Abstract
OBJECTIVE: Left ventricular pressure overload models using adult mice or rats were developed 60 years ago; however, a neonatal mouse model of left ventricular pressure overload was reported only 5 years ago. Moreover, how left ventricular pressure overload reshapes the neonatal left ventricle and how it affects cardiomyocyte proliferation remain largely unexplored. The aim of this study is to develop a simple neonatal rat model with clinical features matched to those of left ventricular pressure overload. METHODS: A neonatal rat model of progressive left ventricular pressure overload was created via abdominal aortic banding microsurgery at postnatal day 1 and verified by gross examination at postnatal day 7, abdominal ultrasound at postnatal day 21, and left upper limb blood pressure measurement from postoperative day 21 to day 35. A surgical video and detailed surgical procedures were documented for learning purposes. RESULTS: RNA sequencing demonstrated that there were only 171 differentially expressed genes between the abdominal aortic banding surgery and sham left ventricles at postnatal day 3, with 406 differentially expressed genes at postnatal day 7. At postnatal day 3, there was little enrichment of proliferation-associated genes and only a small percentage of proliferating cardiomyocytes; at postnatal day 7, there was an abundant enrichment of proliferation-associated genes and a large percentage of proliferating cardiomyocytes, exactly opposite to the neonatal transverse aortic constriction surgery model, which exhibited decreased cardiomyocyte proliferation over time and even inhibited cardiomyocyte proliferation when severe left ventricular pressure overload was induced by transverse aortic constriction surgery. Moreover, abdominal aortic banding surgery does not require a thoracotomy, resulting in a success rate as high as 100%. CONCLUSIONS: A neonatal rat model of progressive left ventricular pressure overload was successfully established and fully documented to provide a platform for pediatric left ventricular pressure overload-associated investigation.