Biomedical subjects

Patrick Mathieu

Publications and source records attributed to Patrick Mathieu.

24 records · Page 2Linked to original sources

PubMed2003

Myocardial infarction in a young woman secondary to a rupture of a noncoronary sinus of Valsalva aneurysm without coronary artery disease.

A 22-year-old woman presented with sudden onset of chest pain. Echocardiography showed a ruptured aneurysm of the noncoronary sinus of Valsalva in the right atrium. Slight ST segment depression was observed on initial electrocardiography (ECG). The patient was transferred to a tertiary care centre 10 h after the onset of symptoms. Surgery consisted of patch closure of the noncoronary sinus and tricuspid valve resuspension through the right atrium. Postoperatively, myocardial infarction (MI) was diagnosed based on a significant increase in cardiac enzymes and a new septal and apical akinesia on echocardiography. The etiology of MI in such a setting is multifactorial. Decreased coronary perfusion secondary to the severe aortic valve regurgitation and increased left ventricular end diastolic pressure, coupled with increased myocardial workload and delay before surgery may be implicated in the genesis of MI.

Adult↗

PubMed2003

[Abdominal complications associated with cardiac surgery. Review of a contemporary surgical experience and of a series done without extracorporeal circulation].

INTRODUCTION: To evaluate the prevalence, risk factors and morbidity associated with gastrointestinal (GI) complications after cardiac surgery, with and without cardiopulmonary bypass, we carried out a retrospective cohort study at a university teaching hospital. METHODS: We divided the 11,405 eligible adult patients into 2 groups: group A (operated on between January 1992 and June 1996) (4657 patients) and group B (operated on between July 1996 and December 2000) (6748 patients). RESULTS: We found 147 GI complications in 134 (1.2%) patients. The incidence of GI morbidity was similar for the 2 groups of patients (group A, n = 59/4657 [1.2%]; group B, n = 75/6748 [1.1%]. Patients from group B were older, obese, diabetic and presented with more peripheral and cerebrovascular disease. Bleeding, gastritis and ulcer with perforation, the most common of these GI events, were associated with the esophagus and stomach (67/147 [45.5%]). Other events that we documented included cholecystitis 10 (6.8%), pancreatitis 13 (8.8%), episodes of small and large bowel ischemia 17 (11.6%), pseudomembranous colitis 12 (8.3%) and diverticulitis 5 (3.4%). Mesenteric ischemia was responsible for 11 (37.9%) of the 29 deaths. Two hundred and ninety-three patients were revascularized without extracorporeal circulation during this study. In this group, we were able to pinpoint 5 (1.7%) GI complications with 3 cases of mesenteric ischemia. Multivariate analysis identified renal insufficiency, prolonged intubation and sepsis as significant, predictive variables of GI complications for the 2 groups of patients whereas the Parsonnet score and stroke were predictive for the second group. CONCLUSIONS: Although cardiac surgery is now being performed on older patients with significant comorbidity, we could not demonstrate a significant increase of GI complications after cardiac surgery. Off-pump coronary artery bypass does not seem to protect patients from these complications.

Aged↗

PubMed2003

Determinants of gastrointestinal complications in cardiac surgery.

We designed this study to define determinants of gastrointestinal complications after cardiac surgery. From January 1992 through December 2000, 11,058 patients underwent cardiac surgery on cardiopulmonary bypass at our institution. Data were prospectively collected and univariate and multivariate analyses conducted. A total of 147 gastrointestinal complications occurred in 129 patients (129/11,058; 1.2%) including gastroesophagitis (18, 12.2%), upper gastrointestinal hemorrhage (42, 28.6%), perforated peptic ulcer (7, 4.7%), cholecystitis (10, 6.8%), pancreatitis (13, 8.8%), intestinal ischemia (17, 11.5%), colitis (18, 12.2%), diverticulitis (5, 3.4%), intestinal occlusion (2, 1.1%), lower gastrointestinal hemorrhage (1, 0.7%), and mixed gastrointestinal complications (14, 9.5%). Patients with gastrointestinal complications were significantly older and had significantly higher comorbidity (unstable angina, chronic renal failure, and peripheral vascular disease), morbidity (prolonged mechanical ventilation, intraaortic balloon pumping, bleeding, acute renal failure, stroke, and infection), and mortality rates (22.5% vs 4%, P < 0.0001). They also had longer cardiopulmonary bypass times and higher valvular surgery rates. Multivariate analysis identified 6 independent predictors for gastrointestinal complications: prolonged mechanical ventilation (odds ratio [OR], 5.5), postoperative renal failure (OR, 4.2), sepsis (OR, 3.6), valve surgery (OR, 3.2), preoperative chronic renal failure (OR, 2.7), and sternal infection (OR, 2.4). Factors such as mechanical ventilation, renal failure, and sepsis are the stronger predictors for GI complications, causing splanchnic hypoperfusion, hypomotility, and hypoxia. Furthermore, excessive anticoagulation after valve replacement may lead to GI hemorrhage. Valve surgery, often requiring anticoagulation, increases bleeding. Monitoring mechanical ventilation and hemodynamic parameters, adopting early extubation and mobilization measures, preventing infections, and strictly monitoring renal function and anticoagulation may prevent catastrophic abdominal complications.

Aged↗

PubMed2002

Prolonged blockade of CD40-CD40 ligand interactions by gene transfer of CD40Ig results in long-term heart allograft survival and donor-specific hyporesponsiveness, but does not prevent chronic rejection.

Previous work on blockade of CD40-CD40 ligand interaction in mice and primates with anti-CD40 ligand mAbs has resulted in a moderate prolongation of allograft survival without the development of true allograft tolerance. In this study, we show in rats that adenovirus-mediated gene transfer of CD40Ig sequences into the graft resulted in prolonged (>200 days) expression of CD40Ig and in long-term (>300 days) survival. Recipients expressing CD40Ig displayed strongly (>90%) inhibited mixed leukocyte reactions and alloantibody production at early (days 5 and 17) and late time points (>100 day) after transplantation, but showed limited inhibition of leukocyte infiltration and cytokine production as evaluated by immunohistology at early time points (day 5). Recipients of long-surviving hearts showed donor-specific hyporesponsiveness since acceptance of second cardiac allografts was donor specific. Nevertheless, long-term allografts (>100 days) displayed signs of chronic rejection vasculopathy. Occluded vessels showed leukocyte infiltration, mainly composed of CD4(+) and CD8(+) cells, macrophages, and mast cells. These recipients also showed antidonor CTL activity. Recipients expressing CD40Ig did not show nonspecific immunosuppression, as they were able to mount anticognate immune responses that were partially inhibited at early time points and were normal thereafter. We conclude that gene transfer-mediated expression of CD40Ig resulted in a highly efficient inhibition of acute heart allograft rejection in rats. This treatment induced donor-specific inhibition of certain alloreactive mechanisms in the short-, but not the long-term, which resulted in long-term survival of allografts concomitant with the development of chronic rejection.

Adenoviridae↗

PubMed2002

Gene transfer of heme oxygenase-1 and carbon monoxide delivery inhibit chronic rejection.

The hallmark of chronic rejection is the occlusion of the artery lumen by intima hyperplasia as a consequence of leukocyte infiltration and vascular smooth muscle cell (VSMC) migration and proliferation. Heme oxygenase-1 (HO-1) is a tissue protective molecule which degrades heme into carbon monoxide (CO), free iron and biliverdin. We analyzed the effects of HO-1 gene transfer into the vessel wall using an adenoviral vector (AdHO-1) and of CO delivery in a model of chronic allogeneic aorta rejection in rats. Carbon monoxide treatment was achieved by a new pharmacological approach in transplantation using methylene chloride (MC), which releases CO after degradation. AdHO-1-mediated gene transfer into aorta endothelial cells (ECs) or CO delivery resulted in a significant reduction in intimal thickness compared to untreated or noncoding adenovirus-treated controls. Aortas transduced with AdHO-1 or treated with CO showed a reduction in the number of leukocytes as well as in the expression of adhesion molecules, costimulatory molecules and cytokines, with the gene transfer treatment displaying a more pronounced effect than the CO treatment. Conversely, CO inhibited VSMC accumulation in the intima more efficiently than AdHO-1 treatment. Gene transfer of HO-1 and pharmacological manipulation of CO are novel approaches to the analysis and treatment of chronic rejection.

Animals↗

PubMed2002

Differential sensitivity of endothelial cells of various species to apoptosis induced by gene transfer of Fas ligand: role of FLIP levels.

BACKGROUND: Fas ligand expression by cells of the vessel wall has been proposed to play a role in normal and pathologic conditions. Genetic engineering of vascularized organs for endothelial cell (EC) expression of FasL could protect the endothelium and underlying tissues from infiltrating Fas+ leukocytes. Nevertheless, the endogenous expression of FasL by ECs of different species and the potential deleterious effects of enforced FasL expression by ECs are largely unknown. In human ECs, levels of FLICE/caspase 8-inhibitory protein (FLIP) have been shown to control apoptosis mediated by Fas. MATERIALS AND METHODS: Cell surface expression of FasL in rat, mouse, human, and pig ECs was obtained using recombinant adenoviruses or transient plasmid transfection assays. FasL expression was evaluated by FACS analysis and cytotoxicity assays. Apoptosis was evaluated using annexin V, TUNEL, and cytotoxicity assays. FLIP levels were evaluated by Western blot analysis and overexpression was obtained by transient transfection. RESULTS: Analysis of ECs from different species showed that FasL was predominantly present in the cytoplasm, and depending on the species, little or no cell surface expression was detected. Enforced cell surface expression of FasL on rat or mouse ECs, either in culture or within the vessel wall resulted in massive apoptosis. In contrast, porcine or human ECs were completely resistant to apoptosis mediated by Fas-FasL interaction. Markedly reduced FLIP levels were observed in rat and mouse ECs compared to human and porcine ECs. Overexpression of FLIP in rat ECs conferred protection against cell surface expression of FasL. CONCLUSIONS: The consequences of FasL overexpression depend on the subcellular compartment and species in which FasL enforced expression is targeted and this is at least partially related to FLIP levels.

Animals↗