Study On Efficacy Of Temperature-responsive Chitosan Hydrogel Containing Basic Fibroblast Growth Factor In A Rat Model Of Acute Myocardial Infarction

Objective: Coronary heart disease is the leading cause of death in the world. The death of cardiomyocytes results in a series of pathological variations that lead to left ventricular (LV) remodeling, LV dilation and eventually heart failure following myocardial infarction (MI). Despite advances in techniques of surgical and catheter interventions, the myo- cardium damage could not be healed. Cardiac transplantation is the treat- ment for hearts that are severely damaged due to MI. Due to shortage of heart donors, alternative strategies are needed to improve the living quail- ties of those with ischemia heart failure.Preclinical studies have demonstrated that angiogenic growth factors could stimulate the development of collateral arteries in animal models of myocardial and peripheral ischemia, named therapeutic angiogenesis. Al- though many studies using growth factors have been carried out in the field of angiogenesis, yet they have not always been successful in vivo. One of the reasons for this difficulty was the high infusibility and the short half- life in vivo to retain their biological activities. Therefore, it is necessary to safely enhance their activity in vivo for angiogenic therapy purposes.In this study, we have developed a sustained release system of basic fibroblast growth factor (bFGF) using temperature-responsive chitosan hydrogel (TCH) as a carrier for injecting into the infarcted area of myo- cardium to evaluate cardiac function and vascular density in the infarcted area.Methods: Twenty-four Female Sprague-Dawley rats weighing 230 to 270g were separated into four groups (6 in each). The left anterior descending (LAD) of coronary artery ligation were performed after lateral thoracotomy to induce acute myocardial infarction. The following sub- stances were injected into the infarcted area: Phosphate-Buffered Saline (PBS) alone (group I); PBS incorporating 2μg of bFGF (group II); TCH alone (group III); TCH incorporating 2μg of bFGF (group IV). Echo- cardiography and cardiac catheterization were performed to examine cardiac function four weeks after treatment, then the animals were sacri- ficed and the hearts were removed. The specimens were sectioned for histopathological examination and immunohistochemical assessment of vascular density in the infarcted area.Results: LV end-diastolic and end-systolic dimensions (LVEDD and LVESD) in Group IV were the smallest among the four groups and significant improvement was observed in left ventricular ejection fraction (LVEF) and the fractional shortening (LVFS) (P<0.001).Significant improvement in Group IV was found in systolic pressure (LVESP),diastolic pressure( LVEDP) and±dp/dt maximum at the left ventricleby cardiac catheterization (P<0.001).Histological observations showed a significant increase of vascular density in the MI area and decrease in infarct size in Group IV (P<0.001). There were no differences in all the results between Group I and Group II (P>0.05).Conclusion: TCH incorporating bFGF induced neovasculature formation, reduced infarct size and improved cardiac function of post-MI in rats after being injected into infarcted myocardium.