Augmentation of abdominal organ perfusion during cardiopulmonary bypass with a novel intra-aortic pulsatile catheter pump.

BACKGROUND: Current pulsatile pumps for cardiopulmonary bypass (CPB) are far from satisfactory because of the poor pulsatility. This study was undertaken to examine the efficiency of a novel pulsatile catheter pump on pulsatility and its effect on abdominal organ perfusion during CPB. METHODS: Twelve pigs weighing 89+/-11 kg were randomly divided into a pulsatile group (n=6) and a non-pulsatile group (n=6). All animals had a CPB for 120 min, aorta clamped for 60 min, temperature down to 32 degrees C, and a perfusion flow of 60 ml/kg/min. In the pulsatile group, a 21 Fr intra-aortic pulsatile catheter, which was connected to a 40 mL membrane pump, was placed in the descending aorta and activated by a balloon pump driver during the first 90 minutes of CPB until aortic declamping. Hemodynamics, organ blood flow, body metabolism, and blood trauma were studied during experiments. RESULTS: Compared with the non-pulsatile group during CPB, the pulsatile group had a higher systolic blood pressure (p<0.01), higher mean arterial pressure (p<0.05), and higher blood flow to the superior mesenteric artery (p<0.05). The hemodynamic energy, indicated by the energy equivalent pressure (EEP) was higher in the gastrointestinal tract and kidney in the pulsatile group (p<0.01, p<0.01). Abdominal organ perfusion status, as indicated by SvO 2 in the inferior vena cava, was higher in the pulsatile group (p<0.05) 30 min after cessation of CPB. Hemolysis indicated by release of free hemoglobin during CPB was similar in the two groups. CONCLUSION: Applying the pulsatile catheter pump in the descending aorta is effective in supplying the pulsatile flow to the abdominal organs and results in improved abdominal organ perfusion during the ischemic phase of CPB.

Instrument-independent flux units for laser Doppler perfusion monitoring assessed in a multi-device study on the renal cortex.

To investigate the feasibility of instrument-independent perfusion units for laser Doppler flowmetry, a comparison was performed of two commercial fiberoptic laser Doppler perfusion monitors measuring the same flux situation for two different types of probes. In vivo measurements were performed on the cortex of pig's kidney, with an ultrasonic arterial flow meter as reference. The flow was mainly varied by internal arterial constriction using a balloon catheter. For each probe, instruments are compared in terms of the ratio of laser Doppler flux and arterial flow. For a given probe, the flux-to-flow ratios of the two instruments show a linear mutual relationship for a wide variety of arterial flows and laser Doppler fluxes. In vitro measurements were performed on an aqueous suspension of polystyrene microspheres. For the probe with interfiber distance 500 microm the ratio of the in vivo fluxes appears to agree within 16% to the value found in vitro, while for the 250-microm probe a difference of 28% was found. For a wide range of fluxes, the in vivo flux values of one instrument can be translated into flux values for the other instrument, in spite of the instrumental differences. This enables the user to render experimental results independent of the specific instrument, thus facilitating multi-center studies.

Scoliosis correction with shape-memory metal: results of an experimental study.

The biocompatibility and functionality of a new scoliosis correction device, based on the properties of the shape-memory metal nickel-titanium alloy, were studied. With this device, the shape recovery forces of a shape-memory metal rod are used to achieve a gradual three-dimensional scoliosis correction. In the experimental study the action of the new device was inverted: the device was used to induce a scoliotic curve instead of correcting one. Surgical procedures were performed in six pigs. An originally curved squared rod, in the cold condition, was straightened and fixed to the spine with pedicle screws. Peroperatively, the memory effect of the rod was activated by heating the rod to 50 degrees C by a low-voltage, high-frequency current. After 3 and after 6 months the animals were sacrificed. The first radiographs, obtained immediately after surgery, showed in all animals an induced curve of about 40 degrees Cobb angle - the original curve of the rod. This curve remained constant during the follow-up. The postoperative serum nickel measurements were around the detection limit, and were not significantly higher compared to the preoperative nickel concentration. Macroscopic inspection after 3 and 6 months showed that the device was almost overgrown with newly formed bone. Corrosion and fretting processes were not observed. Histologic examination of the sections of the surrounding tissues and sections of the lung, liver, spleen and kidney showed no evidence of a foreign body response. In view of the initiation of the scoliotic deformation, it is expected that the shape-memory metal based scoliosis correction device also has the capacity to correct a scoliotic curve. Moreover, it is expected that the new device will show good biocompatibility in clinical application. Extensive fatigue testing of the whole system should be performed before clinical trials are initiated.

Animal study on surface-modified defibrillator systems: Indications for enhanced infection resistance.

One of the most important problems with ICD systems is infection. The aim of this study was an in vivo evaluation of the efficacy of defibrillator systems in terms of infection resistance. The polyurethane leads were coupled with heparin and loaded with the antibiotic gentamicin, while the PGs were modified to release gentamicin. Group I was comprised of 10 pigs implanted with either a standard or a modified system for 2 weeks; group II was implanted during 4 weeks. The lead was inserted into the heart wall via the jugular vein. The other end was subcutaneously tunneled to the armpit where the PG was positioned. A cocktail of Staphylococcus aureus and epidermidis was injected at the site of the PG. Evaluation was performed macroscopically, by taking bacterial swabs during explantation and by microscopic processing. The results showed that 3 out of 5 modified defibrillator-systems in group I and 1-2 out of 5 in group II were judged as noninfected, whereas all standard systems were infected. Infection rates of the remaining modified defibrillators showed variances, as found with the standards, from slight to moderate to high, to even high/severe in group II (1x standard and 1x modified). With the modified systems, this may be related to production of humoral factors by an intensified early tissue reaction, as indicated by a swelling at day 6 at the site of the PG. When infected, whether or not modified, usually only Staphylococcus aureus was present. Spreading of infection seemed to occur by inoculation via blood, for example, based on the observation that group II in general showed an increase in infected fibrotic overgrowth in the heart, while infectious problems were low in the jugular vein. It is concluded that the modification at short term shows enhanced infection resistance. An increased infection rate already at 4 weeks, however, indicates that the modification may not hold in the long run. Special attention is needed concerning the more intense early tissue reaction.

In vivo and in vitro experience with the PUCA-II, a single-valved pulsatile catheter-pump.

The Pulsatile Catheter (PUCA) pump is a trans-arterial pulsatile ventricular assist device that can be used for short-term left ventricular support. The separate inflow and outflow valves in the first version of the device (PUCA-I) were replaced by a single inflow/outflow valve in the latest PUCA pump version (PUCA-II). The new combined valve was tested during in vitro (mock circulation) and in vivo experiments for valve leakage, flow resistance, and thrombus formation. During the in vitro experiments a maximum valve leakage of 6% during ejection and 21% during aspiration was found. The maximum flow resistance coefficient (K) was 4. The animal experiments demonstrated that the PUCA-II could be positioned within a few minutes into the left ventricle without X-ray guidance and without using a vascular graft. Thrombi were not found in the combined valve after total pump time of 3 hours, which proved the good washout of the valve. Initial experiments to position the pump in the right ventricle through the pulmonary artery were successful and contributed to the development of a new application for the device.

Development of acute ischemic heart failure in sheep.

The goal of the present study was to develop a large animal model of acute ischemic left ventricular heart failure (LVHF) that can be used to assess the influence of the PUCA pump on the heart and circulatory system under realistic conditions. We tested the hypothesis that mild stenosis of the coronary artery in combination with mild ventricular pacing induces an acute heart failure condition, whereas the separate phenomena themselves do not lead to impaired heart function. Mean aortic pressure (AoP), left ventricular end-diastolic pressure (LVEDP), stroke volume (SV) and myocardial systolic shortening (MSS) were compared 30 minutes after a pacemaker (PM) induced tachycardia in anaesthetized sheep (n=3) without and with +/- 50% stenosis of the proximal LCx. All parameters measured restored to basic levels when stenosis was absent. When the LCx was partially occluded, mild PM-induced tachycardia resulted in decreased AoP (P=0.045) as well as in decreased SV (P=0.048); the LVEDP remained high (P=0.002). Also the recovery of MSS was impaired when stenosis was present (P=0. 002). These values indicate that acute heart failure conditions were present. The technique used proved to be safe and allowed fine-tuning of the demand ischemia by adapting heart frequency to the required heart failure conditions. The model can be used to study the effect of LV mechanical support during acute heart failure conditions.

Validation in an animal model of the carbon 13-labeled mixed triglyceride breath test for the detection of intestinal fat malabsorption.

OBJECTIVE: To determine, in a rat model of fat malabsorption, the potency of the carbon 13-labeled mixed triglyceride ((13)C-MTG) breath test as a noninvasive, patient-friendly replacement for classic fat balance studies. STUDY DESIGN: Comparison of the percentage of fat absorption, detected by fat balance, with the (13)CO(2) recovery of the (13)C-MTG breath test in rats fed high-fat chow and varying amounts of the lipase inhibitor, orlistat (0, 50, 200, and 800 mg per kilogram of chow), for 5 days. RESULTS: On orlistat administration, total fat absorption decreased from 80.2% +/- 2.2% to 32.8% +/- 3.7% (mean +/- SEM, 0 mg and 800 mg of orlistat per kilogram of chow, respectively; P <.001). Correspondingly, breath (13)CO(2) recovery from (13)C-MTG at 6 hours decreased from 84.5% +/- 7.8% to 42.0% +/- 1.5% of the dose (0 mg and 800 mg of orlistat per kilogram of chow, respectively; P <.001). The 6-hour recovery of breath (13)CO(2) appeared to be highly correlated with the percentage of fat absorption (r = 0.88, P <.001). In rats with fat absorption higher than 70%, however, the coefficient of variation of the (13)C-MTG breath test was 3-fold larger than that of the fat balance. CONCLUSIONS: The (13)C-MTG breath test could potentially replace the fat balance method for comparing fat absorption efficacy between groups. Yet, a considerable interindividual variation of the (13)C-MTG breath test under conditions of relatively mild fat malabsorption does not support its application for diagnostic purposes in individuals.

Evaluation of the optimal driving mode during left ventricular assist with pulsatile catheter pump in calves.

The pulsatile catheter (PUCA) pump, a left ventricular assist device, was tested during acute experiments in calves using asynchronous and ECG-synchronous assist modes. The aim of the study is to compare ECG-synchronous and asynchronous assist and to find the optimal driving mode for the PUCA pump with respect to left ventricular myocardial oxygen consumption (LV MVO2), pump flow, and coronary flow. LV MVO2 decreased significantly during the asynchronous (from 7.77 to 6.46 ml/min/100 g) as well as during the ECG-synchronous mode (from 8.88 to 7.84 ml/min/100 g). The pump flow was highest during the ECG-synchronous assist (2.94 L/min), followed by the asynchronous assist (2.79 L/min). The peak coronary flow depended strongly on pump ejection timing and showed the best flow patterns during the ECG-synchronous assist. We concluded that for PUCA pump support both asynchronous and ECG-synchronous assists significantly reduce LV MVO2 and that the pump flow generated is enough to maintain the systemic circulation. However, we find the ECG-synchronous mode preferable because this mode optimizes coronary flow patterns at the same time.

Hyperthermic Isolated Limb Perfusion with TNF alpha and Cisplatin in the Treatment of Osteosarcoma of the Extremities: A Feasibility Study in Healthy Dogs.

Purpose. The feasibility of hyperthermic isolated limb perfusion (HILP) with tumor necrosis factor-alpha (TNFalpha ) and cisplatin for the management of osteosarcoma was studied in the canine model.Methods. During seven perfusions in six healthy mongrel dogs (weight 32+/-2 kg) technical aspects of HILP under mild hyperthermia (39- 40) were studied. In five experiments HILP was performed with TNFalpha alone (0.5 mg/l extremity volume), and in two experiments TNFalpha was combined with cisplatin (25 mg/l extremity volume). During the perfusions physiological parameters were monitored and TNFalpha and total cisplatin concentrations were determined.Results. Perfusion conditions (pH, PCO(2) , PO(2), flow and pressure) remained within physiological ranges.Three dogs died within 24 h despite a sublethal systemic concentration of TNFalpha that leaked from the perfusion circuit. Three dogs were terminated; one dog after the second experiment in accordance with Dutch ethical rules; one dog showed an invagination of the small bowel resulting in an ileus; one dog because of necrosis of the perfused limb.Conclusions. This feasibility study in healthy dogs demonstrated that HILP with TNFalpha and cisplatin was associated with a high mortality rate and does not allow us to treat dogs with spontaneous osteosarcoma with TNFalpha and cisplatin HILP. Therefore, an alternative model should be used in the search for the ideal combination of perfusion agents for limb sparing treatment in human osteosarcoma.

A novel implantable electromechanical ventricular assist device. First acute animal testing.

A novel ventricular assist device (HIA-EMLVAD-AT1, Helmholtz Institute Aachen-Electromechanical Left Ventricular Assist Device-Animal Test Version 1), driven by a uniformly and unidirectionally rotating actuator and a patented hypocycloidic pusherplate displacement gear unit, was developed and tested in an acute animal experiment. The excellent free filling behavior of the pump chamber with a stroke volume of 65 ml is obtained by a 2:3 ejection-filling time relationship. The uniform motor rotation facilitates simple sensorless pre and afterload detection by motor current analysis. In contrast to common apical cannulation, the inlet cannula was placed via the left atrium through the mitral valve into the left ventricle. This connection mode is preferable for left ventricular recovery and preservation. Left atrial, left ventricular, and aortic pressure curves, as well as pulmonary artery flow data, were obtained. The data show very effective unloading of the natural ventricle and demonstrate the feasibility of this novel assist device. Directions for further improvement of technical features were also identified.

Development of a new introduction technique for the pulsatile catheter pump.

The pulsatile catheter (PUCA) pump is an intraventricular blood pump that can be introduced into the left ventricular cavity through a superficial artery (transarterially) or directly through the thoracic aorta during open chest conditions. When positioned, the pump aspirates blood from the left ventricle and transports it into the ascending aorta. A pneumatic driving system allows the blood to be ejected in early diastole of every second or third heart beat. The main goal of this study was to develop an easy, fast, safe surgical introduction technique. Four different means of catheter introduction were tested in 20 acute open chest experiments with calves: introduction without any guidance at all, introduction by x-ray guidance only, introduction using a guide wire plus x-ray guidance, and introduction using a guiding pressure catheter. Introducing the PUCA pump catheter into the left ventricular cavity using a pigtail guiding pressure catheter proved to be easy. The large bore pump catheter followed the guiding catheter and passed the aortic valve well. The position of the PUCA pump could be monitored from the pressure patterns derived from the guiding catheter.

Blood interaction with a Bioline heparin coated HIA-VAD: a study on calves.

The blood compatibility of ventricular assist devices developed by the Helmholtz Institute Aachen (HA-VAD's) was tested on calves. Seven calves received a non-coated HIA-VAD (control) and three a Bioline heparin coated device. The circulatory support of these HIA-VAD's lasted one week. Mechanical blood cell trauma estimated by hematocrit (Hct), hemoglobin (total Hb) and free plasma hemoglobin (free Hb) levels did not differ in either group. All HIA-VAD's in the control group remained thrombus free, except on one occasion when an inflow cannula was obstructed by a thrombus located in the tip. After circulatory support, the animals in this group seemed clinically healthy. However, thrombus formation was observed in the three heparin coated HIA-VAD's. One animal in this group died from complications after re-operation for pneumothorax on the fifth day of support, whereas the other two animals seemed clinically healthy. In these three animals, a strong decrease in platelet numbers was measured even after 24 hours of support which recovered after 72 hours. This decrease in platelet numbers was associated with a lower degree of platelet aggregation ability stimulated by ADP (p < 0.05). Fibrin(ogen) degradation products (FDP) increased significantly immediately after the implantation procedure (p < 0.05). Fibrinogen levels initially decreased during the implantation procedure, but increased thereafter in both groups. The FDP levels remained high in this group, although the FDP levels in both groups were decreased after the implantation procedure. The ex vivo measured circulating heparin levels were lower in the heparin coated HIV-VAD group despite the equally administrated heparin doses in both animal groups. No differences were measured in either group with regard to white blood cell (WBC) numbers and complement hemolytic activity (CH50). Despite these hemostatic changes, no mechanical trauma could be demonstrated after seven days of circulatory support.

Ex vivo design evaluation of an implantable blood port system.

A prototype of a totally implantable vascular catheter-port system was evaluated on its design using three animals of different species. The catheter was placed either intravenously or intra-arterially, and connected to the port which was retained outside the body. Parameters used for design evaluation or functionality testing were focused on the use and handling of the port-catheter system such as easiness of flushing, injection, blood sampling, septum stiffness to prevent blood reflux after pushing the septum, and possible diffusion of blood into the saline present in the port-catheter system. This pilot experiment showed that the septum of the prototype port system was too flexible, and that the distance between septum and base of the port was too short. These findings have led to a major improvement of the catheter-port system, currently successfully used in cancer chemotherapy.

In-vivo evaluation of the "HIA-VAD": a new German ventricular assist device.

Helmholtz Ventricular Assist Devices (VAD) are pneumatically driven polyurethane membrane pumps with various volumes. The pumps are placed paracorporeally and connected with commercially available cannulas between the left atrium and aorta (left ventricular assist device) and/or right atrium and pulmonary artery (right ventricular assist device, bi-ventricular assist device). The pumps can be driven with a stand-alone driving system or with a Helmholtz IABP-console interface. Seventeen animal experiments (on calves) with Helmholtz VAD's were performed to evaluate experimental protocols, to optimize surgical techniques, and to improve design and manufacturing techniques. Blood chemistry and cell counts demonstrated that the tested HIA-70 produces low mechanical blood damage. In the course of the animal experiments the Helmholtz VAD's were made totally transparent, whereby they became easy to de-air, efficient, and affordable.

Reflectance pulse oximetry in fetal lambs.

Transmission pulse oximetry is used for monitoring in many clinical settings. However, for fetal monitoring during labor and in situations with poor peripheral perfusion, transmission pulse oximetry cannot be used. Therefore, we developed a reflectance pulse oximeter, which uses the relative intensity changes of the reflected red and infrared light (red/infrared ratio) to measure the arterial oxygen saturation. The performance of the reflectance pulse oximeter was studied in acute experiments in fetal lambs. By stepwise reduction of the inspired oxygen concentration of the ewe, measurements were done at the fetal scalp at various arterial oxygen saturation levels (17-82%). Reflectance pulse oximeter readings were averaged over periods of 15 s and compared with simultaneously taken fetal arterial blood samples. A calibration curve for the relationship between red/infrared ratio and arterial oxygen saturation was obtained from 53 measurements in four fetal lambs, by linear regression analysis [red/infrared = 4.088-(0.038.SaO2), r = 0.96]. In these experiments, the pulse oximeter showed a precision of 4.7% oxygen saturation around the calibration curve, with a 95% confidence interval of +/- 9.4%.

Prevention of infection in a porous tracheal prosthesis by omental wrapping.

The ideal tracheal prosthesis has to permit complete incorporation by epithelialization of the luminal surface. This is not possible with the currently available impermeable solid silicone tube. The authors developed a reinforced, porous polyurethane tubular prosthesis which has the potential for complete incorporation. However, because these prostheses are implanted in a contamined area such as the airway, they all become infected. In order to prevent infection, the authors evaluated the effect of omental wrapping in guinea pigs. The authors' tubular prosthesis was implanted subcutaneously in the abdominal area with the ends open to the air. Ten prostheses were wrapped with omentum and 10 prostheses were not. In 4 weeks, all control prostheses were infected and marsupialized. All the wrapped prostheses remained in place and were macroscopically not infected. Microscopically, all wrapped prostheses were well vascularized and were incorporated by granulation tissue, which did not occur in the prostheses of the control group. From these results the authors conclude that omental wrapping would be an effective way to prevent infection of porous tracheal prostheses in an open-to-the-air situation, and allow rapid tissue ingrowth and incorporation in the host.

Clear prime for infant cardiopulmonary bypass: a miniaturized circuit.

The extracorporeal circuit used clinically to perform cardiopulmonary bypass (CPB) in small infants is relatively large requiring blood to prime the circuit to reduce hemodilution. To study the merits of clear prime also in infants, we did experiments in rabbits with two extracorporeal circuits: one employing traditional venous gravity drainage (priming volume 330 ml) and the other employing vacuum drainage (priming volume 90 ml). The first circuit still had to be primed with blood, whereas the second circuit could be primed with a clear solution. Both circuits were automatically controlled to lighten the task of the perfusionist to operate the CPB safely and accurately. We demonstrated that the clear priming solution in the second circuit eliminates the hemodynamic deterioration caused by blood prime in the first circuit. Studying the effect of various modes of regulation, we showed that automatic control of CPB based on venous return is similar to autoregulation of the heart according to Starling's law, and maintains not only normal hemodynamics, but also an optimal microcirculation.

An automatic autotransfusion system with a centrifugal pump: a hematologic evaluation in dogs.

The requirements that have to be met by an on-line autotransfusion system (ATS) in case of massive blood loss are a sufficient capacity for reinfusing the shed blood, an optimal hemocompatibility, ability to prevent reinfusion of aspirated air, and ease of operation. In a previous study we tested a diaphragm pump in our pneumatically driven ATS that met these requirements. In this study a centrifugal pump was used as an outflow pump in otherwise the same system. A centrifugal pump has important advantages: It prevents the occurrence of massive air embolism, accidental obstruction of the outflow line will not cause bursting of the tubing, and there is no spallation. There are also indications that a centrifugal pump causes less stimulation of the coagulation cascade than do other pumps. Because of these advantages, we were interested in the hemocompatibility and pumping characteristics of the centrifugal pump in our ATS. From this study we conclude that the hemocompatibility of the centrifugal pump was not significantly different from that of the previously tested diaphragm pump. Also, the system can easily and safely be operated by non-specialized personnel. Because of the advantages, especially in pumping characteristics, the centrifugal pump is our choice in on-line ATSs.

[Regional isolation perfusion with cisplatinum in dogs with osteosarcoma of an extremity]. / Regionale geïsoleerde perfusie met cisplatinum bij honden met osteosarcoom van een extremiteit.

In the treatment of osteosarcoma, it is possible to differentiate between systemic therapy and local regional treatment. Systemic treatment of human patients with osteosarcomas consists in adjuvant chemotherapy. This has considerably improved the prognosis in these cases. The primary object in local regional treatment is to prevent local recurrences and to preserve function. As regards extremities, the aim is to preserve the limbs. In the present investigations, the value of regional chemotherapy by isolated regional perfusion with cis-platinum to dogs is studied. This approach was based on the hypothesis that considerable necrosis of tumours may be produced after perfusion with cis-platinum, thus making extremity-saving surgery possible. Isolated regional perfusion with cis-platinum (30 mg/litre of extremity volume) was performed in nine dogs with osteosarcomas of an extremity. A marked effect on the tumour was detectable on the basis of clinical, radiological and histological parameters. In the opinion of the present authors, regional perfusion with cis-platinum may contribute to extremity-saving treatment of osteosarcomas in dogs and human subjects. However, further studies will be required in order to achieve more adequate quantitation an improvement of local effects. In view of the synergy with cis-platinum, the latter may possibly be attained by the addition of hyperthermia (temperatures above 41.5 degrees C).