Carvedilol inhibits right ventricular hypertrophy induced by chronic hypobaric hypoxia.

Right ventricular hypertrophy induced by chronic hypoxia is mainly due to a mechanical stress upon the ventricular wall secondary to pulmonary arterial hypertension. However, the hypoxic chronic activation of the sympathetic nervous system can contribute to the development of right ventricular hypertrophy either via myocardial adrenergic receptors and/or a vasoconstriction and remodeling of pulmonary arteries. To highlight the specific role of the sympathetic nervous system on hypoxia-induced right ventricular hypertrophy and particularly the efficiency of carvedilol, our study compared physiological, myocardial, and pulmonary arterial morphometric data in rats treated by alpha-(prazosin), or beta-(propranolol) or alphabeta-(carvedilol) antagonist and exposed to chronic hypobaric hypoxia (2 weeks at 380 mmHg barometric pressure). In chronic hypoxia, both systolic right ventricular pressure and Fulton's ratio (right/(left+septum) ventricular weight) were lower in rats treated by prazosin (-16.7 and -13.6%), propranolol (-28.6 and -12.7%) and carvedilol (-15.9 and -14.3%) respectively when compared to glucose (p<0.05). Surprisingly, prazosin was unable to reduce right ventricular hypertrophy induced by chronic hypoxia, whereas, left ventricular weight increased. Wall thickness index of pulmonary arteries increased in chronic hypoxia and was reduced by carvedilol. In conclusion, the hypoxia-induced activation of the adrenergic system participates in the development of right ventricular hypertrophy. Carvedilol is effective in reducing hypoxia-induced right ventricular hypertrophy, pulmonary arterial hypertension, and muscularization of pulmonary arteries.

Glycoconjugate metabolism in a cystic fibrosis knockout mouse model.

Cystic fibrosis knockout mice (cftr(-/-)) die prematurely of obstruction of the intestine which may result from accumulation of dehydrated glycoconjugate-containing mucus. We noted an increase in the specific activity of [(14)C]glucosamine-labeled high-molecular weight glycoconjugates, probably mucin, in the lumen of the intestine of cftr(-/-) (homozygous) mice compared to cftr(+/+) (wild-type) and cftr(+/-) (heterozygous) mice and a decrease in the turnover of glycoconjugates of several organs of the cftr(-/-) mice. No difference in the anionic composition of secreted intestinal glycoconjugates was detected and no difference in the amount of mucin 1 (Muc1) was found in the small intestine, colon, pancreas, and lungs of the different genotypes. In addition, the spleen of the cftr(-/-) mice was significantly smaller than that of control mice and the small intestine and colon were, respectively, longer and shorter compared to control mice. These results indicate modified glycoconjugate metabolism in cystic fibrosis knockout mice and morphologic changes to the spleen and intestine where the latter modifications are possibly related to the intestinal malabsorption associated with cystic fibrosis.

An in vivo study of the biodegradation of the hydrophilic Mitrathane.

The present study analyzes the kinetics of the in vivo degradation of hydrophilic Mitrathane in the peritoneal cavity of mice over a period ranging from 1 to 180 days. The mechanical milling of the polyurethane films produced regularly flattened fragments that in vivo spontaneously oriented into piles. The morphological observations and analysis with the aid of an image analysis system demonstrated that after seven days of swelling the polymer fragments undergo a continuous degradation that leads to an irregular thinning and phagocytosis of the smaller fragments by macrophages with very little chronic inflammation response from surrounding tissues.

Delayed in vitro immune response to long-term intraperitoneal polymer implant in mice.

This paper presents an original experimental procedure designed to evaluate, by a two step in vivo/in vitro combination, the long-term biocompatibility of synthetic materials developed for clinical applications. The efficacy of the test is illustrated by the experimental results obtained with various materials currently used in medicine (Dacron, RCH) and also with three recently synthesized compounds. In the first step of the procedure, the sample was grafted for at least 5 months in the peritoneal cavity of mice, allowing the possible development of delayed sensitization. In the second step, this sensitization was detected by an in vitro test, the Lymphoblastic Transformation Test (LTT), adapted for this new purpose. On the basis of this experiment, the 5 polymers tested were classified into 2 groups: one group did not significantly differ from the control, and the other had a significantly higher incidence of sensitization. As these results were in agreement with the known biocompatibility of these polymers, they demonstrate the validity of the test to classify new polymers.