Browsing by Author "Obraztsova, Maria"

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    Effects of angiotensin (1-7) upon right ventricular function in experimental rat pulmonary embolism
    (2011) Watts, John A; Gellar, Michael A; Stuart, Lori; Obraztsova, Maria; Marchick, Michael R; Kline, Jeffrey A.
    Right ventricular (RV) dysfunction contributes to poor clinical prognosis after pulmonary embolism (PE). The present studies evaluate the effects of angiotensin (1-7) (ANG (1-7)) upon RV function during experimental PE in rats. Circulating ANG II increased 8-fold 6 hr after PE (47±13 PE vs. 6±3 pg/mL, control, p<0.05). ACE2 protein was uniformly localized in the RV myocardium of control rats, but showed a patchy distribution with some cells devoid of stain after 6 or 18 hr of PE. RV function decreased 18 hr after PE compared with control treated animals (19±4 vs. 41±1 mmHg, respectively, p<0.05; 669±98 vs. 1354±77 mmHg/sec, respectively, p<0.05), while left ventricular function (LV) was not significantly changed. Animals treated with ANG (1-7) during PE showed improved RV +dP/dt and peak systolic pressure development to values not significantly different from control animals. Protection of RV function by ANG (1-7) was associated with improved arterial blood sO2, base excess and pH. Supplemental delivery of ANG (1-7) reduced the development of RV dysfunction, suggesting a novel approach to protecting RV function in the setting of acute experimental PE.
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    Role of inflammation in right ventricular damage and repair following experimental pulmonary embolism in rats
    (2008-10) Watts, John Albert, Jr; Gellar, Michael Aaron; Obraztsova, Maria; Kline, Jeffrey A.; Zagorski, John
    Right ventricular (RV) dysfunction is associated with poor clinical outcome following pulmonary embolism (PE). Previous studies in our laboratory show that influx of neutrophils contributes to acute RV damage seen in an 18 h rat model of PE. The present study describes the further progression of inflammation over 6 weeks and compares the neutrophil and monocyte responses. The RV outflow tract became white in colour by day 1 with influx of neutrophils (tissue myeloperoxidase activity increased 17-fold) and mononuclear cells with characteristics of M1 phenotype (high in Ccl20, Cxcl10, CcR2, MHCII, DNA microarray analysis). Matrix metalloproteinase activities were increased and tissue was thinned to produce a translucent appearance in weeks 1 through 6 in 40% of hearts. RV contractile function was significantly reduced at 6 weeks of PE. In this later phase, there was accumulation of myofibroblasts, the presence of mononuclear cells with M2 characteristics (high in scavenger mannose receptors, macrophage galactose lectin 1, PDGFR1, PDGFRβ), enrichment of the subendocardial region of the RV outflow tract with neovesels (α-smooth muscle immunohistochemistry) and deposition of collagen fibres (picrosirius red staining) beginning scar formation. Thus, while neutrophil response is associated with the early, acute inflammatory events, macrophage cells continue to be present during the proliferative phase and initial deposition of collagen in this model, changing from the M1 to the M2 phenotype. This suggests that the macrophage cell response is biphasic.