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PubMedDate not supplied

Tissue angiotensin-converting enzyme blockade by MC-838 (altiopril calcium) infused intravenously to miniature pigs: comparison with captopril.

The effect of a new orally active angiotensin-converting enzyme (ACE) inhibitor, calcium(-)-N-[(S)-3-[(N-cyclohexyl-carbonyl-D-alanyl)thio]-2-methyl- prolinate (MC-838, altiopril calcium), on cardiohemodynamics and tissue ACE activity was compared with that of captopril in the anesthetized miniature pig. MC-838 and captopril were infused i.v. for 1 or 3 hr at an equimolar rate of 20 and 10 micrograms/kg.hr-1, respectively. When MC-838 was infused i.v., captopril appeared in approximately 40% of MC-838 in serum, indicating that the amount of serum captopril during the equimolar concentration treatment with MC-838 corresponds to half of serum captopril after the dosing of captopril. During the infusion, the drugs did not significantly affect systemic blood pressure (SBP), heart rate (HR), renal blood flow (RBF) and renal vascular resistance (RVR). MC-838 and captopril, in a similar degree, attenuated the vasoconstrictor response to angiotensin-I (A-I) injected into the renal artery (i.a.), and enhanced the vasodilator one to i.a. bradykinin, 3 hr after the onset of the drug infusion. The animals were sacrificed at 1 and 3 hr after the onset of the infusion of MC-838 or captopril, and the ACE activity in serum and some target organs (lung, kidney, heart, brain and aorta) was determined. Effective activities of MC-838 and captopril occurred in the lung and kidney (only at 3 hr for captopril) where higher ACE activity in a variety of tissues was found, to a lesser degree in the serum (only by captopril) and not at all in the brain, heart and aorta.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1989

Experimental frost-bite in Hanford Miniature Swine. I. Epithelial changes.

Frost-bite lesions were produced in five Hanford Miniature Swine exposed to - 75 degrees C air for 1, 3, 5, 10 or 20 min. Biopsies were taken at 0, 3, 6, 12, 24 and 48 h and 1 and 2 weeks. Two hundred slides were evaluated microscopically: pyknosis, vacuolation, individualization of cells, and degeneration were graded from 0-5; 0, no change; 5, severe change. Necrosis, new epithelium, and microabscesses were recorded as present or absent. Early changes of vacuolation of keratinocytes, individualization of cells and pyknosis increased with biopsy time until 1 week, at which time more severe changes predominated. Intermediate changes of advanced degeneration and dermoepidermal microabscesses were seen at 48 h and 1 and 2 weeks. Late changes of necrosis and epithelial regeneration occurred, both separately or together in the same tissue, at 1 and 2 weeks. Regeneration occurred either as complete replacement of epithelium, or as crescents of new epithelium beneath degenerating epithelium. The results show that necrosis is a late development, so prognosis based on early skin biopsies must be guarded to unfavourable. Furthermore, these findings suggest that cold has a direct effect on epithelial cell membranes.

Animals↗
PubMed1989

Experimental frost-bite in Hanford Miniature Swine. II. Vascular changes.

Frost-bite lesions were produced in five Hanford Miniature Swine exposed to - 75 degrees C air for 1, 3, 5, 10, or 20 min. Biopsies were taken at 0, 3, 6, 12, 24, and 48 h, and 1 and 2 weeks. Two hundred slides were evaluated microscopically: superficial and deep hyperaemia, vascular inflammation, medial degeneration, and thrombosis were graded from 0 to 5; 0, no change; 5, severe change. Haemorrhage was recorded as present or absent. Hyperaemia was the earliest change seen, both grossly and microscopically. Leucocyte emigration and vasculitis were intermediate stages seen most commonly in the 6, 12, and 24 h biopsies. Medial degeneration and thrombosis, the most severe vascular changes, were not seen until 1-2 weeks following frost-bite injury. These findings show that the outcome of frost-bite can not be accurately predicted from early frost-bite lesions, because thrombosis and medial degeneration are not evident in early lesions.

Animals↗
PubMed1986

Effects of nicorandil on the rhythmic contractile response of isolated miniature pig coronary artery to 3,4-diaminopyridine: comparison with nitroglycerin.

Effects of 2 antianginal agents, nicorandil and nitroglycerin, on the rhythmic contraction induced by 3,4-diaminopyridine (DAP) were investigated in the isolated coronary artery of the miniature pig. Application of 10(-2) M 3,4-DAP elicited a sustained rhythmic contraction of the artery, lasting more than 3 hr. Nicorandil significantly reduced the peak tension of the contraction phase and the tension of the relaxation phase at concentrations of 10(-6) and 10(-5) M. The cycle length and the reappearance time of the rhythmic contraction were only significantly prolonged at a concentration of 10(-5) M. Finally a concentration of 10(-4) M led to the disappearance of rhythmic contraction. Nitroglycerin (10(-8) - 10(-4) M) significantly reduced the peak tension of the contraction phase and the tension during the relaxation phase in a concentration-dependent manner. At concentrations of 10(-6) to 10(-4) M, it also greatly prolonged the reappearance time of the rhythmic contraction, but the contraction was never eliminated even at the highest concentration (10(-4) M) of nitroglycerin used. The result indicates that nicorandil has an effect on the rhythmic contraction caused by 3,4-DAP through a mechanism somewhat different from nitroglycerin.

4-Aminopyridine↗
PubMed1988

[Functional morphology of the maxillo-mandibular apparatus in the miniature swine MINI-LEWE. 8. The development of the intramuscular nerve ramification pattern in the masticatory muscles].

Postnatal changes in the intramuscular innervation pattern of the masticatory muscles of the miniature pig MINI-LEWE are only gradual. There are no definite relationships between the paths of nerves and the positions of the fasciae. The few anastomoses found were in the masseter muscle. The only other nerve found to be implicated in the motor innervation of the masticatory muscles was the motor root of the trigeminal nerve. Innervation studies are a good way of identifying the bounds of muscles: the masseter and zygomaticomandibularis muscles, for instance, are innervated jointly by the massetericus nerve, so that the zygomaticomandibularis muscle can be regarded as belonging to the masseter muscle.

Animals↗
PubMedDate not supplied

Successful long-term use of a miniaturized plasmapheresis circuit in rabbits.

Dual lumen silicon rubber right atrial catheters were implanted into the jugular of 8 rabbits and tunneled subcutaneously to exit sites between the ears. Using a miniaturized tubing-pump system, blood flow rates of 25 ml/min could be achieved for up to 3 1/2 hours without sign of hemolysis in an extracorporeal blood circuit. Seven catheters functioned an average of 75 +/- SE 19 days (range 24-117). One catheter remains functional after 176 days. Infection and thrombosis were the main reasons for failure. 20 plasmaphoresis experiments were carried out in four heparinized rabbits (blood flow rates 15 ml/min, plasmaflux 1.5-2.0 ml/min) using polypropylene minifilters (average pore size, 0.55 micron) with the plasma recirculated back into the animal. No hemolysis was detectable throughout the 4 hr experiment. Plasma proteins with a MW of 69 X 10(3) to 3 X 10(6) (Albumin, LDH, SGOT, SGPT, CPK, fibrinogen, LDL) showed a sieving coefficient close to 1.0. The good filtration performance and the absence of side effects make this system a possible use for plasmaphoresis in neonates.

Animals↗
PubMed1988

Histochemical fiber type composition in 12 skeletal muscles of miniature pigs.

In 12 skeletal muscles of adult miniature pigs histochemical fiber type analysis was performed. Longissimus dorsi, psoas major, diaphragm and fore- and hind-limb muscles were composed from SO, FOG and FG fiber types showing characteristic clump distribution. The muscles differed in the first place by the frequencies of SO and FG types (7-70% and 19-79% respectively); the proportion of FOG type varied considerably less (10-32%). On the other hand in the masseter muscle only SO and FOG types with a mosaic distribution were demonstrated (28% and 72% respectively). In the majority of muscles the prevailing fiber type has also the largest diameter, but the differences between individual types were mostly insignificant. The largest diameter was found in the masseter muscle fibers--around 70 microns, which is 20-30 microns more than in the other muscles.

Animals↗
PubMed1988

Salicylic acid causes a diuresis and natriuresis in normal and common bile-duct-ligated cirrhotic miniature swine.

In patients with liver disease, or in normal subjects who are sodium-depleted, the administration of either a nonsteroidal anti-inflammatory drug or acetylsalicylate (aspirin) has a detrimental effect on the kidney; profound renal vasoconstriction and the retention of sodium and water may occur. We observed recently that salicylate (SA), in contrast to meclofenamate (MECLO) or aspirin, caused a diuresis and natriuresis in the sodium-depleted dog. To determine if SA would similarly affect the kidneys in a cirrhotic subject, the effects of SA (40 mg/kg) and subsequent MECLO treatment (2 mg/kg) were evaluated in five normal and six common bile-duct-ligated (CBDL) miniature swine. All six CBDL animals showed signs of biliary cirrhosis and four of the six were ascitic at the time of study. SA did not significantly alter renal blood flow or glomerular filtration rate in either the normal or CBDL animals. In both groups, SA caused a significant diuresis and natriuresis. MECLO, given after SA, caused a reduction in renal blood flow in the normal but not in the CBDL animals, but did not alter glomerular filtration rate in either group. In the CBDL animals, when MECLO was given alone a significant decrease in renal blood flow occurred. MECLO abolished the SA-induced diuresis and natriuresis in the normal swine but only affected the SA-mediated natriuresis in the CBDL animals. SA significantly reduced renal prostaglandin E2 excretion in both groups. With MECLO, prostaglandin E2 excretion was reduced further in the normals but not in the CBDL animals. These data demonstrate that SA does not produce detectable renal vasoconstriction in the cirrhotic pig.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

[Microscopic-anatomic changes of the temporomandibular joint structure in miniature swine due to unilateral occlusion disorders].

The influence of artificial unilateral occlusal disturbances on the structure of the temporomandibular joint (TMJ) condyle cartilage was investigated by an experimental study using the miniature pig "MINI-LEWE". After a burden over 20 weeks the side exposed to occlusal disturbance (right TMJ) turned out to have unchanged histological proportions in comparison with control animals. The condyles of the side with pressure loading (left TMJ) exhibited but a changed histological picture. Cartilage resorptions as well as accumulations of large blown chondrocytes indicate an increased tissue reaction within the chondroblastic layer near spongiosa. The morphometric investigations confirm these results. A significant increase was observed in cell density within the chondroblastic layer of the most superior point of the left condylus due to the permanent disturbance of the normal masticatory function.

Animals↗
PubMed1987

Acute changes in pancreatic insulin secretion and hepatic glucose kinetics in endotoxemic miniature pigs.

We have proposed a misinformed B-cell hypothesis to describe the effects of increased glucose flux across the pancreatic B cell early in endotoxemia, whereby those cells might misinterpret the true glycemic state and thus induce increased insulin release. This hypothesis was supported by the observations that [6-3H]glucose-derived rates of glucose disappearance increased before systemic hyperinsulinemia appeared in endotoxemic Yucatan miniature pigs. Reevaluation of this hypothesis later showed that pancreatic insulin secretion increased before any changes in systemic glucose disappearance or insulin concentrations and, because of significant increases in hepatic insulin extraction, may have led to some local effects of insulin on hepatic carbohydrate metabolism. The present study was conducted with more frequent sampling periods early during endotoxemia to further characterize the effects of this initial acute increase in pancreatic insulin secretion on hepatic glucose uptake, concomitant to net hepatic glucose production, as well as to further clarify the temporal relationships between pancreatic insulin release and the onset of hypoglycemia. We found that an increase in pancreatic insulin secretion is, indeed, the first event to occur, 30 minutes after initiation of endotoxin infusion, coincidental to the onset of significant decreases in portal and hepatic venous blood flow. [3(3)H]Glucose-derived rate of glucose disappearance first increased significantly at 60 minutes, and net hepatic glucose output increased significantly after 80 minutes of endotoxin infusion. Net [3(-3)H]glucose uptake by the liver occurred through 50 minutes of endotoxin infusion. After this, there was a significant reversal in transhepatic isotope kinetics, resulting in net release of [3(-3)H]glucose from the liver for the duration of endotoxin infusion (140 minutes).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Ocular pathology in melanomatous Sinclair miniature swine.

Eyes of cutaneous melanoma-bearing miniature Sinclair swine were examined by light and electron microscopy during growth and maturation of animals. The histology of ocular depigmentation, which occurs during melanoma arrest and skin depigmentation, was studied in eyes of animals that had successful and unsuccessful tumor regression. In 12 animals one eye was removed at an early stage and the second eye at a later stage of disease or maturation. The histologic and clinical course of the ocular changes was correlated with changes in the cutaneous tumors. Animals showing rapid cutaneous tumor regression developed acute uveitis that was characterized by an influx of mononuclear cells into the stroma of the ciliary body; later this spread to the iris and choroid. In late stages the cornea sometimes developed a band of calcium precipitates beneath the basal epithelial cells (band keratopathy). Uveal melanocytes developed watery cytoplasm typical of cells with ruptured plasma membranes. Released melanin granules were taken up initially into the lysosomal compartment of mononuclear cells having the various morphologic features of lymphocytes and monocytes; later, melanin also appeared in fibrocyte lysosomes. The relationship of these processes to various cell-mediated immunity phenomena is being studied.

Aging↗
PubMed1988

[The normal electrocardiogram of miniature swine].

Mean normal values for heart rate of 111 (64-190) actions/min, for duration of the PR-interval of 88 (63-120) ms, for the QRS-complex of 36 (26-46) ms and the QT-interval of 252 (183-353) ms were determined from the ECG in 204 male and female Göttinger mini-pigs (mean body weight 12.4 kg). The mean total amplitudes (voltages) of QRSI-III amount to 0.8, 0.9 and 1.1 mV. Considering leads I, II and III positive P-waves are most frequently found in II with 91% and negative ones in III with 23%. Positive T-waves appear in III with 86% and negative ones in I with 88% most frequently. The main polarity of QRS is most frequently positive in I with 56% and negative in III with 48%. The incidence of Q is highest in lead I with 71%, that one of S in II with 55%. The T-waves are mostly discordant with QRS, especially in I with 54%, more seldom concordant yet frequently in II with 30%. A significant negative correlation (r = -0.77) is evident between heart rate and QT-duration, slight negative correlations also exist between heart rate and PR- as well as QRS-duration. The mean angle a QRS from I, II, III and aVR, aVL, aVF in the frontal plane (direction of the cardiac vector; n = 35) amounts to -47 degrees (-150 degrees to +165 degrees). The position of the heart axis is more sagittal with a characteristic deviation of the electrical from the anatomical axis of the heart. Concerning the observed parameters there is also a less intraindividual variability in investigations in series besides the considerable interindividual one. Examples for physiological specialities or variations from the norm of rhythm and configuration of the ECG typical for the miniature pig are presented and discussed.

Aging↗
PubMed1986

Malignant lymphoma in a Sinclair miniature pig.

Malignant lymphoma was diagnosed in a 3-year-old, male Sinclair(S-1) miniature pig with acute anorexia, depression, fever, and markedly enlarged inguinal lymph nodes. Results of an initial hemogram indicated a leukocyte count of 121,489 cells/mm3. Most of the leukocytes were mononuclear cells of various sizes, nuclear chromatin pattern, number of nucleoli, amount of cytoplasm, and amount of staining. Cytochemical staining and flow cytometric evaluation of the leukocytes indicated a large number of hypodiploid lymphoblasts in the peripheral blood. Gross necropsy findings included enlargement of all lymph nodes, a pale liver, and multifocal pale areas scattered throughout the kidneys. Microscopic examination indicated massive infiltration of abnormal lymphoid cells into most major organs and complete loss of normal morphologic features of all lymph nodes.

Animals↗
PubMed1986

Effects of sodium dichloroacetate in awake, healthy, Yucatan miniature swine.

Four healthy, fully conscious, 50- to 80-kg Yucatan miniature swine were fitted with carotid artery and jugular, portal, and hepatic vein catheters and hepatic artery and portal vein flow cuffs to determine transhepatic kinetics and insulin secretion. Three days later, after a 3-hour control period, the pigs were given IV sodium dichloroacetate (30 mg/kg of body weight as a bolus and 30 mg/kg/hr, as an infusion) for 6 hours. Arterial lactate concentrations decreased during the dichloroacetate infusion, but pyruvate concentrations were unaltered. The whole body rate of appearance and disappearance of glucose decreased, but plasma glucose concentrations did not change markedly. Limb skin surface temperatures increased, indicating a peripheral vasodilatory effect. Dichloroacetate had little effect on mean arterial pressure and hepatosplanchnic blood flow. Dichloroacetate may be effective as a hypolactatemic agent for lactic acidosis in pigs.

Acetates↗
PubMed1986

Blood biochemical status of miniature swine during submaximal and exhaustive exercise.

Simultaneous arterial (left atrial) and mixed venous (right atrial) blood samples were anaerobically drawn from 14 miniature swine (mean weight = 25.0 +/- 1.7 [SE] kg) in order to examine the adequacy of these animals as a model for the exercising human. Samples were drawn: 1) at rest; 2) during exercise that elicited 80.4 +/- 1.2% of the animals' measured maximal heart rates; 3) at exhaustion; and 4) during the 4th min of a standing, resting recovery period. At rest, the animals were mildly alkalotic (pHa = 7.497 +/- 0.016) and hypocapnic (pCO2a = 29.6 +/- 1.2 torr), with low hematological values (arterial hemoglobin = 6.66 +/- 0.18 mmol X 1-1; arterial hematocrit = 32.0 +/- 0.9%) and slightly elevated catecholamine concentrations. During the submaximal exercise, there were no statistically significant changes in the arterial blood pH or in plasma sodium (Na+) and chloride (Cl-) concentrations, with significant decreases observed in Hcta, pCO2a, and increases in arterial plasma norepinephrine, total protein, and potassium (K+) concentrations. At exhaustion, pHa and pCO2a decreased further, with increases noted in the arterial plasma concentrations of K+, epinephrine, total protein, and the Hct but not in Na+ or Cl-. During recovery, arterial lactate averaged 20.54 +/- 0.71 mmol X 1-1. Venous changes were similar to those observed in arterial blood, with a mean pHv of 7.168 +/- 0.043 and arterial lactate = 21.08 +/- 0.90 mmol X 1-1 during recovery. Exercise-induced hemoconcentration was similar for both arterial and venous sample sites during both the submaximal and exhaustive exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

The Yucatan miniature pig: characterization and utilization in biomedical research.

Yucatan miniature swine have a variety of applications in biomedical research. Sublines developed from the primary population at Colorado State University have been characterized genetically with special attributes. This report describes this unique laboratory animal, genetic selection programs, and its utilization in biomedical research.

Animal Husbandry↗
PubMed1986

Endotoxemia in Yucatan miniature pigs: metabolic derangements and experimental therapies.

Endotoxemia is a frequent complication of many health disorders. It is characterized by systemic release of a variety of endogenous inflammatory mediators which effect cardiovascular depression, reductions in organ blood flow, tissue ischemia and derangements in cellular metabolism leading to death. During a continuous intravenous infusion of Escherichia coli lipopolysaccharide, the chronology of alterations in hepatosplanchnic blood flow, hepatic carbohydrate metabolism and pancreatic insulin secretion has been studied in awake Yucatan miniature pigs (Sus scrofa). Endotoxic shock in this model is characterized by reductions in portal venous and hepatic arterial blood flow, early transient increases in pancreatic insulin secretion, increases in the 3H-glucose-derived rates of glucose appearance and disappearance, profound hypoglycemia, hyperlactatemia and metabolic acidosis. Reductions in hepatic oxygen delivery are compensated for by enhanced oxygen extraction efficiency, but hepatic gluconeogenesis continues at an inadequate rate to compensate for increased glucose utilization. Experimental therapies including lidocaine, naloxone, captopril, dichloroacetate and glucagon each effect specific improvements in cardiovascular or metabolic function, but none significantly alter the composite derangements responsible for lethality in this model.

Animals↗