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Methylprednisolone and gentamicin effects on hepatosplanchnic blood flow and carbohydrate metabolism in endotoxemic Yucatan miniature pigs.

Conjoint therapy of a glucocorticoid and aminoglycoside antibiotic have been recommended for septic shock. These studies examined the hemodynamic and metabolic effects of methylprednisolone sodium succinate (MPSS) with and without gentamicin sulfate in a nonanesthetized model of nonseptic endotoxemia in Yucatan miniature pigs. Methylprednisolone sodium succinate alone had no effect on endotoxin-induced systemic hypotension. Endotoxemic pigs treated with MPSS in combination with gentamicin sulfate had lower mean arterial pressures than did MPSS-treated and nontreated endotoxemic pigs. Methylprednisolone sodium succinate alone and with gentamicin sulfate improved portal and hepatic venous blood flows moderately. Net hepatic lactate extraction, glucose production, and whole body [6-3H]glucose-derived rates of glucose appearance were also improved, but [6-3H]glucose-derived rates of glucose disappearance and blood lactate concentrations were increased, leading to no improvement in plasma glucose concentration. Pancreatic insulin secretion was higher in treated groups, which may have contributed to greater glucose utilization rates. Hepatic oxygen extraction efficiency was not affected by treatment, but increased in all groups to maintain hepatic oxygenation at base-line values. Although a calcium-antagonistic activity of gentamicin has been reported to synergize with endotoxin, thereby adversely affecting cardiovascular function, such effects did not complicate the metabolic response to steroid in the present studies.

Animals↗

Post-ischemia immunosuppression in a miniature swine model.

Yucatan miniature swine were the experimental model used to examine the effect of ischemia-injury on post-ischemic monocyte (MO) and immune function. Monocyte plasminogen activator (PA) was depressed while MO tissue factor activity was increased. The ability of porcine monocytes to generate a primary in vitro antibody forming cell (AFC) response to sheep red blood cells (SRBC) also was depressed by ischemic injury. The mechanism by which ischemic injury modulated immunosuppression appeared to be through generation of immunosuppressive serum substances.

Animals↗

Characterization of the Yucatan miniature pig skin and small intestine for pharmaceutical applications.

Yucatan miniature pig skin and gastrointestinal tract have been characterized as potential models for human organ systems in in vitro and in vivo pharmaceutical experiments. Histology of pig skin and the flux of one classical drug, caffeine, are described. The Yucatan small intestine was examined morphologically. Both Yucatan skin and GI tract were found to have similarities to man.

Animals↗

Hematologic and serum biochemical values for Yucatan miniature swine.

Hematologic and serum biochemical values were determined for healthy, mature Yucatan miniature swine, Sus scrofa. These values were similar to those reported for other breeds of swine. There was no effect on erythrocyte count, hematocrit, MCV, MCH, MCHC, RDW, platelet count, or leukocyte count attributable to sex (p greater than 0.05). Differential leukocyte counts generated on an automated multichannel blood cell counter, having a three part leukocyte differential capability, were compared to 100-cell manual leukocyte differentials. Determination of lymphocyte and non-lymphocyte fractions on this system were not significantly different from microscopic differentials (p less than 0.001). However, the mononuclear cell count did not correlate well with the percentage of monocytes determined manually (r = 0.084, p greater than 0.5). Leukocytes, erythrocytes, and platelets behaved properly with respect to counting thresholds as modified for counting cells of other common domestic species on this automated cell counter.

Animals↗

Normal and pathological human gait analysis using miniature triaxial shoe-borne load cells.

Miniature triaxial shoe-borne load cells are used to analyze the normal and a below knee amputee's gait. The gait of an amputee is studied from first step on a temporary pylon to a final "normal" gait on a permanent prosthesis. The amputee's gait is compared to that of the normal subject. The load cells are an effective method of analyzing normal and abnormal gait. For an amputee, it is possible to identify misalignments from the output of the various load cells. This method may also be useful for identifying and correcting problems in the painful below knee stump. These load cells are further used to compute the center of pressure of a normal subject and a below knee amputee. Analysis of the resulting patterns has been found to be extremely useful as a measure of the subject's functional mobility.

Adult↗

Miniature swine as an animal model in photodermatology: factors influencing sunburn cell formation.

Swine have played an important role as animal models in dermatological research. In order to evaluate the usefulness of pig skin in photodermatology, sunburn cell (SBC) formation in the epidermis of miniature swine and erythema production were studied. SBCs were readily formed in the epidermis of the swine by ultraviolet radiation. Suberythemal doses of broad-band UVB radiation were effective in producing SBCs, and there was a dose-response relationship between SBC formation and ultraviolet radiation. When SBC formation was related to ultraviolet radiation in terms of biological dose (i.e. minimal erythema dose) neither the spectral characteristics of the sources nor the degree of pigmentation in the skin affected the response. When SBC formation was related to physical dose (J/m2) the protection value of tanning was evident. These results, when coupled with the morphological and physiological similarities between human and porcine skin, demonstrate the usefulness of this animal model in photodermatology.

Animals↗

Cardiovascular effects of a novel antihypertensive agent, SGB-1534, in miniature pigs.

The cardiovascular effects of SGB-1534 (3-[2-[4-(o-methoxyphenyl)-1-piperazinyl]-2,4(1H,3H)-quinazolinedione monohydrochloride) were investigated in pentobarbital-anesthetized miniature pigs. SGB-1534 infused i.v. at a rate of 3 micrograms/kg . hr-1 caused a gradual decrease of systemic blood pressure reaching a plateau level, with a peak fall of about 20% of the preinfusion value, 30-60 min after the start of the infusion. Significant reductions of coronary vascular resistance and left ventricular (LV) end-diastolic pressure were also observed. Changes in LV systolic pressure, coronary blood flow and pressure-rate product were not significant, while heart rate and LVdp/dt max were significantly increased. The pressor response to a bolus i.v. injection of epinephrine (1 microgram/kg) was significantly inhibited during i.v. infusion of SGB-1534. The results indicate that SGB-1534 is an antihypertensive agent, probably related to its alpha-adrenergic blocking action in peripheral vasculatures.

Anesthesia↗

A circumferentially-sensitive miniature pressure sensor for study of human esophageal motility.

Manometric systems in current use for study of human esophageal motility consist of sensors with a restricted radial disposition. Since both upper and lower esophageal sphincters are asymmetrical structures, such sensors are not ideal for sphincteric pressure measurements. In this report, we describe a circumferentially sensitive sensor (MT) which consists essentially of a miniature transducer mounted within a sealed fluid-filled chamber, surrounded by a pressure-sensitive silastic diaphragm. This device is accurate and sensitive. It was compared in 10 young healthy men with a standard perfused catheter system (PC) composed of three catheters, whose side openings were at the same axial level, connected to external transducers. Pressures recorded from the lower esophageal sphincter were significantly higher with the MT than with the PC; and in the upper esophageal sphincter, the rapid pressure changes associated with deglutition were far more faithfully reproduced with the MT. Contractile pressures recorded after swallowing from the body of the esophagus were similar with the two systems, provided that catheters were perfused at a rapid rate (approximately 8 ml/min for each catheter). This preliminary evaluation indicates that this MT has significant advantages as compared with currently available systems.

Adult↗

Effects of a new antianginal agent, nicorandil, on the cardiovascular system of the miniature pig: with special reference to coronary vasospasm.

The cardiovascular and vasospasmolytic effects of a newly developed nicotinamide derivative, N-(2-hydroxyethyl)nicotinamide nitrate(ester) (nicorandil), were examined in anesthetized, open-chest "miniature" pigs, and compared with those of nitroglycerin. Nicorandil, administered i.v. in doses of 10 micrograms/kg to 1 mg/kg, decreased systemic blood pressure, left ventricular (LV) systolic pressure, pressure rate product and coronary and femoral vascular resistance. It pronouncedly increased coronary blood flow and slightly increased heart rate. An increase, often preceded by a decrease, occurred in the LVdP/dt max. In doses of 10 to 100 micrograms/kg, nicorandil induced a slight increase followed by a decrease in femoral blood flow, but larger doses always decreased it. Similar results were obtained with nitroglycerin for all the cardiovascular parameters tested except LVdP/dt max and coronary blood flow. Unlike nicorandil, nitroglycerin induced a decrease often preceded by an increase in the LVdP/dt max. In doses of 1 to 30 micrograms/kg, nitroglycerin caused a decrease preceded by a slight and transient increase in the coronary blood flow. Nicorandil, administered i.v. in doses of 30 micrograms/kg to 1 mg/kg, inhibited coronary vasoconstriction caused by methacholine (3 or 10 micrograms) and norepinephrine (2-4 micrograms in the presence of propranolol) injected directly into the coronary artery. The magnitude and duration of this antagonism depended on the dose of nicorandil used. Although nitroglycerin in a dose of 10 or 30 micrograms/kg also effectively inhibited coronary vasoconstrictor responses to the two vasoactive agents, dipyridamole (60 micrograms/kg) failed to do so. Thus, nicorandil has prominent vasospasmolytic effects and is an efficacious coronary vasodilator which reduces afterload.

Animals↗

[Skin reactions in the miniature pig following a single or fractionated local irradiation with 250 kVX-rays or 6.2 MeV neutron rays].

Skin areas of the miniature pig were irradiated locally with single fractionated (10 X Df in 12 days) doses of 250 kVX-rays or 6.2 MeV neutron rays. Depending on the neutron dose for single irradiations, the acute skin reactions up to 4 months following exposure yielded RBE values significantly less than 3.0, related to a neutron dose of 8 Gy and an X-ray dose of 24.2 Gy. When giving fractionated doses, RBE values greater than 3.1 were obtained, related to a neutron dose fraction of 1.2 Gy and an X-ray dose fraction of 3.7 Gy. For late effects 2 years after a single exposure, RBE values significantly greater than 2.3 were obtained, related to a neutron dose of 8 Gy and an X-ray dose of 18.6 Gy. Fractionated neutron irradiation yielded, as with the acute damage, RBE values greater than 3.1, related to a neutron dose fraction of 1.2 Gy and an X-ray dose fraction of 3.7 Gy. The tendency to higher RBE values for late against acute skin reactions could not be statistically verified by the present results.

Animals↗

[Blood specimen collection and liver biopsy in miniature swine].

The collection of investigational material means a problem occasionally during long-term observations of experimental animals. The described methods for punction of the superior vena cava and the percutaneous liver biopsy by means of a prostatic biopsy needle in miniature swine are carried out easily by one examinator without auxiliary personnel. Sufficient investigational material of good quality is to receive. Complicating factors are shown.

Animals↗

Growth and regression of cutaneous melanomas in Sinclair miniature swine.

Previous studies have demonstrated pathologic similarities between human melanoma and the spontaneous melanoma in the Sinclair miniature swine (SMS) with respect to cutaneous histologic features and patterns of metastasis. The current biopsy series, correlating growth curves and histopathologic features of cutaneous melanomas, was undertaken for documentation of the histologic events associated with the successful regression of melanoma in the SMS. Cutaneous growth and regression was characterized by a series of cellular events that eventually led to depigmentation and scar formation. Mononuclear inflammatory infiltrates, seen in over half of the 104 biopsies, showed several temporal and topographic distribution patterns, similar to that described in human melanoma. Histopathologic observations in the SMS confirm clinical observations that the host can, with consistent effectiveness, react with the tumors to modify their biologic aggressiveness. Although regression is associated with lymphocytic and macrophage infiltration, the exact role of the immune response in the regression of the cutaneous melanoma remains to be elucidated.

Animals↗

An experimental study of intravascular stent in abdominal aorta of atherosclerotic miniature pigs.

To study the effects of nitinol alloy stent in the treatment of atherosclerotic arterial stenosis, eight miniature pigs were subject to abdominal aortic balloon denudation and high-fatty food. Then 8 nitinol alloy stents were implanted into each abdominal aortas of pigs. The pigs were equally divided into two groups. One group was given captopril (3 mg/kg/d). All animals were sacrified for pathological examination 6 to 10 months after stent implantation. The degree of arterial intima proliferation in the areas of stent implantation not significantly different from that of areas of balloon denudation alone; the atherosclerotic lesions were found at the arterial surface of stent implantation sites. The intima layer was rich in smooth muscle cells, with atherosclerotic plaque formed around the stent wire. On the other hand, significant decrease in arterial intima proliferation was found in group II with no atherosclerotic plaque. The arterial stenosis resulting from atherosclerotic lesion could not be prevented by implantation of intravascular stent, and on the contrary, the mechanical stress of stent wire might worsen the atherosclerosis. Captopril might impede the development of atherosclerotic stenosis after stent implantation.

Alloys↗

Nitric oxide controls arteriolar tone in the retina of the miniature pig.

PURPOSE: Experimental evidence indicates that the retinal microcirculation is mainly controlled by factors released from the tissue surrounding the arterioles. This study explores whether nitric oxide (NO), a possible factor, is released in the retina and controls the arteriolar tone. METHODS: Using a NO microprobe, the authors measured [NO] in the preretinal vitreous of miniature pigs as a function of distance from the retinal surface. Additionally, the NO-synthase inhibitor nitro-L-arginine was pressure injected. Finally, the retinal pool size of arginine and its biosynthesis from 14C(U)-glucose were biochemically assessed on retinal tissue and acutely isolated Müller cells. RESULTS: At the retinal surface, [NO] measured 6 to 9 microM, and, in the vitreous, it fell to zero approximately 180 microns away from the retina. Therefore, NO is degraded faster in the vitreous (65 to 80 microM.minute-1) than in aqueous solution. Light flicker stimulation of the dark-adapted retina induced a reversible increase of [NO] (approximately 1.6 microM). Preretinal juxta-arteriolar microinjections of nitro-L-arginine (0.6 mM) induced a segmental and reversible arteriolar vasoconstriction of 45%; in contrast, intravenous infusion of nitro-L-arginine had no measurable effect on arteriolar diameter. The retinal pool size of arginine was small (< or = 200 microM), but there was an important rate of arginine biosynthesis in Müller cells. CONCLUSIONS: These results strongly suggest that cells in the retina, other than endothelial cells, produce and release NO, which in turn controls the basal dilating arteriolar tone in the inner retina.

Animals↗

Augmentation of coronary responsiveness to serotonin at the site of X-ray-induced intimal thickening in miniature pigs.

OBJECTIVE: X-irradiation is known to enhance atherosclerotic change. We tested whether coronary vasoconstrictor responses are augmented at the sites of X-ray-induced intimal thickening in Göttingen miniature pigs. METHODS: In 17 pigs, a major branch of the left coronary artery was denuded with a balloon catheter. In 10 pigs, the denuded portion of the left coronary artery was selectively irradiated with 15 Gy of X-rays twice at 3 and 4 months after denudation (group 1). The remaining 7 pigs were not irradiated (group 2). The effects of intracoronary administration of serotonin, histamine and phenylephrine on the coronary diameter were studied 3 (3M) and 5 months (5M) after denudation. After the angiographical study at 5M, the vessels were isolated and isometric tension was measured in an organ chamber. RESULTS: The percent reduction in coronary diameter evoked with 10 micrograms.kg-1 of serotonin increased from 39(s.e.m. 4)% before X-irradiation (3M) to 75(6)% after X-irradiation (5M) in group 1 (P < 0.01), while it did not differ in group 2 [39(6)% at 3M vs. 33(8)% at 5M[ [39(6)% at 3M vs. 33(8)% at 5M]. In group 1, serotonin-induced coronary constriction was frequently accompanied by ischemic ECG changes. Histamine (10 micrograms.kg-1)-induced vasoconstriction was also augmented but to a smaller degree [47(6)% at 3M vs. 62(4)% at 5M; P < 0.05] in group 1, while it remained unchanged in group 2[52(5)% at 3M vs. 44(7)% at 5M]. Phenylephrine did not cause detectable contraction in either group at 3M or 5M. Methysergide and ketanserin attenuated serotonin-induced hypercontraction in a dose-dependent fashion. In the in vitro studies, endothelium-dependent relaxation to serotonin was impaired at the denuded site with (group 1) and without (group 2) X-irradiation to a similar extent. Isometric tension of medial smooth muscle developed by serotonin was significantly greater at the denuded site with X-irradiation (group 1) than the control site and the denuded site without X-irradiation (group 2) (P < 0.05). Intimal thickening was significantly greater at the denuded sites with X-irradiation [group 1, 238(45) microns] than at the denuded sites without X-irradiation [group 2, 58(5) microns] (P < 0.05). CONCLUSIONS: These results indicate that X-irradiation augments the coronary vasoconstrictor responses to autacoids, predominantly to serotonin, and that this augmentation is accompanied by enhanced intimal thickening. Serotonin-induced hypercontraction after X-irradiation resulted mainly from the hyperreactivity of medial smooth muscle.

Animals↗

Mechanism of cyclosporin-induced tolerance to primarily vascularized allografts in miniature swine. Effect of administration of exogenous IL-2.

Indefinite tolerance to kidney allografts across a two-haplotype class I disparity can be induced in miniature swine in 100% of cases by a short course of cyclosporin A (CyA). Without CyA, all recipients reject kidney allografts within 2 wk. These animals therefore provide a unique opportunity to study the mechanisms of induction and maintenance of tolerance in a large animal model. Previous studies of cellular and humoral immunity suggested that a T cell help deficit at the time of the first exposure of the host's immune system to alloantigens was involved in tolerance induction. We have now studied the effect of exogenous T cell help in the form of an IL-2 infusion during both the induction and maintenance phases of tolerance. Lymphoid infiltrates were seen in class I mismatched renal allografts by day 8 in all animals whether treated with CyA or not. Administration of i.v. IL-2 on postoperative days 8, 9, and 10 to animals receiving the full CyA tolerizing regimen led to acute rejection in four of four animals. These rejecting animals showed induction of IL-2R expression on graft infiltrating cells in the kidney, suggesting that the infiltrates present before IL-2 administration were capable of causing rejection once T cell help was provided. Treatment with IL-2 did not abrogate long-term tolerance. Thus, limitation of T cell help at the time of first exposure to Ag in this model appears to be required to prevent rejection during the time required for active tolerance to develop. Once established, this tolerance does not appear to require continuous limitation of T cell help to be maintained, suggesting loss, inactivation, or suppression of the cells capable of causing rejection.

Animals↗

Relation between body temperature and dexmedetomidine-induced minimum alveolar concentration and respiratory changes in isoflurane-anesthetized miniature swine.

Dexmedetomidine (DEX), an alpha 2-receptor agonist, is the pharmacologically active d-isomer of medetomidine, a compound used as a sedative in veterinary medicine. Isoflurane anesthetic requirement (minimum alveolar concentration; MAC), rectal temperature, and cardiorespiratory variables were studied in chronically instrumented Yucatan miniature swine during DEX (20 micrograms/kg of body weight)-induced changes in body temperature. All studies were performed at room temperature of 22 C. The DEX was given as a 2-minute infusion into the left atrium. Each pig was studied twice. For protocol 1, the core temperature of the pigs was maintained at (mean +/- SD) 38.2 +/- 0.5 C by use of a thermostatically controlled water blanket and a heating lamp. For protocol 2, the core temperature was not externally manipulated and it decreased from 38.2 +/- 0.4 C to 32.2 +/- 1.2 C during the more than 3 hours of the protocol. Control isoflurane MAC was 1.66 +/- 0.2% and was 1.74 +/- 0.3% for protocols 1 and 2, respectively; DEX decreased MAC by 34 and 44%, respectively. For protocol 1, reduction in MAC after DEX administration returned by 50 and 80% at 84 and 138 minutes, respectively. If rectal temperature was not maintained (eg, allowed to decrease), MAC was reduced by 57% at the same time as the return to 80% in the swine with maintained body temperature. Respiratory rate and minute ventilation were significantly higher in swine with maintained temperature. The PaCO2 was lower and, accordingly, pH was higher in these swine. Blood pressure and heart rate were not affected by temperature changes.

Adrenergic alpha-Agonists↗