Attenuation of Myocardial Dysfunction in Hypertensive Cardiomyopathy Using Non-R-Wave-Synchronized Cardiac Shock Wave Therapy.

Cardiac shock wave therapy (CSWT) is a novel therapeutic procedure for patients with angina that is refractory to conventional therapy. We investigated the potential mechanism and therapeutic efficacy of non-R-wave-triggered CSWT to attenuate myocardial dysfunction in a large animal model of hypertensive cardiomyopathy. Sustained elevated blood pressure (BP) was induced in adult pigs using a combination of angiotensin-II and deoxycorticosterone acetate (DOCA). Two sessions of non-R-wave-triggered CSWT were performed at 11 and 16 weeks. At 10 weeks, systolic and diastolic blood pressure, LV posterior wall thickness and intraventricular septum thickness significantly increased in both the hypertension and CSWT groups. At 20 weeks, +dP/dt and end-systolic pressure-volume relationship (ESPVR) decreased significantly in the hypertension group but not the CSWT group, as compared with week 10. A significant improvement in end-diastolic pressure-volume relationship (EDPVR) was observed in the CSWT group. The CSWT group exhibited significantly increased microvascular density and vascular endothelial growth factor (VEGF) expression in the myocardium. Cytokine array demonstrated that the CSWT group had significantly reduced inflammation compared with the hypertension group. Our results demonstrate that non-R-wave-triggered CSWT is safe and can attenuate LV systolic and diastolic dysfunction via enhancement of myocardial neovascularization and anti-inflammatory effect in a large animal model of hypertensive cardiomyopathy.

Repeated intravenous administration of hiPSC-MSCs enhance the efficacy of cell-based therapy in tissue regeneration.

We seek to demonstrate whether therapeutic efficacy can be improved by combination of repeated intravenous administration and local transplantation of human induced pluripotential stem cell derived MSCs (hiPSC-MSCs). In this study, mice model of hind-limb ischemia is established by ligation of left femoral artery. hiPSC-MSCs (5 × 105) is intravenously administrated immediately after induction of hind limb ischemia with or without following intravenous administration of hiPSC-MSCs every week or every 3 days. Intramuscular transplantation of hiPSC-MSCs (3 × 106) is performed one week after induction of hind-limb ischemia. We compare the therapeutic efficacy and cell survival of intramuscular transplantation of hiPSC-MSCs with or without a single or repeated intravenous administration of hiPSC-MSCs. Repeated intravenous administration of hiPSC-MSCs can increase splenic regulatory T cells (Tregs) activation, decrease splenic natural killer (NK) cells expression, promote the polarization of M2 macrophages in the ischemic area and improved blood perfusion in the ischemic limbs. The improved therapeutic efficacy of MSC-based therapy is due to both increased engraftment of intramuscular transplanted hiPSC-MSCs and intravenous infused hiPSC-MSCs. In conclusion, our study support a combination of repeated systemic infusion and local transplantation of hiPSC-MSCs for cardiovascular disease.