Alain Tabib

Accelerated coronary atherosclerosis and arteriosclerosis in young human-immunodeficiency-virus-positive patients.

ObjectiveTo determine the type of lesions observed in young patients infected with human immunodeficiency virus‐1 (HIV‐1). DesignExamination of coronary networks in corpses of 13 men and two women who had died aged 23–32 years after having been infected with HIV‐1 virus, having been seropositive for 2–5 years. Causes of death were infectious complications (five cases), infection with cytomegalovirus leading to gastro‐intestinal haemorrhaging (one case), infection with cytomegalovirus and Kaposis sarcoma (one case), overdoses of drugs (five cases) and sudden death (three cases). MethodsThe pathological analysis was carried out on the proximal and distal coronary networks. In order to characterize the lesions better, the cells and the cytokines involved were characterized by immunohistochemistry. ResultsIn all 15 cases we observed thickening of intima in the proximal network at least as great as that of the media, caused by a proliferation of secreting cells, phenotypically identified as smooth muscle cells, with exaggerated production of elastic fibres and in association with an increase in the expression of tumor necrosis factor‐α and interleukin‐1α. In nine cases, atherosclerosis had developed from and on the surface of this proliferation and in four cases arteriosclerosis had an unusual appearance, in the form of mamillated vegetations with endoluminal protrusions. A similar proliferation was found in the distal network in four cases, but with a significantly smaller proportion of elastic fibres ConclusionsThe lesions we examined in these young HIV‐1‐ infected patients presented particular features and were intermediate between the lesions observed during common coronary atherosclerosis and atherosclerosis associated with chronic rejection of cardiac transplants.

Thoracoscopic Epicardial Radiofrequency Ablation for Vagal Atrial Fibrillation in Dogs

Epicardial radiofrequency catheter ablation of the atria in the open‐chest dog has been shown to reduce inducibility of atrial fibrillation. Video‐assisted endoscopic techniques decrease the operative trauma in adult thoracic surgery. We report our results of video‐assisted thoracoscopic radiofrequency catheter ablation of the atria for the prevention of atrial fibrillation induction in canines. In 12 consecutive anesthetized dogs, induction of sustained atrial fibrillation was reproducibly obtained by burst pacing and cervical vagal stimulation. In six dogs, biatrial ablation was performed through right and left minithoracotomies and guided by video‐assisted endoscopic techniques. The remaining six dogs underwent a video‐guided left atrial procedure. Long continuous and transmural lesions were produced using epicardial temperature controlled radiofrequency energy delivered according to a simplified maze approach. Transmural lesions were demonstrated at the end of the study by examination of the heart. Sustained atrial fibrillation was still inducible after the right atrial ablation but sustained atrial fibrillation could not be induced following left atrial ablation. In acute canine studies: (1) epicardial radiofrequency catheter ablation of the atria is feasible using video‐assisted endoscopic techniques; (2) ablation extended or confined to the left atrium appears to be effective in preventing the inducibility of sustained vagal atrial fibrillation; and (3) ablation of the right atrium alone had no antiarrhythmic effect.

A Selenium Supplement Associated or Not with Vitamin E Delays Early Renal Lesions in Experimental Diabetes in Rats

Abstract Seventy rats were separated into five groups: one group of 12 was used as a control and received a purified diet, and four groups of streptozotocin-induced diabetic rats, totalling 58, were fed the same diet without or with selenium (Se) supplementation. Of the noncontrol rats, 14 were without supplementation (Group D), 14 were fed a Se-rich yeast diet (i.e., selenion) (Group DSel), 14 received selenomethionine (Group DSm), and 16 received selenomethionine + tocopherol acetate (Group DSmE). Supplementation with Se in all groups was 0.99 μmole/100 g of diet and with tocopherol acetate was 0.145 μmole/100 g. All diabetic rats were mildly balanced by insulin. After 24 weeks of diet, plasma glucose tended to decrease in diabetic Sesupplemented groups DSmE>DSm>DSel versus Group D. In DSm and DSmE groups, plasma lipid peroxides also decreased compared with Group D, but this decrease reached significance only for DSmE (P<0.01 for both TBARS and conjugated dienes). Plasma triglycerides also decreased in DSm and DSmE groups versus Group D (P<0.01; P<0.05, respectively). At the same time, Se increased significantly in kidneys of Groups DSel and DSm versus D and more weakly in Group DSmE, but in this case was associated with a large increase of vitamin E. These beneficial effects of selenium supplement and more so of selenium combined with vitamin E were associated with a protection of kidneys in diabetic rats which found expression in a significant correction of renal hyperfiltration (P<0.05) and in a diminution of the number and severity of glomerular lesions (P<0.0005). [P.S.E.B.M. 1996, Vol 211]

Fulminant Myocardial Failure in a Previously Healthy Young Man

### History A 15-year-old boy was admitted to the intensive care unit of our institution in early November 1992 because of rapidly progressive heart failure with fever. The patient was a secondary school pupil, living with his parents and his brother, all of whom were well and resided in a city suburb, spending occasional weekends in the country. There was no family history of heart disease. The boy had no cardiovascular risk factors, history of intravenous drug abuse, or risk factors for human immunodeficiency virus. The patient had undergone an appendectomy 8 years earlier. He had been exposed to a parturient cat in July 1992, and his brother had been hospitalized for 2 days in October 1992 for unexplained fever and abdominal pain. The patient had been well until 7 days earlier, when headaches and fever occurred. Three days later, he developed a cough, followed by upper abdominal discomfort and vomiting. The general practitioner diagnosed an acute bronchitis and prescribed oral amoxicillin. At that time, physical examination and cardiac auscultation were noted as normal. Over the course of the following days, the patient became dyspneic and was admitted to the hospital. ### Initial Clinical Findings On admission the boy was pale and anxious. He had pyrexia of 38°C, a heart rate of 120 beats per minute, a respiratory rate of 30 breaths per minute, and a blood pressure of 110/82 mm Hg. Physical examination revealed an S3 sound with a 2/6 precordial murmur. Bibasilar inspiratory crackles were also present; the liver extended 3 cm below the right costal margin, and the jugular veins were distended to 10 cm above the sternal angle. No peripheral edema, cyanosis, rash, or lymphadenopathy was found. The abdominal and neurological examinations were normal. Most of the laboratory findings, including white blood cell count, hemoglobin, platelets, erythrocyte sedimentation rate, C-reactive protein, …

Hidden Cardiac Lesions and Psychotropic Drugs as a Possible Cause of Sudden Death in Psychiatric Patients: A Report of 14 Cases and Review of the Literature

Objective: To confirm the hypothesis that psychotropic drugs, especially neuroleptics, lithium, and antidepressants, are implicated as a cause of unexpected sudden death in psychiatric patients because of their cardiotoxicity, especially when hidden cardiac lesions are present. Method: We performed a full pathological examination of 14 psychiatric patients who unexpectedly and suddenly died between 1980 and 1999. Results: Neuroleptics were involved in 13 instances, antidepressants in 9, and anxiolytics in 5. Psychotropic drugs were combined in all but a single patient. In all 14 patients, toxicological analyses discarded drug overdose as cause of death. At postmortem examination, the brain and abdominal organs were normal. In 13 patients, the following lesions were found in the heart and lungs: dilated cardiomyopathy (6 patients), left ventricular hypertrophy (2 patients, 1 of which was associated with mitral prolapse and anomalies of His bundle), arrhythmogenic cardiopathy of the right ventricle (1 patient), pericarditis (1 patient), mitral prolapse (1 patient), muscular bridge on the anterior interventricular artery (1 patient), and Mendelsons syndrome (1 patient). In 1 case, no changes were seen. Most of the drugs that were taken immediately prior to death can induce arrhythmias either by prolonging the QT interval, potentially resulting in torsades de pointes, or by widening QRS complexes, possibly leading to reentry and ventricular fibrillation. Conclusion: Our findings suggest that the arrhythmogenic effects of psychotropic drugs can be exacerbated when preexisting hidden cardiac lesions are present and can result in sudden death. Patients should be systematically evaluated for cardiac lesions prior to starting any treatment with psychotropic drugs; the minimal effective dosage should be used.

Selenium in diabetes: Effects of selenium on nephropathy in type I streptozotocin‐induced diabetic rats

Oxidative stress is involved in diabetes mellitus and its complications. Selenium is a nutritional antioxidant, especially because it is required for the activity of selenium-dependent glutathione peroxidase. Selenium also may have insulin-like properties and improve insulin sensitivity. However, its effects are not sufficiently documented in diabetes and its complications. Thus we supplemented type I diabetic rats with a selenium-rich yeast, selenomethionine and selenomethionine + vitamin E for 24 weeks. Selenium supplementations increased selenium levels in plasma. Selenium and more efficiently Sm + vitamin E decreased plasma glucose level and glycated hemoglobin. Supplementations increased selenium levels in kidney and double supplementation increased renal vitamin E level. However, no differences were observed in thiobarbituric acid-reactive substances in kidneys in the different groups. Selenium decreased or normalized the increased arachidonic acid content observed in diabetic kidneys and so may reduce the level of thromboxane involved in nephropathy. Glomerular hyperfiltration is common in early stages of diabetic nephropathy. We observed an increased renal creatinine clearance in diabetic rats, indicating renal hyperfiltration. Nevertheless, this hyperfiltration was corrected by selenium supplementations. Renal lesions were markedly increased in diabetic rats, but very significantly reduced or corrected by supplementations. Thus we concluded that selenium supplementation could be a useful additive therapeutic to delay diabetic nephropathy. J. Trace Elem. Exp. Med. 12:379–392, 1999.

Ivabradine but not propranolol delays the time to onset of ischaemia-induced ventricular fibrillation by preserving myocardial metabolic energy status

OBJECTIVE Heart rate reduction (HRR) has shown a beneficial impact on the prevention of ventricular fibrillation, which could be explained by increased myocardial blood flow and preservation of mitochondrial structure. Here, we assessed the HRR impact on time to onset of ventricular fibrillation (TOVF) and myocardial metabolic energy status. METHODS AND RESULTS An acute myocardial ischaemia was induced in pigs until ventricular fibrillation onset and TOVF was then measured. High-energy phosphates were measured in ventricular samples from the ischaemic region by nuclear magnetic resonance. Saline, ivabradine (IVA, a selective heart rate-lowering agent) and propranolol (PROPRA, a β-blocker) were administered intravenously, 30 and 60 min respectively prior to ischaemia to ensure stable HRR. To study specifically the HRR impact, another set of animals received IVA and was submitted to rapid atrial pacing (200 bpm) to abolish HRR. IVA and PROPRA induced a similar HRR (IVA: 22-26%, PRORA: 20-21%, p<0.01 vs. control), which was associated with a significant increase in TOVF with IVA (2325s) compared to PROPRA (682s) and saline (401s). This effect was abolished by atrial pacing performed during ischaemia and throughout the entire experimental session. Only IVA partially prevented the decrease in phosphocreatine-to-ATP ratio (CrP/ATP) ratio and the ADP accumulation at the onset of ventricular fibrillation. Finally, CrP/ATP ratio levels were correlated with TOVF (r=0.74, p<0.001). CONCLUSION Unlike PROPRA, IVA delayed the time to onset of ischaemia-induced ventricular fibrillation by preserving myocardial energy status, supporting the pertinence of IVA in the management of patients with coronary artery disease.

Involvement of neuroleptic drugs in selenium deficiency and sudden death of cardiac origin: Study and human post-mortem examination

The involvement of psychotropic drugs in sudden deaths has been highlighted. The objective of this work was to establish a link between selenium levels in heart tissue, psychotropic treatment and sudden death. Selenium levels were measured by electrothermal atomic absorption spectroscopy post-mortem in heart, brain and liver. Histological examination evidenced dilated cardiomyopathy in 45% of cases, left ventricular hypertrophy in 36%, and ischemic coronaropathy in 18%. A significant reduction of myocardial selenium levels compared to controls was seen in patients treated with neuroleptic drugs or meprobamate. No changes in brain or liver selenium levels were seen. These results suggest that selenium deficiency can facilitate sudden death in patients on psychotropic drugs. The reduced activity of glutathione peroxidase due to selenium deficiency can result in augmented oxidative stress in myocardial cells and myocardiopathy leading to sudden death.