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OBJECTIVES The study evaluated a nonsurgical means of intramyocardial cell introduction using the coronary venous system for direct myocardial access and cell delivery. BACKGROUND Direct myocardial cell repopulation has been proposed as a potential method to treat heart failure. METHODS We harvested bone marrow from Yorkshire swine (n = 6; 50 to 60 kg), selected culture-flask adherent cells, labeled them with the gene for green fluorescence protein, expanded them in culture, and resuspended them in a collagen hydrogel. Working through the coronary sinus, a specialized catheter system was easily delivered to the anterior interventricular coronary vein. The composite catheter system (TransAccess) incorporates a phased-array ultrasound tip for guidance and a sheathed, extendable nitinol needle for transvascular myocardial access. A microinfusion (IntraLume) catheter was advanced through the needle, deep into remote myocardium, and the autologous cell-hydrogel suspension was injected into normal heart. Animals were sacrificed at days 0 (n = 2), 14 (n = 1, + 1 control/collagen biogel only), and 28 (n = 2), and the hearts were excised and examined. RESULTS We gained widespread intramyocardial access to the anterior, lateral, septal, apical, and inferior walls from the anterior interventicular coronary vein. No death, cardiac tamponade, ventricular arrhythmia, or other procedural complications occurred. Gross inspection demonstrated no evidence of myocardial perforation, and biogel/black tissue dye was well localized to sites corresponding to fluoroscopic landmarks for delivery. Histologic analysis demonstrated needle and microcatheter tracts and accurate cell-biogel delivery. CONCLUSIONS Percutaneous intramyocardial access is safe and feasible by a transvenous approach through the coronary venous system. The swine offers an opportunity to refine approaches used for cellular cardiomyoplasty.

A new mock circulatory loop was developed for hemolysis studies associated with the Penn State electric ventricular assist device (EVAD). This flow loop has several advantages over previously designed loops. It is small enough to accommodate experiments in which only single units of blood are available, it is made out of biocompatible materials, it incorporates good geometry, and it provides normal physiological pressures and flows to both the aortic outlet and the venous inlet of the pumping device. Experiments with reduced aortic pressure but normal cardiac output showed that hemolysis in a loop with normal aortic blood pressure was significantly higher than that in a loop with lowered aortic pressure, thereby illustrating the importance of maintaining loop pressures as close as possible to those found in vivo. This data also imply that blood traveling through the left ventricle in an artificial heart may be subject to higher hemolysis rates than that traversing the right ventricle. Another set of experiments to determine the effects of 4 hemolysis or drag-reducing agents (Pluronic F-68, Dextran-40, Polyox WSR-301, and Praestol 2273TR) on blood trauma due to the EVAD and associated valves was performed. Results indicated that none of the additives significantly reduced hemolysis under the conditions found in the mock loop. Finally, a compilation of data gathered in these experiments showed that the index of hemolysis (IH) is dependent on hematocrit (HCT), which suggests that another parameter, IH/HCT, may be more suited to the quantification of hemolysis.

Blood flow through a prosthetic heart valve operating in a ventricular assist device can be subdivided into three phases: a) forward flow through an open valve, b) rapid valve closure, and c) regurgitant back flow through a closed valve. Recent studies of fluid stresses in the Penn State Electric Left Ventricular Assist Device (PS LVAD) operating under physiologic conditions indicate that Reynolds stresses of possibly hemolytic magnitude may exist in the valve area. Although several studies have been made of the fluid stresses seen in forward flow through an open valve, few have looked at valve closure or backflow, and none have related these stresses directly to blood damage. In this study, novel in vitro blood flow loops were developed to allow for the separate analysis of the three flow phases of a Bjork-Shiley monostrut Delrin disk valve operating in a PS LVAD. Forward flow through fully open aortic and mitral valves and backflow through closed valves are studied separately in flow loops driven by a roller pump with the LVAD acting as a valve housing and compliance vessel. Valve closure is investigated with a PS LVAD operating in a low volume mock circulatory loop characterized by cavitation potential through stroboscopic videography of this mock loop, using saline as the working fluid. Rate of hemolysis, characterized by the index of hemolysis, IH, is determined for each of the three flow loops charged with fresh porcine blood.(ABSTRACT TRUNCATED AT 250 WORDS)

A volume compensation chamber is a device used to reduce large pressure fluctuations created in electric ventricular assist devices during the emptying and filling of the blood sac. In this study, the effect of motor casing pressure variation (pressure swing) on the performance of the Penn State electric ventricular assist device (EVAD) was investigated. Design criteria were established for the maximum pressure swing tolerated by the EVAD and the optimal mean chamber pressure at which to operate. At the chosen mean chamber pressure of -15 mm Hg, it was found that pressure swing should be maintained below 45 mm Hg. A two-phase fluid volume compensation chamber was developed that reduced the pressure swing enough to ensure adequate pump performance. The device consists of a metal chamber with a high-heat-flux porous coating applied to the inside surface. The chamber uses Freon as the working fluid and is isolated from the EVAD by a metal bellows. It was found that the high-flux coating significantly reduces the pressure swing, in some cases by as much as 50% when compared with an identical chamber with no coating. In the coated chamber the pressure swing was maintained between 22 and 30 mm Hg at a beat rate of 60 beats/min, for a wide range of Freon volumes (4-38 ml). Even at 100 beats/min the pressure swings obtained with the coated chamber are well within an acceptable range.

A 100 cc size roller screw electric total artificial heart has been implanted in IO animals at The Pennsylvania State University; four of those animals have survived in excess of 100 days, with one animal living 205 days. The 205 day animal. Agnes, had a preoperative weight of 103 kg and gained 73 kgs over the 205 day implant duration. The calf was under automatic electronic control the entire duration of the experiment, and tolerated weekly exercise very well. The cause of death in the animal was corrosion debris lodging between the rotor and stator; this corrosion debris was corrosion generated by the electric motor stack. Subsequent experiments utilize a coated stack to eliminate corrosion.

A method for real-time in vitro observation of cavitation on a prosthetic heart valve has been developed. Cavitation of four blood analog fluids (distilled water, aqueous glycerin, aqueous polyacrylamide, and aqueous xanthan gum) has been documented for a Medtronic/Hall™ prosthetic heart valve. This method employed a Penn State Electrical Ventricular Assist Device in a mock circulatory loop that was operated in a partial filling mode associated with reduced atrial filling pressure. The observations were made on a valve that was located in the mitral position, with the cavitation occurring on the inlet side after valve closure on every cycle. Stroboscopic videography was used to document the cavity life cycle. Bubble cavitation was observed on the valve occluder face. Vortex cavitation was observed at two locations in the vicinity of the valve occluder and housing. For each fluid, cavity growth and collapse occurred in less than one millisecond, which provides strong evidence that the cavitation is vaporous rather than gaseous. The cavity duration time was found to decrease with increasing atrial pressure at constant aortic pressure and beat rate. The area of cavitation was found to decrease with increasing delay time at a constant aortic pressure, atrial pressure, and beat rate. Cavitation was found to occur in each of the fluids, with the most cavitation seen in the Newtonian fluids (distilled water and aqueous glycerin).