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Biomedical subjects

M Carrier

Publications and source records attributed to M Carrier.

At least 127 records · Page 7Linked to original sources

[Effects of acute rejection on the endothelium-dependent relaxation of coronary arteries of the transplanted heart in dogs].

Chronic rejection has been linked to premature coronary atherosclerosis in heart transplantation and may be related to altered vascular reactivity. However, the effect of acute rejection on coronary reactivity remains uncertain. To evaluate this aspect, coronary artery reactivity was studied during acute rejection in a canine model of heart transplantation. Two groups of mongrel dogs (n = 7) (20 to 30 kg) underwent heterotopic heart transplantation (cervical position), and received either no treatment (noTx) or cyclosporine (CyA), 10 mg/kg/day. On day 7, recipient native (NH) and grafted hearts (GH) were harvested and 4-mm rings from the circumflex coronary artery were studied in organ chambers for endothelium and smooth muscle reactivity. At the harvesting, GHnoTx displayed a grade IV/IV histologic rejection while GHCyA (CyA dosage 250-350 nM) reached grade IIIa-IV. Intimal hyperplasia was found in coronary arteries of treated and non-treated GH [4/7 (noTx) vs 3/7 (CyA)]. Endothelium-dependent relaxation to thrombin was impaired in GH compared to NH and was not influenced by CyA treatment [EC50 (-log M): GHnoTx: 1.12 +/- 0.18 vs NHnoTx: 1.67 +/- 0.16 (p = 0.06); GHCyA: 0.99 +/- 0.22 vs NHCyA: 1.64 +/- 0.09 (p = 0.02)]. Conversely, endothelium-dependent relaxation to 5-hydroxytryptamine (5-HT) was enhanced in both CyA-treated and noTx groups [EC50 (-log M); GHnoTx: 5.96 +/- 0.12 vs NHnoTx: 5.54 +/- 0.14 (p = 0.046); GHCyA: 6.65 +/- 0.19 vs NHCyA: 5.66 +/- 0.16 (p = 0.004)]. A facilitating effect of CyA on 5-HT was also seen in GH [GHnoTx vs GHCyA (p = 0.01)], suggesting a CyA intrinsic effect. Responses to acetylcholine and adenosine diphosphate were similar in all groups as well as endothelium-independent relaxation to sodium nitroprusside and contractile response to KCl and PGF2 alpha. We conclude that, in our model, acute rejection does not specifically impair cGMP-mediated relaxation but affects in a receptor-specific manner the endothelium-dependent relaxation. CyA did not prevent these effects but furthermore appeared to enhance the coronary endothelial sensitivity to 5-HT.

Acute Disease↗

Cytokine regulation of endothelin-1 release from bovine aortic endothelial cells.

The action of cytokines on the endothelium is a pivotal event in a number of vascular pathologies and inflammatory conditions. Here we have tested the effect of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, and IL-2 on endothelial-1 (ET-1) release from cultured bovine aortic endothelial cells. TNF-alpha and IL-1 beta caused concentration-dependent increases in ET-1 release. IL-2 up to concentrations of 100 ng/ml did not stimulate ET-1 release. The induction of ET-1 synthesis by cytokines may be of underlying importance in the endothelial cell dysfunction observed in a number of vascular diseases.

Animals↗

[Coronary angioplasty in cardiac transplantation].

Coronary artery disease is a common complication of cardiac transplantation threatening long-term survival and its management is not well defined. Percutaneous transluminal coronary angioplasty has been proposed as a palliative and exceptional technique in some patients with limited lesions. Of 145 patients undergoing cardiac transplantation between April 1983 and January 1994, 7 underwent 10 coronary angioplasty procedures. The majority was performed in asymptomatic patients, 4 for angigraphic abnormalities alone and 3 for documented painless ischaemia. Primary angiographic success was obtained in 90% (9 out of 10) of lesions. Complication included one acute occlusion and one arteriovenous fistula. Three patients died, 1, 8 and 10 months after angioplasty. After an average of 24 months' follow-up, 3 (out of 7) patients had no cardiac events (myocardial infarction, second angioplasty, second transplantation or death). A multicentre prospective controlled trial is necessary to assess the impact of this procedure on graft and patient survival.

Adult↗

[Assessment of the need for organ transplantation in Quebec].

OBJECTIVES: To evaluate the demand for organs for transplantation and to recommend a reorganization of transplantation services in Quebec. DESIGN: Retrospective study. SETTING: Province of Quebec, 1988 to 1992. PATIENTS: All patients on waiting lists for organ transplantation and patients who received transplants registered in national data banks. MAIN OUTCOME MEASURES: The actual annual demand for organ transplantation and the rate of transplantations performed. RESULTS: The rates of heart transplantation were lower than the actual annual demand, which resulted in many patients dying while awaiting transplantation. The actual annual demand for heart transplantation decreased during the last 5 years from 10.9 per million people in 1987 to 6.7 in 1992. The rates of heart transplantation in Quebec were higher than the Canadian average. The actual demand for lung transplantation was only 2.9 per million people on average in 1992. Demand for liver transplantation increased annually, reaching 8.6 per million in 1992. The rate of transplantation increased likewise but remained insufficient. The demand for kidney transplantation reached 27.2 per million people in 1992, and the transplantation rate was 17.8. CONCLUSIONS: Taking into account the actual demand for and supply of organ transplantation, to insure high-quality service and to control costs associated with organ transplantation, we recommend that the present system in Quebec be reorganized so that transplantations are performed in 12 centres: 7 for kidney transplantation, 2 for hearts, 2 for livers and 1 for lungs.

Databases, Factual↗

Vasoconstrictor effect of cyclosporin on the mesenteric artery in the dog.

To evaluate the effect of cyclosporin (CyA) on the mesenteric arterial bed, studies were performed on the isolated mesenteric artery perfused at a constant flow in 20 dogs. Changes in mesenteric perfusion pressure reflected variations in vascular resistance. Pure powder CyA was dissolved in autologous blood and injected at doses of 5, 10, 20 and 40 mg. Infusions of 5 and 10 mg CyA caused nonsignificant mean increases of 3 +/- 2 mm Hg [95% confidence interval (CI) -2 to +7; P > 0.05] and 3 +/- 3 mm Hg (95% CI -3 to +9; P > 0.05) in mesenteric perfusion pressure, with CyA blood levels in the mesenteric vein averaging 466 +/- 153 and 692 +/- 130 nmol/l, respectively, at the end of the injections. Infusions of 20 and 40 mg CyA caused significant increases in mesenteric perfusion pressure averaging 11 +/- 3 mm Hg (95% CI 3-18; P < 0.05) and 26 +/- 4 mm Hg (95% CI 16-34; P < 0.05), respectively. CyA blood levels at the end of infusion averaged 806 +/- 85 and 1118 +/- 89 nmol/l, respectively, in the mesenteric vein. Blockade of alpha-adrenergic receptors with phentolamine abolished the CyA vasoconstriction of the mesenteric artery, with the increase in perfusion pressure averaging 16 +/- 4 mm Hg before and 3 +/- 3 mm Hg after phentolamine (P < 0.05). Thus, in the dog, CyA causes an acute vasoconstriction of the mesenteric artery through stimulation of alpha-adrenergic receptors.

Animals↗

Total gastrectomy in a patient with an in situ right gastroepiploic artery graft.

A 60-year-old man in whom coronary artery bypass grafting was performed with an in situ right gastroepiploic artery presented with a gastric adenocarcinoma 22 months after myocardial revascularization. He underwent a total gastrectomy with preservation of the patent right gastroepiploic artery graft to the right coronary artery. Because of the difficulty of abdominal reoperations in patients with in situ right gastroepiploic artery grafts, surgeons must consider right gastroepiploic artery free graft or alternative conduits.

Adenocarcinoma↗

Effects of cold and warm blood cardioplegia assessed by myocardial pH and release of metabolic markers.

The optimal temperature of blood cardioplegia remains controversial. Interstitial myocardial pH was monitored online with a probe that was inserted in the anterior wall of the left ventricle. Venous pH, lactate production, and creatine kinase and troponin T release were measured in coronary sinus blood obtained in 14 dogs after ischemic arrest periods of 5, 10, 20, and 40 minutes with warm (n = 7; mean myocardial temperature, 35 degrees +/- 2 degrees C) and cold (n = 7; mean myocardial temperature, 12 degrees +/- 1 degree C) blood cardioplegic protection. Blood cardioplegic solution was delivered at a rate of 100 mL/min during the 10 minutes between each ischemic arrest. The interstitial myocardial pH decreased significantly (p < 0.05) from 7.1 +/- 0.3 to 6.53 +/- 0.3 after ischemia in animals perfused with warm blood cardioplegia and from 7.04 +/- 0.3 to 6.64 +/- 0.1 in those receiving cold blood cardioplegic protection; however, the difference between the groups was not significant (p > 0.05). Lactate production and creatine kinase and troponin T release increased significantly after ischemia, but there was no difference in the changes between the warm and cold blood cardioplegia groups. In conclusion, ischemia caused significant changes in all variables measured, and these changes were directly proportional to the duration of ischemia. However, there was no significant difference (p > 0.05) in the myocardial metabolic changes between the warm and cold blood cardioplegia groups in terms of the duration of ischemic arrest studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Cholesterol-lowering intervention and coronary artery disease after cardiac transplantation.

Allograft coronary artery disease is a major threat to long-term survival after cardiac transplantation. It has been suggested that hyperlipidemia plays a major role in allograft coronary disease. The objective of the present study was to evaluate the effect of a lipid-lowering intervention with diet and drug therapy after cardiac transplantation. Forty-six patients who underwent transplantation between 1988 and 1991 and who were treated with the American Heart Association phase 1 diet and an HMG coenzyme A reductase inhibitor (lovastatin or simvastatin) when low-density lipoprotein cholesterol levels were higher than 3.4 mmol/L were compared with 35 untreated patients having transplantation between 1983 and 1988. Annual coronary angiograms were obtained in both groups. Cholesterol, triglyceride, and low-density lipoprotein levels were significantly lower in the treated group. Actuarial survival and event-free survival (survival free from allograft coronary artery disease) were similar in both groups. Low-density lipoprotein levels lower than 3 mmol/L at the last follow-up had a positive effect on event-free survival. The cholesterol-lowering intervention was not effective in decreasing the prevalence of allograft coronary artery disease. This study suggests that more aggressive measures to lower low-density lipoprotein levels may be necessary to significantly affect allograft disease. Clinical trials should be developed to address this hypothesis.

Adult↗

Intermittent antegrade warm versus cold blood cardioplegia: a prospective, randomized study.

A prospective, randomized study was performed in 200 patients undergoing coronary artery bypass grafting to compare the myocardial protection obtained with intermittent antegrade warm versus cold blood cardioplegia. Preoperative and surgical characteristics of the two cohorts were similar. Intermittent antegrade infusion of warm blood cardioplegia failed to achieve sustained electromechanical arrest of the heart in 13%. The only difference in clinical outcomes was the more frequent spontaneous return to sinus rhythm after the unclamping of the aorta in the warm group (88% versus 70%, p = 0.002). Mortality (1% each) and myocardial infarction (2% and 4%) rates were similar. Rates of increase in serum activity of the isoenzyme of creatine kinase (CK-MB), CK-MB mass concentration, and cardiac troponin-T level as well as total release of troponin T were significantly lower in the warm group, and fewer patients in this group had a clinically significant increase in serum CK-MB mass (20% versus 39%, p = 0.005) and troponin T (20% versus 56%, p = 0.00001). Thus, intermittent antegrade warm blood cardioplegia is appropriate and clinically safe; the lower release of biochemical markers of myocardial damage suggests improved protection during first-time coronary artery bypass grafting.

Biomarkers↗

Differential induction of nitric oxide synthase in various organs of the mouse during endotoxaemia: role of TNF-alpha and IL-1-beta.

BALB/c mice injected intraperitoneally with bacterial lipopolysaccharide (LPS) developed lethal septic shock. This was accompanied by significantly elevated concentrations of nitrite and nitrate in the plasma and expression of high levels of nitric oxide (NO) synthase activity in the lungs, heart, spleen and peritoneal macrophages. Mice pretreated with anti-tumour necrosis factor-alpha (TNF-alpha) monoclonal antibody or anti-interleukin-1 beta (IL-1 beta) polyclonal antibody were protected, in a dose-dependent manner, from endotoxin-induced mortality. This effect was accompanied by a significant reduction in plasma levels of nitrite and nitrate. Antibody treatment also reduced the level of NO synthase activity in peritoneal macrophages, spleen and heart but had no effect on enzyme expression in the lung. These results demonstrate that TNF-alpha and IL-1 beta play an important role in the induction of NO following administration of LPS and in the development of endotoxin-induced shock. In addition, NO synthase activity is differentially expressed in various organs and this may not always require TNF-alpha and IL-1 beta.

Amino Acid Oxidoreductases↗

Bacterial and fungal flora in healthy eyes of birds of prey.

Birds of prey are often affected with external ocular injuries that are routinely treated with antimicrobial agents used for small animals. The resident ocular bacterial and fungal flora is still unknown in birds of prey and this knowledge would be very useful in assessing the accuracy of treatments. In a study involving 65 raptors with healthy eyes, swabs were taken from both eyes to identify the resident bacterial and fungal flora. Fifty-five birds had a positive culture in one or both eyes. Both gram-positive and gram-negative organisms were isolated, with a predominance of Staphylococcus spp., which were found in 52.3% of cultures. Only two fungal species, Aspergillus spp. and Cladosporium spp. were found. The overall results of this study are similar to previous studies carried out in humans and other animals.

Animals↗

[Urinary excretion of acetylated polyamines after heart transplantation in dogs].

Increase in urinary polyamine levels after transplantation was suggested to be an indicator of organ rejection but immunosuppression therapy could also give rise to these polyamines. To test this hypothesis, the urinary excretion of N-acetylputrescine (Nap) and N-acetylspermidine (Nas) was studied in 36 dogs. Two groups (n = 6) underwent cervical heterotopic heart transplantation. Three other groups (n = 6) were given different immunosuppression treatments without having any surgery and one group (n = 6) had a sham cervical operation. Urine samples and percutaneous transmural biopsy of the transplanted heart were collected daily. The acetylated polyamines were measured with high performance liquid chromatography (HPLC). Immunosuppression of the transplanted dogs with cyclosporine, imuran and prednisone during the postoperative period caused a significant increase (p < 0.05) in the excretion of Nas averaging 512 +/- 122, 929 +/- 337, 507 +/- 207, 1008 +/- 665, 674 +/- 273 nmol/mg of creatinine respectively compared to 197 +/- 31, 149 +/- 30, 203 +/- 56, 177 +/- 40, 226 +/- 62 nmol/mg of creatinine. The excreted levels of Nap for the same group were 594 +/- 202, 707 +/- 138, 1007 +/- 270, 1055 +/- 358, 827 +/- 270 nmol/mg of creatinine compared to 71 +/- 24, 169 +/- 36, 150 +/- 23, 136 +/- 29, 197 +/- 32 nmol/mg of creatinine (p < 0.05) in the control group of sham operated animals. A significant excretion of Nas and Nap was also observed between the transplanted dogs under immunosuppression and the immunosuppressed but non-operated animals, as well as with the non-operated animals that were given cyclosporine only.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Myocardial distribution of retrograde cardioplegic solution assessed by myocardial thallium 201 uptake.

Perfusion of the right ventricular myocardium with retrograde infusion of cardioplegic solution through the coronary sinus has been reported to be less than optimal. To study left and right ventricular perfusion during retrograde and antegrade coronary sinus cardioplegia, we added 0.5 mCi of thallium 201 to 500 ml of hyperkaliemic crystalloid cardioplegic solution injected retrogradely into the coronary sinus at low perfusion pressure (20 to 40 mm Hg) in 14 dogs and antegradely in the ascending aorta in seven dogs. The cardioplegic solution was cold (4 degrees C) in eight animals perfused retrogradely and warm (21 degrees C) in 13 animals. After aortic crossclamping, the ascending aorta and the left and right ventricles were vented and cardioplegic solution was injected retrogradely into the coronary sinus. Antegrade injections were performed after aortic crossclamping and venting of the left and right ventricles and of the left and right atrium. After cardioplegic arrest, the heart was harvested, fixed, and scanned with a gamma camera. With cold retrograde cardioplegia, 82% +/- 5% of the injected thallium 201 activity was identified in the myocardium--71% +/- 9% for warm retrograde perfusion and 80% +/- 3% for antegrade perfusion (p > 0.05). Focal areas of hypoactivity in the septum and in the right ventricular free wall were present at scintigraphic imaging in all animals receiving retrograde perfusion. In conclusion, most thallium 201 activity of cardioplegic solution injected retrogradely in the coronary sinus was identified in the myocardium, but focal areas of hypoactivity in the septum and in the right ventricular free wall were present, indicating uneven distribution. Temperature of the crystalloid solution had no effect on the myocardial distribution of the thallium 201 radiotracer in the myocardium.

Animals↗

Mediastinal and pericardial complications after heart transplantation. Not-so-unusual postoperative problems?

Of a total of 133 patients who underwent heart transplantation, 16(12%) had pericardial and mediastinal complications. Non-infectious pericardial complications, pericardial effusion and constriction were noted in ten patients, and infectious pericarditis or mediastinitis in six. Cardiac echocardiography, catheterization and magnetic resonance imaging were useful in assessing these problems. All patients underwent surgical treatment, pericardial drainage, pericardectomy or muscle flap closure. Twelve (75%) of these 16 patients are long-term survivors. In conclusion, pericardial and mediastinal complications are common after heart transplantation, and aggressive surgical treatment is most often effective in their control.

Adult↗

Outcome of rationing access to open-heart surgery: effect of the wait for elective surgery on patient outcome.

OBJECTIVE: To assess the effect of the waiting period before elective open-heart surgery on patient outcomes. DESIGN: Retrospective analysis. SETTING: The Montreal Heart Institute, a referral centre in cardiology and cardiac surgery. PATIENTS: All 568 patients who underwent open-heart surgery on an elective basis or following urgent admission or interhospital transfer between October 1991 and February 1992. MAIN OUTCOME MEASURES: In-hospital death rate, incidence of postoperative complications, length of stay in the intensive care unit (ICU) and total length of hospital stay. RESULTS: A total of 206 patients (151 men and 55 women with an average age of 59.0 [standard error of the mean (SEM) 1] years) underwent elective surgery, and 362 patients (264 men and 98 women with an average age of 62.0 [SEM 1] years) underwent urgent surgery. The mean wait for elective surgery was 2.8 (SEM 0.2) months. There was no significant difference between the two groups in the in-hospital death rate (4% v. 4%), the average length of stay in the ICU (4.4 [SEM 0.2] days v. 5.8 [SEM 1] days) or the average total length of hospital stay (9.0 [SEM 0.4] days v. 9.1 [SEM 1] days). As would be expected, postoperative complications developed in significantly more patients in the urgent group (27%) than the elective group (18%) (p = 0.02). Eight patients were admitted on an urgent basis for surgery owing to worsening symptoms or acute myocardial infarction after a mean wait of 4.6 months. One patient died suddenly at home 1 month after medical investigation while awaiting repeat coronary artery bypass grafting. Among the 206 patients who underwent elective surgery there was no relation between waiting time and adverse clinical outcomes after surgery. CONCLUSIONS: The results suggest that the wait before elective open-heart surgery had no effect on patient outcome after surgery in our institution. A policy of a short waiting period before elective open-heart surgery for patients whose condition is stable is safe and acceptable only if rapid access to medical and surgical treatment is available should it become necessary.

Analysis of Variance↗