Pulmonary hypertension(PH) is clinically divided into 5 major types, characterized by elevation in pulmonary arterial pressure(PAP) and pulmonary vascular resistance(PVR), finally leading to right heart failure and de...Pulmonary hypertension(PH) is clinically divided into 5 major types, characterized by elevation in pulmonary arterial pressure(PAP) and pulmonary vascular resistance(PVR), finally leading to right heart failure and death. The pathogenesis of this arteriopathy remains unclear, leaving it impossible to target pulmonary vascular remodeling and reverse the deterioration of right ventricular(RV) function. Different animal models have been designed to reflect the complex mechanistic origins and pathology of PH, roughly divided into 4 categories according to the modeling methods: noninvasive models in vivo, invasive models in vivo, gene editing models, and multi-means joint modeling. Though each model shares some molecular and pathological changes with different classes of human PH, in most cases the molecular etiology of human PH is poorly known. The appropriate use of classic and novel PH animal models is essential for the hunt of molecular targets to reverse severe phenotypes.展开更多
Background: Right ventricle failure(RVF) is associated with serious cardiac and pulmonary diseases that contribute significantly to the morbidity and mortality of patients. Currently, the mechanisms of RVF are not ful...Background: Right ventricle failure(RVF) is associated with serious cardiac and pulmonary diseases that contribute significantly to the morbidity and mortality of patients. Currently, the mechanisms of RVF are not fully understood and it is partly due to the lack of large animal models in adult RVF. In this study, we aim to establish a model of RVF in adult ovine and examine the structure and function relations in the RV.Methods: RV pressure overload was induced in adult male sheep by revised pulmonary artery constriction(PAC). Briefly, an adjustable hydraulic occluder was placed around the main pulmonary artery trunk. Then, repeated saline injection was performed at weeks 0, 1, and 4, where the amount of saline was determined in an animal-specific manner. Healthy, age-matched male sheep were used as additional controls. Echocardiography was performed bi-weekly and on week 11 post-PAC, hemodynamic and biological measurements were obtained.Results: This PAC methodology resulted in a marked increase in RV systolic pressure and decreases in stroke volume and tricuspid annular plane systolic excursion, indicating signs of RVF. Significant increases in RV chamber size, wall thickness, and Fulton's index were observed. Cardiomyocyte hypertrophy and collagen accumulation(particularly type III collagen) were evident, and these structural changes were correlated with RV dysfunction.Conclusion: In summary, the animal-specific, repeated PAC provided a robust approach to induce adult RVF, and this ovine model will offer a useful tool to study the progression and treatment of adult RVF that is translatable to human diseases.展开更多
Pulmonary hypertension due to left heart disease(PH-LHD) is regarded as the most prevalent form of pulmonary hypertension(PH). Indeed, PH is an independent risk factor and predicts adverse prognosis for patients with ...Pulmonary hypertension due to left heart disease(PH-LHD) is regarded as the most prevalent form of pulmonary hypertension(PH). Indeed, PH is an independent risk factor and predicts adverse prognosis for patients with left heart disease(LHD). Clinically, there are no drugs or treatments that directly address PH-LHD, and treatment of LHD alone will not also ameliorate PH. To target the underlying physiopathological alterations of PH-LHD and to develop novel therapeutic approaches for this population, animal models that simulate the pathophysiology of PH-LHD are required. There are several available models for PH-LHD that have been successfully employed in rodents or large animals by artificially provoking an elevated pressure load on the left heart, which by transduction elicits an escalated pressure in pulmonary artery. In addition, metabolic derangement combined with aortic banding or vascular endothelial growth factor receptor antagonist is also currently applied to reproduce the phenotype of PH-LHD. As of today, none of the animal models exactly recapitulates the condition of patients with PH-LHD. Nevertheless, the selection of an appropriate animal model is essential in basic and translational studies of PH-LHD. Therefore, this review will summarize the characteristics of each PH-LHD animal model and discuss the advantages and limitations of the different models.展开更多
To explore the feasibility of the full automatic animal experimental cabin to establish the animal models in normobaric/hypobaric hypoxic and high carbon dioxide environment. Methods： Sixty SPF-class male DS rats wer...To explore the feasibility of the full automatic animal experimental cabin to establish the animal models in normobaric/hypobaric hypoxic and high carbon dioxide environment. Methods： Sixty SPF-class male DS rats were divided into 2 groups, 20 for normobaric, hypoxic conditions and the other 40 for hypobaric, hypoxic conditions. For each group, the pulmonary arterial pressure and carotid arterial pressure indicators of rats were examined by using the physiological multi-detector, and the pulmonary vascular changes in the structure were observed. Results： The normobaric/hypobaric hypoxic with high carbon dioxide environment can promote the formation of pulmonary hypertension and accelerate changes in pulmonary vascular remodeling, and promote the right ventricular hypertrophy. Conclusion： Clinical applications showed that the animal experimental cabin has observed and controlled accurately. The result was safe, reliable and reproducible. The cabin can successfully establish the pulmonary hypertension model in normobaric/hypobaric hypoxic with high carbon dioxide environment, and in order to study the physiological mechanism of a variety of circulation and respiratory diseases caused by lack of oxygen, which provided an experimental technology platform for clinical research.展开更多
Objective： To explore the feasibility of the full automatic animal experimental cabin to establish the animal models in normobaric/hypobarie hypoxic and high carbon dioxide environment. Methods： 60 SPF-class male SD...Objective： To explore the feasibility of the full automatic animal experimental cabin to establish the animal models in normobaric/hypobarie hypoxic and high carbon dioxide environment. Methods： 60 SPF-class male SD rats were divided into two groups, 20 for normobaric, hypoxie conditions and the other 40 for hypobarie, hypoxic conditions. For each group, we examined the pulmonary arterial pressure and carotid arterial pressure indicators of rats by using the physiological muhi-detector measurement, and observed the pulmonary vascular changes in the structure. Results： The normobaric/hypobarie hypoxic with high carbon dioxide environment can promote the formation of pulmonary hypertension and accelerate changes in pulmonary vascular remodeling, and promote the right ventricular hypertrophy. Conclusion： Clinical applications showed that the animal experimental cabin has observed and controlled accurately. The result was safe, reliable and reproducible. The cabin can successfully establish the pulmonary hypertension model in normobaric/hypobaric hypoxie with high carbon dioxide enviromnent, and in order to study the physiological mechanism of a variety of circulation and respiratory diseases caused by lack of oxygen, which provided an experimental technology platform tor clinical research.展开更多
IM To produce a new rat model of portal hypertension by intraportal injection of microspheres.METHODS Measured aliquots of single or differentsized microspheres (15, 40, 80μm) were injected into the portal vein to...IM To produce a new rat model of portal hypertension by intraportal injection of microspheres.METHODS Measured aliquots of single or differentsized microspheres (15, 40, 80μm) were injected into the portal vein to block intrahepatic portal radicals. The resultant changes in arterial, portal, hepatic venous and splenic pulp pressures were monitored. The liver and lungs were excised for histological examination.RESULTS Portal venous pressure was elevated from basal value of 089-102 kPa to a steadystate of 198-319 kPa following the sequential injections of single or differentsized microspheres, with a markedly lowered mean arterial pressure. However, a smalldose injection of 80μm microspheres (18×105) produced a steadystate portal venous pressure of 253±017 kPa, and all rats showed normal arterial pressures. In addition, numerous microspheres were found in the lungs in all experimental groups.CONCLUSION Portal hypertension can be reproduced in rats by intraportal injection of microspheres at a small dose of 80μm (18×105). Intrahepatic portalsystemic shunts probably exist in the normal rat liver..展开更多
In order to rind a simple but satisfying method to make animal model with portal hypertension, a new method is designed by constricting half of the POrtal lumen and embolizing the portalvein chronically with silk thre...In order to rind a simple but satisfying method to make animal model with portal hypertension, a new method is designed by constricting half of the POrtal lumen and embolizing the portalvein chronically with silk thread. Twenty-two dogs were used in the experiment, among which onedied, and the others' portal venous pressure went up to (2. 83±0. 66) kpa 3～4 weeks arter the operation (1. 33±0.28) kpa before the operation (P < 0. 001 ). The results or gastrofiberscopic, portoveuographic and pathological examination showed that 17 dogs had esophagogastric varices with aformation rate or 80. 97 %. The 14 or which were achieved with a 100% formation rate as the methodwas improved. 12 dogs suffered portal hypertentive gastropathy (the rate of formation was57. 14% ). One dog was observed for 4 months arter the operation, still with portal hypertension. Allthis Indicates that the method is simple and time-saving, with high success rate, reliable quality andlong duration.展开更多
Objective To establish rat models of chronic obstructive pulmonary disease (COPD) and study the pathological characteristics of airflow obstruction Method SO 2 inhalation method was used to establish rat mod...Objective To establish rat models of chronic obstructive pulmonary disease (COPD) and study the pathological characteristics of airflow obstruction Method SO 2 inhalation method was used to establish rat models After exposure to SO 2 for 7 weeks, peak expiratory flow (PEF), peak inspiratory flow (PIF), intratracheal pressure (IP) and IP slope in rat were measured by Maclab data recording and analysis system Experimental rats with PEF less than 80% of the mean of the normal rats were classified as airflow obstructed, while those with PEF greater than 80% of mean of normal rats were non obstructed Pathological changes in airway and lung tissue were compared between these two groups Result In experimental animals, PEF was significantly decreased ( P <0 005) and IP slope increased ( P <0 001) as compared with normal rats Epithelial damage, goblet cell hyperplasia and inflammatory cell infiltration in cartilaginous bronchi were more remarkable in experimental rats with airflow obstruction than those without airflow obstruction ( P <0 001, <0 01, <0 001, respectively) Furthermore, pathological changes in airway lumen, epithelium and airway wall in membranous and respiratory bronchioles were more marked in experimental rats with airflow obstruction than those without airflow obstruction ( P <0 001 or P <0 05) There was a negative correlation between PEF values and epithelial hyperplasia, goblet cell hyperplasia, inflammatory cell infiltration, smooth muscle hyperplasia and mucous plug in membranous and respiratory bronchioles ( P <0 001 or P <0 05) Conclusion SO 2 inhalation may cause chronic bronchitis with airflow obstruction, i e COPD in rats COPD was induced in 64% (16 of 25) of the experimental group rats展开更多
基金CAMS Innovation Fund for Medical Sciences (CIFMS):2021-I2M-1-018。
文摘Pulmonary hypertension(PH) is clinically divided into 5 major types, characterized by elevation in pulmonary arterial pressure(PAP) and pulmonary vascular resistance(PVR), finally leading to right heart failure and death. The pathogenesis of this arteriopathy remains unclear, leaving it impossible to target pulmonary vascular remodeling and reverse the deterioration of right ventricular(RV) function. Different animal models have been designed to reflect the complex mechanistic origins and pathology of PH, roughly divided into 4 categories according to the modeling methods: noninvasive models in vivo, invasive models in vivo, gene editing models, and multi-means joint modeling. Though each model shares some molecular and pathological changes with different classes of human PH, in most cases the molecular etiology of human PH is poorly known. The appropriate use of classic and novel PH animal models is essential for the hunt of molecular targets to reverse severe phenotypes.
文摘Background: Right ventricle failure(RVF) is associated with serious cardiac and pulmonary diseases that contribute significantly to the morbidity and mortality of patients. Currently, the mechanisms of RVF are not fully understood and it is partly due to the lack of large animal models in adult RVF. In this study, we aim to establish a model of RVF in adult ovine and examine the structure and function relations in the RV.Methods: RV pressure overload was induced in adult male sheep by revised pulmonary artery constriction(PAC). Briefly, an adjustable hydraulic occluder was placed around the main pulmonary artery trunk. Then, repeated saline injection was performed at weeks 0, 1, and 4, where the amount of saline was determined in an animal-specific manner. Healthy, age-matched male sheep were used as additional controls. Echocardiography was performed bi-weekly and on week 11 post-PAC, hemodynamic and biological measurements were obtained.Results: This PAC methodology resulted in a marked increase in RV systolic pressure and decreases in stroke volume and tricuspid annular plane systolic excursion, indicating signs of RVF. Significant increases in RV chamber size, wall thickness, and Fulton's index were observed. Cardiomyocyte hypertrophy and collagen accumulation(particularly type III collagen) were evident, and these structural changes were correlated with RV dysfunction.Conclusion: In summary, the animal-specific, repeated PAC provided a robust approach to induce adult RVF, and this ovine model will offer a useful tool to study the progression and treatment of adult RVF that is translatable to human diseases.
基金funded by the China Scholarship Council(CSC)(no.202108080221)。
文摘Pulmonary hypertension due to left heart disease(PH-LHD) is regarded as the most prevalent form of pulmonary hypertension(PH). Indeed, PH is an independent risk factor and predicts adverse prognosis for patients with left heart disease(LHD). Clinically, there are no drugs or treatments that directly address PH-LHD, and treatment of LHD alone will not also ameliorate PH. To target the underlying physiopathological alterations of PH-LHD and to develop novel therapeutic approaches for this population, animal models that simulate the pathophysiology of PH-LHD are required. There are several available models for PH-LHD that have been successfully employed in rodents or large animals by artificially provoking an elevated pressure load on the left heart, which by transduction elicits an escalated pressure in pulmonary artery. In addition, metabolic derangement combined with aortic banding or vascular endothelial growth factor receptor antagonist is also currently applied to reproduce the phenotype of PH-LHD. As of today, none of the animal models exactly recapitulates the condition of patients with PH-LHD. Nevertheless, the selection of an appropriate animal model is essential in basic and translational studies of PH-LHD. Therefore, this review will summarize the characteristics of each PH-LHD animal model and discuss the advantages and limitations of the different models.
文摘To explore the feasibility of the full automatic animal experimental cabin to establish the animal models in normobaric/hypobaric hypoxic and high carbon dioxide environment. Methods： Sixty SPF-class male DS rats were divided into 2 groups, 20 for normobaric, hypoxic conditions and the other 40 for hypobaric, hypoxic conditions. For each group, the pulmonary arterial pressure and carotid arterial pressure indicators of rats were examined by using the physiological multi-detector, and the pulmonary vascular changes in the structure were observed. Results： The normobaric/hypobaric hypoxic with high carbon dioxide environment can promote the formation of pulmonary hypertension and accelerate changes in pulmonary vascular remodeling, and promote the right ventricular hypertrophy. Conclusion： Clinical applications showed that the animal experimental cabin has observed and controlled accurately. The result was safe, reliable and reproducible. The cabin can successfully establish the pulmonary hypertension model in normobaric/hypobaric hypoxic with high carbon dioxide environment, and in order to study the physiological mechanism of a variety of circulation and respiratory diseases caused by lack of oxygen, which provided an experimental technology platform for clinical research.
文摘Objective： To explore the feasibility of the full automatic animal experimental cabin to establish the animal models in normobaric/hypobarie hypoxic and high carbon dioxide environment. Methods： 60 SPF-class male SD rats were divided into two groups, 20 for normobaric, hypoxie conditions and the other 40 for hypobarie, hypoxic conditions. For each group, we examined the pulmonary arterial pressure and carotid arterial pressure indicators of rats by using the physiological muhi-detector measurement, and observed the pulmonary vascular changes in the structure. Results： The normobaric/hypobarie hypoxic with high carbon dioxide environment can promote the formation of pulmonary hypertension and accelerate changes in pulmonary vascular remodeling, and promote the right ventricular hypertrophy. Conclusion： Clinical applications showed that the animal experimental cabin has observed and controlled accurately. The result was safe, reliable and reproducible. The cabin can successfully establish the pulmonary hypertension model in normobaric/hypobaric hypoxie with high carbon dioxide enviromnent, and in order to study the physiological mechanism of a variety of circulation and respiratory diseases caused by lack of oxygen, which provided an experimental technology platform tor clinical research.
文摘IM To produce a new rat model of portal hypertension by intraportal injection of microspheres.METHODS Measured aliquots of single or differentsized microspheres (15, 40, 80μm) were injected into the portal vein to block intrahepatic portal radicals. The resultant changes in arterial, portal, hepatic venous and splenic pulp pressures were monitored. The liver and lungs were excised for histological examination.RESULTS Portal venous pressure was elevated from basal value of 089-102 kPa to a steadystate of 198-319 kPa following the sequential injections of single or differentsized microspheres, with a markedly lowered mean arterial pressure. However, a smalldose injection of 80μm microspheres (18×105) produced a steadystate portal venous pressure of 253±017 kPa, and all rats showed normal arterial pressures. In addition, numerous microspheres were found in the lungs in all experimental groups.CONCLUSION Portal hypertension can be reproduced in rats by intraportal injection of microspheres at a small dose of 80μm (18×105). Intrahepatic portalsystemic shunts probably exist in the normal rat liver..
文摘In order to rind a simple but satisfying method to make animal model with portal hypertension, a new method is designed by constricting half of the POrtal lumen and embolizing the portalvein chronically with silk thread. Twenty-two dogs were used in the experiment, among which onedied, and the others' portal venous pressure went up to (2. 83±0. 66) kpa 3～4 weeks arter the operation (1. 33±0.28) kpa before the operation (P < 0. 001 ). The results or gastrofiberscopic, portoveuographic and pathological examination showed that 17 dogs had esophagogastric varices with aformation rate or 80. 97 %. The 14 or which were achieved with a 100% formation rate as the methodwas improved. 12 dogs suffered portal hypertentive gastropathy (the rate of formation was57. 14% ). One dog was observed for 4 months arter the operation, still with portal hypertension. Allthis Indicates that the method is simple and time-saving, with high success rate, reliable quality andlong duration.
文摘Objective To establish rat models of chronic obstructive pulmonary disease (COPD) and study the pathological characteristics of airflow obstruction Method SO 2 inhalation method was used to establish rat models After exposure to SO 2 for 7 weeks, peak expiratory flow (PEF), peak inspiratory flow (PIF), intratracheal pressure (IP) and IP slope in rat were measured by Maclab data recording and analysis system Experimental rats with PEF less than 80% of the mean of the normal rats were classified as airflow obstructed, while those with PEF greater than 80% of mean of normal rats were non obstructed Pathological changes in airway and lung tissue were compared between these two groups Result In experimental animals, PEF was significantly decreased ( P <0 005) and IP slope increased ( P <0 001) as compared with normal rats Epithelial damage, goblet cell hyperplasia and inflammatory cell infiltration in cartilaginous bronchi were more remarkable in experimental rats with airflow obstruction than those without airflow obstruction ( P <0 001, <0 01, <0 001, respectively) Furthermore, pathological changes in airway lumen, epithelium and airway wall in membranous and respiratory bronchioles were more marked in experimental rats with airflow obstruction than those without airflow obstruction ( P <0 001 or P <0 05) There was a negative correlation between PEF values and epithelial hyperplasia, goblet cell hyperplasia, inflammatory cell infiltration, smooth muscle hyperplasia and mucous plug in membranous and respiratory bronchioles ( P <0 001 or P <0 05) Conclusion SO 2 inhalation may cause chronic bronchitis with airflow obstruction, i e COPD in rats COPD was induced in 64% (16 of 25) of the experimental group rats
