Ocular surface microcirculation is better preserved with pulsatile versus continuous flow during cardiopulmonary bypass-An experimental pilot.

BACKGROUND: Non-pulsatile cardiopulmonary bypass (CPB) may induce microvascular dysregulation. In piglets, we compared ocular surface microcirculation during pulsatile versus continuous flow (CF) bypass. METHODS: Ocular surface microcirculation in small tissue volumes (~0.1 mm3 ) at limbus (high metabolic rate) and bulbar conjunctiva (low metabolic rate) was examined in a porcine model using computer assisted video microscopy and diffuse reflectance spectroscopy, before and after 3 and 6 h of pulsatile (n = 5 piglets) or CF (n = 3 piglets) CPB. Functional capillary density, capillary flow velocity and microvascular oxygen saturation were quantified. RESULTS: At limbus, velocities improved with pulsatility (p < 0.01) and deteriorated with CF (p < 0.01). In bulbar conjunctiva, velocities were severely reduced with CF (p < 0.01), accompanied by an increase in capillary density (p < 0.01). Microvascular oxygen saturation decreased in both groups. CONCLUSION: Ocular surface capillary densities and flow patterns are better preserved with pulsatile versus CF during 6 h of CPB in sleeping piglets.

Hemodynamic evaluation of a new pulsatile blood pump during low flow cardiopulmonary bypass support.

BACKGROUND: The VentriFlo® True Pulse Pump (VentriFlo, Inc, Pelham, NH, USA) is a new pulsatile blood pump intended for use during short-term circulatory support. The purpose of this study was to evaluate the feasibility of the VentriFlo and compare it to a conventional centrifugal pump (ROTAFLOW, Getinge, Gothenberg, Sweden) in acute pig experiments. METHODS: Pigs (40-45 kg) were supported by cardiopulmonary bypass (CPB) with the VentriFlo (n = 9) or ROTAFLOW (n = 5) for 6 h. Both VentriFlo and ROTAFLOW circuits utilized standard CPB components. We evaluated hemodynamics, blood chemistry, gas analysis, plasma hemoglobin, and microcirculation at the groin skin with computer-assisted video microscopy (Optilia, Sollentuna, Sweden). RESULTS: Pigs were successfully supported by CPB for 6 h without any pump-related complications in either group. The VentriFlo delivered an average stroke volume of 29.2 ± 4.8 ml. VentriFlo delivered significantly higher pulse pressure (29.1 ± 7.2 mm Hg vs. 4.4 ± 7.0 mm Hg, p < 0.01) as measured in the carotid artery, with mean aortic pressure and pump flow comparable with those in ROTAFLOW. In blood gas analysis, arterial pH was significantly lower after five hours support in the VentriFlo group (7.30 ± 0.07 vs. 7.43 ± 0.03, p = 0.001). There was no significant difference in plasma hemoglobin level in both groups after six hours of CPB support. In microcirculatory assessment, VentriFlo tended to keep normal capillary flow, but it was not statistically significant. CONCLUSIONS: VentriFlo-supported pigs showed comparable hemodynamic parameters with significantly higher pulse pressure compared to ROTAFLOW without hemolysis.

Anti-clogging mechanisms of a motion-activated chest tube patency maintenance system: Histology and high-speed camera assessment.

The motion-activated system (MAS) employs vibration to prevent intraluminal chest tube clogging. We evaluated the intraluminal clot formation inside chest tubes using high-speed camera imaging and postexplant histology analysis of thrombus. The chest tube clogging was tested (MAS vs. control) in acute hemothorax porcine models (n = 5). The whole tubes with blood clots were fixed with formalin-acetic acid solution and cut into cross-sections, proceeded for H&E-stained paraffin-embedded tissue sections (MAS sections, n = 11; control sections, n = 11), and analyzed. As a separate effort, a high-speed camera (FASTCAM Mini AX200, 100-mm Zeiss lens) was used to visualize the whole blood clogging pattern inside the chest tube cross-sectional view. Histology revealed a thin string-like fibrin deposition, which showed spiral eddy or aggregate within the blood clots in most sections of Group MAS, but not in those of the control group. Histology findings were compatible with high-speed camera views. The high-speed camera images showed a device-specific intraluminal blood "swirling" pattern. Our findings suggest that a continuous spiral flow in blood within the chest tube (MAS vs. static control) contributes to the formation of a spiral string-like fibrin network during consumption of coagulation factors. As a result, the spiral flow may prevent formation of thick band-like fibrin deposits sticking to the inner tube surface and causing tube clogging, and thus may positively affect chest tube patency and drainage.

Development and Evaluation of Motion-activated System for Improved Chest Drainage: Bench, In Vivo Results, and Pilot Clinical Use of Technology.

Objective. The aim of this study was to evaluate a motion-activated system (MAS) that applies motion-activated energy (vibration) to prevent chest tube clogging and maintain tube patency. We performed chest tube blood flow analysis in vitro, studied MAS effects on intraluminal clot deposition in vivo, and conducted a pilot clinical test. Background. Chest tube clogging is known to adversely contribute to postoperative cardiac surgery outcomes. Methods. The MAS was tested in vitro with a blood-filled chest tube model for device acceleration and performance. In vivo acute hemothorax studies (n = 5) were performed in healthy pigs (48.0 ± 2 kg) to evaluate the drainage in MAS versus control (no device) groups. Using a high-speed camera (FASTCAM Mini AX200, 100 mm Zeiss lens) in an additional animal study (n = 1), intraluminal whole-blood activation imaging of the chest tube (32 Fr) was made. The pilot clinical study (n = 12) consisted of up to a 30 minutes device tolerance test. Results. In vitro MAS testing suggested optimal device performance. The 2-hour in vivo evaluation showed a longer incremental drainage in the MAS group versus control. The total drainage in the MAS group was significantly higher than that in the control group (379 ± 144 mL vs 143 ± 40 mL; P = .0097), indicating tube patency. The high-speed camera images showed a characteristic intraluminal blood "swirling" pattern. Clinical data showed no discomfort with the MAS use (pleural = 4; mediastinal = 8). Conclusions. The MAS showed optimal performance at bench and better drainage profile in vivo. The clinical trial showed patients' tolerance to the MAS and device safety.

The design modification of advanced ventricular assist device to enhance pulse augmentation and regurgitant flow shut-off.

The new Advanced ventricular assist device (Advanced VAD) has many features such as improving pulsatility and preventing regurgitant flow during pump stoppage. The purpose of this study was to evaluate the effects of design modifications of the Advanced VAD on these features in vitro. Bench testing of four versions of the Advanced VAD was performed on a static or pulsatile mock loop with a pneumatic device. After pump performance was evaluated, each pump was run at 3000 rpm to evaluate pulse augmentation, then was stopped to assess regurgitant flow through the pump. There was no significant difference in pump performance between the pump models. The average pulse pressure in the pulsatile mock loop was 23.0, 34.0, 39.3, 33.8, and 37.3 mm Hg without pump, with AV010, AV020 3S, AV020 6S, and AV020 RC, respectively. The pulse augmentation factor was 48%, 71%, 47%, and 62% with AV010, AV020 3S, AV020 6S, and AV020 RC, respectively. In the pump stop test, regurgitant flow was -0.60 ± 0.70, -0.13 ± 0.57, -0.14 ± 0.09, and -0.18 ± 0.06 L/min in AV010, AV020 3S, AV020 6S, and AV020 RC, respectively. In conclusion, by modifying the design of the Advanced VAD, we successfully showed the improved pulsatility augmentation and regurgitant flow shut-off features.

New Technology Mimics Physiologic Pulsatile Flow During Cardiopulmonary Bypass.

The VentriFlo True Pulse Pump (Design Mentor, Inc., Pelham, NH, USA) is the first blood pump designed to mimic human arterial waveforms in a standard oxygenation circuit. Our aim was to demonstrate the feasibility and safety of this pump in preparation for future studies to determine possible clinical advantages. We studied four piglets (41.4-46.2 kg): three with an implanted VentriFlo pulsatile pump and one with the nonpulsatile ROTAFLOW pump (MAQUET Holding B.V. & Co. KG, Rastatt, Germany) as a control. Hemodynamics was monitored during 6-h cardiopulmonary bypass (CPB) support and for 2 h after weaning off CPB. The VentriFlo demonstrated physiologic arterial waveforms with arterial pulse pressure of 24.6 ± 5.7 mm Hg. Pump flows (2.0 ± 0.1 L/min in ROTAFLOW; 1.9 ± 0.1 L/min in VentriFlo) and plasma free hemoglobin levels (27.9 ± 12.5 mg/dL in ROTAFLOW; 28.5 ± 14.2 mg/dL in VentriFlo) were also comparable, but systemic O2 extraction (as measured by arterial minus venous O2 saturation) registered slightly higher with the VentriFlo (63.2 ± 6.9%) than the ROTAFLOW (55.4 ± 6.5%). Histological findings showed no evidence of ischemic changes or thromboembolism. This pilot study demonstrated that the VentriFlo system generated pulsatile flow and maintained adequate perfusion of all organs during prolonged CPB.

Lumbar muscle atrophy caused by harness replacement in a chronic calf model of total artificial heart implantation.

The postoperative care of animals implanted with mechanical circulatory support devices is complex. The standard of care requires continuous monitoring of hemodynamic parameters post implant, wound care, and maintenance of the animal's well-being, but also includes controlling the animal's biomechanics under conditions of continuous restraint and harnessing. In such studies, a harness provides secure fixation of the exteriorized device driveline and pressure lines and aids animal handling (lifting, position adjustment, and assistance with standing up). Harnessing is a key element in large-animal surgery. It affects the animal's conditions, safety, and post-procedure troubleshooting and thus may drastically worsen postoperative outcomes if improperly handled. Here we report a case associated with an unplanned harness replacement in a chronic animal model implanted with the Cleveland Clinic continuous-flow total artificial heart. Inadvertent changes to the harness resulted in posture change caused by muscular atrophy of the calf's spine that had been under long-term harness support.

Anatomical study of the Cleveland Clinic continuous-flow total artificial heart in adult and pediatric configurations.

The purpose of this study was to assess the smallest possible body sizes of patients in whom the Cleveland Clinic continuous-flow total artificial heart for adult (CFTAH) and pediatric configurations (P-CFTAH) can fit. One of the most critical dimensions is the vertebra-to-sternum distance at the junction of the right atrium to the inferior vena cava (V-S distance). Our previous CFTAH anatomical fitting study suggested that the CFTAH would fit patients of V-S distance ≥ 7.5 cm and the P-CFTAH of V-S distance ≥ 5.25 cm (70% of 7.5 cm). To confirm this, we assessed the relationship between body surface area (BSA) and V-S distance in 15 adult patients (BSA 1.86-2.62 m2) and 31 pediatric patients (BSA 0.17-1.80 m2) whose computed tomography scans were available. We found a highly significant correlation between BSA and V-S distance (p < 1.0 × 10-25). It appears that the CFTAH will fit in most patients with BSA ≥ 1.0 m2 (corresponding height of ≥ 130 cm and age of 9 years) and the P-CFTAH in patients with BSA ≥ 0.3 m2 (corresponding height of ≥ 55 cm and age of 1 month). Further anatomical fitting studies are needed to evaluate the two pump models inside human chests to determine the smallest patient size/critical dimensions and device port configurations.

Moderate hypothermia technique for chronic implantation of a total artificial heart in calves.

The benefit of whole-body hypothermia in preventing ischemic injury during cardiac surgical operations is well documented. However, application of hypothermia during in vivo total artificial heart implantation has not become widespread because of limited understanding of the proper techniques and restrictions implied by constitutional and physiological characteristics specific to each animal model. Similarly, the literature on hypothermic set-up in total artificial heart implantation has also been limited. Herein we present our experience using hypothermia in bovine models implanted with the Cleveland Clinic continuous-flow total artificial heart.

Novel technique for airless connection of artificial heart to vascular conduits.

Successful implantation of a total artificial heart relies on multiple standardized procedures, primarily the resection of the native heart, and exacting preparation of the atrial and vascular conduits for pump implant and activation. Achieving secure pump connections to inflow/outflow conduits is critical to a successful outcome. During the connection process, however, air may be introduced into the circulation, traveling to the brain and multiple organs. Such air emboli block blood flow to these areas and are detrimental to long-term survival. A correctly managed pump-to-conduit connection prevents air from collecting in the pump and conduits. To further optimize pump-connection techniques, we have developed a novel connecting sleeve that enables airless connection of the Cleveland Clinic continuous-flow total artificial heart (CFTAH) to the conduits. In this brief report, we describe the connecting sleeve design and our initial results from two acute in vivo implantations using a scaled-down version of the CFTAH.

Generating pulsatility by pump speed modulation with continuous-flow total artificial heart in awake calves.

The purpose of this study was to evaluate the effects of sinusoidal pump speed modulation of the Cleveland Clinic continuous-flow total artificial heart (CFTAH) on hemodynamics and pump flow in an awake chronic calf model. The sinusoidal pump speed modulations, performed on the day of elective sacrifice, were set at ±15 and ± 25% of mean pump speed at 80 bpm in four awake calves with a CFTAH. The systemic and pulmonary arterial pulse pressures increased to 12.0 and 12.3 mmHg (±15% modulation) and to 15.9 and 15.7 mmHg (±25% modulation), respectively. The pulsatility index and surplus hemodynamic energy significantly increased, respectively, to 1.05 and 1346 ergs/cm at ±15% speed modulation and to 1.51 and 3381 ergs/cm at ±25% speed modulation. This study showed that it is feasible to generate pressure pulsatility with pump speed modulation; the platform is suitable for evaluating the physiologic impact of pulsatility and allows determination of the best speed modulations in terms of magnitude, frequency, and profiles.

Hemodynamic differences between the awake and anesthetized conditions in normal calves.

There is insufficient information in the literature about baseline circulatory parameters in normal calves in the anesthetized versus postoperative awake conditions under which a large volume of medical research is conducted. Eleven calves (mean body weight, 78.1 ± 14.3 kg) were implanted with a flow probe and fluid-filled pressure lines to measure cardiac output (CO), aortic (AoP), central venous (CVP), pulmonary arterial (PAP), and left atrial pressures (LAP). Systemic (SVR) and pulmonary vascular resistance (PVR) were also calculated. We obtained the above hemodynamic data (n = 11) and epicardial echocardiography (n = 7) during open-chest surgery under isoflurane anesthesia. After full recovery from surgery, animals were evaluated in the awake condition on postoperative days 6-9 using transthoracic echocardiography (n = 7) and the hemodynamic monitoring lines and probes noted (n = 11). CO, AoP, and PAP levels in the anesthetized condition were significantly lower than in the awake condition. Other hemodynamic parameters (CVP, LAP, SVR, and PVR) were not significantly different. In conclusion, data from this study quantify changes in CO, AoP, and PAP in anesthetized calves that may affect the hemodynamic response to experimental therapeutics such as new cardiac assist devices, prosthetic valves, and surgical interventions. Our study also provides baseline data for the translation of the hemodynamic data obtained in acute in vivo calf studies to that of an awake subject.

In vivo biocompatibility evaluation of a new resilient, hard-carbon, thin-film coating for ventricular assist devices.

The purpose of this study was to evaluate in vivo the biocompatibility of BioMedFlex (BMF), a new resilient, hard-carbon, thin-film coating, as a blood journal bearing material in Cleveland Heart's (Charlotte, NC, USA) continuous-flow right and left ventricular assist devices (RVADs and LVADs). BMF was applied to RVAD rotating assemblies or both rotating and stator assemblies in three chronic bovine studies. In one case, an LVAD with a BMF-coated stator was also implanted. Cases 1 and 3 were electively terminated at 18 and 29 days, respectively, with average measured pump flows of 4.9 L/min (RVAD) in Case 1 and 5.7 L/min (RVAD) plus 5.7 L/min (LVAD) in Case 3. Case 2 was terminated prematurely after 9 days because of sepsis. The sepsis, combined with running the pump at minimum speed (2000 rpm), presented a worst-case biocompatibility challenge. Postexplant evaluation of the blood-contacting journal bearing surfaces showed no biologic deposition in any of the four pumps. Thrombus inside the RVAD inlet cannula in Case 3 is believed to be the origin of a nonadherent thrombus wrapped around one of the primary impeller blades. In conclusion, we demonstrated that BMF coatings can provide good biocompatibility in the journal bearing for ventricular assist devices.

In vivo evaluation of zirconia ceramic in the DexAide right ventricular assist device journal bearing.

Zirconia is a ceramic with material properties ideal for journal bearing applications. The purpose of this study was to evaluate the use of zirconium oxide (zirconia) as a blood journal bearing material in the DexAide right ventricular assist device. Zirconia ceramic was used instead of titanium to manufacture the DexAide stator housing without changing the stator geometry or the remaining pump hardware components. Pump hydraulic performance, journal bearing reliability, biocompatibility, and motor efficiency data of the zirconia stator were evaluated in six chronic bovine experiments for 14-91 days and compared with data from chronic experiments using the titanium stator. Pump performance data including average in vivo pump flows and speeds using a zirconia stator showed no statistically significant difference to the average values for 16 prior titanium stator in vivo studies, with the exception of a 19% reduction in power consumption. Indices of hemolysis were comparable for both stator types. Results of coagulation assays and platelet aggregation tests for the zirconia stator implants showed no device-induced increase in platelet activation. Postexplant evaluation of the zirconia journal bearing surfaces showed no biologic deposition in any of the implants. In conclusion, zirconia ceramic can be used as a hemocompatible material to improve motor efficiency while maintaining hydraulic performance in a blood journal bearing application.

Mitral annular remodeling to treat functional mitral regurgitation: a pilot acute study in a canine model.

BACKGROUND: The aim of this study was to evaluate the feasibility and efficacy of the injection of a nonabsorbable substance into the base of the left ventricle (LV) to treat functional mitral regurgitation (MR). METHODS: Tyramine-based hyaluronan hydrogel was injected into the base of the LV of the beating heart in a canine model of rapid ventricular pacing-induced functional MR (n = 4). The severity of MR was evaluated by epicardial echocardiography before and after hydrogel injection. RESULTS: The injection improved MR grade from 3.4 +/- 0.8 to 1.3 +/- 0.5 (P = .006) without inducing hemodynamic instability or any evidence of myocardial ischemia. We noted significant decreases in the septal-lateral dimension at the mitral annulus (3.4 +/- 0.4 cm to 2.9 +/- 0.3 cm; P = .039) and MR volume (20.6 +/- 7.3 mm3 to 5.2 +/- 2.2 mm3; P = .044). CONCLUSIONS: A novel treatment consisting of hydrogel injection into the base of the LV between the 2 papillary muscles was found to be feasible and effective for reducing functional MR in a canine model.

Use of a Virtual Mock Loop model to evaluate a new left ventricular assist device for transapical insertion.

We are developing a novel type of miniaturized left ventricular assist device that is configured for transapical insertion. The aim of this study was to assess the performance and function of a new pump by using a Virtual Mock Loop system for device characterization and mapping. The results, such as pressure-flow performance curves, from pump testing in a physical mock circulatory loop were used to analyze its function as a left ventricular assist device. The Virtual Mock Loop system was programmed to mimic the normal heart condition, systolic heart failure, diastolic heart failure, and both systolic and diastolic heart failure, and to provide hemodynamic pressure values before and after the activation of several left ventricular assist device pump speeds (12,000, 14,000, and 16,000 r/min). With pump support, systemic flow and mean aortic pressure increased, and mean left atrial pressure and pulmonary artery pressure decreased for all heart conditions. Regarding high pump-speed support, the systemic flow, aortic pressure, left atrial pressure, and pulmonary artery pressure returned to the level of the normal heart condition. Based on the test results from the Virtual Mock Loop system, the new left ventricular assist device for transapical insertion may be able to ease the symptoms of patients with various types of heart failure. The Virtual Mock Loop system could be helpful to assess pump performance before in vitro bench testing.

Phasic coronary blood flow patterns in dogs vs. pigs: an acute ischemic heart study.

BACKGROUND: Canine and porcine hearts have been widely used to investigate diagnoses, interventions, and surgical therapies for ischemic heart disease. Dogs and pigs are known to vary with regard to the anatomic distribution of their coronary arteries. However, the mechanisms of these differences and the differing phasic coronary blood flow patterns between the two species are not well characterized. MATERIAL/METHODS: Phasic coronary blood flow patterns and hemodynamic data were analyzed using three flow probes placed around the left anterior descending (LAD), left circumflex (LCX), and right coronary (RCA) arteries in both canine and porcine models. RESULTS: Systolic left ventricular pressure, arterial pressure, and systemic vascular resistance in dogs were higher than in pigs. Likewise, total coronary blood flow, LAD flow, and LCX flow were higher in dogs than in pigs. LCX flow was higher in dogs, but RCA flow was higher in pigs. Diastolic fraction and diastolic/systolic peak velocity ratio of the LAD, LCX, and RCA showed no significant differences at baseline between dogs and pigs. Systolic LAD flow in dogs decreased after the creation of an LAD stenosis, whereas systolic LAD flow in pigs increased. CONCLUSIONS: Coronary blood flow patterns in dogs and pigs are quite different. These findings are potentially relevant to understanding the physiology of myocardial blood perfusion in dogs and pigs with ischemic heart disease.

Innovative, replaceable heart valve: concept, in vitro study, and acute in vivo study.

The purpose of this study was to evaluate the feasibility of our innovative, replaceable heart valves that can be easily detached from the sewing ring at the time of repeat replacement. The prototype devices consist of the base magnet ring assembly and the valve magnet ring assembly that utilize magnetic coupling force for the locking mechanism. Magnetic coupling strength was evaluated in vitro. Prototype bioprosthetic valves were implanted acutely in three sheep to confirm the feasibility of the replaceable mitral valve. The static separation force of prototype size #25 was 12.5 lb, meeting the design goal. In situ attachment and detachment of the valve magnet ring assembly from the base magnet ring assembly were very easily accomplished in all animals. The magnetic coupling did not decouple even under extremely high left ventricular pressures. We have demonstrated the feasibility of this innovative concept of a replaceable mitral valve.

Early in vivo experience with the pediatric continuous-flow total artificial heart.

BACKGROUND: Heart transplantation in infants and children is an accepted therapy for end-stage heart failure, but donor organ availability is low and always uncertain. Mechanical circulatory support is another standard option, but there is a lack of intracorporeal devices due to size and functional range. The purpose of this study was to evaluate the in vivo performance of our initial prototype of a pediatric continuous-flow total artificial heart (P-CFTAH), comprising a dual pump with one motor and one rotating assembly, supported by a hydrodynamic bearing. METHODS: In acute studies, the P-CFTAH was implanted in 4 lambs (average weight: 28.7 ± 2.3 kg) via a median sternotomy under cardiopulmonary bypass. Pulmonary and systemic pump performance parameters were recorded. RESULTS: The experiments showed good anatomical fit and easy implantation, with an average aortic cross-clamp time of 98 ± 18 minutes. Baseline hemodynamics were stable in all 4 animals (pump speed: 3.4 ± 0.2 krpm; pump flow: 2.1 ± 0.9 liters/min; power: 3.0 ± 0.8 W; arterial pressure: 68 ± 10 mm Hg; left and right atrial pressures: 6 ± 1 mm Hg, for both). Any differences between left and right atrial pressures were maintained within the intended limit of ±5 mm Hg over a wide range of ratios of systemic-to-pulmonary vascular resistance (0.7 to 12), with and without pump-speed modulation. Pump-speed modulation was successfully performed to create arterial pulsation. CONCLUSION: This initial P-CFTAH prototype met the proposed requirements for self-regulation, performance, and pulse modulation.

Acute Swine Model for Assessing Biocompatibility of Biomedical Interface Materials.

We established an acute animal model for early, straightforward, and reproducible assessment of a biocompatible material interface. Bilateral femoral artery-to-vein shunts were created in 12 pigs: two tubes per shunt, the left two coated and the right two uncoated. We evaluated two groups: uncontrolled flow (UF; shunt flow unregulated) and controlled flow (CF; shunt flow ∼50 mL/min). For each case on each side, two shunts were evaluated: one for 1 h and the other for 3 h. Arterial blood gas and complete blood count were recorded at baseline, 1, and 3 h. Mean shunt flows were 532 ± 88 mL/min UF and 52 ± 8 mL/min CF. Differences in flow were much smaller in CF (0.5 mL/min; 1% of mean flow) than UF (24.8 mL/min; 5% of mean flow). In UF, significant changes occurred: in pH, from start of shunting through 1 h; in pO2 and pCO2, from start through 3 h. This swine model using bilateral femoral shunts with controlled blood flow provides a reliable, reproducible, easily implemented method by which to evaluate biocompatibility of device coatings at an early stage of investigation.