A repeated-measures study was conducted on 5 dogs to clinically, radiographically, and echocardiographically characterize the actions of the angiotensin-converting enzyme inhibitor, enalapril, before and after development of experimentally induced heart failure. Heart failure was artificially induced, using a surgically implanted programmable ventricular pacemaker, which stimulated the heart at a rate of 245 beats/min until a low-output cardiomyopathic a state developed. This condition was then stabilized by decreasing the pacing rate to 190 beats/min. Pacing-induced heart failure was successfully induced in a mean +/- SD 4.2 +/- 1.95 weeks. The condition closely resembled the clinical, radiographic, and echocardiographic features of naturally acquired idiopathic dilated cardiomyopathy in dogs. Enalapril was well tolerated by dogs, and clinical adverse reactions did not develop. Results of echocardiographic studies indicated that enalapril treatment during the control period resulted in a significant (P < 0.05) increase in velocity of circumferential fiber shortening and a significant (P < 0.05) decrease in left ventricular ejection time. Therapeutic responses to enalapril were evident after development of heart failure. These included reduced severity of clinical signs of disease, evidence of decreased radiographically determined cardiac size (2 of 5 dogs), radiographic evidence of a reduction in pulmonary edema and congestion (4 of 5 dogs), significant (P < 0.05) reductions in left atrial and ventricular chamber dimensions (left atrial dimension, diastolic left ventricular internal dimension as determined echocardiographically), and improvement in some echocardiographic indices of left ventricular performance (velocity of circumferential fiber shortening and left ventricular ejection time).

The effect of bethanechol, neostigmine, metoclopramide, and propranolol on myoelectric activity of the ileum, cecum, and proximal loop of the ascending colon was determined in 6 healthy Jersey cows implanted with 8 pairs of bipolar electrodes. Assigned at random, each cow received each of 5 treatments in 3-day intervals. The treatments included bethanechol (0.07 mg/kg of body weight, SC), neostigmine (0.02 mg/kg, SC), metoclopramide (0.15 mg/kg, IM), DL-propranolol (0.2 mg/kg, IM), and 0.9% sodium chloride (NaCl) solution (20 ml, SC). All drugs were administered during early phase I of the migrating myoelectric complex in the ileum. Myoelectric activity was recorded for 4 hours after treatment, and data were analyzed for each hour separately. Bethanechol and neostigmine significantly (P < 0.05) increased the number of cecocolic spikes per minute per electrode, duration of cecocolic spike activity (%), and number of cecocolic propagated spike sequences per 10 minutes, relative to NaCI, during 1 or more hours of the recording period. The effect of bethanechol was more pronounced on duration of spike activity and number of propagated spike sequences, whereas neostigmine mainly increased the number of (uncoordinated) spikes. Metoclopramide and propranolol had no significant effect on cecocolic myoelectric activity, relative to NaCl. It was concluded that bethanechol and, less likely, neostigmine at the dosage used in this study may be suitable for medical treatment of cecal dilatation in cattle in which hypomotility of the cecum and proximal loop of the ascending colon has to be reversed. The potential advantage of bethanechol vs neostigmine for medical treatment of cecal dilatation is worth further evaluation.

We defined methods for use of luminol-dependent chemiluminescence (LDCL) and superoxide anion (O2-) production as parameters of the oxidative metabolism of neutrophils isolated from 1.5- to 5-week-old neonatal calves. We determined how variations in blood sample handling, agonist preparation, individual variability, and age of calves influenced the LDCL and O2- responses to certain agonists, and defined concentrations of soluble and particulate agonists that maximally stimulated the oxidative metabolism of bovine neutrophils. Oxidative responses, particularly LDCL, were characterized by marked dayto-day variability, differed greatly within and between calves, were partially age-dependent, and were partially dependent on the individual agonist. Superoxide anion production had substantially less variability. We compared the in vitro oxidative (LDCL and O2-) responses of neutrophils isolated from neonatal calves stimulated by defined concentrations of the agonists-latex, phorbol myristate acetate, calcium ionophore, and opsonized zymosan-with responses to formylated oligopeptides and zymosan-activated serum, and to live, dead, live opsonized, and dead opsonized Pasteurella haemolytica organisms. Opsonization of particulates, pathogenic or nonpathogenic, enhanced the LDCL and O2- responses of stimulated neutrophils although P haemolytica was a less potent stimulant of oxidative functions than were nonbiological agonists. We conclude that the generation of reactive oxygen species by bovine neutrophils in response to P haemolytica is highly dependent on the presence of opsonins and is greatly enhanced in live vs killed bacteria. Futhermore, the in vitro generation of reactive oxygen species, including O2- by stimulated neutrophils, may be of biologic importance if similar events occur in vivo, and could have a major role in the pathogenesis of the acute lung injury associated with pneumonic pasteurellosis.

Thirty horses were randomly assigned to 1 of 5 groups. All horses were anesthetized and subjected to ventral midline celiotomy, then the large colon was exteriorized and instrumented. Colonic arterial blood flow was reduced to 20% of baseline (BL) and was maintained for 3 hours. Colonic blood flow was then restored, and the colon was reperfused for an additional 3 hours. One of 5 drug solutions was administered via the jugular vein 30 minutes prior to colonic reperfusion: group 1, 0.9% NaCl; group 2, dimethyl sulfoxide: 1 g/kg of body weight; group 3, allopurinol: 25 mg/kg; group 4, 21-aminosteroid U-74389G: 10 mg/kg; and group 5, manganese chloride (MnCl2): 10 mg/kg. Hemodynamic variables were monitored and recorded at 30-minutes intervals. Systemic arterial, systemic venous (SV), and colonic venous (CV) blood samples were collected for measurement of blood gas tensions, oximetry, lactate concentration, PCV, and plasma total protein concentration. The eicosanoids, 6-keto prostaglandin F1alpha, prostaglandin E2, and thromboxane B2, were measured in CV blood, and endotoxin was measured in CV and SV blood. Full-thickness biopsy specimens were harvested from the left ventral colon for histologic evaluation and determination of wet weight-to-dry weight ratios (WW:DW). Data were analyzed, using two-way ANOVA for repeated measures, and statistical significance was set at P < 0.05. Heart rate, mean arterial pressure, and cardiac output increased with MnCl2 infusion; heart rate and cardiac output remained increased throughout the study, but mean arterial pressure returned to BL values within 30 minutes after completion of MnCl2 infusion. Other drug-induced changes were not significant. There were significant increases in mean pulmonary artery and mean right atrial pressures at 2 and 2.5 hours in horses of all groups, but other changes across time or differences among groups were not observed. Mean pulmonary artery pressure remained increased through 6 hours in all groups, but mean right atrial pressure had returned to BL values at 3 hours. Mean colonic arterial pressure was significantly decreased at 30 minutes of ischemia and remained decreased through 6 hours; however, by 3.25 hours it was significantly higher than the value at 3 hours of ischemia. Colonic arterial resistance decreased during ischemia and remained decreased throughout reperfusion in all groups; there were no differences among groups for colonic arterial resistance. Colonic venous PO2, oxygen content, and pH decreased, and PCO2 and lactate concentration increased during ischemia but returned to BL values during reperfusion. Compared with BL values, colonic oxygen extraction ratio was increased from 0.5 to 3 hours. By 15 minutes of reperfusion, colonic oxygen extraction ratio had decreased from the BL value in all groups and either remained decreased or returned to values not different from BL through 6 hours. Colonic venous 6-keto prostaglandin F1alpha and prostaglandin E2 concentrations increased during ischemia, but returned to BL on reperfusion; there were no changes in thromboxane2 concentration among or within groups. Endotoxin was not detected in CV or SV blood after ischemia or reperfusion. There were no differences among or within groups for these variables. Low-flow ischemia and reperfusion (I-R) of the large colon caused mucosal injury, as evidenced by increases in percentage of surface mucosal disruption, percentage depth of mucosal loss, mucosal hemorrhage, mucosal edema, mucosal interstitial-to-crypt ratio, mucosal neutrophil index, submucosal venular neutrophil numbers, and mucosal cellular debris index. There was a trend (P = 0.06) toward greater percentage depth of mucosal loss at 6 hours in horses treated with dimethyl sulfoxide, compared with the vehicle control solution. There were no differences in the remainder of the histologic variables among groups. Full-thickness and mucosal WW:DW increased with colonic I-R, but there were no differences among groups. There was a trend (P = 0.09) toward neutrophil accumulation, as measured by myeloperoxidase activity, in the lungs after colonic I-R, but there were no differences among groups. There was no change in lung WW:DW after colonic I-R. There were no beneficial effects of drugs directed against oxygen-derived free radical-mediated damage on colonic mucosal injury associated with low-flow I-R. Deleterious drug-induced hemodynamic effects were not observed in this study.

Microvascular permeability of the jejunum of clinically normal equids and microvascular permeability associated with 60 minutes of ischemia (25% baseline blood flow) and subsequent reperfusion were investigated. Eight adult horses were randomly allotted to 2 equal groups: normal and ischemic/repertusion injury. Lymphatic flow rates, mesenteric blood flow, and lymph and plasma protein concentrations were determined at 15-minute intervals throughout the study. Microvascular permeability was determined by estimates of the osmotic reflection coefficient, which was determined when the ratio of lymphatic protein to plasma protein concentration reached a constant minimal value as lymph flow rate increased (filtration-independent lymph flow rate), which occurred at venous pressure of 30 mm of Hg. Full-thickness jejunal biopsy specimens were obtained at the beginning and end of each experiment, and were prepared for light microscopy to estimate tissue volume (edema) and for transmission electron microscopy to evaluate capillary endothelial cell morphology. The osmotic reflection coefficient for normal equine jejunum was 0.19 + 0.06, and increased significantly (P < 0.0001) to 0.48 + 0.05 after the ischemia/reperfusion period. Microscopic evaluation revealed a significant increase (P < 0.0001) in submucosal and serosal volume and capillary endothelial cell damage in horses that underwent ischemia/ reperfusion injury. Results indicate that ischemia/reperfusion of the equine jejunum caused a significant increase in microvascular permeability.

Twenty-four horses were randomly allocated to 3 groups. Horses were anesthetized, subjected to a ventral midline celiotomy, and the large colon was exteriorized and instrumented. Group-1 horses served as sham-operated controls. Group-2 horses were subjected to 6 hours of low-flow colonic arterial ischemia, and group-3 horses were subjected to 3 hours of ischemia and 3 hours of reperfusion. Baseline (BL) samples were collected, then low-flow ischemia was induced by reducing ventral colonic arterial blood flow to 20% of BL. All horses were monitored for 6 hours after BL data were collected. Blood samples were collected from the colonic vein and main pulmonary artery (systemic venous [SV]) for measurement of plasma endotoxin, 6-keto prostaglandin F1alpha (6-kPG), thromboxane B2 (TXB2), and prostaglandin E2 (PGE2) concentrations. Tumor necrosis factor and interleukin-6 activities were measured in colonic venous (CV) serum samples. Data were analyzed, using two-was ANOVA, and post-hoc comparisons were made, using Dunnett's and Tukey's tests. Statistical significance was set at P < 0.05 Endotoxin was not detected in CV or SV plasma at any time. There was no detectable tumor necrosis factor or interleukin-6 activity in CV samples at any time. There were no differences at BL among groups for CV or SV 6-kPG, PGE2, or TXB2 concentrations, nor were there any changes across time in group-1 horses. Colonic venous 6-kPG concentration increased during ischemia in horses of groups 2 and 3; CV 6-kPG concentration peaked at 3 hours in group-3 horses, then decreased during reperfusion, but remained increased through 6 hours in group-2 horses. Systemic venous 6-kPG concentration increased during reperfusion in group-3 horses, but there were no changes in group-2 horses. Colonic venous PGE2 concentration increased during ischemia in horses of groups 2 and 3, and remained increased for the first hour of reperfusion in group-3 horses and for the 6-hour duration of ischemia in group-2 horses. There were no temporal alterations in SV PGE2 concentration. There was no difference in CV or SV TXB2 concentration among or within groups across time; however, there was a trend (P = 0.075) toward greater CV TXB2 concentration at 3.25 hours, compared with BL, in group-3 horses. Eicosanoid concentrations were significantly lower in SV, compared with CV plasma. Prostaglandin E2 and 6-kPG concentrations were approximately 3 to 8 and 5 to 10 times greater, respectively, in CV than in SV plasma. The increased concentrations of 6-kPG and PGE2 in CV plasma were likely attributable to their accumulation secondary to colonic ischemia. The increased values of these vasodilator eicosanoids may have a role in the reactive hyperemia observed during reperfusion. The increased 6-kPG concentration in SV plasma may represent spillover from the colonic vasculature, but more likely reflects systemic production.

The effect of xylazine, cisapride, and naloxone on myoelectric activity of the ileum, cecum, and proximal loop of the ascending colon (PLAC) was determined in 4 healthy Jersey cows implanted with 8 pairs of bipolar electrodes. A 4 X 4 Latin square design was used. The treatments included xylazine (0.04 mg/kg of body weight), cisapride (0.08 mg/kg), naloxone (0.05 mg/kg), and 0.9% sodium chloride solution (20 ml). All treatments were administered IV during early phase I of the migrating myoelectric complex in the ileum. Myoelectric activity was recorded for 4 hours after treatment, and data were analyzed for each hour separately. Xylazine significantly (P < 0.05) increased the duration of phase I of the first migrating myoelectric complex in the ileum to 220.72 +/- 26.89 minutes, compared with 30.91 +/- 10.11 minutes after administration of 0.9% sodium chloride solution. The number of cecocolic spikes per minute per electrode and the duration of cecocolic spike activity (percentage of recording time) were significantly (P < 0.05) decreased for the first 3 hours, and the number of propagated spike sequences in the cecum and PLAC was significantly (P < 0.05) decreased for the first 2 hours after administration of xylazine. Significant difference was not found between control and either,cisapride or naloxone treatment of healthy cows. However, during hour 1 after treatment with cisapride, number of spikes per minute, duration of spike activity, and number of propagated spike sequences were highest, compared with the other treatments. It was concluded that naloxone at the dosage used in this study was not suitable for medical treatment of cecal dilatation in cattle, when hypomotility of the cecum and PLAC must be reversed. Xylazine should not be used for relief of signs of pain in cases of cecal dilatation, because it significantly reduced myoelectric activity of the cecum and PLAC for at least 2 hours after treatment. Furthermore, results of this study indicated a trend (P > 0.05) toward increase of cecocolic myoelectric activity after administration of cisapride. It is the authors' opinion that the potential benefit of cisapride for medical treatment of cecal dilatation in cattle needs further evaluation.

The effect of premedication with phenylbutazone on systemic hemodynamic and diuretic effects of furosemide was examined in 6 healthy, conscious, mares. Mares were instrumented for measurement of systemic hemodynamics, including cardiac output and pulmonary arterial, systemic arterial, and intracardiac pressures, and urine flow. Each of 3 treatments was administered in a randomized, blinded study; furosemide (1 mg/kg of body weight, IV) only, phenylbutazone (8.8 mg/kg PO, at 24 hours and 4.4 mg/kg IV, 30 minutes before furosemide) and furosemide, or 0.9% NaCl. Phenylbutazone administration significantly attenuated, but did not abolish, the diuretic effect of furosemide. Phenylbutazone completely inhibited the immediate effect of furosemide on cardiac output, stroke volume, total peripheral resistance, and right ventricular peak pressure. Premedication with phenylbutazone did not inhibit equally the diuretic and hemodynamic effects of furosemide, indicating that some of furosemide's hemodynamic effects are mediated by an extrarenal activity of furosemide.

We evaluated the single-cycle structural properties for axial compression, torsion, and 4-point bending with a central load applied to the caudal or lateral surface of a diaphyseal segment from the normal adult equine humerus, radius, third metacarpal bone, femur, tibia, and third metatarsal bone. Stiffness values were determined from load-deformation curves for each bone and test mode. Compressive stiffness ranged from a low of 2,690 N/mm for the humerus to a high of 5,670 N/mm for the femur. Torsional stiffness ranged from 558 N.m/rad for the third metacarpal bone to 2,080 N.m/rad for the femur. Nondestructive 4-point bending stiffness ranged from 3,540 N.m/rad for the radius to 11,500 N.m/rad for the third metatarsal bone. For the humerus, radius, and tibia, there was no significant difference in stiffness between having the central load applied to the caudal or lateral surface. For the third metacarpal and metatarsal bones, stiffness was significantly (P < 0.05) greater with the central load applied to the lateral surface than the palmar or plantar surface. For the femur, bones were significantly (P < 0.05) stiffer with the central load applied to the caudal surface than the lateral surface. Four-point bending to failure load-deformation curves had a bilinear pattern in some instances, consisting of a linear region at lower bending moments that corresponded to stiffness values from the nondestructive tests and a second linear region at higher bending moments that had greater stiffness values. Stiffness values from the second linear region ranged from 4,420 N.m/rad for the humerus to 13,000 N.m/rad for the third metatarsal bone. Differences in stiffness between nondestructive tests and the second linear region of destructive tests were significant (P < 0.05) for the radius, third metacarpal bone, and third metatarsal bone. Difference between stiffness values of paired left and right bones was not detected for any test. Four-point bending ultimate failure bending moments ranged from 260 N.m for the femur to 940 N.m for the third metatarsal bone. There was no difference in failure bending moment between the directions of applied central load for a given bone.

Ultrasonographic cross-sectional area (CSA) measurements of equine superficial digital flexor (SDF) tendon were obtained to determine the feasibility of ultrasonography for CSA measurement of tendon in vivo and in vitro. Ultrasonographic measurements were compared with a more traditional CSA measurement method, ink-blot analysis. In addition, values for ultrasonographic SDF tendon mean echogenicity were obtained in vivo and in vitro. The left forelimb SDF tendons of 23 horses were evaluated ultrasonographically. Cross-sectional images were acquired at 4-cm intervals distal to the base of the accessory carpal bone (DACB) to the level of the proximal sesamoid bones while horses were standing squarely. After euthanasia, the left forelimbs were mounted in a materials testing system (MTS) and loaded under tension to standing load. Ultrasonographic images were again acquired at the same locations. The ultrasonographic images were digitized, and values for ultrasonographic CSA and mean echogenicity were obtained for each level. Immediately after mechanical testing, a 1-cm-thick transverse section of SDF tendon at 12 cm DACB was removed. Three ink blots were prepared from each end of the removed tendon section and digitized. The 6 CSA values were averaged to generate a value for morphologic CSA for each SDF tendon at 12 cm DACB. Standing ultrasonographic tendon CSA at 12 cm DACB was consistently smallest (mean +/- SD CSA = 86 +/- 11 mm2), followed by MTS ultrasonographic CSA (mean, 95 +/- 12 mm2), with ink-blot morphologic CSA being largest (mean, 99 +/- 15 mm2). Comparison of standing and MTS ultrasonographic values at 12 cm DACB revealed a strong positive linear correlation between methods (R2 = 0.74, P = 0.001). Comparison of ink-blot CSA at 12 cm DACB with standing and MTS ultrasonographic CSA revealed strong positive linear correlations (R2 = 0.64, P = 0.001 and R2 = 0.72, P = 0.001, respectively). For ultrasonographic mean echogenicity, standing values insignificantly exceeded MTS values at each level. The authors conclude that ultrasonography is a useful technique for the noninvasive assessment of SDF tendon CSA that can be applied in vivo and in vitro.