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R C Shumaker

Publications and source records attributed to R C Shumaker.

7 recordsLinked to original sources
PubMed1979

Pathophysiology of dehydromonocrotaline-induced pulmonary fibrosis in the beagle.

The purpose of this study was to characterize the sequential hemodynamic alterations and pulmonary vascular lesions produced by a single pulmonary artery injection of the vasotoxic pyrrolic alkaloid dehydromonocrotaline in the young beagle. Normotensive pulmonary pressure was replaced by hypertension 21 days after injection. By 28 days, the pulmonary pressure and total pulmonary vascualr resistance of the experimental animals were significantly greater than the controls (p less than 0.01). Right ventricular work increased from a baseline mean of 0.58 to 1.40 kg . m/min. Morphological and morphometrical analyses revealed alveolar edema, increased numbers of alveolar macrophages, cellular hyperplasia in the alveolar septa, and a progressive interstitial fibrosis. The precise mechansims by which dehydromonocrotaline injection initiates and promotes pulmonary hypertension and pulmonary fibrosis still needs clarification; however, our data indicate that the fraction of air space is reduced relative to the fraction of tissue space, and this change occurs with concurrent fibrosis in the alveolar septa and an increased pulmonary arterial pressure although hypoxia was not clinically detectable.

Animals↗
PubMed1977

Fibrin thrombosis in monocrotaline pyrrole-induced cor pulmonale in rats.

Investigations were carried out to determine the lung lesions responsible for the development of pulmonary heart disease, cor pulmonale, in rats treated with monocrotaline pyrrole or monocrotaline. Animals with right ventricular hypertrophy showed microscopic lung alterations consisting of alveolar edema; fibrin thrombi with partial to complete occlusion of arteries, arterioles, capillaries, and veins; connective tissue proliferation of alveolar septae; cellular hyperplasia of septae; and medial hypertrophy of arterioles. Due to the high incidence of fibrin thrombi in animals with right ventricular hypertrophy, we believe that formation of fibrin thrombi plays a decisive role in the development of chemically induced cor pulmonale.

Animals↗
PubMed1976

Localisation and tissue effects of tritiated dehydroretronecine in young rats.

Sixteen male Spraque-Dawley rats were injected with 3H-dehydroretronecine. The rats were subsequently evaluated for gross and microscopic changes. Scintillation counts and autoradiographic studies of the various organs demonstrated that the pyrrole accumulates in organs which were shown here and by others (Peterson et al; Allen and Hsu) to be affected most severely by dehydroretronecine and dehydroheliotridine. In the present experiment 3H-dehydroretronecine was shown to decrease the growth rate of the rats, decrease the percentage of circulating neutrophils and alter the hepatic mitotic index. Histologically, accumulations of label were seen in the glandular region of the stomach, in the liver, in Huxley's and Henle's layers of the hair follicles and in the epithelial cells lining the convoluted tubules of the kidney. Scintillation counts on the various tissues and autoradiographic evaluations of tissue sections indicate that there is a preferential localisation of radioactivity in the gastric mucosa which is postulated to be related to the pH in this area.

Animals↗
PubMed1976

Neoplastic transformation in tissues of rats exposed to monocrotaline or dehydroretronecine.

Male Sprague-Dawley rats received sc injections biweekly of either the pyrrolizidine alkaloid monocrotaline or its metabolite dehydroretronecine for 1 year. The animals were then observed for an additional 12 months for the induction of neoplasms. Of 60 rats that received dehydroretronecine, 39 developed rhabdomyosarcomas at the injection site, and 5 of these neoplasms metastasized. In the 60 monocrotaline-treated rats, 31 widely dispersed tumors of various cell types were recorded. The reason suggested for the variation in tissue response was that the metabolite dehydroretronecine is a proximate carcinogen, whereas monocrotaline must first be metabolized before its carcinogenic potential is realized.

Animals↗
PubMed1976

Disenecioyl dehydroretronecine--synthesis and acute hepatic toxicity of a pyrrolizidine alkaloid pyrrole analog.

Disenecioyl dehydroretronecine (DSDR), a semi-synthetic analog of the highly reactive pyrrole metabolites of the pyrrolizidine alkaloids, has been synthesized from disenecioyl retronecine. Rats which received 40 mg DSDR/kg body weight via the mesenteric vein showed multiple depressed areas (less than 2 mm in diameter) on the surface of the median lobe of the liver. Microscopically these areas consisted of hepatic venous occlusion, necrosis, and proliferation of fibroblasts and bile ducts in and around the portal triad. These hepatic lesions were similar to those produced by dehydroretrorcine.

Animals↗
PubMed1975

Binding of tritiated dehydroretronecine to macromolecules.

In vivo and in vitro experiments have shown that the pyrrolizidine alkaloid metabolite dehydroretronecine binds readily to macromolecules. In the in vivo experiment there was a preferential binding of dehydroretronecine to the gastric mucosa. Further extraction of the mucosa revealed a large percentage of the 3H was bound to the protein fraction and to a much lesser extent to DNA and RNA. The influence of pH on the binding of dehydroretronecine was substantiated in the in vitro experiment. Dehydroretronecine bound to calf thymus DNA and bovine serum albumin most readily under acidic conditions. These data suggest a direct correlation of the levels of dehydroretronecine binding to cellular macromolecules with the lesions that develop in affected organs.

Animals↗