Laparoscopic inferior vena cava and right atrial thrombectomy utilizing deep hypothermic circulatory arrest.

BACKGROUND AND PURPOSE: Surgery for renal cancer associated with a level III or IV tumor thrombus often involves cardiopulmonary bypass, deep hypothermia, and exploration of the right atrium and inferior vena cava (IVC). This major open operation necessitates a large median sternotomy incision and a midline abdominal or chevron incision. Herein, we investigate the feasibility of purely laparoscopic IVC and right atrial thrombectomy utilizing deep hypothermic circulatory arrest. MATERIALS AND METHODS: In six male calves weighing 70 to 80 kg, the right common carotid artery and right internal jugular vein were cannulated for subsequent cardiopulmonary bypass. One laparoscopic team performed right radical nephrectomy and complete mobilization of the intra-abdominal IVC by a four-port approach. Simultaneously, a second laparoscopic team obtained three-port thoracoscopic access to incise the pericardium and expose the right atrium. In sequence, cardiopulmonary bypass, complete exsanguination, cardiac arrest, and core hypothermia of 18 degrees C were achieved. A coagulum thrombus was created by needle injection into the IVC. Combined laparoscopic and thoracoscopic incision, exploration, and thrombectomy of the IVC and the right atrium were then performed in a bloodless field. An angioscope was inserted inside the heart and the IVC to confirm complete thrombus clearance visually. The IVC and right atrium were then laparoscopically suture repaired, cardiopulmonary bypass was reestablished, and the animal was gradually rewarmed. Once sinus rhythm was reestablished at normal body temperature, the animal was weaned off the pump. RESULTS: The mean total operative time was 494.5 minutes (range 355-705 minutes). The mean time needed to lower the core temperature was 63.5 minutes (range 50-120 minutes), and the mean time required to rewarm the animal was 101.8 minutes (range 70-130 minutes). The mean blood volume drained into the pump was 2633.3 mL (range 1400-3200 mL), and the mean estimated blood loss was 350 mL (range 200-750 mL). Reestablishment of sinus cardiac rhythm and weaning off the pump was successful in all animals prior to acute euthanasia. CONCLUSIONS: Laparoscopic radical nephrectomy with thrombectomy for level III or IV tumor thrombi utilizing deep hypothermic circulatory arrest is feasible in the calf model using minimally invasive techniques exclusively. The procedure is technically complex and requires the combined efforts of expert urologic and cardiac operative teams. Survival studies are planned.

Evaluation of platelet and coagulation function in different animal species using the xylum clot signature analyzer.

Platelet and coagulation function were evaluated in four different animal species with a newly developed clot signature analyzer (CSA). CSA is unique in that it simultaneously measures global platelet and coagulation function under flow using whole blood. No anticoagulant, chemical, or immunologic agent is required. Three CSA parameters are measurable: platelet mediated hemostasis time (PHT), collagen induced thrombus formation time (CITF), and clotting time (CT). Bovine, ovine, and canine species were chosen because these are the animal models most frequently used in in vivo testing of cardiovascular implants. These parameters, as well as data from whole blood platelet aggregometry (commonly used for platelet function studies because of the response to exogenous agonists), and platelet counts from these animals, were measured and compared with those in humans. In all three parameters, the canine species showed distinctively shorter time values than other species, including humans, suggesting that the dog is not an ideal animal model for the evaluation of blood-surface interactions. Ovine and human blood showed similar PHT and CT values, but CITF time values were significantly shorter in sheep than in humans. With bovine blood, PHT was most prolonged among the four species compared. CT and CITF times in calves were shorter than those in humans, although the difference in CITF time was not statistically significant. Adenosine diphosphate induced platelet aggregation showed the same order of responsiveness in four species as did CITF. It was noted that the intermeasurement variation was rather high for CSA parameters, especially in PHT, warranting caution when this parameter is used to study time-dependent changes after device implantation.

Short exposure time sensitivity of white cells to shear stress.

White cells are a critical functional element circulating in blood. This study sheared fresh whole bovine blood in stainless steel and polymeric capillary tubes of various lengths and diameters. Flow rate was constant, resulting in a range of exposure times and shear stresses. White cell count, cell integrity (trypan blue exclusion), and phagocytic index (latex bead ingestion) were assayed. It was found that cell function declined at lower stresses than cell count. White cell count was maintained at higher stress levels at the short exposure times used here compared with the published results at longer times. This study suggests that function, not count, is the critical parameter when studying shear effects on white cells, and that, like red cells, there may be an exposure time effect and that white cell function is impacted at stresses lower than are required for hemolysis.

Blood compatibility of a newly developed trileaflet mechanical heart valve.

An ideal heart valve prosthesis, which has both the flow dynamic properties and blood compatibility of a tissue valve prosthesis and the durability of a mechanical prosthesis, does not exist. The Triflo trileaflet mechanical heart valve (MHV; Triflo Medical Inc., Irvine, CA) is a newly developed MHV prosthesis with the following design goals: central flow, minimal flow disturbance and stasis around the hinge region, and durability. The current study was conducted to evaluate the blood compatibility of a 29 mm Triflo MHV in the mitral position of eight calves for 5 months without any postoperative anticoagulation. Whole blood platelet aggregometry and the Xylum Clot Signature Analyzer (Xylum Corporation, Scarsdale, NY) were used to evaluate the postoperative changes in platelet and coagulation functions. Full autopsies, histological examinations of major internal organs, and scanning electron microscopy analyses of the explants were performed. Early termination occurred in two cases; one was because of valve thrombosis on the 25th day, and the other was killed because of a nonvalvular complication on the 105th day. The valve thrombosis was attributed to prolonged ventricular fibrillation at the time of valve replacement surgery. Whole blood platelet aggregometry and clot signature analyzer parameters did not show any sign of activation of platelets or the coagulation system. No hemolysis was observed. There was no macroscopic valve thrombosis or embolism observed in the remaining seven cases. Scanning electron microscopy analyses showed clean leaflet and valve ring surfaces, with only occasional minute platelet aggregations. Excellent blood compatibility of the Triflo MHV was demonstrated in this study.

In vivo studies of the MagScrew total artificial heart in calves.

The purpose of this study was to evaluate the in vivo pump performance of our total artificial heart (TAH), the "MagScrew TAH." The TAH consists of a blood pump and control logic developed at the Cleveland Clinic and the MagScrew actuator and electronic control system developed by Foster-Miller Technologies, Inc. (Albany, NY). MagScrew TAH implantation was performed in two calves. Study durations were 50 and 5 days. The causes of termination were prosthetic valve endocarditis in one case and cable failure in the other. Mean left pump flow ranged from 8.0 to 9.7 L/min, with left atrial pressure of 3.0 to 16.0 mm Hg. Preload sensitivity of the MagScrew TAH demonstrated a Frank-Starling response to preload in automatic mode. The relationship between right and left atrial pressure was well balanced. Mean arterial pressure and mean pulmonary artery pressure were maintained within physiologic ranges over study duration. There were no signs of bleeding, hemolysis, or organ failure. The MagScrew TAH showed physiologic pump performance, and hemodynamics were well maintained without any organ failure. Further development testing will bring the MagScrew TAH to the point of preclinical readiness testing.

In vivo evaluation of the biocompatibility of the totally implantable ventricular assist device (HeartSaver VAD).

A series of multicenter in vivo studies have been conducted to assess the biocompatibility and device performance of the HeartSaver VAD, a totally implantable pulsatile ventricular assist device (VAD). The experiments (n = 23) were conducted in calves with a mean weight of 101 (75-152) kg. Implants took place at four centers using two different surgical procedures of implantation (one with cardiopulmonary bypass and one without). Three anticoagulation regimens were used (one with continuous intravenous heparin, one with oral warfarin, and one with oral warfarin combined with antiplatelet clopidogrel therapy). Device function and biochemistry were monitored during the study, and organs and device analysis were conducted at explant. There were six nonsurvivors because of early surgical complications (during the first week of support). The postoperative courses in the remaining 17 (74%) calves were uneventful. Hemodynamic and biocompatibility indicators were monitored throughout the study. The mean duration of device support for those cases was 48 (13-92) days. Mean device flow was 7.15 (+/- 1.68) L/min. There were no deaths caused by infection; however, two animals developed endocarditis believed to be caused by the percutaneous instrumentation lines used for the study. No severe bleeding requiring reoperation occurred during the study. The mean plasma free hemoglobin was within normal limits at 6.8 +/- 2.6 mg/dl. Renal and hepatic functions were normal with a mean creatinine of 0.6 +/- 0.1 mg/dl and a mean aspartate aminotransferase of 68.7 +/- 42.6 mg/dl. Several device related improvements were identified and have now been implemented. Additional bovine implants with an optimized device are currently underway in preparation for human trials.

Model analysis of tissue responses to transient and chronic heating.

Thermal models are used to analyze responses of muscle and lung tissue to transient (30-45 min) and chronic (4-7 week) heating in vivo. The general bioheat model, which describes one-dimensional temperature dynamics, incorporates heat conductance and perfusion. In general, perfusion changes with time and distance from a heated surface. One of the main objectives of this study was to analyze long-term perfusion change, which reflects tissue adaptation associated with angiogenesis. The database for these models was obtained using heated disks implanted in calves for up to seven weeks. Tissue temperature distributions were obtained repeatedly from thermistors protruding 1 to 10 mm from the heated disk surface. The perfusion parameter was estimated from the transient experiments at least several times each week by nonlinear, least-squares fitting of the model predicted temperature to the measured temperature response. Chronic heating at a heat flux 0.08 W/cm2 caused perfusion of muscle tissue to increase with postimplant day (PID). Under the same conditions, lung tissue perfusion increased with chronic heating from early to late PID, but less than that for muscle tissue. During chronic heating above 42 degrees C and below 50 degrees C, a decrease in tissue temperature is associated with higher perfusion that develops with time. Over seven weeks, perfusion of muscle tissue near the heated disk surface increased by about 70% at 0.08 W/cm2 and 40% at 0.06 W/cm2. Furthermore, the model can be used to predict tissue and perfusion changes continuously over weeks for heat fluxes around 0.08 W/cm2.

Comparison of pulsatile and non-pulsatile cardiopulmonary bypass on regional renal blood flow in sheep.

OBJECTIVE: The purpose of the present study was to evaluate the effects of pulsatile cardiopulmonary bypass (CPB) on sheep regional renal blood flow by comparing pulsatile and non-pulsatile perfusion at two different flow rates. DESIGN: Seven female Suffolk sheep were used and the animals were perfused with pulsatile and non-pulsatile CPB at flow rates of 60 and 100 ml/min/kg. Regional renal blood flow was measured by the colored microsphere method. General linear model ANOVA was performed to analyze the data. RESULTS: Regional renal blood flow was significantly higher in both outer and middle cortices of pulsatile CPB compared with non-pulsatile CPB (outer cortex: pulsatile CPB, 381+/-192 ml/min/100 g, non-pulsatile CPB, 255+/-151 ml/min/100g, p=0.002; middle cortex: pulsatile CPB, 239+/-114 ml/min/100 g, non-pulsatile CPB, 176+/-80 ml/min/100 g, p=0.02). The increase of flow rate from 60 to 100 ml/min/kg improved renal cortical blood flow significantly. CONCLUSION: The regional renal blood flow was significantly higher in both outer and middle cortices of pulsatile CPB compared with the non-pulsatile CPB.