Development of morphologic, hemodynamic, and biochemical changes in lungs of rats given monocrotaline pyrrole

Reindel, J. F.; Ganey, P.E.; Wagner, James G.; Slocombe, R. F.; Roth, Robert A.

doi:10.1016/0041-008x(90)90239-q

Cited by 69 publications

(50 citation statements)

References 22 publications

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“…We injected rats with monocrotaline intraperitoneally at 60 mg/kg body weight to cause them to develop pulmonary hypertension. Fourteen days after monocrotaline injection, animals were ready for experimentation (15).…”

Section: Methodsmentioning

confidence: 99%

“…The mean moving effects were measured by γ 1 and γ 2 . The parameters β 0 ,K,β 15 were of most interest, as they represented the expected effects of concentrated particles for hours since exposure. Because the three rats were randomly selected from a population, the effects obtained from each rat would be different from the population mean effects because of different characteristics of the sampled rats.…”

Section: Methodsmentioning

confidence: 99%

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Effects of concentrated ambient particles on heart rate and blood pressure in pulmonary hypertensive rats.

Cheng

Hwang

Wang

et al. 2003

Environ Health Perspect

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Epidemiologic studies have shown that increased concentrations of ambient particles are associated with cardiovascular morbidity and mortality (1,2). However, the mechanisms of such associations have not been clearly defined. Recent epidemiologic studies have found associations of increased air particles with increased heart rate and blood pressure and decreased heart rate variability (3-6). It has been speculated that particles cause the activation of autonomic nervous system, leading to changes in heart rates (7). To clarify the relationship of particles with mortality and morbidity, animal models have been used to investigate the effects of particles (8,9). Preliminary studies revealed increased heart rates and arrhythmia in pulmonary hypertensive rats after exposure to concentrated ambient particles (8,10,11). However, a recent study revealed a decreased heart rate when residual oil fly ash was instilled into the rats (12). To investigate further the mechanisms of particleinduced cardiotoxicity, we used heart rate and blood pressure as outcome indicators to assess their association with concentrated ambient particles in pulmonary hypertensive rats. Studies have also indicated that particles with aerodynamic diameter < 2.5 µm (PM 2.5 ) exert greater adverse health effects than coarse particles (1,13). To investigate the effects of PM 2.5 on cardiovascular diseases, we used an ambient particle concentrator, which generated PM 2.5 , to test our hypothesis (14).It is a common practice to divide experimental animals into exposure and control groups to study the effects of air particles. Because of the wide variation among diseased animals, this method requires large numbers of animals to delineate the true effect of air particles (9). Furthermore, variation in circadian cycle for individual rats also makes comparisons of heart rate or blood pressure difficult. To overcome this problem, we used each animal as its own control by exposing the individual animals repeatedly to concentrated air and filtered air and successfully detected the effects of particles on heart rate and mean blood pressure in three rats. Materials and MethodsAnimals and development of pulmonary hypertension. Male Sprague-Dawley rats 60 days old were obtained from the National Laboratory Animal Breeding and Research Center, housed in plastic cages on Aspen chip bedding, and provided with Lab Diet 5001(PMI Lab, Montville, NJ, USA) and water ad libitum except during exposure.Animals were maintained on a 12-hr light/ dark cycle at 22 ± 1°C and 55 ± 10 % relative humidity. We injected rats with monocrotaline intraperitoneally at 60 mg/kg body weight to cause them to develop pulmonary hypertension. Fourteen days after monocrotaline injection, animals were ready for experimentation (15).Experimental design. Ambient particles from the Chung-Li area, a suburb of Taipei, were concentrated through a modified ultrafine particle concentrator developed by Sioutas et al. (14). Briefly, the particle concentrator used virtual impactor technology in which 110 L...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Effects of concentrated ambient particles on heart rate and blood pressure in pulmonary hypertensive rats.

Cheng

Hwang

Wang

et al. 2003

Environ Health Perspect

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“…A rise in pulmonary artery hypertension induces right ventricular hypertrophy and right ventricular failure and eventually leads to premature death. It is well known that a single subcutaneous administration of the pyrrolizidine alkaloid monocrotaline to rats causes cardiovascular and pulmonary disorders similar to those seen in patients with pulmonary artery hypertension (1,2), including severe right ventricular hypertrophy (3,4) and right ventricular failure (5 -8). Despite extensive studies, the fundamental mechanisms responsible for the development and progression of right ventricular failure have not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

Possible Involvement of Mitochondrial Energy-Producing Ability in the Development of Right Ventricular Failure in Monocrotaline-Induced Pulmonary Hypertensive Rats

et al. 2009

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Abstract. The present study was undertaken to explore the possible involvement of alterations in the mitochondrial energy-producing ability in the development of the right ventricular failure in monocrotaline-administered rats. The rats at the 6th week after subcutaneous injection of 60 mg/kg monocrotaline revealed marked myocardial hypertrophy and fibrosis, that is, severe cardiac remodeling. The time-course study on the cardiac hemodynamics of the monocrotalineadministered rat by the cannula and echocardiographic methods showed a reduction in cardiac double product, a decrease in cardiac output index, and an increase in the right ventricular Tei index, suggesting that the right ventricular failure was induced at the 6th week after monocrotaline administration in rats. The mitochondrial oxygen consumption rate of the right ventricular muscle isolated from the monocrotaline-administered animal was decreased, which was associated with a reduction in myocardial high-energy phosphates. Furthermore, the decrease in mitochondrial oxygen consumption rate was inversely related to the increase in the right ventricular Tei index of the monocrotaline-administered rats. These results suggest that impairment of the mitochondrial energy-producing ability is involved in the development of the right ventricular failure in monocrotaline-induced pulmonary hypertensive rats.

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“…In addition to remodeling of arterioles and perhaps venules, pulmonary parenchymal changes including alveolar thickening, edema, and inflammation with frank endothelial and epithelial cell damage is evident (229,230). Hypoxemia, perhaps as a result of damage to the pulmonary vasculature and increased edema, is also apparent in this model (231) and oxygen therapy decreases pulmonary vascular resistance if given 10 to 21 days after treatment (232).…”

Section: Cardiopulmonary Vascular Diseasesmentioning

confidence: 97%

Rodent Models of Cardiopulmonary Disease: Their Potential Applicability in Studies of Air Pollutant Susceptibility

Kodavanti¹,

Costa²,

Bromberg³

1998

Environmental Health Perspectives

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The mechanisms by which increased mortality and morbidity occur in individuals with preexistent cardiopulmonary disease following acute episodes of air pollution are unknown. Studies involving air pollution effects on animal models of human cardiopulmonary diseases are both infrequent and difficult to interpret. Such models are, however, extensively used in studies of disease pathogenesis. Primarily they comprise those developed by genetic, pharmacologic, or surgical manipulations of the cardiopulmonary system. This review attempts a comprehensive description of rodent cardiopulmonary disease models in the context of their potential application to susceptibility studies of air pollutants regardless of whether the models have been previously used for such studies. The pulmonary disease models include bronchitis, emphysema, asthma/allergy, chronic obstructive pulmonary disease, interstitial fibrosis, and infection. The models of systemic hypertension and congestive heart failure include: those derived by genetics (spontaneously hypertensive, Dahl S, renin transgenic, and other rodent models); congestive heart failure models derived by surgical manipulations; viral myocarditis; and cardiomyopathy induced by adriamycin. The characteristic pathogenic features critical to understanding the susceptibility to inhaled toxicants are described. It is anticipated that this review will provide a ready reference for the selection of appropriate rodent models of cardiopulmonary diseases and identify not only their pathobiologic similarities and/or differences to humans but also their potential usefulness in susceptibility studies.

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Development of morphologic, hemodynamic, and biochemical changes in lungs of rats given monocrotaline pyrrole

Cited by 69 publications

References 22 publications

Effects of concentrated ambient particles on heart rate and blood pressure in pulmonary hypertensive rats.

Effects of concentrated ambient particles on heart rate and blood pressure in pulmonary hypertensive rats.

Possible Involvement of Mitochondrial Energy-Producing Ability in the Development of Right Ventricular Failure in Monocrotaline-Induced Pulmonary Hypertensive Rats

Rodent Models of Cardiopulmonary Disease: Their Potential Applicability in Studies of Air Pollutant Susceptibility

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