Yorkshire Cross Pigs Research Articles

Effect of adenoviral titer and instillation pressure on gene transfer efficiency to arterial and venous grafts ex-vivo

Objective: Adenoviral-mediated gene transfer to arterial and venous grafts has potential in the treatment of a number of vascular diseases. Despite widespread use of these vectors to mediate gene transfer to blood vessel walls, the optimal transduction conditions for each type of vessel has yet to be determined. Our objective was to study the effect of adenoviral titer and instillation pressure on efficiency of gene transfer to arterial and venous grafts ex-vivo. Methods: Jugular vein and carotid artery segments of 8 cm were harvested from Yorkshire Cross pigs. Tissue culture media or different titers of an adenoviral vector encoding human placental alkaline phosphatase (hpAP) were instilled into venous and arterial grafts at 0 mm Hg or 80 to 100 mm Hg of pressure and bathed externally in the same solution at 37° C for 30 minutes. The grafts were rinsed, opened longitudinally, and incubated in culture media at 37° C for 48 hours. Grafts were fixed and stained for hpAP transgene expression to quantitate percent luminal transduction or homogenized for alkaline phosphatase (AP) activity to determine total transmural transduction. Results: For venous grafts, the percent luminal area stained for hpAP was greatest with 10 8 plaque-forming units/mL at 0 mm Hg (81% ± 7%) and decreased with increasing titers (53% ± 9% at 10 9 pfu/mL and 44% ± 11% at 5 × 10 9 pfu/mL; n = 7; P < .05). No increase in percent luminal area stain was achieved with an instillation pressure of 80 to 100 mm Hg at any viral titer. The inverse finding was observed in arterial grafts. For arterial grafts, the greatest percent luminal area stained was achieved with 5 × 10 9 pfu/mL at 80 to 100 mm Hg (76% ± 7%). An instillation pressure of 80 to 100 mm Hg increased the percent luminal area stained at 10 8 pfu/mL from 31% ± 9% to 66% ± 8% (n = 8; P = .01). For venous grafts, total AP activity peaked with 10 9 pfu/mL at 0 mm Hg and decreased with an instillation pressure of 80 to 100 mm Hg (30.6 ± 9.7 U/mg versus 10.9 ± 2.5 U/mg; n = 7; P < .01). However, for arterial grafts, total AP activity peaked with 5 × 10 9 pfu/mL (0 mm Hg) and increased with an instillation pressure of 80 to 100 mm Hg (32.8 ± 9.9 U/mg versus 63.4 ± 20.5 U/mg; n = 8; P < .05). Conclusion: High transduction efficiency can be achieved with adenoviral-mediated gene transfer of arterial and venous grafts. Gene transfer with the vascular graft's physiologic pressure conditions improved transduction efficiency for the artery (80 to 100 mm Hg) and vein (0 mm Hg). Comprehensive analysis of adenoviral transduction conditions is important to realize the full promise of adenoviral-mediated gene transfer. (J Vasc Surg 2002;36:263-70.)

High Chromium Yeast Supplementation Improves Glucose Tolerance in Pigs by Decreasing Hepatic Extraction of Insulin

Twenty Landrace x Yorkshire cross pigs (body wt, 47.9+/-2.9 kg) were used to evaluate effects of dietary high chromium (Cr) yeast supplementation on plasma kinetics of glucose, insulin and C-peptide. Pigs were provided free access to either a control diet (C) containing 204 microg Cr/kg or a diet supplemented with an additional 200 microg Cr/kg as high Cr yeast (CR) for between 23 and 30 d. After overnight food deprivation, dextrose (500 g/L) was infused through a jugular vein catheter at a dose of 0.5 g glucose/kg body weight with an infusion rate of 10 g glucose/min within 6 min. High Cr yeast supplementation did not affect body weight gain or food intake. There were no differences in fasting plasma concentrations of either glucose or C-peptide, although basal plasma concentration of insulin tended to be higher in pigs fed CR (P<0.10). Plasma glucose concentrations were lower (P<0.01) at postinfusion times 5, 10, 15 and 20 min in pigs fed CR. Plasma insulin concentrations in pigs fed CR were higher (P<0.05) at 2 and 0 min before the completion of dextrose infusion. However, the increase in plasma insulin concentrations was not accompanied by a comparable elevation in plasma C-peptide concentrations. The 30-min (postinfusion) area of plasma glucose concentrations tended to be lower (P<0.10) in pigs fed CR, but there were no differences in 30-min areas of either plasma insulin or plasma C-peptide concentrations between treatments. Plasma clearance rates of glucose, insulin and C-peptide were higher and their half-lives shorter (P<0.05) in pigs fed CR. In conclusion, dietary high Cr yeast supplementation improved glucose tolerance, possibly through a decrease in hepatic extraction of insulin.

Assessment of cutaneous sulfur mustard injury in the weanling pig

Background/aims:The euthymic hairless guinea pig was the animal model of choice at this laboratory for vesicant injury research. The supply of these animals, however, was interrupted in 1993 by an outbreak of Lisferia monocyfogenes at the commercial supplier's breeding facility, thereby forcing a search for alternative animal models. This report describes the development of a weanling pig model for use in evaluating the severity of skin lesions induced by sulfur mustard [bis(2‐chloroethyl)sulfide; SM] using a variety of bioengineering techniques. These methods include reflectance colorimetry (erythema response), high frequency ultrasound imaging (edema response) and a modified dermal torque meter procedure to test for Nikolsky's sign (damage at the dermal‐epidermal junction). The time course and exposure time‐dependence of SM‐induced lesions for these parameters were characterized in this model and compared with previous results in the haired and hairless guinea pig.Methods:Six male Yorkshire Cross pigs (7–10 kg) were used in this study. The hair on the dorsal surface of each animal was shaved the afternoon prior to SM exposure. Twenty‐four dorsal skin sites on each pig were exposed to saturated SM vapor (1.4 mg/l) using 14‐mm diameter vapor cups for 0 (control), 5, 10, 15, 20, or 25 min, with four sites per exposure level. Control and exposure sites were rotated to prevent site‐specific biases. Lesions were evaluated for erythema (reflectance colorimeter) at 4, 6, 12, 24 and 48 h post‐exposure, and for edema (high frequency ultrasound) at 6, 12, 24, and 48 h post‐exposure. Evaluations for Nikolsky's sign and histopathology were conducted at 48 h post‐exposure.Results:Maximum erythema responses occurred at 24 h postexposure for all SM exposure times (5, 10, 15, 20 and 25 min). The overall maximum response occurred with a 15‐min SM vapor exposure at 24 h post‐exposure. Exposures longer than 15 min did not induce significantly greater erythema at any of the time points examined. The earliest time point at which significant edema was noted was at 12 h for the 15‐ and 25‐min SM vapor groups. Maximum edema occurred at 48 h following a 15‐min exposure. No significant increase in edema was noted at any observation time point with exposures longer than 15 min. Allsites showed a weakening of the dermal‐epidermal junction (positive Nikolsky's sign) 48 h after a 15‐min or longer SM vapor challenge. The histologic severity of the lesions did not significantly worsen as the vapor exposure was increased beyond 15 min. (Following a 15‐min SM exposure, incidences of epidermal necrosis, pustular epidermitis, microblisters and vascular damage had reached 100%, with maximum mean severity scores.) The weanling pig is more resistant to the effects of SM vapor than either the haired or hairless guinea pig, showing a delayed response and requiring a longer exposure time to generate the same (quantitative and qualitative) response in erythema, Nikolsky's sign and microblister formation. SM vapor‐induced edema formation in the weanling pig is not as severe as in the guinea pig models.Conclusions:Erythema, Nikolsky's sign and microblisters all appear to be excellent parameters for evaluating SM vapor‐induced cutaneous damage in the weanling pig. Even though the exposure time‐dependent response of cutaneous exposure to SM vapor in humans more closely parallels those of the haired and hairless guinea pig with respect to dermal‐epidermal separation, weanling pig skin shares many more similarities to human skin and has the potential to be a useful model for antivesicant research. This model should prove valuable in 1) efficacy testing of pretreatments, treatments and topical skin protectants; 2) wound healing studies; 3) evaluationlof skinlwound decontamination systems; and 4) basic vesicant research.

Growth and Functional Assessment of Pulmonary Valves in Pigs After Replacement of Sinuses of Valsalva

Neopulmonary artery stenosis may occur after the arterial switching procedure to correct transposition of the great arteries. One technique to reduce this complication is to use a single rectangular piece of autogenous pericardium to reconstruct two adjacent sinuses of Valsalva and maintain pulmonary artery size. The long-term effect of this technique on pulmonary artery and valve growth and function is unknown. To assess this technique, Yorkshire-cross pigs (n = 5) weighing 29 +/- 1.7 kg (mean +/- SEM) were anesthetized, and during cardiopulmonary bypass, the pulmonary artery was transected distal to the pulmonary valve. Pulmonary artery diameter and commissure distances were measured. Two adjacent pulmonary artery sinuses of Valsalva were completely excised from the anulus to 4 mm distal to the commissures, leaving 2 mm of pulmonary artery tissue attached to the skeletonized commissure and on each side of the one remaining intact sinus of Valsalva. A single rectangular patch of fresh autologous pericardium was sutured to the anulus and remnant of the pulmonary artery along the commissure and edges of the one intact sinus of Valsalva. Pericardium composed two thirds of the circumference of the proximal pulmonary artery; this was anastomosed to the distal pulmonary artery. Weight gain occurred at a rate of 0.6 kg/day (median). The animals underwent right heart catheterization and cineangiography. They were killed 157.2 +/- 12.9 days post-operatively. The reconstructed pulmonary artery grew from 17.6 +/- 0.8 mm to 30.8 +/- 1.5 mm (p < 0.01), and the commissure distances grew from 17.0 +/- 1 mm to 27.2 +/- 1.6 mm (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Sensory and processing properties of cured semimembranosus muscle from stress-susceptible pigs treated with porcine somatotropin

Forty-eight Yorkshire cross pigs of three stress susceptibility classes (stress positive, stress-carrier, and stress negative) were injected daily with porcine somatotropin (pST; 4 mg/d) or placebo. Each pig was injected in the neck once daily until taken off test, starting when the pigs weighed 59 kg. Porcine somatotropin treatment was terminated at weekly intervals as individual pigs reached 109 kg, but animals continued to be fed for six additional days to allow for required withdrawal time. The effect of pST and stress classification on the sensory, physical, chemical, and processing characteristics of cured semimembranosus (SM) muscle was evaluated. Treatment of animals with pST had no effect on the sensory scores, lipid and protein content, cooking yields, or color values of SM muscle slices. Semimembranosus muscles from stress-positive animals, however, had reduced sensory scores for texture, flavor, and overall palatability. Semimembranosus muscles from stress-positive pigs also had smaller cooking yields and greater Hunter a and b values of processed slices. The greater Hunter a and b values suggested that the color of these slices were redder and yellower than the color of SM muscle slices from negative and carrier animals. Semimembranosus muscles from stress-susceptible animals also had a significantly lower lipid content. Treatment of animals with pST did not significantly alter sensory, chemical, or processing characteristics of SM muscle slices from these animals.

Performance of Landrace, Yorkshire and Duroc Sired Pigs from Landrace Sows

One-hundred thirty-three litters out of Landrace females bred to Landrace, Duroc and Yorkshire males were evaluated for maternal performance, and the offspring resulting from these matings were evaluated for postweaning performance. Crossing Landrace females with either Duroc or Yorkshire males resulted in heavier 21-day and 42-day postweaning litter weights than did crossing Landrace females with Landrace boars (P<.01). Crossbred pigs had a higher survival rate from birth to weaning at 42 days of age (P<.05) and were heavier at birth (P<.01), 21 (P<.05) and 42 days of age (P<.01) than purebred pigs. Postweaning gains were .05 kg/day less (P<.01), days to 100 kg was 10.7 days more (P<.01) and feed conversion was .27 kg feed/kg gain higher in the Landrace sired pigs than the Duroc and Yorkshire sired pigs (P<.01). Carcasses of the Landrace sired pigs had more backfat (P<.05), smaller loineye areas (P<.01) and a lower percentage lean cuts (P<.01) than the Duroc and Yorkshire sired pigs. Duroc sired litters tended to have heavier 21- and 42-day litter weights (P<.10) than Yorkshire sired litters. Duroc sired pigs grew more slowly during the postweaning period (P<.01), reached 100 kg 2.1 days later (P<.05) but converted feed to gain more efficiently (P<.01) than Yorkshire cross pigs and had a higher percentage lean cuts (P<.01), less backfat (P<.01) and larger loineye areas (P<.01).