[New biological concepts in cardiovascular pathology].
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Biomedical subjects
Publications and source records attributed to P Fornes.
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This paper presents the feasibility of three-dimensional (3D) magnetic resonance (MR) histology of atheromatous coronary lesions in the entire human heart ex vivo using a standard 1.5 T scanner and a 12 mm high-temperature superconducting (HTS) surface coil. The HTS coil was a five-turn transmission-line resonator operated at 77 K, affording a signal-to-noise ratio (SNR) gain of about ninefold as compared to a similar, room-temperature copper coil. Local microscopy at the surface of an explanted, entire heart was achieved by a 3D spoiled gradient echo sequence and assessed by comparison with conventional histology. One hundred and twenty four adjacent cross sections of the coronary artery, with voxels of 59 x 59 x 100 microm3 and an SNR of about 20, were obtained in 25 min. Consecutive data sets were combined to reconstruct extended views along the artery. Compared to histology, MR microscopy allowed precise nondestructive 3D depiction of the architecture of the atheromatous plaques. This is the first report of microscopic details (less than 10(-3) mm3 voxels) of diseased arteries obtained in an entire human heart preserving the arterial integrity and the spatial geometry of atheroma. This noninvasive microscopy approach using a HTS surface coil might be applied in vivo to study the architecture and components of superficial human structures, using routine MR scanners.
Congestive cardiac failure could be as important as cardiac arrhythmias in the natural history of arrhythmogenic right ventricular dysplasia. This can be related to the progressive replacement of myocardium by fat and fibrosis of the right ventricle. The left ventricle may also be involved by the same disease process. Moreover, inflammation can be superimposed on ARVD, resulting in a wide spectrum of clinical presentation which can mimick idiopathic dilated cardiomyopathy. Right ventricular cardiac failure has been controlled by anterior dynamic cardiomyoplasty.
We report on a sudden cardiac death case involving a 40-year-old man with no known medical history. Forensic autopsy showed lymphocytic myocarditis associated with lymphocytic thyroiditis. In both the heart and the thyroid gland, the inflammatory foci often had a nodular pattern with a germinal centre. Virological and toxicological analyses were negative. Postmortem biochemistry showed a slight increase in TSH in combination with normal T3 and T4 blood levels suggesting hypothyroidism. High titres of antiperoxidase and antithyroglobulin antibodies with normal levels of TSH receptor antibodies, in addition to biological hypothyroidism and lymphocytic inflammation were consistent with the diagnosis of Hashimoto's thyroiditis. Immunohistochemical studies excluded a lymphoma and showed no evidence of viral myocarditis. In contrast to Grave's disease, Hashimoto's thyroiditis has never been reported in association with myocarditis as a cause of sudden death. We conclude that the cardiac immunological and histological pattern, similar to that found in the thyroid gland suggests an autoimmune myocarditis.
Two cases of invasive aspergillosis (IA) in immunocompetent patients with a fulminant fatal outcome are reported. Both patients were elderly and had a history of chronic lung disease treated with prolonged inhaled corticosteroids and a short course of systemic corticosteroids. They presented with dyspnea and fever, their respiratory function deteriorated rapidly, and they died 7 days after admission. Aspergillus fumigatus was cultured from respiratory samples. IA was confirmed in one case by necropsy that showed diffuse bilateral necrotizing pneumonitis and myocarditis. In the other case, IA diagnosis was established by thoracic CT scan plus detection of Aspergillus antigen in two blood samples. These two cases demonstrate that short-term corticosteroid therapy in immunocompetent patients with underlying chronic lung conditions is a risk factor for IA, and that its evolution can be fulminant.
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A growing number of people are involved in recreational physical activity. We examined the clinical and cardiac pathological patterns in 29 persons who died suddenly during a sport activity and were autopsied at the Institute of Forensic Medicine of Paris, 1990-1999. Twenty-seven males ranging in age from 13 to 57 years, mean 30.5, and two females, 8 and 60 years old, died suddenly during a sport activity. The sports included running, 11 cases; cycling, 4; soccer, 3; swimming, 2; basket-ball, 2; rugby, 1, gymnastic exercises, 2; tennis, 1; gockart, 1; skiing, 1; hand-ball, 1 case. The causes of deaths were as follows; coronary artery disease, 9 cases; congenital anatomic anomaly of a coronary artery, 1; hypertrophic cardiomyopathy, 5; right ventricular dysplasia, 3; myocarditis, 2; endomyocardial fibrosis, 1; bridging of the left anterior descending coronary artery, 2; stroke, 2; rupture of aortic aneurysm, 4. Despite severity of lesions, only 4 victims had a known cardiovascular disease. Efforts should be continued to improve sensitivity and specificity of diagnostic tools and screening strategies. Therefore, medico-legal autopsies should be systematically performed for a better knowledge of sport-related mortality.
BACKGROUND: Ingestion of illicit drug packages is a well known method for transportation. These packages are prone to rupture causing overdose. The body packer syndrome may be overlooked in medical practice as illustrated by the following case report. CASE REPORT: A 19-year old male had convulsions followed by cardiac arrest during a flight. He was resuscitated in the plane, but he died a few hours after admission in intensive care unit. Chest and abdominal X-rays were considered normal. Cocaïne métabolites were found in his urine. The death was considered suspicious. X-rays performed before medicolegal autopsy showed numerous packages in his digestive tract. Thirty-six packages were found in the stomach and intestine. Two were ruptured in the stomach. The cause of death was cocaïne overdose caused by package rupture. DISCUSSION: The packages are usually visible on an standard abdomen X-ray. The drug is often wrapped in latex membranes or condoms. The air is trapped between the condoms by the nodes, forming two crescents visible on the X-ray. Surgery is preferred to laxatives when the packages are fragile with a high risk of rupture.
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1. The aim of the present study was to investigate left and right ventricular (LV and RV, respectively) coronary vasodilatation reserve (CVR; fluorescent microsphere technique) in rats with hypertension (spontaneously hypertensive rats (SHR)) or congestive heart failure (CHF) and the effects of early and chronic renin-angiotensin system (RAS) blockade thereupon. 2. In adult SHR, both LV and RV CVR were impaired, especially in the non-hypertrophied RV, the main factor involved being coronary vascular remodelling. Blockade of the RAS normalized both LV and RV CVR, mainly through the prevention of hypertension and suppression of the resulting pericoronary fibrosis. 3. In postischaemic CHF rats, there was an early and severe degradation of LV and RV CVR that developed before any significant vascular remodelling and appeared to be linked to the deterioration of cardiac hypertrophy and haemodynamics. This degradation in CVR further worsened over the longer term due to late-developing pericoronary fibrosis and endothelial dysfunction. Blockade of the RAS had no early effects on LV and RV CVR, but improved RV CVR over the long term, mainly by limiting RV hypertrophy and by preventing the development of pericoronary fibrosis and coronary endothelial dysfunction. 4. In kallikrein-kinin system-deficient mice, CVR was not different from that of wild-type mice, suggesting that this system is not implicated in normal CVR regulation.
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BACKGROUND: Angiotensin I-converting enzyme inhibition (ACEI) and angiotensin II AT(1)-receptor blockade are effective at improving survival and limiting cardiac remodeling in the rat model of postischemic heart failure. Whether their combination yields additive/synergistic effects is unknown. METHODS AND RESULTS: Rats underwent coronary artery ligation and 7 days later were treated orally for 9 months with placebo (controls), 5 mg/kg valsartan, 1 mg/kg enalapril (doses submaximally effective at reducing mortality in the experimental model used), or 5 mg/kg valsartan and 1 mg/kg enalapril combined. Compared with controls, valsartan, enalapril, and their combination decreased mortality by 40% (P =.006), 21% (P =.065), and 33% (P =.032), respectively, but there was no significant difference between the 3 treatments. At the doses used, valsartan, but neither enalapril nor the combination, slightly limited cardiac hypertrophy and fibrosis development and reduced left ventricular end-diastolic pressure as assessed in the surviving animals at 9 months. CONCLUSIONS: In experimental chronic heart failure in rats, valsartan reduces mortality similar to other AT(1)-receptor blockers and a combination of AT(1)-receptor blockade (valsartan) and ACEI (enalapril) at submaximal doses does not exert additive/synergistic beneficial effects on mortality.
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BACKGROUND: Animal studies have suggested that apoptosis could play a significant role in the myocardial aging process. Although no information is available in humans, the paradigm that cardiomyocyte apoptosis is increased in the aged human heart has been widely propagated. Moreover, it is unknown whether gender differences may influence cardiomyocyte apoptosis. METHODS: Cardiomyocyte apoptosis was compared between subjects ranging in age from 21 to 93 years (22 men and 19 women), free of any cardiovascular disease, who died of either violent or natural causes. Strict inclusion and exclusion criteria were used to ensure that the selected hearts accurately represented normal aging. RESULTS: Apoptosis was detected using the TdT-mediated dUTP digoxigenin nick end labeling (TUNEL) technique (controls for TUNEL included negative staining for splicing factor SC-35 and for Ki-67 antigen). The percentage of cardiomyocyte death ranged from 0% to 0.0437%, with no correlation with the age of the subject (p =.85). However, the percentage of apoptosis was threefold higher in men than in women (0.0133% +/- 0.0030% vs 0.0042% +/- 0.0008%, respectively; p <.01). CONCLUSIONS: Our results in humans do not support the hypothesis that aging influences the percentage of cardiomyocyte apoptosis. However, gender appears to be an important determinant of the occurrence of apoptosis.
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