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Biomedical subjects

M M Swindle

Publications and source records attributed to M M Swindle.

At least 37 records · Page 2Linked to original sources
PubMed1993

Prophylactic treatment of swine with bretylium for experimental cardiac catheterization.

We evaluated a cryothermic ablation catheter for potential use in treating supraventricular tachycardia by cardiac catheterization in miniature swine. Cardiac catheterization was performed on anesthetized miniature swine by using multiple catheters that were inserted bilaterally by either percutaneous or cutdown techniques into the femoral veins. We performed electrophysiologic tests according to standard atrial and ventricular electrical stimulation protocols. Manipulation of catheters in the tricuspid valve area and right ventricle was an essential part of the study. During an initial study of five swine, catheter manipulation produced sustained and nonsustained ventricular tachycardia and ventricular fibrillation. To prevent arrhythmias, bretylium (5 mg/kg) was administered intravenously 10 minutes before catheter manipulation and repeated every 30 minutes throughout the procedure. Since the use of bretylium was instituted, there have been no cases of ventricular fibrillation in a series of 20 animals. We determined that bretylium is effective in the suppression of ventricular arrhythmias in swine undergoing cardiac catheterization.

Animals↗
PubMed1992

Effects of isoflurane anesthesia on glucose tolerance and insulin secretion in Yucatan minipigs.

Isoflurane's effect on intravenous glucose tolerance and insulin secretion was studied in six Yucatan minipigs. Unanesthetized animals, with previously placed indwelling venous catheters, were tested while resting comfortably in slings. The same animals were then retested during isoflurane anesthesia. Serum glucose and insulin concentrations were measured at predetermined times in response to an intravenous bolus of dextrose. The glucose disappearance rate (k), baseline plasma insulin concentration, the area under the insulin response curve, and the insulinogenic index were significantly lower in the anesthetized animals than in controls. The results of this study indicate that anesthesia with isoflurane significantly alters the glucose/insulin response to an intravenous glucose tolerance test and, therefore, is unsuitable for studies when glucose tolerance is to be assessed.

Anesthesia, Inhalation↗
PubMed1991

Ventricular septal defects in a family of Yucatan miniature pigs.

We have studied the hearts from a colony of Yucatan miniature pigs with spontaneously occurring congenital defects. Ventricular septal defect was encountered in 57 of 81 neonates from 15 consecutive litters. Of 73 hearts preserved for morphological assessment, 52 were found to have defects within the ventricular septum remarkably similar to those observed in humans with deficient ventricular septum. The defects, including 3 which had closed spontaneously, were perimembranous in 34, muscular in 12 and doubly committed and juxtaarterial in 6 hearts. Atrial septal defects were found in 12 of the 52 hearts with deficient ventricular septation; only 1 atrial septal defect was seen among 21 hearts with an intact ventricular septum. Anomalies of the aortic arch were associated with ventricular septal defect in 2 cases; 1 with a solitary arterial trunk and one with hypoplasia of the aorta and patent arterial duct. All these findings are replicated in human hearts. This strain of pig provides an ideal large animal model for morphologic and genetic investigations concerning the details of ventricular septation, including potential mechanisms of late spontaneous closure.

Animals↗
PubMed1991

Transvenous cryoablation of the bundle of His.

Cardiac dysrhythmias are a prominent cause of morbidity and mortality. Pharmacological treatment is ineffective in a large number of patients and is associated with many serious side effects. Thus, direct treatment of cardiac arrhythmias has been used with increasing frequency. Each form of direct treatment, such as surgical ablation, DC catheter ablation, radiofrequency catheter ablation, laser catheter ablation suffer serious drawbacks. Thus, we investigated the utility of transvenous catheter cryoablation of the bundle of His in five miniature swine, 40-60 lbs. in weight. Complete atrioventricular block was produced in each animal during cryothermia and persisted for 1 hour of observation in four out of five swine. In the fifth animal, 2:1 atrioventricular block within the atrioventricular node persisted for 1 hour of observation. Morphological and histologic examination revealed no dysfunction of capillaries and myofibriles in the atrioventricular node and proximal bundle of His. This potential mode of transcatheter therapy deserves further investigation.

Animals↗
PubMed1991

Depressed contractile function due to canine mitral regurgitation improves after correction of the volume overload.

It is known that long-standing volume overload on the left ventricle due to mitral regurgitation eventually leads to contractile dysfunction. However, it is unknown whether or not correction of the volume overload can lead to recovery of contractility. In this study we tested the hypothesis that depressed contractile function due to volume overload in mitral regurgitation could return toward normal after mitral valve replacement. Using a canine model of mitral regurgitation which is known to produce contractile dysfunction, we examined contractile function longitudinally in seven dogs at baseline, after 3 mo of mitral regurgitation, 1 mo after mitral valve replacement, and 3 mo after mitral valve replacement. After 3 mo of mitral regurgitation (regurgitant fraction 0.62 +/- 0.04), end-diastolic volume had nearly doubled from 68 +/- 6.8 to 123 +/- 12.1 ml (P less than 0.05). All five indices of contractile function which we examined were depressed. For instance, maximum fiber elastance (EmaxF) obtained by assessment of time-varying elastance decreased from 5.95 +/- 0.71 to 2.25 +/- 0.18 (P less than 0.05). The end-systolic stiffness constant (k) was also depressed from 4.2 +/- 0.4 to 2.1 +/- 0.3. 3 mo after mitral valve replacement all indexes of contractile function had returned to or toward normal (e.g., EmaxF 3.65 +/- 0.21 and k 4.2 +/- 0.3). We conclude that previously depressed contractile function due to volume overload can improve after correction of the overload.

Animals↗
PubMed1991

Anesthetic and postoperative protocols for a canine model of reversible left ventricular volume overload.

The purpose of this study was to develop anesthetic and postoperative methods that could be used in a canine model of reversible left ventricular volume overload (LVVO). LVVO was created by inducing mitral regurgitation (MR) in adult conditioned dogs. Using fluoroscopy, MR was induced by passing urologic grasping forceps into the left ventricle through a carotid artery and rupturing one or more chordae tendinea. Cardiac catheterization was performed after significant cardiac dysfunction developed (3 months after creation of MR) in order to collect data to confirm reduced contractile function. The MR was repaired by replacing the damaged valve with a bovine pericardial xenograft. Dogs were followed with sequential cardiac catheterizations to determine if the valvular replacement reversed the cardiac dysfunction. To develop this model, unique anesthetic and post-operative care protocols had to be instituted. In order not to exacerbate the existing cardiac dysfunction, a high dose narcotic anesthetic regimen using a sufentanil infusion at 9-13 microgram/kg h-1 was developed in association with cardiopulmonary bypass and hypothermia for the mitral valve replacement surgery. Intensive postoperative care protocols that involved major personnel and pharmaceutic interventions were necessary. Using our methods 11/17 dogs survived the procedure and were included in the protocol for study of mechanisms involved in reversal of cardiac dysfunction.

Anesthesia↗
PubMed1991

Sedative and cardiovascular effects of midazolam in swine.

The ability to reliably produce sedation in swine is hampered by the paucity of agents available. This project examined the use of a new water soluble benzodiazepine, midazolam, as a sedative in swine. Echocardiographic studies were performed on thirty 23 to 30 kg Yorkshire swine before and 20 minutes after each animal received a single intramuscular dose of 100 micrograms/kg midazolam. Heart rate and respiratory rate decreased significantly compared to nonsedated values (93 +/- 7 versus 117 +/- 2 bpm and 10 +/- 1 versus 20 +/- 1 breaths/min, respectively [p less than 0.05]). However, there was no effect on left ventricular fractional shortening (29.9 greater than 0.05 versus 29.5 +/- 0.05% [p greater than 0.05]). An additional five pigs were instrumented for a dose response study in order to collect hemodynamic data and blood gas values at baseline, and 15 min after the intravenous administration of incremental doses of midazolam (100 to 1,000 micrograms/kg). Despite a significant decrease in heart rate and respiratory rate, cardiac output, blood gases, and pH remained within normal ranges at all dosage levels. Both routes of administration produced sedation for 20 min in all animals. Midazolam is an effective swine sedative that is associated with stable cardiac function.

Animals↗
PubMed1990

The programmable implantable medication system (PIMS): design features and pre-clinical trials.

This report describes the clinically significant design features of a variable rate implantable insulin infusion pump, the Programmable Implantable Medication System (PIMS), and its function in pre-clinical trials. PIMS has a number of unique features, including a solenoid, pulsatile pump design requiring minimal power (less than 15 microwatts) and a less-than-atmospheric pressure reservoir. Two-way communication is accomplished by radiotelemetry. The implanted device stores programs, and records its own hourly history of insulin delivery. Limits are set on total insulin delivery over time. Basal rates are adjustable, and patterned prandial insulin delivery curves can be programmed. Initial trials (3.1 dog-years) identified four problems which were corrected prior to final pre-clinical trials: microcracks in the diaphragm, a valve-seating leak, electronic failure of prototype microchips, and insulin aggregation. Sixteen dog-years of final pre-clinical trials with a single system design demonstrated that 5 pumps were still working continuously after up to 3.75 years (mean 3.3 years) without mechanical or electronic pump failure. The longest interval between reservoir refills was 5 months. Remaining potential causes of flow stoppage, however, include blockage of the peritoneal catheter by omentum (which occurred once), and air lock (which occurred two times).

Animals↗
PubMed1990

Cardiac function and morphology of Hanford miniature swine and Yucatan miniature and micro swine.

The use of miniature swine in biomedical research is increasing; however, a comparison of cardiac function and morphology between strains has yet to be characterized. The purpose of this project was to examine comprehensive hemodynamics and cardiac morphology of three groups of ten normal, 4 months old, age-matched Yucatan miniature (MINI) pigs, Yucatan micropigs (MICRO) and Hanford (HAN) miniature pigs, 5 males and five females per group. Closed chest cardiac catheterization under equivalent conditions was performed followed by post mortem cardiac morphometry. Mean arterial pressure was significantly greater in the Hanford group when compared to both the minipig and micropig pigs (HAN: 89 +/- 4; MINI: 48 +/- 3; MICRO: 53 +/- 2 mmHg). Pulmonary vascular resistance was significantly different between the three groups (HAN: 9 +/- 1; MINI: 60 +/- 12; MICRO: 111 +/- 29 dyne x sec/cm x m2). The Hanford strain had a significantly smaller heart weight to body weight ratio than the other two groups (HAN: 4.6 +/- 1.0; MINI: 5.7 +/- 0.1; MICRO: 5.5 +/- 1.0). Variations in cardiovascular parameters occur among these strains and should be considered when constructing experimental designs.

Animals↗
PubMed1990

Heritable ventricular septal defect in Yucatan miniature swine.

A heritable ventricular septal defect (VSD) was found in a strain of Yucatan miniature swine. The defect was determined to be a high membranous VSD analogous in anatomic location to the most common from of VSD in humans. Eighteen animals were studied clinically, hemodynamically and at necropsy to characterize the defect. Three mature animals developed pulmonary hypertension. Three animals were found to have a patent foramen ovale (PFO) in addition to the VSD. VSD is heritable probably due to polygenic factors. VSD in Yucatan miniature swine may be a suitable model of the human disease syndrome.

Animals↗
PubMed1989

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.

Animals↗
PubMed1988

Mechanism of decreased forward stroke volume in children and swine with ventricular septal defect and failure to thrive.

Children with ventricular septal defect (VSD) often demonstrate failure to thrive (FTT). Such patients usually have reduced systemic cardiac output which has been postulated as a cause for their growth retardation. This study was conducted to ascertain the mechanism of the reduced cardiac output in children with VSD and FTT and also in a porcine model of VSD. Forward stroke volume was reduced in VSD-FTT children, 31 +/- 8 ml/m2, compared to normal children, 49 +/- 15 ml/m2 (P less than 0.05), but was not reduced in children with VSD and normal growth and development (41 +/- 16 ml/m2). Forward stroke volume was also reduced in swine with VSD compared to controls. Contractility assessed by mean velocity of circumferential shortening (Vcf) corrected for afterload was similar in normals and VSD-FTT children. Contractile performance was also similar in normal and VSD swine. Afterload assessed as systolic stress was similar in FTT-VSD children and normal subjects. Preload assessed as end-diastolic stress was increased in the VSD-FTT group. End-diastolic volume was not larger in the VSD-FTT group. We conclude that the reduced stroke volume seen in VSD-FTT children and VSD-swine was not due to reduced contractility, increased afterload or reduced preload. The reduced stroke volume may have been due to failure of end-diastolic volume to increase adequately.

Animals↗
PubMed1988

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.

Anesthesia↗
PubMed1988

Bretylium and diltiazem in porcine cardiac procedures.

The use of miniature swine as a model for cardiovascular diseases of humans is becoming more popular for many reasons. One of the problems involved in using swine is their propensity for fatal cardiac arrhythmias during surgical procedures requiring general anesthetics, especially cardiac procedures. In preparation for use as a model of human atherosclerotic coronary artery disease, 30 three-month-old (15 kg) Hanford miniature swine underwent left heart catheterization, coronary angiography, and abrasion of the left anterior descending coronary artery. All pigs were treated with diltiazem HCl 30-60 mg (2-4 mg/kg) three times daily and aspirin 25 mg once daily, both given orally for three days before surgery. General anesthesia was induced with a combination of ketamine HCl 25 mg/kg, atropine sulfate 0.1 mg/kg, and acepromazine 0.22 mg/kg, all given intramuscularly. Halothane 1-2% and nitrous oxide 30% were used to maintain general anesthesia after endotracheal intubation. After successful cannulation of the femoral artery, all animals were given 200 units/kg heparin and 5 mg/kg bretylium tosylate intravenously. The electrocardiogram and mean blood pressure were monitored throughout the procedure. No significant change in blood pressure was noted during the procedure. Intracoronary nitroglycerin 200 micrograms was administered prior to abrasion of the left anterior descending with a 2.0-mm angioplasty balloon. The pigs were allowed to recover after routine closure of the incision. One pig (1/30) died during the abrasion procedure as a result of ventricular fibrillation. This represents a low, acceptable mortality using the present regimen compared with other regimens.

Animals↗
PubMed1988

Pancreatectomized swine as a model of diabetes mellitus.

The development of a model of diabetes mellitus using swine offers the potential for new investigations in the study of human diabetic complications. In particular, animal models for the study of accelerated atherosclerosis associated with diabetes are important and presently lacking. Swine were selected because they have a natural susceptibility to atherosclerosis and have plasma lipoprotein patterns which are close to those of humans. Diabetes mellitus was induced in nine miniature swine by total pancreatectomy. Following surgery, they were maintained on porcine derived insulin at doses predicated on blood glucose levels. Pancreatic enzymes were replaced by dietary supplementation. Eight of the nine pigs were pancreatectomized successfully and stabilized with insulin. After initial weight loss, the pancreatectomized pigs maintained growth rates comparable to controls. Hypoglycemia and bacterial infections were the major problems experienced. Post-operative survival ranged from 50 days to 455 days. Our study shows that swine can be pancreatectomized successfully and maintained as insulin dependent animals, presenting a realistic model for research on the complications of diabetes.

Animals↗
PubMed1986

Anatomic and anesthetic considerations in experimental cardiopulmonary surgery in swine.

We have used immature commercial swine (13-25 kg) successfully in a variety of experimental cardiopulmonary surgical procedures in our laboratories since 1981. Multiple drug anesthetic protocols using barbiturates, narcotics, paralytic and antiarrhythmic agents have been employed in over 400 procedures per year. Complications, including fatal cardiac arrhythmias, have been greatly reduced by anesthetic protocols and surgical procedures developed through experience.

Acepromazine↗