Objective： To establish a good recoverable rat model of cardiopulmonary bypass （CPB） to lay the foundation for studying the pathophysiology of CPB. Methods： Twenty adult male Sprague-Dawley rats weighing 480 g &#...Objective： To establish a good recoverable rat model of cardiopulmonary bypass （CPB） to lay the foundation for studying the pathophysiology of CPB. Methods： Twenty adult male Sprague-Dawley rats weighing 480 g ±20 g were randomly divided into CPB group （n = 10 ） and Sham group （ n = 10 ）. All rats were anaesthetized, intubated and ventilated. The carotid artery and jugular vein were cannulated. The blood was drained from the right atrium via the right jugular vein and further transferred by a miniaturized roller pump to a hollow fiber oxgenator and back to the rat via the left carotid artery. Priming consisted of 8 ml of homologous blood and 6 ml of colloid. The surface of the hollow fiber oxgenator was 0.075 m^2. Rats were catheterized and brought in bypass for 120 rain at a flow rate of 100-120 ml/kg/min. Oxygen flow/ perfnsion flow was 0.8 to 1.0, the mean arterial pressure （MAP） kept in 60-80 mmHg. Blood gas analysis, lactate dehydrogenase （LDH）, and survival rate were examined subsequently. Results： AH CPB rats recovered from the operative process without incident and remained uneventful within one week. Normal cardiac function after successful weaning was confirmed by electrocardiography and blood pressure measurements. MAP remained stable. The results of blood gas analysis at different time points were within a normal range. No significant haemolysis could be detected in the given time frame under bypass condition by using LDH. Conclusions： The rat model of CPB can principally simulate the clinical setting of human CPB. The nontrausthoracic model is easy to establish and is associated with excellent recovery. This well reproducible model may open the field for various studies on pathophysiological process of CPB and also of systemic ischemia-reperfusion injury in vivo.展开更多
Cancer metastasis is a process with multi-step complexity and apparent randomness. In this study, we aimed to establish a stochastic mathematical model to describe the random process of cancer metastasis and predict t...Cancer metastasis is a process with multi-step complexity and apparent randomness. In this study, we aimed to establish a stochastic mathematical model to describe the random process of cancer metastasis and predict the drug effect of QAP14 on metastasis in a mouse model. The data of lung metastases on the 22^(nd) day after cancer cell implantation with or without the treatment of QAP14, a new chemical compound, were collected in 4T1 breast cancer BALB/c mice. Based on the exponential growth of the primary tumor and metastatic loci, a joint distribution model of metastasis size and number was developed. Disease progression of metastasis and preclinical efficacy of QAP14 were modeled. Parameters M and m representing maximum and minimum of metastasis volume were 3.24 and 0.0184 mm^(3), respectively. The metastasis growth rate γ and metastasis promotion time ρ were estimated and fixed to be 0.0216 d^(-1) and 7.8 d, respectively. The efficacy of QAP14 acted on metastasis promotion time and metastasis growth rate constant in an exponential term, and the effect parameter Effectρ and Effectγ were 16.6 and 0.327 g/mg, respectively. In the present study, we comprehensively characterized the random process of lung metastasis and efficacy of QAP14 in 4T1 breast cancer mice, which might provide a useful reference for the establishment of a clinical population model of cancer metastasis.展开更多
文摘Objective： To establish a good recoverable rat model of cardiopulmonary bypass （CPB） to lay the foundation for studying the pathophysiology of CPB. Methods： Twenty adult male Sprague-Dawley rats weighing 480 g ±20 g were randomly divided into CPB group （n = 10 ） and Sham group （ n = 10 ）. All rats were anaesthetized, intubated and ventilated. The carotid artery and jugular vein were cannulated. The blood was drained from the right atrium via the right jugular vein and further transferred by a miniaturized roller pump to a hollow fiber oxgenator and back to the rat via the left carotid artery. Priming consisted of 8 ml of homologous blood and 6 ml of colloid. The surface of the hollow fiber oxgenator was 0.075 m^2. Rats were catheterized and brought in bypass for 120 rain at a flow rate of 100-120 ml/kg/min. Oxygen flow/ perfnsion flow was 0.8 to 1.0, the mean arterial pressure （MAP） kept in 60-80 mmHg. Blood gas analysis, lactate dehydrogenase （LDH）, and survival rate were examined subsequently. Results： AH CPB rats recovered from the operative process without incident and remained uneventful within one week. Normal cardiac function after successful weaning was confirmed by electrocardiography and blood pressure measurements. MAP remained stable. The results of blood gas analysis at different time points were within a normal range. No significant haemolysis could be detected in the given time frame under bypass condition by using LDH. Conclusions： The rat model of CPB can principally simulate the clinical setting of human CPB. The nontrausthoracic model is easy to establish and is associated with excellent recovery. This well reproducible model may open the field for various studies on pathophysiological process of CPB and also of systemic ischemia-reperfusion injury in vivo.
基金Natural Science Foundation of Beijing Municipality (Grant No. 7192100)。
文摘Cancer metastasis is a process with multi-step complexity and apparent randomness. In this study, we aimed to establish a stochastic mathematical model to describe the random process of cancer metastasis and predict the drug effect of QAP14 on metastasis in a mouse model. The data of lung metastases on the 22^(nd) day after cancer cell implantation with or without the treatment of QAP14, a new chemical compound, were collected in 4T1 breast cancer BALB/c mice. Based on the exponential growth of the primary tumor and metastatic loci, a joint distribution model of metastasis size and number was developed. Disease progression of metastasis and preclinical efficacy of QAP14 were modeled. Parameters M and m representing maximum and minimum of metastasis volume were 3.24 and 0.0184 mm^(3), respectively. The metastasis growth rate γ and metastasis promotion time ρ were estimated and fixed to be 0.0216 d^(-1) and 7.8 d, respectively. The efficacy of QAP14 acted on metastasis promotion time and metastasis growth rate constant in an exponential term, and the effect parameter Effectρ and Effectγ were 16.6 and 0.327 g/mg, respectively. In the present study, we comprehensively characterized the random process of lung metastasis and efficacy of QAP14 in 4T1 breast cancer mice, which might provide a useful reference for the establishment of a clinical population model of cancer metastasis.
