Eccentric mitral regurgitation jets among patients having sustained inferior wall myocardial infarction.

A strong association has been recognized between partial or complete mitral leaflet flail and highly eccentric mitral regurgitation jets. In light of anecdotal observation of eccentric mitral regurgitation apparently due to geometric and functional changes accompanying inferior wall myocardial infarction, the present study was performed to systematically study the eccentricity of mitral regurgitation jets complicating nonacute inferior wall myocardial infarction. Forty-eight consecutive patients with evidence of prior isolated inferior wall myocardial infarction and at least moderate mitral regurgitation but without other valvular, annular, chordal, or ventricular pathology potentially contributory to mitral regurgitation were studied. Mitral regurgitation jets were characterized with respect to eccentricity and anterior versus posterior direction. Regurgitant jet and mitral leaflet position were quantified relative to the mitral annulus. Five of 48 patients (10.4%) had eccentric jets, of which four were directed posterior and one anterior. Although not reaching statistical significance, patients with eccentric jets tended to have somewhat smaller left atrial size (41.2 +/- 7.8 vs 47.2 +/- 9.3 mm, P = 0.17) and left ventricular size (51.5 +/- 3.4 vs 55.1 +/- 7.8 mm, P = 0.13), and higher left ventricular ejection fraction (0.52 +/- 0.11 vs 0.46 +/- 0.09, P = 0.25) compared with patients with noneccentric jets. Leaflet position relative to the mitral annulus was significantly different among patients with eccentric compared with noneccentric posterior jets (54 +/- 10 degrees vs 33 +/- 11 degrees, P = 0.02), implying greater leaflet restriction toward the left ventricular apex. In conclusion, approximately one in 10 patients with isolated inferior wall myocardial infarction and at least moderate mitral regurgitation was found to have marked eccentricity of the regurgitant jet. Leaflet position was more apically displaced among patients with eccentric jets, suggesting greater leaflet restriction in systole. The finding of a highly eccentric posterior mitral regurgitation jet can be due to inferior wall myocardial infarction with posterior leaflet restriction as well as partial or complete anterior mitral leaflet flail.

p53 gene transfer to the injured rat carotid artery decreases neointimal formation.

PURPOSE: We studied the effect of adenovirus-mediated p53 gene transfer on the injured rat carotid artery to determine its ability to decrease the formation of neointima. METHODS: In vivo gene transfer was used in isolated segments of balloon-injured rat carotid arteries. Genetically modified adenovirus containing the gene encoding for wild-type p53 (AdWTp53) was applied in three concentrations: 8 x 10(10), 1.6 x 10(10), and 8 x 10(9) pfu/mL. Control rats received either adenovirus null (AdNull), 8 x 10(10) pfu/mL, or Medium-199 solution (vehicle). Expression of p53 was determined 4 days after gene transfer by Western blotting. Neointimal formation was assessed after 14 days by harvesting carotid arteries and determining the intima/media (I/M) ratio based on cross-sectional area measurement. Simultaneously, immunohistochemistry was done to detect the presence of p53 on smooth muscle cell nuclei. RESULTS: P53 expression was confirmed by Western blotting. There was a significant reduction in neointimal formation on all treated animals compared with controls. The highest dose of AdWTp53 (8 x 10(10) pfu/mL) resulted in a near-total arrest of neointimal formation (I/M = 0.09 +/- 0.03, mean +/- SEM) with P <. 0001 versus vehicle (I/M = 2.23 +/- 0.15) or AdNull (I/M = 2.12 +/-. 12). The intermediate dose of AdWTp53 (1.6 x 10(10) pfu/mL) resulted in an I/M value of 1.04 +/- 0.18, with P <.001 versus vehicle and P =.001 versus AdNull. The lowest dose (8 x 10(9) pfu/mL) resulted in an I/M value of 1.12 +/- 0.18, with P <.001 versus vehicle and P <. 002 versus AdNull. The immunohistochemistry was positive for the presence of p53 in rats infected with AdWTp53. CONCLUSIONS: Adenovirus-mediated gene transfer of p53 protein significantly decreases the formation of neointima in the rat carotid injury model. This may represent a potential therapy for restenosis in humans.