Alison C. Smith

Swine as Models in Experimental Surgery

The use of swine in surgical research has undergone a dramatic increase in recent years, due to decreasing availability of dogs as surgical models and a renewed interest in the porcine model based on anatomic and physiologic characteristics. This article reviews the issues involved in selection of swine as experimental surgical subjects including procurement considerations, anesthetic selection, housing methods, and anatomic and physiologic characteristics.

Relationship of bioimpedance to thermodilution and echocardiographic measurements of cardiac function

Bioimpedance cardiography has been suggested as a noninvasive means to monitor cardiac function. However, this method has not been compared to more conventional techniques such as echocardiography. This study compared simultaneously obtained thermodilution cardiac output and right ventricular ejection fraction (RVEF), and echocardiographic left ventricular fractional shortening (LVFS), to bioimpedance cardiac output and the maximum first derivative of the bioimpedance signal (dZ/dtmax) during positive inotropic stimulation and preload reduction. Eight pigs were instrumented with a rapid response thermistor (positioned in the pulmonary artery) and bioimpedance electrodes. Simultaneous thermodilution, echocardiographic, and bioimpedance measurements were performed at baseline and after 5,10, and 15 min of isoproterenol infusion (0.5 μg/kg.min). In six pigs, measurements were also performed after balloon occlusion of the inferior vena cava. A significant correlation was observed between LVFS and dZ/dtmax (r = .88, n = 35) over all time points. Thermodilution and bioimpedance cardiac output were in close agreement (r = .92, n = 35). However, bioimpedance overestimated cardiac output in the very low and high output states. The mean difference between thermodilution and bioimpedance cardiac outputs was — 0.02 ± 0.37 L/min. There was a positive relationship between RVEF and dZ/dtmax (r = .54, n = 35). In summary, bioimpedance was significantly correlated with thermodilution cardiac output over a wide hemodynamic range. The peak first derivative of the bioimpedance signal dZ/dtmax may provide a noninvasive index of ventricular pump performance. Further studies are required to evaluate the diagnostic value of bioimpedance cardiography in the clinical setting. (Crit Care Med 1990; 18:414)

Anesthesia and Analgesia in Swine

Publisher Summary Swine are prone to vasospasm and many of the peripheral vessels are not readily visualized, which may make vascular access difficult for inexperienced personnel. Swine are also highly susceptible to ventricular arrhythmias, have fragile pulmonary tissue that may be damaged by overinflation with mechanical respirators, and have a left hemiazygous vein that drains the intercostal vessels into the coronary sinus. The semimembranous and semitendinosus muscles of the caudal thigh as well as the gluteal muscles of the cranial thigh are both acceptable sites for giving large volume IM injections. The muscle mass of the dorsolateral neck region is a good site for small volume injections. Subcutaneous injections may be given in the neck or in the flank. The pig is a fixed-skin animal, like humans, and does not have a SC region as large or accessible as other animal species. Consequently, large volume SC injections are not as easily delivered. The peripheral blood vessels are not easily visualized in most pigs. The ear veins are the most common site for IV injections. The veins are located on the lateral and medial dorsal ear margins and the artery is central. If combination injections are being used, administration of the tranquilizer/sedative portion may help reduce the stress.

Chronic Cannulation and Fistulization Procedures in Swine: A Review and Recommendations

Swine are important animal models in biomedical research. Some experimental procedures may require chronic access to blood vessels, organs, and structures. Chronic access procedures may be utilized for collection of blood and body fluids as well as for the infusion of test substances. This manuscript reviews methodologies that have been reported to be effective for these procedures. It also makes recommendations on the maintenance of indwelling catheters, cannulas, and fistulas.

Best Practices for Performing Experimental Surgery in Swine

ABSTRACT The authors have extensive experience in surgery, anesthesia, and perioperative care in both miniature and domestic swine in the research setting. This manuscript describes the techniques that have been developed over the last four decades while developing porcine surgical models and their use in translational research. Swine are conditioned and socialized during a seven-day period prior to entering into a survival surgical protocol. Housing is designed to be nonstressful and accommodate the needs of the species. Induction of anesthesia is generally performed in the animals pen. Injectable agents are administered sc in the neck using a butterfly catheter technique. The anesthetic protocol is designed to consider the physiologic effects of the agents and their potential effects on the research being performed. Complete aseptic technique is performed and includes final application of adhesive iodine impregnated drapes over the surgical site. Preemptive analgesia is performed using parenteral analgesics, local anesthetics, and/or epidural analgesics. Animals are monitored intensively intraoperatively and during the postoperative period with frequent recordings of physiologic parameters. Observation during the postoperative period is continuous until the animal fully recovers the righting reflex. Observations of the animals in the postoperative period are performed at least daily until surgical incisions are healed. In protocols which create defects or impede physiologic function daily monitoring may have to be performed in conjunction with specific therapies or tests throughout the duration of the protocol.

Technical aspects of cardiac catheterization of swine.

Long-term cardiovascular studies requiring repeated cardiac catheterizations often pose technical problems for investigator using swine. The purpose of this paper is to describe two reliable methods of cardiac catheterization that are used in swine to acquire complete hemodynamic data. Due to the depth of the vessels, vascular cut-downs are usually required. Hemodynamic, angiographic, and interventional cardiac catheters are introduced into either the femoral vessels or the external jugular vein and internal carotid artery. An alternative technique that obviates the need for multiple surgeries involves implantation of silastic catheters into both atria. This allows the passage of catheters directly into the heart chambers. A disadvantage of repeated vascular cut-downs is that a reduction of vascular access occurs. Chronic lines require careful attention to prevent infection and maintain patency.

Swine in Biomedical Research

This chapter provides an overview of the use of domestic and miniature breeds of swine in biomedical research. Differences between breeds of pigs and the most significant anatomic and physiological characteristics of the species related to their selection as biomedical research models are discussed. Husbandry and handling techniques that have proven to be beneficial for using these animals in research are detailed. Also included are the key references for developing and using swine and resources for additional training and refinement are listed.

A Technique for Conducting Noninvasive Cardiac Electrophysiology Studies in Conscious Swine

A noninvasive method was developed in swine for conducting cardiac electrophysiology (EP) studies without the potential confounding effects of sedatives or anesthetics. Following a 1-week conditioning regimen in the EP laboratory, 1-month-old Hanford miniature swine underwent transvenous pacemaker (PM) implantation under isoflurane anesthesia. Two bipolar screw-in pacing leads were inserted into the left external jugular vein, with one positioned in the right atrial appendage and one in the myocardium at the right ventricular apex. The leads were attached to a multiprogrammable pulse generator, and the pacing system was placed in a subcutaneous pocket. At weekly intervals following implantation, conscious, unsedated swine were remained in a sling for noninvasive programmed stimulation (NIPS) using a programmable telemetry system. A NIPS protocol to induce arrhythmias was performed separately for the atrium and ventricle. Data for this model are reported. Complications occurred in 6 of 26 animals studied and included one infection of the PM pocket, three cases of dislodgement of the atrial lead, and rotation of the generator within the pocket in two animals, preventing communication with the PM. This technique has been used to perform EP studies successfully in swine and has been utilized in a variety of studies of the cardiac conduction system.

Pregnant Yucatan Miniature Swine as a Model for Investigating Fetal Drug Therapy

Initially it was felt that during maternal drug therapy the placenta served as a protective barrier preventing fetal exposure. This concept was invalidated as a result of the thalidomide tragedy in the early 1960s. Maternal thalidomide use in the first trimester of pregnancy resulted in approximately 7,000 limb anomalies, with or without gastrointestinal or cardiac malformations.1 As a result of this disaster, research was focused on toxicologic and teratogenic effects of drugs on the fetus. Despite 3 decades of research, approximately 20 drugs and chemicals, e.g., isotretinoin, valproic acid, phenytoin, polychlorinated biphenyls, have been confirmed to be teratogenic. Most drugs, when used appropriately, do not pose a threat to the fetus.2 In the 1970s, therapeutic benefits started to be recognized in the pharmacologic management of fetal disorders. The discovery inspiring research in this area was the observation that maternal beclomethasone administration enhanced fetal lung maturity decreasing the incidence of neonatal respiratory distress syndrome.3 Considerable data have accumulated to indicate that nearly all maternally administered drugs enter the fetal circulation and may exert pharmacologic effects on the fetus. These observations have led to the increasing use of the maternal route of drug administration to manage the compromised fetus. Pharmacologic management has extended into the treatment of fetal arrhythmias4, toxoplasmosis5, congenital adrenal hyperplasia6 and preventing vertical transmission of HIV during pregnancy.7 We will discuss factors that influence the kinetics of drug transfer to the fetus, pharmacologic management of fetal tachyarrhythmias and the application of pregnant Yucatan miniature swine as a model for investigating fetal antiarrhythmic drug therapy.

An Adult Canine Model of Progressive Left Ventricular Pressure Overload

This article details the development of a model of progressive left ventricular pressure overload (LVPO) in the adult dog. LVPO was induced by banding the proximal ascending aorta in 69 adult conditioned dogs. The base of the aorta was exposed through a right thoracotomy. A tunnel was created by blunt dissection between the aorta and pulmonary arteries. An aortic band was constructed by passing umbilical tapes through the lumen of gortex tubing. This band was placed through the tunnel, then tied around a balloon dilatation catheter. The distal end of the balloon catheter was closed with an injection cap and positioned in a subcutaneous pocket. Aortic stenosis was induced by filling the balloon catheter with saline. A predetermined amount of LVPO was created by adjusting the amount of aortic stenosis. At 2, 4, and 6 weeks after aortic banding the LVPO was increased by transcutaneous injection of saline into the balloon catheter. At 8 weeks the dogs were evaluated for sufficiently decreased cardiac contractility and used acutely in one of several studies. The article also discusses perioperative management, postoperative care, and complications that were encountered during the development of the model. Postoperative pain was managed by the combined use of preemptive and postoperative opioids, local nerve blocks, and nonsteroidal anti-inflammatory drugs. Notable intraoperative complications included atrial and ventricular arrhythmias and pulmonary artery laceration during the banding procedure. The most significant postoperative complications were aortic ruptures and congestive heart failure. The success rate of this model has increased from 20% (year 1) to 65% (year 3). This success has been attributed to improvements in band design, surgical technique, and postoperative management.