Allogeneic pASC transplantation in humanized pigs attenuates cardiac remodeling post-myocardial infarction.

Cell therapy repair strategies using adult mesenchymal stromal cells have shown promising evidence to prevent cardiac deterioration in rodents even in the absence of robust differentiation of the cells into cardiomyocytes. We tested whether increasing doses of porcine adipose-tissue derived mesenchymal stem cells (pASCs) increase cardiac tissue perfusion in pigs post-myocardial infarction (MI) receiving angiotensin-converting-enzyme inhibitor (ACE inhibitors) and Beta-blockers similarly to patients. Female pigs were subjected to MI induction by sponge permanent occlusion of left circumflex coronary artery (LCx) generating approximately 10% of injured LV area with minimum hemodynamic impact. We assessed tissue perfusion by real time myocardial perfusion echocardiography (RTMPE) using commercial microbubbles before and following pASCs treatment. Four weeks after the occlusion of the left circumflex artery, we transplanted placebo or pASCs (1, 2 and 4x106 cells/Kg BW) into the myocardium. The highest dose of pASCs increased myocardial vessel number and blood flow in the border (56% and 3.7-fold, respectively) and in the remote area (54% and 3.9-fold, respectively) while the non-perfused scar area decreased (up to 38%). We also found an increase of immature collagen fibers, although the increase in total tissue collagen and types I and III was similar in all groups. Our results provide evidence that pASCs-induced stimulation of tissue perfusion and accumulation of immature collagen fibers attenuates adverse remodeling post-MI beyond the normal beneficial effects associated with ACE inhibition and beta-blockade.

Projeto, construção e testes de um dispositivo de assistência ventricular pulsátil / Design, manufacturing and testing of a pulsatile ventricular assist device

PURPOSE--To describe the design of a ventricular assist device (VAD), its manufacturing and testing. METHODS--The VAD is pulsatile, with a free floating membrane, smooth internal surfaces, and pericardium valves. It comprises also a pneumatic driving unit capable of operating in the ®full to empty®, EKG synchronized or asynchronous modes. The system was tested ®in vitro® to assess its mechanical durability, hydrodynamic performance and hemolysis. ®In vivo® tests were performed in 22 sheep and 8 calves aiming at optimizing cannulas and implant techniques. In these experiments, hemolysis and the device's capacity of restoring to normal hemodynamic parameters during induced cardiac failure were evaluated. RESULTS--The device was worked 4,000 hours without failure in a mock circulatory loop. Hydrodynamic performance was satisfactory for adult circulatory support. In ®full to empty® mode it displayed a frequency mediated ®Starling like® performance. Optimum output was achieved with a systole duration of 40//of the cycle. ®In vitro® hemolysis index was 6.7 +/- 2.1. Hemolysis in animal experiments was clinically non significant. In calves under induced cardiac failure the VAD was able to normalize hemodynamic parameters within 120 minutes. CONCLUSION--This VAD is capable to circulatory assist for cardiogenic shock in conditions needed for an adult patient and the average time span anticipated for bridge to transplantation or post cardiotomy cardiogenic shock