Modifications in surgical implantation of the Penn State electric total artificial heart.

BACKGROUND: Two modifications of the surgical implantation protocol for the Penn State Total Artificial Heart (ETAH) were evaluated: Phrenic nerve ischemia was prevented by minimizing dissection and traction; and hemostasis was augmented and ETAH cuff anastomoses reinforced by using fibrin glue. METHODS: Thirteen Holstein calves underwent orthotopic surgical implantation of the Penn State ETAH between February 1998 and August 2000. Mean hemodynamic and laboratory chemistry variables from the first postoperative week were compared between calves receiving the original (n = 7) and modified (n = 6) protocol. RESULTS: Calves assigned to the modified protocol displayed an improvement in the Po2/FiO2 ratio compared to original (419.4 +/- 17.5 vs 336.3 +/- 35.4, respectively; p = 0.05). All additional parameters were equivalent between groups. The percent survival of animals receiving the modified protocol at 2, 4, and 12 weeks was higher than that of animals that underwent the original protocol. Original-protocol calf deaths consisting of hemothorax (n = 3), and respiratory failure (n = 1) were prevented in the modified protocol. CONCLUSIONS: Our results suggest that manipulations in surgical protocol may promote increased survival in calves implanted with the Penn State ETAH.

Testing of a 50 cc stroke volume completely implantable artificial heart: expanding chronic mechanical circulatory support to women, adolescents, and small stature men.

The development of a completely implanted total artificial heart at our institution has progressed to successful in vivo and in vitro testing of a device that is nearing clinical testing. This system consists of a 70 cc stroke volume pump originally designed to be used in men of average stature. Implantation of this system remains limited by patient size; hence, many women and adolescent patients will likely be precluded from support because of their smaller stature. A system similar in design, but with a 50 cc stroke volume pump has been developed. The first in vivo study of this device has been undertaken. A calf was supported for 33 days. The animal was extubated and ambulatory within the first 6 hours of implantation, and remained healthy until the thirty-third postoperative day when it suffered an embolic neurologic event. The pump and operating system worked flawlessly throughout the period of support. Further in vivo and in vitro testing will be undertaken. Development of a scaled down total artificial heart system expands this type of circulatory support to those critically ill patients previously deemed poor candidates because of their smaller body habitus.

Computer-assisted endoscopic coronary artery bypass anastomoses: a chronic animal study.

BACKGROUND: With traditional instruments, endoscopic coronary artery bypass grafting (ECABG) has not been possible. This study was designed to determine the feasibility of using a robotically-assisted microsurgical system to perform ECABG in a chronic animal model. METHODS: Nine calves were placed on cardiopulmonary bypass after harvesting the left internal mammary artery (LIMA). Subxiphoid endoscopic ports (2 instrument, 1 camera) were placed, and a robotic system was used to perform ECABG between the LIMA and left anterior descending coronary artery. LIMA graft flow (LIMAQ) was measured. Animals were sacrificed at 1 month, and hearts underwent angiographic and histologic analyses. RESULTS: Acute graft patency was 89% (8/9). Two animals died suddenly within the first 48 hours. There was no significant difference in mean acute and chronic (n = 6) LIMAQ (40.9+/-4.7 and 38.5+/-5.0 ml/min, respectively). Survivors had an angiographic patency rate of 100% (6/6), confirmed by histology. CONCLUSIONS: This study shows that ECABG is feasible in a chronic animal model with excellent results.

Potassium-channel opener cardioplegia is superior to St. Thomas' solution in the intact animal.

BACKGROUND: In isolated hearts, the potassium-channel opener pinacidil is an effective cardioplegic agent. This study tested the hypothesis that pinacidil is superior to St. Thomas' solution in the more clinically relevant intact animal. METHODS: Sixteen pigs were placed on full cardiopulmonary bypass. Hearts underwent 2 hours of global ischemia (10 degrees to 15 degrees C). Either St. Thomas' or 100 micromol/L pinacidil was administered every 20 minutes (10 mL/kg). Preischemic and postreperfusion slopes of the preload-recruitable stroke work relationship were determined. Changes in myocardial adenine nucleotide levels and cellular ultrastructure were analyzed. RESULTS: Pinacidil cardioplegia resulted in an insignificant change in the slope of the preload-recruitable stroke work relationship (40.6+/-2.1 mm Hg/mm before ischemia and 36.5+/-3.7 mm Hg/mm after ischemia; p = 0.466). In contrast, St. Thomas' solution resulted in a significant decrease in the slope after reperfusion (34.3+/-5.5 mm Hg/mm and 13.5+/-2.3 mm Hg/mm; p = 0.003). Adenine nucleotide levels, myocardial tissue water, and ultrastructural changes were similar between groups. CONCLUSIONS: Pinacidil ameliorated myocardial stunning associated with traditional hyperkalemic cardioplegia without causing significant differences in cellular metabolism.

Postoperative pulmonary complications in calves after implantation of an electric total artificial heart.

In long-term studies testing the Penn State Total Artificial Heart involving 30 calves, seven calves died of pulmonary complications within 2 weeks after receiving the implant (Group 1 [G1]) and seven calves survived from 2 weeks to 3 months without infection (Group 2 [G2]). Comparative studies were performed using multiple variables: cardiopulmonary bypass (CPB) time, cardiac index, central venous pressure, leukocyte count, hematocrit, total protein, albumin, serum glutamic oxaloacetic transaminase (GOT), creatinine, water balance, and transfused blood volume. In G1, CPB time was longer than in G2 (182 +/- 19 vs 156 +/- 17 minutes, respectively, p = 0.018). Postoperative minimum total protein and albumin in G1 were lower than those in G2 (56.5% +/- 6.0% and 59.0% +/- 5.5% of preoperative values vs 68.4% +/- 8.5% and 67.8% +/- 6.1%, respectively, p = 0.011 and 0.015). Water balance in G2 was more positive than in G1 (11.7 +/- 6.8 vs 1.4 +/- 8.3 L, respectively, p = 0.020). Other variables showed no significant differences. Microscopic findings of the lung in G1 were congestion, hemorrhage, aggregation of neutrophils, and proteinaceous material within the interstitial tissues and alveoli.

Dynamic in vitro and in vivo performance of a permanent total artificial heart.

In vivo characterization studies were performed to compare the dynamic in vivo performance of the Penn State/3M Health Care electric total artificial heart to existing in vitro data. Fully implanted systems were utilized including the artificial heart, controller, backup batteries, compliance chamber, and transcutaneous energy transmission. Catheters were implanted to measure central venous pressure (CVP), left atrial pressure (LAP), right atrial pressure (RAP), pulmonary artery pressure (PAP), and aortic pressure (AoP). Cardiac output (CO) was determined from the implanted controller, and systemic vascular resistance (SVR) was calculated. Steady state data were collected for each animal along with data regarding the transient responses to changes in preload and afterload. Preload was manipulated through volume changes. Afterload changes were accomplished through vasoactive agents. Increased preload caused little change in cardiac output because the pump output was nearly maximum at baseline. LAP, AoP, and SVR increased with increasing RAP. Decreased preload caused a reduction in CO, LAP, and SVR. Afterload increase resulted in a slight decrease in flow and an increase in system power and SVR. Afterload reduction was accompanied by a decrease in preload and a concomitant reduction in flow. Overall, the system response was similar to the response observed in vitro.

Recent improvements in a completely implanted total artificial heart.

The total artificial heart under development by the Pennsylvania State University and 3M Health Care has undergone a number of design improvements to improve reliability, manufacturability, implantability, and performance. These improvements are nearing completion in preparation for formal durability testing. The redesigned implanted electronics canister, consisting of a welded titanium shell with hermetic connectors, contains the control, telemetry, and energy transmission electronics, as well as a 9 cell, 800 mAhr Ni-Cd battery pack. Functional changes include a reduction in the battery recharge time from 14 hours to 4 hours, and a new inductive telemetry system. The energy transmission system operating frequency has been increased from 160 kHz to 200 kHz. Electromagnetic interference filters and a more efficient control mode have also been implemented. The energy converter has been modified to incorporate a new motor with integral Hall effect position sensors, and new cable, and compliance chamber conduit fittings. High flex life cable is now used for the motor and coil cables. Two prototype durability mock circulatory loops have been built and are being tested. Substantial progress has been made in the completion of manufacturing documentation, and in the implementation of a quality system.

In vivo testing of a completely implanted total artificial heart system.

The authors performed 14 implants of a completely implanted total artificial heart (TAH) system in calves. The system consisted of a dual pusher plate rollerscrew energy converter, two sac type blood pumps, an implanted electronic control and battery package, and a transcutaneous energy transmission system. Ten of the implants included a percutaneous lead for monitoring of the implant; the remainder made use of wireless two way telemetry between the implant and the outside. Three animals survived the perioperative period. These calves survived for 98 to 118 days, and one was still alive at 150 days. Causes for termination of the 98 and 118 day cases were abdominal pocket sepsis originating at a monitoring line, and systemic sepsis acquired perioperatively. Death or termination in the shorter cases was mainly due to respiratory complications or bleeding. The TAH system proved capable of providing adequate cardiac outputs at modest atrial pressures. Wireless monitoring and wireless intervention for weaning from cardiopulmonary bypass were readily achieved. All organ systems functioned normally in the presence of the device. Once recovery from implantation in these very young animals was achieved, the system proved its ability to reliably support these animals until body mass exceeded its cardiac output capabilities.

An electrically powered total artificial heart. Over 1 year survival in the calf.

An electric motor driven orthotopic artificial heart was implanted in a 110 kg female Holstein calf as part of a series of 12 such implants intended to demonstrate the in vivo durability and compatibility of the device. The device uses pusher plates set into motion by a reversing brushless DC motor and roller screw to alternately eject two cylindrical sac type blood pumps. The pumps use Bjork-Shiley Delrindisc convexo-concave or monostrut valves. The left pump provides an 88-90 ml dynamic stroke volume. Woven Dacron grafts and polyurethane coated Dacron/Lycra cuffs are used to attach the device to the major arteries and atria, respectively. A polyurethane conduit and anchoring skin button bring motor wires percutaneously to an extracorporeal controller. The controller provides balanced cardiac output sensitive to atrial or aortic pressures, without operator intervention. The system is hermetically sealed and uses a simple compliance sac to maintain thoracic pressure between the pumps. The calf recovered uneventfully from surgery and thrived thereafter. She was killed on the 388th post-operative day because of worsening cardiac insufficiency. The previous three operative survivors in this series lived 131, 134, and 204 days. These results indicate the device's good potential for durability and body compatibility.

Hemostatic evaluation of Sarns/3M-VAD implantation in calves.

The authors evaluated the potential for thrombotic complications arising from implantation of a ventricular assist device (Sarns/3M-VAD) in four calves. Coagulation screening tests (prothrombin time [PT], partial thromboplastin time [PTT], thrombin time [TT]), fibrinogen levels, and antithrombin III functional activity were found to be of little value as predictors of the degree of activation of the hemostatic system. However, platelet counts, adenosine diphosphate (ADP)- and collagen-induced platelet aggregation, and thromboxane (TXB2) levels were good indicators of changes in platelet reactivity. Platelet counts (initial value 6 x 10(5) rose, and were associated with increased rate and extent of ADP- and collagen-induced platelet aggregation, which remained elevated during the entire 25 day postimplantation period. The first 5 days postimplantation revealed a typical acute inflammatory response, with increased platelet levels, but with TXB2 levels significantly decreased during this period. A monoclonal antibody based bovine D-dimer assay and Western blot studies indicated a small but significant increase in circulating bovine D-dimer, indicating localized fibrin formation and its dissolution.

Hemodynamic effects of a new right ventricular assist device.

A right ventricular assist device (VAD) based on the principle of counterpulsation has been developed at our institution. The device is a valveless, pneumatically actuated, 40 cc, sac-type pump, with a single inlet-outlet port. For right ventricular support, the "Uniport" pump is anastamosed end-to-side to the pulmonary artery. In previous experimental trials, the device has been shown to impart minimal trauma to blood components. In this study, biventricular failure was induced in eight Holstein calves by normothermic ischemia during cardiopulmonary bypass. A Pierce-Donachy left VAD (LVAD) was used for left ventricular support following the ischemic insult. Hemodynamic measurements were obtained throughout the study, and each animal served as its own control. A significant increase in post injury cardiac output (33.5 +/- 11.4%) was obtained with use of the Uniport and LVAD, as compared to use of the LVAD alone (p less than or equal to 0.005). Other hemodynamic parameters of right heart failure, including right atrial pressure (RAP), pulmonary artery pressure (PAP), and left atrial pressure (LAP) were not significantly affected. These data suggest that the Uniport right ventricular assist device significantly improves cardiac output in this model of moderate right ventricular failure. Additional studies are required, however, to optimize pump stroke volume, and to further define the performance envelope of the device.

A permanent arterial access system.

Now that long-term survival can be achieved in animals with mechanical circulatory devices, reliable permanent arterial access for physiologic and pharmacologic studies has become important. A novel approach has been developed eliminating the need for repeated arterial cannulation. The arterial access system (AAS) consists of a 7 Fr Silastic catheter, which is threaded into the internal mammary artery, and an attached access well, which is placed in the subcutaneous tissue over the sixth rib. The AAS is implanted during the initial operation. The access well is punctured percutaneously with a 23 gauge needle to obtain arterial blood or to measure arterial pressure, and patency is maintained by flushing the access well with 2,000 U of heparin each week. The AAS was implanted in six calves (three with a total artificial heart, three with a ventricular assist device) for a mean duration of 124 days (range, 20-323 days). There were no infections related to the AAS, and none of them thrombosed. All of the AAS had excellent arterial wave forms when punctured. The AAS is simple to implant, provides reliable long-term arterial access, and does not appear to increase the risk of infection.

Pulmonary circulatory support. A quantitative comparison of four methods.

Profound right ventricular failure was produced in 16 goats by inducing ventricular fibrillation after the systemic circulation had been supported with a left atrial-aortic bypass pump. In each animal, four methods of providing pulmonary blood flow were compared quantitatively: passive flow through the pulmonary artery due to a right atrial to left atrial pressure gradient; pulmonary artery pulsation via a 40 ml intra-aortic type balloon within a 20 mm Dacron graft anastomosed to the main pulmonary artery; pulmonary artery pulsation via a 65 ml single-port, valveless, sac type pulsatile assist device; and right atrial-pulmonary arterial bypass via a valved pneumatic pulsatile pump. Average cardiac index of the 16 animals for each method was 31.1 +/- 12.9, 44.4 +/- 13.6, 64.3 +/- 16.9, and 102.0 +/- 20.7 ml/min/kg, respectively. Passive pulmonary artery flow alone provided inadequate pulmonary circulatory support. Addition of pulmonary artery pulsation via the intra-aortic balloon within a conduit increased cardiac index 13.3 ml/min/kg (43%) above passive pulmonary artery flow (p less than 0.0005); however, the cardiac index remained inadequate. Increasing pulmonary artery pulsation volume with a 65 ml sac device provided a 32.2 ml/min/kg (106%) increase in cardiac index above passive flow (p less than 0.0005) to a level that was marginally adequate. The valved right atrial-pulmonary arterial bypass pump increased cardiac index 70.9 ml/min/kg (228%) above passive pulmonary artery flow (p less than 0.0005) to a satisfactory level and is the recommended method of pulmonary circulatory support in profound right ventricular failure.

Vascular anastomoses in growing vessels: the use of absorbable sutures.

Primary end-to-end infrarenal aortic anastomoses were performed in 36 piglets using two synthetic absorbable suture materials: polydioxanone and coated polyglactin. Animals were killed at 1, 4, and 11 weeks and 6 months following operation. Each aorta was removed, burst-tested to 300 mm Hg, radiographed, and examined histologically. All anastomoses were patent, and no burst-test failures occurred. Stenosis occurred in 14 of 17 animals at 1 and 4 weeks, respectively. One of 5 animals exhibited stenosis at 11 weeks, and none of the 14 animals had stenosis 6 months postoperatively. Histological examination revealed fibrosis replacing areas of disrupted elastica at 6 months in both suture groups. This study suggests that absorbable suture material, in particular polydioxanone, because of its excellent handling characteristics and prolonged tensile strength retention, will be useful for the repair of vascular and cardiac anomalies where growth of the suture line is required.

Approaches to the artificial heart. Invited speaker.

Over the last two decades, the implantable artificial heart has evolved from an idea to a device capable of completely supporting the circulation for periods now exceeding 5 months. Although initial animal studies were limited by thromboembolism and device breakage, the usual causes of death in experimental animals are now infection, atrioventricular valve obstruction, elastomer bladder calcification, or inadequate cardiac output because of the relatively rapid growth of the young calves. As a result of the bulky nature of the energy converter and the substantial risk of infection with large diameter percutaneous tubes, clinical use of their air-powered artificial hearts will be limited to patients who are awaiting or being prepared for heart transplantation. Artificial hearts with implanted energy converters are being developed for permanent heart replacement. These devices require well-designed, durable mechanical components and sophisticated control systems. Although initial designs centered around thermal engines powered by a completely implantable nuclear energy source, the excessive cost and potential dangers have shifted the focus away from the nuclear system. Several electrically driven artificial hearts, based on samarium-cobalt magnet brushless direct-current motors, are now undergoing bench testing and will be ready for long-term animal studies within 2 years. This research will culminate with the availability of an "off-the-shelf" electrically powered artificial heart for use in patients with a wide range of nonrepairable forms of end-stage heart disease.

Primary vascular anastomosis in growing pigs: comparison of polypropylene and polyglycolic acid sutures.

Stenosis remains a significant problem in vascular anastomoses performed in the growing patient. This study compares the growth of vascular anastomoses performed with either polypropylene or polyglycolic acid sutures. End-to-end infrarenal aortic anastomoses were performed in 18 piglets. Twelve were performed with polypropylene; in six all sutures were placed in a continuous fashion (Group 1A), and in the other six the posterior sutures were continuous and the anterior were interrupted (Group B). Six anastomoses were performed with polyglycolic acid sutures placed in a continuous fashion (Group 2). The animals were killed 6 months following operation. The abdominal aorta was removed, measured, burst tested, and subjected to histologic studies. All anastomoses were patent. There were no burst failures at 300 mm Hg mean pressure. All polypropylene sutures in Group 1A and the continuous portion in Group 1B had straightened without breaking. Straightening without polypropylene suture breakage resulted in stricture in three Group 1A anastomoses and one Group 1B anastomosis; there was intraluminal polypropylene suture material in two Group 1A and five Group 1B anastomoses. Bowstring formation of the straightened, continuous portion of the polypropylene suture in two Group 1A anastomoses and one Group 1B anastomosis resulted in adherent thrombus. Group 2 anastomoses were without stricture and were grossly indistinguishable from adjacent normal vessel. Histologic examination showed varying degrees of chronic inflammation in the polypropylene anastomoses but negligible inflammation in the polyglycolic acid anastomoses. These results suggest that continuous suture techniques with polypropylene in growing vessels may result in stenosis and/or thrombosis. Moreover, synthetic absorbable polyglycolic acid sutures will be of use in vascular anastomoses in growing patients and in cases in which exacting technique with minimal postsurgical inflammation may be crucial to patency.