Egemen Tuzun

Biventricular support with the Jarvik 2000 axial flow pump: a feasibility study.

Patients with congestive heart failure who are supported with a left ventricular assist device (LVAD) may experience right ventricular dysfunction or failure that requires support with a right ventricular assist device (RVAD). To determine the feasibility of using a clinically available axial flow ventricular assist device as an RVAD, we implanted Jarvik 2000 pumps in the left ventricle and right atrium of two Corriente crossbred calves (approximately 100 kg each) by way of a left thoracotomy and then analyzed the hemodynamic effects in the mechanically fibrillated heart at various LVAD and RVAD speeds. Right atrial implantation of the device required no modification of either the device or the surgical technique used for left ventricular implantation. Satisfactory biventricular support was achieved during fibrillation as evidenced by an increase in mean aortic pressure from 34 mm Hg with the pumps off to 78 mm Hg with the pumps generating a flow rate of 4.8 L/min. These results indicate that the Jarvik 2000 pump, which can provide chronic circulatory support and can be powered by external batteries, is a feasible option for right ventricular support after LVAD implantation and is capable of completely supporting the circulation in patients with global heart failure.

Total heart replacement using dual intracorporeal continuous-flow pumps in a chronic bovine model: a feasibility study.

Continuous-flow pumps are small, simple, and respond physiologically to input variations, making them potentially ideal for total heart replacement. However, the physiological effects of complete pulseless flow during long-term circulatory support without a cardiac interface or with complete cardiac exclusion have not been well studied. We evaluated the feasibility of dual continuous-flow pumps as a total artificial heart (TAH) in a chronic bovine model. Both ventricles of a 6-month-old Corriente crossbred calf were excised and sewing rings attached to the reinforced atrioventricular junctions. The inlet portions of 2 Jarvik 2000 pumps were positioned through their respective sewing rings at the midatrial level and the pulseless atrial reservoir connected end-to-end to the pulmonary artery and aorta. Pulseless systemic and pulmonary circulations were thereby achieved. Volume status was controlled, and systemic and pulmonary resistance were managed pharmacologically to keep mean arterial pressures at 100±10 mmHg (systemic) and 20±5 mmHg (pulmonary) and both left and right atrial pressures at 15±5 mmHg. The left pump speed was maintained at 14,000 rpm and its output autoregulated in response to variations in right pump flow, systemic and pulmonary pressures, fluid status, and activity level. Hemodynamics, end-organ function, and neurohormonal status remained normal. These results suggest the feasibility of using dual continuous-flow pumps as a TAH.

In vivo response to an implanted shape memory polyurethane foam in a porcine aneurysm model

Cerebral aneurysms treated by traditional endovascular methods using platinum coils have a tendency to be unstable, either due to chronic inflammation, compaction of coils, or growth of the aneurysm. We propose to use alternate filling methods for the treatment of intracranial aneurysms using polyurethane-based shape memory polymer (SMP) foams. SMP polyurethane foams were surgically implanted in a porcine aneurysm model to determine biocompatibility, localized thrombogenicity, and their ability to serve as a stable filler material within an aneurysm. The degree of healing was evaluated via gross observation, histopathology, and low vacuum scanning electron microscopy imaging after 0, 30, and 90 days. Clotting was initiated within the SMP foam at time 0 (<1 h exposure to blood before euthanization), partial healing was observed at 30 days, and almost complete healing had occurred at 90 days in vivo, with minimal inflammatory response.

In vivo testing of an intra-annular aortic valve annuloplasty ring in a chronic calf model

OBJECTIVE To increase applicability and stability of aortic valve repair, a three-dimensional aortic annuloplasty ring has been developed for intra-annular placement. The goal of this study was to test the safety of this device with in vivo implantation in the calf model. METHODS In 10 chronic calves, the HAART annuloplasty ring was sutured to the aortic valve annulus using cardiopulmonary bypass. The animals were recovered and followed for 1-2 months. Serial echocardiography was used to evaluate valve competence, and contrast aortograms and CT angiograms were obtained in selected animals. After completion of follow-up, each animal was euthanized, and aortic endoscopy was performed under water distension in five. Full autopsies with histologic examinations were performed. RESULTS All animals survived surgery. Two were euthanized in the first week for complications, and the remaining eight calves were followed uneventfully for the 1-2 months. Serial echocardiography showed completely competent valves in all but one animal, in which the ring was intentionally up-sized to test the sizing strategy. Contrast aortographic and CT angiographic findings were similar to the echocardiograms. Postmortem examination showed proper seating of all rings with endothelialization at 1-2 months. All valves demonstrated good leaflet coaptation and no abnormalities. CONCLUSIONS In vivo testing of a three-dimensional aortic annuloplasty ring in a chronic calf model proved to be very successful and safe. Using the sizing and implant strategies developed, human trials seem indicated.

Continuous flow total artificial heart: Modeling and feedback control in a mock circulatory system

We developed a mock circulatory loop and used mathematical modeling to test the in vitro performance of a physiologic flow control system for a total artificial heart (TAH). The TAH was constructed from two continuous flow pumps. The objective of the control system was to maintain loop flow constant in response to changes in outflow resistance of either pump. Baseline outflow resistances of the right (pulmonary vascular resistance) and the left (systemic vascular resistance) pumps were set at 2 and 18 Wood units, respectively. The corresponding circuit flow was 4 L/min. The control system consisted of two digital integral controllers, each regulating the voltage, hence, the rotational speed of one of the pumps. The in vitro performance of the flow control system was validated by increasing systemic and pulmonary vascular resistances in the mock loop by 4 and 8 Wood units (simulating systemic and pulmonary hypertension conditions), respectively. For these simulated hypertensive states, the flow controllers regulated circuit flow back to 4 L/min within seconds by automatically adjusting the rotational speed of either or both pumps. We conclude that this multivariable feedback mechanism may constitute an adequate supplement to the inherent pressure sensitivity of rotary blood pumps for the automatic flow control and left-right flow balance of a dual continuous flow pump TAH system.

Baseline hemodynamic and echocardiographic indices in anesthetized calves.

The experimental calf model is used to assess mechanical circulatory support devices and prosthetic heart valves. Baseline indices of cardiac function have been established for the normal awake calf but not for the anesthetized calf. Therefore, we gathered hemodynamic and echocardiographic data from 16 healthy anesthetized calves (mean age, 189.0 ± 87.0 days; mean body weight, 106.9 ± 32.3 kg) by cardiac catheterization and noninvasive echocardiography, respectively. Baseline hemodynamic data included heart rate (65 ± 12 beats per minute), mean aortic pressure (113.5 ± 17.4 mm Hg), left ventricular end-diastolic pressure (16.3 ± 38.9 mm Hg), and mean pulmonary artery pressure (21.7 ± 8.3 mm Hg). Baseline two-dimensional echocardiographic data included left ventricular systolic dimension (3.5 ± 0.7 cm), left ventricular diastolic dimension (5.6 ± 0.8 cm), end-systolic intraventricular septal thickness (1.7 ± 0.2 cm), end-diastolic intraventricular septal thickness (1.2 ± 0.2 cm), ejection fraction (63 ± 10%), and fractional shortening (37 ± 10%). Doppler echocardiography revealed a maximum aortic valve velocity of 0.9 ± 0.5 m/s and a cardiac index of 3.7 ± 1.1 L/minute/m2. The collected baseline data will be useful in assessing prosthetic heart valves, cardiac assist pumps, new cannulation techniques, and robotics applications in the anesthetized calf model and in developing calf models of various cardiovascular diseases.

In vitro and in vivo evaluation of a shape memory polymer foam‐over‐wire embolization device delivered in saccular aneurysm models

Current endovascular therapies for intracranial saccular aneurysms result in high recurrence rates due to poor tissue healing, coil compaction, and aneurysm growth. We propose treatment of saccular aneurysms using shape memory polymer (SMP) foam to improve clinical outcomes. SMP foam-over-wire (FOW) embolization devices were delivered to in vitro and in vivo porcine saccular aneurysm models to evaluate device efficacy, aneurysm occlusion, and acute clotting. FOW devices demonstrated effective delivery and stable implantation in vitro. In vivo porcine aneurysms were successfully occluded using FOW devices with theoretical volume occlusion values greater than 72% and rapid, stable thrombus formation.

Correlation of Ischemic Area and Coronary Flow With Ameroid Size in a Porcine Model

BACKGROUND Ameroid constriction has long been used to induce chronic hibernating myocardium in animal models. MATERIALS AND METHODS Thirty-six pigs underwent surgical implantation of an ameroid constrictor around their left circumflex (LCx) coronary artery. The device had an internal diameter of 2.25 (n=9), 2.50 (n=16), or 2.75 (n=11) mm. Thrombolysis in Myocardial Infarction (TIMI) grade coronary flow was assessed angiographically during device placement and on postoperative d 30. The ischemic and total left ventricular (LV) areas were measured with endocardial voltage mapping (NOGA) on d 30. RESULTS For ameroid constrictor diameters of 2.25, 2.50, and 2.75 mm, the ratio of the ischemic area versus the total LV area averaged 24% ± 10%, 21% ± 6%, and 23% ± 9%, respectively (P=NS). Coronary angiography revealed complete LCx occlusion in all animals. TIMI grade-1 flow was the statistical mode for all groups and was independent of constrictor diameter. Normalization of the device diameter with the vessel diameter did not affect the statistical results. CONCLUSIONS For the range of ameroid constrictor sizes evaluated in this study, coronary flow and the ischemic LV area were independent of device size. The ischemic area and coronary flow created by ameroid constrictor placement were highly homogeneous and accurate for an experimental model of hibernating myocardium.

Ventricular assist device outflow-graft site: effect on myocardial blood flow.

BACKGROUND Recent advances in left ventricular assist device (LVAD) technology have resulted in small, durable, energy-efficient, continuous-flow blood pumps that can support patients with end-stage heart failure. However, the effects of reduced or nonpulsatile flow on end-organ function are unclear. We performed a pilot study in calves with a continuous-flow LVAD to assess the effects of the pumps outflow-graft location (ascending versus descending aorta) on myocardial blood flow. MATERIALS AND METHODS In 8 healthy calves, we implanted the Jarvik 2000 LVAD in the left ventricular apex without the use of cardiopulmonary bypass. We anastomosed the outflow graft to either the ascending aorta (group 1; n = 4) or the descending aorta (group 2; n = 4). Hemodynamic parameters, myocardial oxygen consumption, and regional myocardial blood flow (analyzed with colored microspheres) were assessed at baseline (pump off) and during pump operation at 8000, 10,000, and 12,000 rpm. RESULTS No intergroup differences were found in the aortic pressure, heart rate, central venous pressure, pump-flow to total-cardiac-flow ratio, or blood flow in the left anterior descending and right posterior descending coronary arteries at increasing pump speeds. Neither myocardial oxygen consumption nor myocardial tissue perfusion differed significantly between the two groups. CONCLUSIONS Regardless of the outflow-graft location (ascending versus descending aorta), the continuous-flow LVAD unloaded the left ventricle and did not adversely affect myocardial perfusion in either the right or left ventricle. Owing to the small number of animals studied, however, the most we can conclude is that neither outflow-graft location appeared to be inferior to the other.

Assessment of aortic valve pressure overload and leaflet functions in an ex vivo beating heart loaded with a continuous flow cardiac assist device

OBJECTIVES Aortic valve regurgitation, fusion and thrombosis are commonly reported clinical complications after continuous flow ventricular assist device implantations; however, the complex interaction between reduced pulsatile flow physiology and aortic valve functions has not been studied experimentally. To address this, a continuous flow left ventricular assist device was implanted in four swine ex vivo beating hearts and then operated at baseline (device off, no flow) and at device speeds ranging between 8500 and 11,500 rpm under healthy and experimentally created failing heart conditions. METHODS At baseline and after each speed increase, aortic, left ventricular, left atrial and pulse pressure signals were monitored to assess the haemodynamic status of the ex vivo heart, aortic valve opening time and the transvalvular pressure changes. Aortic root and device flows were recorded with flow probes. Left ventricular pressure-volume loops were measured with a conductance catheter. Changes in aortic leaflet motion and end-diastolic aortic root diameter were recorded with epicardial echocardiography. RESULTS A two-chamber healthy and failing ex vivo beating heart model was successfully created. At increasing device flows, aortic valve open time steadily decreased from 36±7% of the baseline cardiac cycle to 0% at 11,500 rpm in the healthy heart and from 18±16 to 0% in failing heart mode (P<0.05). Aortic transvalvular pressure increased from 25±5 mmHg (baseline) to 67±7 mmHg (11,500 rpm) in the healthy heart and from 10±9 mmHg (baseline) to 73±8 mmHg (11,500 rpm) in failing heart mode (P<0.05). Aortic root diameters were significantly increased at speeds exceeding 10 500 rpm in the healthy heart mode (P<0.05 vs baseline) and approached statistical significance in failing hearts. CONCLUSIONS Increasing assist device flows resulted in pressure overload above the aortic leaflets, impaired leaflet functions, caused aortic root dilatation and altered leaflet coaptation at the central portion of the aortic valve in both modes. We conclude that the deleterious effect of the reduced pulsatile flow on the aortic valve functions and haemodynamics is immediate and such an insult may explain the structural changes of the aortic valve causing leaflet fusion and/or regurgitation in the chronic phase.