CarboMedics valve. Mean aortic gradients were high with the 19-mm aortic prostheses, but all other valve sizes showed good hemodynamic performance, as measured using transthoracic echocardiography.
Effect of sternotomy and extracorporeal circulation on pulmonary neutrophil kinetics in pigs.
Pulmonary margination of neutrophils may contribute to lung damage after extracorporeal circulation for cardiac surgery. We evaluated single-pass pulmonary neutrophil kinetics using the multiple indicator-dilution technique in control pigs (n = 10), after sternotomy alone (sterno, n = 10) or after 30 min of observation following a period of 90 min extracorporeal circulation (n = 7). Blood neutrophils increased in the control and sterno groups (p < 0.05) but remained unchanged in the extracorporeal circulation group. The transfer coefficient for neutrophil margination from the circulating to the lung-marginated pool (k(c-m)) and pulmonary neutrophil clearance (Cl(c-m)) were similar between the three groups. There was an inverse correlation between k(c-m) and the degree of lung tissue perfusion evaluated from the tracer-accessible extravascular lung water (r = -0.54, p < 0.01). There was no arterio-venous gradient of neutrophils in any of the groups, suggesting a dynamic equilibrium of the margination/demargination processes. We conclude that extracorporeal circulation does not significantly modify single pass pulmonary neutrophil kinetics 30 min after reperfusion. The rate of neutrophil margination to the tracer-accessible lung tissue suggests that lung tissue de-recruitment is associated with increased neutrophil margination.
Concomitant surgical myocardial revascularization is still the gold standard for combined valvular and coronary heart disease.
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Additive effects of hyperlipidemia and rejection on development of graft coronary vasculopathy following cardiac transplantation.
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Cardiac lymphoma following mitral valve replacement.
A primary cardiac lymphoma was encountered in a patient with prosthetic mitral valve dysfunction. Although rare, this tumor could be related to the presence of prosthetic material and specifically that of Dacron. Primary cardiac tumors have to be considered in the differential diagnosis of prosthetic valve dysfunction.
On decreasing distal endothelial damage after intracoronary shunt insertion.
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