Validation of hypertension-induced heart failure in mice
Hypertensive heart disease can be studied in a model leading to hypertension and heart failure (HF). Although various animal models of HF exist, we will study this in a mouse model of abdominal aortic constriction (AAC), where the abdominal aorta is constricted by rubber O-rings of a fixed diameter during surgery. The goal of these pilot experiments is to validate AAC so as to have a working model for evaluation of HF progression and future studies of the underlying mechanisms of HF at the Cardiovascular Research Group.
Mice will undergo surgery in anesthesia with adequate preemptive and post-operative analgesia. Following an abdominal incision, a rubber ring is inserted around the abdominal aorta and then constricted. ACC results in hypertension and HF but our aim is to study the heart prior to the development of clinical HF symptoms, and we will reach the end-point of our study before these potentially stressful symptoms are observed. Continuous monitoring over several weeks is necessary to determine the correct time-points for the model. In-vivo monitoring of cardiovascular function includes measuring blood-pressure (tail-cuff), Doppler flow, echocardiography and analysis of blood samples. The overall severity of the study is classified as moderate.
The present application is for a total of 50 mice, to validate O-ring diameter and HF progression following AAC. To increase surgical success, an experienced researcher will perform the surgeries and train local staff (applicant).
There are currently no cell models that accurately model the heart, mainly because cell cultures lack the calcium delivery system found in the intact, beating heart. Thus, as these studies require the use of animals, all surgeries to be used are designed to minimize pain, fear and distress. Strict animal welfare protocols will be used throughout the study to evaluate levels of distress in the mice in addition to close collaboration with experienced staff at the animal facility. Use of in vivo techniques to evaluate cardiac function, such as echocardiography allows for multiple evaluations in the same animal over an extended time period, and will reduce the number of mice to be used and help to assess the health of the animals and the endpoint of the study.
Habituation of mice and other routines to minimize stress in the mice include the training of researchers and use of surgical expertise, as well as the use of well-established analgesic and appropriate scoring protocols to assess animal discomfort. Mice will be provided necessary housing area and materials for mice to thrive, and free access to food and water.
Aortic constriction in mice is well-established but the use of 1) O-rings and 2) constriction of the abdominal aorta are modifications to reduce surgery-related death as compared to other constriction techniques, and improve reproducibility of results. Statistical power analysis has been performed to obtain the necessary group size for the present pilot experiments. For these reasons, and based on the experience from previous studies using animal surgeries at the department, a lower total number of animals will be required to validate this model.
Mice will undergo surgery in anesthesia with adequate preemptive and post-operative analgesia. Following an abdominal incision, a rubber ring is inserted around the abdominal aorta and then constricted. ACC results in hypertension and HF but our aim is to study the heart prior to the development of clinical HF symptoms, and we will reach the end-point of our study before these potentially stressful symptoms are observed. Continuous monitoring over several weeks is necessary to determine the correct time-points for the model. In-vivo monitoring of cardiovascular function includes measuring blood-pressure (tail-cuff), Doppler flow, echocardiography and analysis of blood samples. The overall severity of the study is classified as moderate.
The present application is for a total of 50 mice, to validate O-ring diameter and HF progression following AAC. To increase surgical success, an experienced researcher will perform the surgeries and train local staff (applicant).
There are currently no cell models that accurately model the heart, mainly because cell cultures lack the calcium delivery system found in the intact, beating heart. Thus, as these studies require the use of animals, all surgeries to be used are designed to minimize pain, fear and distress. Strict animal welfare protocols will be used throughout the study to evaluate levels of distress in the mice in addition to close collaboration with experienced staff at the animal facility. Use of in vivo techniques to evaluate cardiac function, such as echocardiography allows for multiple evaluations in the same animal over an extended time period, and will reduce the number of mice to be used and help to assess the health of the animals and the endpoint of the study.
Habituation of mice and other routines to minimize stress in the mice include the training of researchers and use of surgical expertise, as well as the use of well-established analgesic and appropriate scoring protocols to assess animal discomfort. Mice will be provided necessary housing area and materials for mice to thrive, and free access to food and water.
Aortic constriction in mice is well-established but the use of 1) O-rings and 2) constriction of the abdominal aorta are modifications to reduce surgery-related death as compared to other constriction techniques, and improve reproducibility of results. Statistical power analysis has been performed to obtain the necessary group size for the present pilot experiments. For these reasons, and based on the experience from previous studies using animal surgeries at the department, a lower total number of animals will be required to validate this model.