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Biomedical subjects

D Langleben

Publications and source records attributed to D Langleben.

41 records · Page 3Linked to original sources
PubMed1986

The platelet thromboxane inhibitor, dazmegrel, does not reduce monocrotaline-induced pulmonary hypertension.

Monocrotaline injures rat pulmonary endothelium, and pulmonary vascular remodeling, pulmonary hypertension, and right ventricular hypertrophy then develop. Platelets contribute to development of the pulmonary hypertension because platelet depletion 1 wk after monocrotaline administration reduces the right ventricular hypertrophy. To determine whether the platelet action is through thromboxane A2 generation, we administered the long-acting thromboxane synthetase inhibitor dazmegrel (UK-38,485) to rats receiving monocrotaline. Both before and after monocrotaline treatment, dazmegrel effectively (p = 0.01) reduced thromboxane release during clotting, platelets being the main source. We then studied 4 groups of rats: 1 group of rats received only monocrotaline as a single subcutaneous injection at 0 h; a second group received, in addition, dazmegrel in drinking water starting at -48 h, then daily until Day 21; a third group received only dazmegrel; a control group received no treatment. Dazmegrel did not prevent monocrotaline-induced growth retardation. Despite adequate intake and coverage of the critical period at approximately 1 wk after monocrotaline treatment, dazmegrel did not significantly prevent the development by Day 21 of right ventricular hypertrophy. On Day 21, platelet counts and plasma thromboxane B2 levels were similar in all 4 groups, suggesting no major platelet involvement at that time. It seems that the platelet contribution to pulmonary hypertension after monocrotaline treatment is not mediated by thromboxane A2.

Animals↗
PubMed1985

Participation of blood cells in exercise-induced fibrinolysis.

The fibrinolytic response to maximal exercise on a bicycle ergometer was studied in 42 normal young adults (21 males, 21 females) by euglobulin lysis and by 125I-fibrin radiometric assay of whole blood and plasma fibrinolytic activities. Increases in plasma activity by 125I-fibrin assay were similar (mean increase, 3- to 4-fold) to those observed by euglobulin lysis, and were inhibited (90-93% inhibition) by tranexamic acid at a concentration (10 mmol/l) which inhibits plasmin-mediated fibrinolysis. In addition, there was a considerable increment in the cellular phase component, evident from simultaneous 125I-fibrin assay of whole blood and plasma activities. This cellular increment occurred in 70% of subjects (16 of 21 males, and 13 of 21 females). It represented, on average, 73% of the activity increase induced in plasma by exercise, and was not inhibited by tranexamic acid. Counts of all blood cell types were increased with exercise, but there was no correlation between absolute values for or increments in counts of any cell type and the increments in cellular activity. Thus, the fibrinolytic response to exercise in the majority of normal individuals includes not only the well-known plasmin-mediated increase in plasma, which is inhibitable by tranexamic acid, but also a similar increment in cell-mediated activity, which is due to qualitative functional rather than quantitative changes in one or more as yet unidentified cell types, acting alone or in conjunction with plasma factors which are not inhibited by tranexamic acid.

Adult↗
PubMed1985

Congenital diaphragmatic hernia: arterial structural changes and persistent pulmonary hypertension after surgical repair.

Some infants with congenital diaphragmatic hernia who die after surgical correction have a transient postoperative period during which systemic oxygenation is adequate (honeymoon period), whereas others have persistent hypoxemia. Using morphometric techniques, we analyzed lung structure, especially the arterial bed, in seven infants who died within 1 week of surgical repair. Three infants comprised the honeymoon group, the PaO2 transiently being greater than 150 mm Hg in the descending aorta (FiO2 1.0); four infants comprised the no-honeymoon group and never had PaO2 greater than 85 mm Hg. All lungs were hypoplastic for age; with one exception, infants in the no-honeymoon group had smaller lungs. Arterial structure in the no-honeymoon group contributed to a greater reduction in pulmonary arterial cross-sectional area. Each infant in the no-honeymoon group had muscularization of intra-acinar arteries and failure of perinatal increase in compliance of small preacinar arteries, features not seen in the honeymoon group or in the normal newborn infant. In addition, compared with the honeymoon group, luminal area of preacinar and intra-acinar arteries in the no-honeymoon group was decreased by reduced external diameter or increased medial thickness. Clinical deterioration in the honeymoon group is based on a vasoconstrictive response of the hypoplastic vascular bed. Persistent hypoxemia in the no-honeymoon group is based on both severity of pulmonary hypoplasia and structural remodeling of the pulmonary arteries.

Arteries↗
PubMed1985

Effect of methylprednisolone on monocrotaline-induced pulmonary vascular disease and right ventricular hypertrophy.

Methylprednisolone (MP) has been shown to reduce acute lung edema caused by monocrotaline (MCT), but its effect on MCT-induced pulmonary hypertension has not previously been reported. We have examined the effects of MP on MCT-induced pulmonary vascular remodeling and right ventricular hypertrophy using five groups of rats. Group 1 received nothing and acted as control; group 2 and all other groups received MCT as a single injection; group 3 was given low-dose MP by daily injection starting 24 hours after the MCT; group 4 was given MP as two high-dose pulses 2 hours before and 22 hours after MCT; group 5, acting as control for injection, received an injection of water 2 hours before MCT and daily for 21 days. All animals were killed 21 days after the MCT was given; ventricular weights were determined, and the lung vasculature was analyzed morphometrically. In each of the last three groups, the "treatment" reduced the increase in arterial medial thickness, "extension" of muscle to intraacinar pulmonary arteries, number of vessels with "occluded" lumen, and right ventricular hypertrophy--the features caused by MCT alone. For all four features, the effectiveness of a given regimen was similar. Daily MP prevented three-quarters of the ventricular ratio change, whereas pulse MP and daily water prevented one-half. The protection given by daily water injection may relate to autologous hormone production (steroid or other) from stress of injections. Daily MP, given after the acute MCT injury has occurred, protects more effectively than a high-dose pulse given at the time of injury. We suggest that the acute phase of MCT injury causes secondary changes that, although triggered by the acute lesion, become self-sustaining and are more significant for vascular structural remodeling.

Animals↗