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Biomedical subjects

M M Swindle

Publications and source records attributed to M M Swindle.

At least 19 recordsLinked to original sources

Male fetal pig lower urinary tract function. Part II: free voiding pattern close to term and in the newborn.

PURPOSE: We assessed the development of natural voiding function late in gestation and in the immediate postnatal period in a porcine model. MATERIALS AND METHODS: The study comprised 7 male fetal minipigs (median age 94 days, 0.88 gestation) and 7 male newborn pigs. In all pigs an ultrasonic probe was placed around the subcutaneous urethra and pressure catheters were placed in the bladder and rectum and in the amnionic cavity in the fetal pigs. The catheters were connected to pressure transducers as the flow probe was connected to a flow meter, and the recordings were sampled at a rate of 10 Hz on a personal computer. RESULTS: The newborns had a median voiding frequency of 3.3 times per hour while the fetuses voided a median of 5.9 times per hour (p = 0.16). Both groups voided with a staccato flow at a frequency of 1 to 2 Hz, indicating voiding dyscoordination between the detrusor and urethra. Maximum flow rate increased from median 4.4 ml per minute (range 2.0 to 8.8) in the fetal group to median 10.9 (5.4 to 18.3) in the newborns (p = 0.07). While the minimum opening pressure remained unchanged (median 7.0 cm H2O, range 5.7 to 13.0) vs median 7.6, (range 7.7 to 14.0, p = 0.57) the detrusor pressure at maximum flow decreased from median 22.4 cm H2O (range 16.6 to 39.0) in the fetal pigs to 12.1 cm H2O (8.3 to 22.3) in the newborns. CONCLUSIONS: Fetal and newborn pigs have dyscordinated voiding with a staccato flow. While the urethral opening pressure appears to be unchanged, the detrusor pressure at maximum flow decreases during the last period of gestation, indicating decreased urethral resistance. These findings are in accordance with observations made in human infants.

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Male fetal pig lower urinary tract function in mid second and early third trimester of gestation.

PURPOSE: Routine use of ultrasound during pregnancy has emphasized the need for greater knowledge about normal and abnormal voiding function during fetal live. We describe the developmental changes in lower urinary tract function from the middle of the second to the early third trimester of gestation. MATERIALS AND METHODS: The study included 22 male fetal pigs of 13 pregnant Goettingen minipigs (gestational period 111 to 115 days) with 11 fetuses in the middle of the second (median 61.5 days, 0.55 of term) and 11 fetuses in the beginning of the third trimester of gestation (median 80 days, 0.72 of term). With the sow under isoflurane anesthesia catheters were placed in the bladder, rectum and amniotic cavity of the fetuses, and a flow probe was placed around the distal urethra. After the sow was at light sleep urethral flow, amniotic pressure, abdominal pressure and bladder pressure were recorded a median of 241 minutes. RESULTS: The recordings of 14 fetuses were evaluable. In the middle of the second trimester the fetuses showed an almost constant dribbling with a median flow of 0.2 ml. per minute and a median of 4 concomitant bladder contractions per minute of median 3.5 cm. H2O (detrusor pressure). At the beginning of the third trimester the fetuses had periods of staccato flow (median 0.2 ml. per minute, staccato frequency 1 to 2 Hz.) on top of contractions (median 4 contractions per minute, median detrusor pressure 5.5 cm. H2O) with no flow between voidings. CONCLUSIONS: Development of storage and voiding function in male pigs occurs between the mid-second and early third trimester of gestation, together with emergence of striated sphincter bursting activity, which interrupts flow in the urethra during the voiding phase.

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Effects of feed withdrawal and transport on cecal environment and Campylobacter concentrations in a swine surgical model.

The objective of the present study was to evaluate how feed withdrawal and transportation influenced the cecal environment and cecal populations of Campylobacter in swine. Four miniature Yucatan gilts (8.8 kg), naturally infected with Campylobacter jejuni, were surgically implanted with cecal cannulas. The gilts were fasted for 48 h. Samples of cecal contents were collected for 7 days prior to and for 7 days after the fast, and mean values were determined for pH, volatile fatty acids (VFA), and CFU enumeration of C. jejuni. This was replicated three times. In another trial, gilts (full-fed) were transported in a livestock trailer for 4 h and cecal samples were collected before and after transport and analyzed for pH, VFA, and CFU. Following a 48-h fast, cecal pH increased (P < 0.05) by 1 unit; acetic and propionic acids decreased (P < 0.05) by 61% and 71%, respectively; and there was a twofold log10 increase (P < 0.05) in CFU/g cecal content of C. jejuni. Values of pH, VFA, and CFU of C. jejuni did not change in cecal samples from gilts following transportation. These data are important for food safety considerations because feed withdrawal, commonly associated with shipping and slaughter, can increase Campylobacter concentrations in the pig intestinal tract.

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Non-invasive measurement of blood pressures in the Yucatan micropig (Sus scrofa domestica), with and without midazolam-induced sedation.

Current literature suggests that the effects of midazolam, a water-soluble benzodiazepine, on blood pressure in swine are minimal. The hypothesis of the study reported here was that a light sedative dose would induce a decrease in blood pressure in this species. Healthy female Yucatan Micropigs (n = 20), 16 to 30 (mean, 22) kg, aged four six months, were individually placed in a humane restraint sling and allowed to acclimate. Systolic (SBP), diastolic (DBP), and mean (MBP) blood pressures (mmHg) and heart rate (HR; beats per min [bpm]) were measured by use of oscillometry. The pressure cuff was placed at the base of the tail, and five sets of values were recorded at five-min intervals, beginning at 10 and ending 30 min after cuff placement. Following a three- to four-day rest period, this procedure was repeated with the addition of a dose of 0.5 mg of midazolam HCl/kg of body weight given intramuscularly at the time of cuff placement. A paired one-way Student's t-test was used to compare the means of the five measures between control and midazolam treatment. Mean (+/- SD) differences for SBP, DBP, MBP, and HR were 18.9 (+/- 3.97), 17.8 (+/- 5.27), and 18.6 (+/- 5.09) mmHg and 20.7 (+/- 3.73) bpm, respectively. All four parameters were significantly reduced in the midazolam-sedated group (P < 0.001). The maximal decrease in SBP, DBP, and MBP occurred at 15 and 20 min after dosing. Mean values based on the means of the five measures were 128 (+/- 12.6), 80 (+/- 9.4), and 99 (+/- 9.2) mmHg and 135 (+/- 17.4) bpm, and 109 (+/- 15.4), 63 (+/- 12.6), and 80 (+/- 13.6) mmHg and 115 (+/- 15.5) bpm for SBP, DBP, MBP, and HR in the control (n = 20) and midazolam (n = 20) groups, respectively. The control values can serve as normal oscillometric values for this age, sex, and breed of Micropig. We conclude that midazolam, given intramuscularly at a sedative dosage, negatively affects cardiovascular parameters measured by use of a blood pressure cuff, in sexually mature female Micropigs, compared with values in untreated pigs, which is similar to reports for humans.

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Defining appropriate health status and management programs for specific-pathogen-free swine for xenotransplantation.

Swine are expected to be utilized as xenograft donors for both whole-organ and cellular transplantation. In order to meet the criteria for regulatory guidelines, donor animals are going to have to be free of potential zoonoses and other complicating diseases. Screening of animals will have to include tests for viruses, bacteria, parasites, congenital defects, and other inapparent diseases such as neoplasia or metabolic dysfunctions. The term Specific-Pathogen-Free (SPF) swine is a proprietary designation in the U.S. that does not include screening for all appropriate organisms for xenotransplantation. A program for breeding animals as xenograft donors will have to be conducted in a biomedical research facility rather than a conventional farm setting. The research programs at such a facility should include serology, microbiology, necropsy, histology and parasitology. The use of sentinel animal monitoring in a research facility is one method to ensure compliance. It will be impossible to provide complete individual animal screening in a timely fashion prior to performing a xenograft transplant. Quality control measures need to ensure that there is a reasonable confidence that the donor tissue is appropriate for the procedure to be performed. It is suggested that a term such as xenograft-defined flora be used to designate the appropriate health status of donor animals rather than SPF in order to avoid confusion with existing standards.

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Premorbid determinants of left ventricular dysfunction in a novel model of gradually induced pressure overload in the adult canine.

BACKGROUND: When a pressure overload is placed on the left ventricle, some patients develop relatively modest hypertrophy whereas others develop extensive hypertrophy. Likewise, the occurrence of contractile dysfunction also is variable. The cause of this heterogeneity is not well understood. METHODS AND RESULTS: We recently developed a model of gradual proximal aortic constriction in the adult canine that mimicked the heterogeneity of the hypertrophic response seen in humans. We hypothesized that differences in outcome were related to differences present before banding. Fifteen animals were studied initially. Ten developed left ventricular dysfunction (dys group). Five dogs maintained normal function (nl group). At baseline, the nl group had a lower mean systolic wall stress (96 +/- 9 kdyne/cm2; dys group, 156 +/- 7 kdyne/cm2; P < .0002) and greater relative left ventricular mass (left ventricular weight [g]/body wt [kg], 5.1 +/- 0.36; dys group, 3.9 +/- 0.26; P < .02). On the basis of differences in mean systolic wall stress at baseline, we predicted outcome in the next 28 dogs by using a cutoff of 115 kdyne/cm2. Eighteen of 20 dogs with baseline mean systolic stress > 115 kdyne/cm2 developed dysfunction whereas 6 of 8 dogs with resting stress < or = 115 kdyne/cm2 maintained normal function. CONCLUSIONS: We conclude that this canine model mimicked the heterogeneous hypertrophic response seen in humans. In the group that eventually developed dysfunction there was less cardiac mass despite 60% higher wall stress at baseline, suggesting a different set point for regulating myocardial growth in the two groups.

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Toward optimizing a preshaped catheter and system parameters to achieve single lead DDD pacing.

P wave electrogram amplitudes and atrial stimulation thresholds were determined in eight Hanford miniature swine using a preshaped catheter with an "S" curve in the SVC, and a major lobe in the atrium to enhance electrode contact with the atrial wall. The catheter was designed for pacing and sensing in the DDD mode. P wave amplitudes were also ascertained with two commercially available VDD leads and compared to the data from the experimental catheters. The preshaped catheter used two 6-mm2 platinum iridium atrial electrodes with a 7-mm separation. Both atrial electrodes are on the same side of the catheter, facing outward on the major atrial lobe formed in the catheter. The P wave amplitudes were tested only in the differential bipolar configuration. For the eight preshaped catheters, the mean was 6.6 +/- 3.8 mV while for the conventional leads it was 2.9 +/- 1.6 mV. The mean atrial stimulation thresholds ranged from 1.1 +/- 0.2 V to 2.3 +/- 1.2 V, with still lower thresholds of 0.9-1.3 V when using the parallel unipolar atrial electrode configuration, in which both parts of the bipolar atrial electrode are configured as a unipolar electrode. The data suggest that bipolar simulation may be effective if sequential reverse polarity pulses are used to achieve cathodal stimulation from each electrode of the bipolar pair, on a beat-to-beat basis.

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Fetal surgical protocols in Yucatan miniature swine.

Thirty-nine Yucatan miniature swine were used in three fetal surgical experimental protocols. They involved antiarrhythmic administration, pacemaker implantation, and in-utero diagnosis of ventricular septal defect by intraoperative echocardiography. Because of problems encountered with surgical protocols in the initial stages, modifications were made to prevent fetal hypothermia and intraoperative mortality. These modifications included environmental temperature support, staple surgical techniques to reduce operative time, and development of fetal catheters designed to facilitate cannulation of small vessels. Postoperative care protocols were intensive and included antibiotics, analgesics, and supportive care designed to reduce discomfort and prevent abortion and sepsis. Thirty-seven of 39 sows survived the surgical procedures; experiments were performed on 117 fetuses. Twenty-two fetuses died either intraoperatively or postoperatively because of complications related to the experimental protocols. Modification of surgical and postsurgical protocols for these projects demonstrates the feasibility of using miniature swine as a model for fetal surgery, when their use was appropriate for anatomic and physiologic reasons.

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Normal serum biochemical and hematological values of the Sulawesi macaques.

Sulawesi macaque (SM) species are currently of interest to primatologists for genetic and behavioral studies world wide. However, there are no published reference hematological and serum biochemical profile values for several of the seven SM species. Twenty-five clinically healthy, outdoor housed, ketamine sedated Macaca tonkeana and Macaca maurus were serially sampled (two to four times) over a 16-month period (N = 68). Normal ranges were defined to include two standard deviations and 2.5-97.5 percentile. Significant differences in single sample data comparisons (P < 0.05) of species (serum Ca, MCHC), age (BUN, BUN/creatinine, alkaline phosphatase, phosphorus), gender (total protein, RBC, hemoglobin, HCT) and pregnancy (phosphorus and neutrophil count) groups were found. This normative data facilitates clinical evaluation of SM species and allows comparison to other macaque species.

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Normal hematology, serology, and serum protein electrophoresis values in fetal Yucatan miniature swine.

We are currently developing fetal models of congenital heart disease in Yucatan miniature swine for pharmacologic, diagnostic, and interventional methods used to treat cardiac arrhythmias and ventricular septal defect. Fifty-four fetuses from 12 pregnant sows were included in this study. Eleven were fetuses between 76 and 88 days of gestation (early gestation fetuses). A second population of 43 fetuses were between 96 and 110 days of gestation (late gestation fetuses). Erythrocyte, leukocyte, serum electrolyte, enzyme, lipid, carbohydrate, and metabolite values were measured. Complete serum protein profiles were also obtained by electrophoresis. Significant differences could be shown between the sows and fetuses and between the early and late gestation fetuses in all of the categories studied, though not for every parameter. This study provides a large normal database for development of Yucatan miniature swine as an animal model in the rapidly expanding field of fetal medicine.

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Echocardiographic and anatomic correlation of ventricular septal defect morphology in newborn Yucatan pigs.

With the use of a Yucatan micropig strain with a high incidence of ventricular septal defects (VSDs), results of two-dimensional and color-flow Doppler echocardiography of VSD morphology in newborn piglets were correlated with autopsy findings. A spectrum of perimembranous, muscular outlet, and doubly committed subarterial VSDs was found. Echocardiography was performed in 29 piglets weighing 1.2 to 4.4 (mean 2.8) kg, studied at age 4 to 18 (mean 8) days. VSD was diagnosed by means of echocardiography in 16 of 29 subjects; morphologic findings included perimembranous defects in 12, muscular outlet in two, and doubly committed subarterial defect in two. At autopsy the presence and location of defects were confirmed in all pigs. No additional defects were found. VSD diameters were 1.0 to 5.0 (mean 3.94) mm on echocardiography and 1.0 to 6.0 (mean 2.84) mm at autopsy. After aortic valve diameter was used as an internal control for tissue shrinkage during fixation, echocardiography/color Doppler imaging tended to overestimate VSD diameter by 21% (0.6 mm). In conclusion, echocardiography/Doppler imaging accurately identified the presence, morphology, and size of even the smallest VSDs in newborn Yucatan micropigs. Echocardiographic classification of VSD morphology in vivo will facilitate future research on specific types of VSDs in this animal model.

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Histologic study of chronic catheter cryoablation of atrioventricular conduction in swine.

To evaluate the efficacy of catheter cryoablation, we studied histologic changes of the atrioventricular (AV) junction in eight pigs 6 weeks after cryoablation of central conducting tissue. Cryothermia at -60 degrees C was applied to the AV junction through an 8F or 11F cryocatheter with no electrode and was maintained for 3 minutes after complete AV block was obtained. Six weeks later, gross inspection revealed a distinct, oval-shaped scar 5 to 8 mm in length along or above the septal leaflet of the tricuspid valve in each animal. Microscopically, ablated sites were discrete and were replaced by dense connective tissue with no signs of chronic inflammation. Neovascularization was often seen in scar tissue, and small branches of coronary vasculature within lesions appeared patent with mild intimal proliferation. Ablated lesions involved a small area of the summit of the muscular interventricular septum in three animals, but lesions were never found in the base of the aortic wall or aortic valve. The proximal AV conduction system, either the penetrating bundle or a portion of the AV node, was ablated in all five animals with complete AV block. Three animals that did not maintain complete AV block showed scar formation in the atrial septum above the AV node or penetrating bundle; two of these lesions had small islands of viable atrial myocardium embedded within scar tissue. Catheter cryoablation can produce lesions as effectively as those created during open-heart surgery and is a possible procedure for treatment of intractable supraventricular tachycardia. Improvements in technique or in the cryocatheter may be needed to create more reliably located and homogeneous scar.

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