Potentially fatal interaction between erythromycin and disopyramide.
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Aged↗
Biomedical subjects
M Ragosta
Publications and source records attributed to M Ragosta.
Death during recreational exercise in the State of Rhode Island.
From January 1, 1975 to May 1, 1982, 81 individuals died during or immediately after recreational exercise in the State of Rhode Island. Deaths occurred during a variety of activities, but the majority of deaths occurred during golf (23%), jogging (20%), and swimming (11%). Atherosclerotic coronary heart disease (ASHD) was the presumed cause of 88% of the deaths, primarily in subjects over age 29 with known cardiac abnormalities. Only 7% of ASHD victims had no relevant medical history or ASHD risk factors and were considered healthy by their families and physicians. In contrast, deaths in young subjects were rarely associated with ASHD or prior knowledge of cardiovascular disease. Only six deaths in individuals aged 29 or younger occurred during the study period. These deaths were associated with congenital cardiovascular disease (N = 2), valvular heart disease (N = 1), hemorrhagic gastritis (N = 1), idiopathic myocardial hypertrophy (N = 1), and hypertrophic cardiomyopathy with ASHD (N = 1). A diagnosis was made before death only in the individual with valvular disease. We conclude that death during recreational exercise is predominantly due to ASHD and occurs in men with recognized ASHD risk factors, relevant medical histories, or known disease. Death during exercise in asymptomatic subjects is rare and relatively more frequent in younger age groups.
Adolescent↗
Fatal collisions between joggers and automobiles in Rhode Island.
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Accidents, Traffic↗
Extent of myocardial viability in regions of left ventricular dysfunction by rest-redistribution thallium-201 imaging: a powerful predictor of outcome.
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Cardiac Catheterization↗
Local adenovirus-mediated delivery of hirudin in a rabbit arterial injury model.
UNLABELLED: Intravascular delivery of an E1/E3 deleted adenovirus encoding the hirudin protein reduces neointimal formation in the rat arterial injury model. Given the interspecies variability in response to adenoviral vectors, we tested this same construct in the hirudin-sensitive cholesterol-fed rabbit arterial balloon injury model. We hypothesized that local delivery of an E1/E3-deleted adenovirus encoding hirudin (Ad-Hir) in addition to early hirudin infusion would limit neointimal formation compared to early hirudin alone. METHODS AND RESULTS: Local delivery of Ad-Hir, 2.5 x 10(10) PFU/ml, using a double balloon catheter [n = 6 vessels (v)] produced a 79% reduction in vessel wall thrombin activity at 48 h after balloon angioplasty (BA) compared with vehicle (Veh, n = 6v; p = 0. 05). In chronic experiments, hypercholesterolemic rabbits underwent femoral BA, and received either early hirudin alone (n = 9v) or early hirudin plus locally delivered Ad-Hir (early hirudin + Ad-Hir; n = 9v), an E1/E3-deleted adenovirus encoding beta-galactosidase (early hirudin + AdGal; n = 7v), or Veh (early hirudin + Veh; n = 10v). Early hirudin + Ad-Hir did not limit the arterial response to injury versus the other groups at 4 weeks after BA. Plaque area, cross-sectional luminal area narrowing by plaque, and T cell infiltration were significantly increased in the adenovirus- versus non-adenovirus-treated arteries. Plaque area correlated with T cell density. CONCLUSION: Following BA in cholesterol-fed rabbits, local transduction with A-Hir produced a marked reduction in vessel wall-associated thrombin activity. However, this strategy increased rather than decreased the arterial response to BA injury. Our results suggest that the lack of therapeutic effect resulted from adenovirus-stimulated plaque formation, possibly resulting from a T cell-mediated inflammatory response.
Adenoviruses, Human↗
Arterial injury increases expression of inflammatory adhesion molecules in the carotid arteries of apolipoprotein-E-deficient mice.
Recent studies demonstrate increased cellular adhesion molecule expression by neointimal endothelium overlying primary and restenotic atherosclerotic plaque. In this study, we developed an atherosclerotic mouse model of arterial injury and characterized adhesion molecule expression after injury. Sixteen apolipoprotein-E-(ApoE)-deficient mice fed a Western-type diet for 4 weeks underwent carotid artery wire denudation at week 2. For each segment, the extent of neointima formation and medial thickening, or adhesion molecule expression, were scored separately on a scale from 0 (no plaque/thickening or expression) to 3 (extensive plaque/thickening or expression) using Movat staining (n = 3) or immunohistochemical analysis (n = 13). Histology revealed significant medial thickening (1.8 +/- 0.9 vs. 0.3 +/- 0.5, p < 0. 001) versus controls and pronounced staining for monocytes/macrophages in the wall of injured vessels. Immunohistochemical analysis showed more robust expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the luminal surface of injured arteries versus controls (2.2 +/- 0.6 vs. 1.4 +/- 0.7, p < 0.01, and 2.5 +/- 0.5 vs. 1.2 +/- 0.6, p < 0.001, respectively). Injury increased adventitial ICAM-1 expression (2.6 +/- 0.5 vs. 1.6 +/- 0.5, p < 0.002) and medial VCAM-1 expression (2.2 +/- 0.6 vs. 1.2 +/- 0. 7, p < 0.004). Thus, carotid injury results in significant medial thickening and increases adhesion molecule expression beyond that induced in ApoE-deficient mice fed a Western diet alone. The observation of macrophage infiltration into the media at sites of increased ICAM-1 and VCAM-1 expression suggests that these molecules may mediate monocyte/macrophage trafficking into the wall of injured arteries.
Animals↗
Effectiveness of hirulog in reducing restenosis after balloon angioplasty of atherosclerotic femoral arteries in rabbits.
BACKGROUND: Thrombin may play an important role in restenosis after balloon angioplasty (BA). Angiographic and pathologic restenosis have been shown to be reduced after BA in an atherosclerotic rabbit model using recombinant desulfatohirudin, a selective and direct thrombin inhibitor. We hypothesized that potent and specific thrombin inhibition with the synthetic peptide hirulog given intravenously at the time of angioplasty would reduce restenosis in rabbits, confirming a specific role of thrombin in restenosis. METHODS AND RESULTS: Focal femoral atherosclerosis was induced in 27 rabbits by air desiccation endothelial injury followed by a 2% cholesterol diet for 1 month. Rabbits received either heparin (150 units/kg bolus, n = 14) or hirulog (5 mg/kg bolus followed by 5 mg/kg/h for 2 h, n = 13) at the time of BA (2.5-mm balloon with three 60-second, 10-atm inflations 60 s apart). Angiograms performed before and after BA and before sacrifice were analyzed quantitatively. Rabbits were sacrificed 28 days after BA for quantitative histopathologic analysis. Minimum luminal diameter (mm) did not differ between treatment groups before (1.1 +/- 0.2 vs. 1.2 +/- 0.1 mm) or after (1.5 +/- 0.2 vs. 1.6 +/- 0.1) BA in arteries from heparin-versus hirulog-treated rabbits, respectively. At 28 days, however, minimum luminal diameter was significantly less (1.0 +/- 0.4 vs. 1.5 +/- 0.2, p = 0.0001) and percent stenosis was greater (0.46 +/- 0.25 vs. 0.22 +/- 0.08, p = 0.0002) in arteries from heparin- versus hirulog-treated rabbits, respectively. Similarly, quantitative histopathology showed less cross-sectional area narrowing by plaque in the hirulog group (56 +/- 24 vs. 42 +/- 21%, p = 0.04). CONCLUSION: A 2-hour infusion of hirulog at the time of angioplasty improved late angiographic luminal dimensions and reduced cross-sectional area narrowing by plaque in rabbits compared with heparin controls. Together with previous studies, this confirms a specific role for thrombin in restenosis after angioplasty.
Angioplasty, Balloon↗