Thermal and hydrodynamic modelling of active catheters for interventional radiology

Interventional radiologists desire to improve their operating tools such as catheters. Active catheters in which the tip is moved using shape memory alloy actuators activated using the Joule effect present a promising approach for easier navigation in the small vessels. However, the increase in temperature caused by this Joule effect must be controlled in order to prevent damage to blood cells and tissues. This paper is devoted to the simulation and experimental validation of a fluid-thermal model of an active catheter prototype. Comparisons between computer-predicted and experimentally measured temperatures are presented for both experiments in air and water at 37°C. Good agreement between the computational and experimental results is found, demonstrating the validity of the developed computer model. These comparisons enable us to highlight some important issues in the modelling process and to determine the optimal current for the activation of the catheter.     

Long-term subarachnoid catheter placement in the middle cranial fossa of the rat

Research using rats sometimes requires long-term placement of catheters in the subarachnoid space, the cavity between the arachnoid mater and the pia mater in the brain. These catheters can be used to experimentally induce subarachnoid bleeding by injecting blood or to locally administer drugs or other substances. To date, published techniques for penetrating the subarachnoid space of small experimental animals require the use of inflexible or relatively inflexible catheters. These catheters typically consist of metal or stiff plastic and are used to access the occipital or frontal cranial cavity or to directly access the cisterna magna via the atlantooccipital membrane. However, inflexible catheters are not ideal for long-term placement in the subarachnoid space. In this paper, the authors describe a reliable procedure for long-term catheterization of the subarachnoid cavity of the rat. For this method, personnel insert the catheter and keep it in place in the rat's middle cranial cavity, in the vicinity of the cerebral arterial circle. This new approach allows personnel to repeatedly use the catheter for a period of at least 2 weeks. The catheter, which is well-tolerated by rats, can be used for administering saline solutions and for injecting blood that has not been treated with heparin into the subarachnoid space.     

Simultaneous sampling of portal, hepatic and systemic blood during intragastric loading and tracer infusion in conscious pigs

A surgical model for catheterization at multiple sites has been developed for use in long-term metabolic studies. For blood sampling, catheters were inserted into the portal and hepatic veins and the common carotid artery. The hepatic vein catheter was inserted from the margin of a liver lobe and led through the venous system, until the tip was close to the bifurcation with the inferior vena cava. A new technique was developed to ensure correct placement of the hepatic vein catheter using the specific extraction of indocyanin-green over the liver during surgery. Gastrostomy was performed using a Pezzer catheter. Catheters in the artery and hepatic and portal veins were patent for blood withdrawal for up to 4 weeks, and thus allowed repeated metabolic studies. Studies were performed in conscious animals familiar with the experimental situation.     

Customized vascular catheters for rodents

Custom arterial and venous catheters were made for rodents from polyurethane tubing. The low thrombogenicity and toxicity index, chemical stability and resiliency of polyurethane made this tubing an ideal catheter material. The tubing is shaped using peanut oil heated to 160 degrees C. Sealing these catheters is accomplished simply by heating the tube end with a hot object and pinching it between the fingers. Chronic catheter patency was maintained using Burr's solution (9:1 mixture of glycerine and heparin). No flushing was necessary.     

Multifunctional testing of PTCA balloon catheters]

New in vitro measuring methods for balloon catheters used for percutaneous transluminal coronary angioplasty (PTCA) and their verification in a complex test device are presented. This system can mimic all relevant application situations. The central element of the test device is a coronary vessel model matching the physiological situation in terms of geometrical structure and frictional properties. Reactive force sensors are used to measure the application-relevant forces exerted by the catheter on the model vessel walls and accessories, such as guide wire and guiding catheter. To generate a kink-free advancement of the catheter and permit measurement of the active forces, an alternating drive unit has been specially developed. The testing and application of the newly developed methods revealed statistically significant differences between various types of catheter. The test device closes a gap between complex but subjective clinical tests, and individual objective, but application-removed in vitro test setups for PTCA catheters. While the initial prototype had shortcomings with regard to the reproducibility of measurements, successor systems developed for industrial use are now in production. The properties of these measuring systems developed for the benefit of manufacturer and reprocessor of PTCA catheters are discussed.     

Design and "in vivo" evaluation of two adapted catheters for intrauterine transcervical insemination in sheep

In order to obtain better fertility, we evaluated two ovine artificial insemination (AI) catheters that were manufactured according to the anatomical structure of the ewe cervix. Morphometric data of the cervix in Churra and Assaf breeds were used to design two types of curved catheters: CAT06 with one curvature and ZIGZAG with five curvatures in a zigzag shape. Two commercial catheters (IMV(?) and Minitüb(?)) were used as controls. In experiment 1, cervical penetration and the degree of reflux were measured in a Cervical AI simulated assay both Churra (n=28) and Assaf ewes (n=28). In experiment 2, a fertility study was performed with three catheters (only one commercial control catheter - IMV) in 465 inseminations (Assaf); and a second study analyzed only the top two catheters (IMV and CAT06) in 428 inseminations (210 Assaf and 218 Churra). The ewes were synchronized using intravaginal sponges (40 FGA mg during 14 days) and 500 IU of eCG. Deeper penetration of the cervix was obtained with the new catheters compared with the commercial ones (1.5, 1.3, 3.5 and 3.2 cm for the IMV, Minitüb, CAT06 and ZIGZAG catheters, respectively). The cervical penetration and the reflux grade of each catheter showed no differences between breeds. In experiment 2, the degree of penetration had no correlation with fertility of different catheters. The best percentage of lambing ewes was obtained with the IMV and CAT06 catheters (39.5 and 48.1%, respectively. vs 27.2% for ZIGZAG catheter, in the Assaf breed). Regarding effect of breed, Assaf (39.3% and 49.5 for IMV and CAT06, respectively) showed better lambing rates than Churra (29.0% and 39.0%, respectively), and the CAT06 catheter showed significantly higher rates for each breed.     

Local effect of vanadate on interstitial glucose and lactate concentrations in human skeletal muscle

The aim of this study was to investigate the local effect of the insulin-mimetic agent vanadate on glucose metabolism in human skeletal muscle in vivo. Interstitial concentrations of glucose and lactate were determined by microdialysis at a low flow rate in the quadriceps femoris muscle of 18 men. In the same leg two microdialysis catheters were inserted. In one catheter, the perfusion medium was supplemented with sodium metavanadate (10-100 mM) after a basal period, the other catheter served as control. In the catheter perfused with metavanadate, the interstitial glucose concentration was decreased by 13-50% compared to the control catheter (p<0.05). The lactate concentration was higher in the 50 mM and 100 mM metavanadate catheters compared to control (39-89%, p<0.05). There was no difference between control and metavanadate catheters in urea concentrations. Five of the subjects were insulin-resistant and for them the results were similar, although the effect was somewhat smaller. The decreased interstitial glucose concentration, and the increased lactate concentration, in the vicinity of the microdialysis catheter most likely reflects an increased cellular glucose uptake. The present study thus indicates that vanadate mimics the effect of insulin in human skeletal muscle in vivo.     

Epidural Intracranial Pressure Measurement in Rats Using a Fiber-optic Pressure Transducer

Elevated intracranial pressure (ICP) is a significant problem in several forms of ischemic brain injury including stroke, traumatic brain injury and cardiac arrest. This elevation may result in further neurological injury, in the form of transtentorial herniation^1,2,3,4, midbrain compression, neurological deficit or increased cerebral infarct^2,4. Current therapies are often inadequate to control elevated ICP in the clinical setting^5,6,7 . Thus there is a need for accurate methods of ICP measurement in animal models to further our understanding of the basic mechanisms and to develop new treatments for elevated ICP.In both the clinical and experimental setting ICP cannot be estimated without direct measurement. Several methods of ICP catheter insertion currently exist. Of these the intraventricular catheter has become the clinical ''gold standard'' of ICP measurement in humans⁸. This method involves the partial removal of skull and the instrumentation of the catheter through brain tissue. Consequently, intraventricular catheters have an infection rate of 6-11%⁹. For this reason, subdural and epidural cannulations have become the preferred methods in animal models of ischemic injury. Various ICP measurement techniques have been adapted for animal models, and of these, fluid-filled telemetry catheters¹⁰ and solid state catheters are the most frequently used^{11,12,13,14,15}. The fluid-filled systems are prone to developing air bubbles in the line, resulting in false ICP readings. Solid state probes avoid this problem (Figure 1). An additional problem is fitting catheters under the skull or into the ventricles without causing any brain injury that might alter the experimental outcomes. Therefore, we have developed a method that places an ICP catheter contiguous with the epidural space, but avoids the need to insert it between skull and brain. An optic fibre pressure catheter (420LP, SAMBA Sensors, Sweden) was used to measure ICP at the epidural location because the location of the pressure sensor (at the very tip of the catheter) was found to produce a high fidelity ICP signal in this model. There are other manufacturers of similar optic fibre technologies¹³ that may be used with our methodology. Alternative solid state catheters, which have the pressure sensor located at the side of the catheter tip, would not be appropriate for this model as the signal would be dampened by the presence of the monitoring screw. Here, we present a relatively simple and accurate method to measure ICP. This method can be used across a wide range of ICP related animal models.     

Quantitative T2 mapping for detection and quantification of thrombophlebitis in a rabbit model

Short peripheral catheter thrombophlebitis (SPCT), a sterile inflammation of the vein wall, is the most common complication associated with short peripheral catheters (SPCs) and affects up to 80% of hospitalized patients receiving IV therapy. Extensive research efforts have been devoted for improvement and optimization of the catheter material, but means for examination of any novel design are limited, inaccurate and require costly comprehensive pre-clinical and clinical trials. Therefore, there is a conclusive need for a reliable quantitative method for evaluation of SPCT, in particular for research purposes examining the thrombophlebitis-related symptoms of any novel catheter design. In this study, we developed for the first time a quantitative MRI based tool for evaluation of SPCT. The extent and severity of SPCT caused by two different commercially available SPCs with known predisposition for thrombophlebitis, were studied in a rabbit model. MRI analysis was consistent with the standardized pathology evaluation and showed remarkable difference in the percent of edema between the experimental groups. These differences were in line with previous studies and provide evidence that this type of analysis may be useful for future assessment of SPCT in vivo. As a non-invasive method, it may constitute a cost effective solution for examination of new catheters and other medical devices, thereby reducing the need for animal sacrifice.     

Catheter related bacteremia in rats: A preliminary report on the effect of methylene blue coated catheter

The safety and efficacy of methylene blue (MB) coated indwelling jugular vein/cranial vena cava catheter made up of polyurethane material was tested in a rat model, receiving bacterial culture suspension of Pseudomonas aeruginosa, and Staphylococcus aureus. Daily blood samples were collected from the catheter and peripheral vein for bacterial culture. The clinical parameters (rectal temperature, respiratory rate, total white blood cell count, and loss in body weight) were not different between the groups. All the rats became bacteremic with similar changes in the number of colony forming units in the catheter and peripheral samples. Histopathological lesions were not different between the groups. The findings suggest that rats receiving MB coated catheters behaved similar to non-coated catheters. Based on the results it can be concluded that for this type of gross contamination, catheter coating alone may not eliminate infection/bacteremia.     

A self-powered constant infusion device for use in unrestrained rats

We developed a device that delivers fluid through a catheter at a constant rate and can be used in conscious animals to solve a variety of problems. For example, this device can be used for delivering drugs and maintaining intravascular catheter patency. The device provides infusions at low flows (1.0-1.5 ml/day), so that experimental agents may be administered with minimal volume loading of the rat. Arterial and venous catheter patency is maintained by infusion of heparinized saline through indwelling catheters attached to the device. The catheters exit from the rat in the intrascapular area and are routed through a protective spring to the device, which is suspended above the cage. The catheters may be attached to pressure transducers, blood may be sampled, and injections or infusions may be made without disturbing the rat. Because the device is self-contained, it can be suspended by a fluid-free swivel that rotates through 360 degrees, providing minimal restraint. The device has been used successfully to measure arterial and central venous blood pressures in two studies using rats.     

The problem of catheter encrustation

Catheter encrustation was studied in a group of long-stay hospital patients using both latex and silicone catheters. Moisture accounted for 80% by weight of the encrusted material with both catheters. Of the dry weight 90% was composed of protein, calcium, phosphorus, magnesium and uric acid. No relationship was found between the amounts of these substances in the urine and in the encrusted material. High levels of calcium, phosphorus and magnesium were found in the encrusted material from patients infected with Proteus organisms. No direct relationship was found between the duration of catheter drainage and the degree of encrustation, and there was a variation in patient susceptibility to encrustation irrespective of the catheter material. There was significantly less encrustation associated with silicone catheters.     

Mouse models of short- and long-term foreign body in the urinary bladder: analogies to the bladder segment of urinary catheters.

Catheter-associated bacteriuria is the most common infection occurring in hospitals, where urethral catheters are generally in place for a few days, and in nursing homes, where catheters may be in place for months or years. We developed murine models with intrabladder urinary catheters for studying complications of bacteriuria in short- and long-term catheterization. In the short-term model, a catheter segment was inserted transurethrally and lay free within the bladder lumen. Half of the animals expelled segments during a 2-to-7-day period, durations similar to catheterizations in hospitalized patients. For studies of long-term catheter use, the catheter segment was secured within the bladder by a single suture for up to 12 months. Antibiotics administered for 7 days after catheter placement and housing mice in cages with wire screen floors reduced spontaneous bacteriuria to an acceptably low incidence rate of only 7%. Proteus mirabilis bacteriuria of high concentration provoked the same complications that are common in patients with long-term catheters: acute pyelonephritis, chronic renal inflammation, and struvite stone formation. These models allow inoculation of the bacteria of interest and are suitable for studies of short- and long-term foreign body-associated bacteriuria and its complications.     

Femoral Arterial and Venous Catheterization for Blood Sampling,Drug Administration and Conscious Blood Pressure and Heart Rate Measurements

In multiple fields of study, access to the circulatory system in laboratory studies is necessary. Pharmacological studies in rats using chronically implanted catheters permit a researcher to effectively and humanely administer substances, perform repeated blood sampling and assists in conscious direct measurements of blood pressure and heart rate. Once the catheter is implanted long-term sampling is possible. Patency and catheter life depends on multiple factors including the lock solution used, flushing regimen and catheter material. This video will demonstrate the methodology of femoral artery and venous catheterization of the rat. In addition the video will demonstrate the use of the femoral venous and arterial catheters for blood sampling, drug administration and use of the arterial catheter in taking measurements of blood pressure and heart rate in a conscious freely-moving rat. A tether and harness attached to a swivel system will allow the animal to be housed and have samples taken by the researcher with minimal disruption to the animal. To maintain patency of the catheter, careful daily maintenance of the catheter is required using lock solution (100 U/ml heparinized saline), machine-ground blunt tip syringe needles and the use of syringe filters to minimize potential contamination. With careful aseptic surgical techniques, proper catheter materials and careful catheter maintenance techniques, it is possible to sustain patent catheters and healthy animals for long periods of time (several weeks).     

In vivo quantitative assessment of catheter patency in rats

Formation of fibrin sleeves around catheter tips is a central factor in catheter failure during chronic implantation, and such tissue growth can occur despite administration of anticoagulants. We developed a novel method for monitoring catheter patency. This method recognizes the progressive nature of catheter occlusion, and tracks this process over time through measurement of changes in catheter resistance to a standardized 1 mL bolus infusion from a pressurized reservoir. Two indirect measures of catheter patency were used: (a) reservoir residual pressure and (b) reservoir discharge time. This method was applied to the study of catheter patency in rats comparing the effect of catheter material (silastic, polyurethane, Microrenathanetrade mark), lock solution (heparin, heparin/dexamethasone) and two different cannulation sites (superior vena cava via the external jugular vein, inferior vena cava via the femoral vein). Our findings reveal that application of flexible smaller-size silastic catheters and a dexamethasone lock solution resulted in prolonged catheter patency. Patency could be maintained over nine weeks with the femoral vein catheters, compared with five weeks with the external jugular vein catheters. The current method for measuring catheter patency provides a useful index for the assessment of tissue growth around the catheter tip. The method also provides an objective and quantitative way of comparing changes in catheter patency for different surgical methods and catheter types. Our method improves on the conventional method of assessing catheter occlusion by judging the ability to aspirate from the catheter.     

A long-term porcine model for measurement of gastrointestinal motility

Animal models have become an essential tool in the investigations of gut motility under experimental conditions. To determine the influence of various anaesthetic drugs on the motility pattern of the gastroduodenal tract, a new long-term model has had to be developed for allowing measurements in conscious and unrestrained as well as in sedated and analgosedated pigs. Since mechanical ventilation influences gut motility, it was necessary that this animal model enabled the investigation of the effect of drugs causing sedation and analgosedation during spontaneous breathing. Seven male, castrated pigs, German landrace, 32-40 kg bodyweight (BW) were investigated in this study. After habituation of the pigs to local housing conditions over 5 days, the animals were trained over 4 days to prepare for experimental situations and investigators. Pigs were inserted with a central venous catheter and with percutaneous enterogastrostomy (PEG) under general anaesthesia. Intestinal motility was measured by intraluminal impedancometry. The catheter was introduced over the PEG into the stomach and positioned into the duodenum by duodenoscopy. Measurements were done in conscious, unrestrained pigs and with sedated, and analgosedated animals on subsequent days. The habituation and training of the pigs to the investigators and for the laboratory conditions took between 7 and 9 days. The initial anaesthesia protocol for the instrumentation using remifentanil/propofol led to pyloric spasm and was thus unsuitable for duodenal intubation with an endoscope. In contrast, a combination of ketamine/propofol enabled this procedure. It was practicable to measure gut motility in conscious, unrestrained pigs. Spontaneous breathing was sufficient under propofol sedation and analgosedation using fentanyl-propofol. Systematically local application of polividon iodine in the area of the subcutaneous catheters avoided the necessity of using systemic prophylactic antibiotics. In conclusion, the habituation and training for 9 days enabled the measurement of gut motility by intraluminal impedancometry in conscious pigs. The insertion of the catheter was done during general anaesthesia using a combination of propofol and ketamine. For the future determination of gut motility performed under general anaesthesia, each sedation and analgosedation concept has to be evaluated to see whether it allows spontaneous breathing or whether mechanical ventilation is necessary.     

Chronic vascular catheters in growing piglets

Chronic vascular catheterization of growing piglets is problematic because the animals grow rapidly and disrupt each others catheters when housed together. We successfully maintained chronic arterial and venous catheters in growing piglets for the first two months of life using the Vascular-Access-Port, a totally implantable catheter system. Two Vascular-Access-Ports (one venous and one arterial) were surgically placed in each of ten, 3-7 days-old piglets. Nine piglets survived the perioperative period, and for eight piglets the ports were successfully used for experimental purposes to infuse drugs, monitor arterial blood pressure and obtain blood samples for approximately two months. During this period the piglets averaged an eight-fold increase in body weight. This technique of chronic vascular catheterization is useful for experiments employing conscious, growing animals.     

Catheter position and blood gases during constant-flow ventilation

We studied the effect of catheter position and flow rate on gas exchange during constant-flow ventilation (CFV) in eight anesthetized, paralyzed dogs. The distal tips of the insufflation catheters were positioned 0.5, 2.0, 3.5, and 5.0 cm from the tracheal carina. Flow rates were varied between 10 and 55 l/min and steady-state arterial blood gases were measured. At a given flow rate, arterial CO2 pressure (PaCO2) decreased as CFV was administered further into the lung up to a distance of 3.5 cm from the carina; there were no significant differences in PaCO2 at 3.5 and 5.0 cm. For a given catheter position, PaCO2 decreased with increasing flow rate up to a flow rate of 40 l/min. Further increases in flow rate had no significant effect on PaCO2. Arterial O2 pressure (PaO2) was relatively constant at all flow rates and catheter positions. We conclude that, up to a point, CO2 elimination can be improved by positioning the catheters further into the lung; advancing the catheters further than 3.5 cm from the carina may cause over-ventilation of specific lung regions resulting in a relative plateau in CO2 elimination and relatively constant PaO2's. Positioning the catheters further into the lung permits the use of lower flow rates, thus potentially minimizing the risk of barotrauma.     

Modified procedure for implantation of subcutaneous central venous access devices in macaques (Macaca mulatta)

A nonhuman primate model comprising adult male rhesus monkeys (Macaca mulatta) with chronically indwelling subcutaneous central venous access devices provides a unique opportunity to determine plasma pharmacokinetics of new drugs such as anticancer and anti- retroviral agents. The central venous access we use is a low-profile, single-septum, titanium port that is attached to a radiopaque, indwelling catheter; the catheter is implanted in an internal jugular vein. A common complication following placement of the venous access device was migration of the catheter tip. We therefore modified the standard procedure by cutting the silicone catheter and introducing the rigid connector to secure the catheter to the vessel at the insertion site (approximately 9 to 13 cm from the distal end of the catheter). Prior to the use of the connector, three of five catheters migrated within 4 weeks after placement. In contrast, all 13 internal jugular catheters with connectors have remained patent without migration of the catheter tip. Therefore, incorporation of the catheter connector appears to have eliminated the problem of catheter migration.     

Catheter-tract infections in rhesus macaques (Macaca mulatta) with indwelling intravenous catheters

Development of catheter-tract infections in experimental animals can have devastating consequences on animal health and the functional lifespan of surgical implants. To measure the incidence of catheter-tract infections in animals with exteriorized intravenous catheters in this facility and assess the effects of these infections on mean catheter lifespan, health records of 31 Macaca mulatta with catheters were reviewed. Records spanned the interval of January 1, 1996 through October 1, 1997. Catheter-tract infections in 16 of 53 (30.2%) monkeys with catheters were diagnosed based on a combination of clinical signs of infection and results of bacterial culture. Segmental catheter-tract infections reduced mean catheter lifespan to 147 days, compared with 354 days for uninfected catheters. Exit-wound, local tunnel, and surgical-site infections did not significantly reduce catheter lifespan. Bacterial culture reports documented 31 isolates; 41.9% (13 of 31) were coagulase-negative staphylococci, and 22.6% (7 of 31) were Staphylococcus aureus. Of 20 isolates tested, 15 (75%) were resistant to methicillin/oxacillin in vitro. Antimicrobial susceptibility testing of methicillin-resistant and methicillin-susceptible isolates indicated that, compared with methicillin-sensitive isolates, methicillin-resistant isolates had a pattern of multiple antibiotic resistance. Catheter-tract infections were common in this colony of rhesus macaques, and clinically severe infections caused a drastic reduction in catheter lifespan. Approximately half (48%) the bacterial isolates were methicillin-resistant gram-positive bacteria.