Spontaneous in vitro contractile activity of specimens from the abomasal wall of healthy cows and comparison among dairy breeds

OBJECTIVE: To characterize and compare in vitro contractility patterns of sections of abomasal wall harvested from cattle of 3 dairy breeds. SAMPLE POPULATION: Longitudinal and circular smooth muscle preparations harvested from the antrum and body of the abomasum of 30 recently slaughtered Holstein-Friesian, Brown Swiss, and Simmental X Red Holstein cows. PROCEDURE: Spontaneous isometric contractions of specimens in tissue baths of modified Krebs solution were recorded during a 4-hour period. Maximal amplitude, frequency of contractions, and change of basal tension were used to characterize contractility. Statistical analyses were used to test for differences among time periods, among breeds, between specimen locations, and between fiber orientations. RESULTS: Myoactivity patterns of abomasal smooth muscle preparations are highly variable and differ on the basis of location and fiber orientation. Frequency of contractions differed significantly among time periods for longitudinally oriented specimens with decreasing frequencies of contractions over time. Maximal amplitude of the longitudinally oriented specimens from the antrum increased significantly, whereas maximal amplitude of the circularly oriented specimens from the antrum decreased significantly. Values did not differ significantly among breeds. CONCLUSIONS AND CLINICAL RELEVANCE: Patterns of spontaneous contractility of abomasal wall specimens are not homogeneous. During a 4-hour recording period, maximal amplitude and frequency of contractions of specimens varied significantly with respect to orientation and location; however, spontaneous contractile myoactivity did not differ significantly among breeds. Therefore, breed predisposition for displaced abomasum is not correlated with spontaneous activity of smooth muscle specimens.     

Estrous cycle-dependent differences in responsiveness to prostaglandins and contractile agents in sheep (Ovis aries) cervical smooth muscle

We investigated the influence of the phase of the estrous cycle on mechanical responses elicited in sheep cervix by potassium chloride (KCl), acetylcholine chloride (ACh), prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E1 (PGE1). The cervix of adult ewes (n = 48) were classified according to the presence or absence of corpora lutea (luteal or follicular phase, respectively). Muscle strips of the circular and longitudinal layers were prepared in an organ bath and coupled to an isometric force transducer. Concentration-response curves were obtained noncumulatively. KCl and ACh produced concentration-dependent contractions in all preparations in both phases of the estrous cycle. However, maximum effect, EC50 and slope values of KCl and ACh were not significantly different between muscle layers, as well as between the phases of the estrous cycle. The prostanoid, PGF2 alpha, produced a significant reduction in the amplitude of spontaneous contractions for all preparations. The depressant effect of PGF2 alpha on spontaneous contractions of circular smooth muscle was significantly greater during the follicular than the luteal phase, whilst the depressant effect of PGF2 alpha on the longitudinal layer did not differ between phases of the estrous cycle. PGE1 significantly reduced the amplitude of spontaneous contractions on circular but not on longitudinal preparations. In conclusion, we have characterized with in vitro preparations of circular and longitudinal muscle layers of ewes during the follicular and luteal phases of the estrous cycle, the parameters of the K- and ACh-induced contractions on cervix and the efficacy of PGF2 alpha and PGE1 on inhibition spontaneous contractile activity.     

Effect of endotoxins on contractility of smooth muscle preparations from the bovine abomasal antrum

The effects of endotoxin (ET) on spontaneous contractility and of carbachol- and alpha-methyl-5-hydroxytryptamine-(alpha-M-5-HT; 5-HT2 receptor agonist) induced contractions of smooth muscle preparations from the bovine abomasal antrum were investigated in vitro. Preparations from the abomasal antrum of freshly slaughtered healthy dairy cows were cut parallel to the longitudinal and circular fibres, suspended in isolated organ baths, and contractility was recorded and analyzed, using digitalized data. The traits maximum amplitude, time till maximum amplitude, frequency, basal tone, and area under curve were calculated. The contractile effect of Carbachol (CH) was concentration dependent. Repeated administration of CH (3.75 x 10(-6) M), each time interrupted by flushing of the organ baths, did not reveal any significant effect on contractility traits of CH-induced contractions. Endotoxin (10 micrograms/ml; lipopolysaccharide from E. coli, O26:B6) significantly reduced some of the spontaneously occurring contractility traits and of carbachol-(3.75 x 10(-6) M) and alpha-M-5-HT-induced (2.14 x 10(-5) M) contractions. The effects of higher and lower concentrations of ET occurred less consistently. The inhibitory effect of endotoxin was more pronounced after 6 hours as compared to 2 hours of incubation. The results of the present study (i) support the hypothesis of a possible role of endotoxin in reducing motility of the abomasum during the development of spontaneous abomasal displacement in dairy cows, and (ii) may serve as the basis for the development of an in vitro model of abomasal displacement with endotoxemia for future studies on the effect of motility modulating drugs.     

Expression and function of 5-HT7 receptors in smooth muscle preparations from equine duodenum, ileum, and pelvic flexure

In horses, gastrointestinal (GI) disorders occur frequently and cause a considerable demand for efficient medication. 5-Hydroxytryptamine receptors (5-HT) have been reported to be involved in GI tract motility and thus, are potential targets for treating functional bowel disorders. Our studies extend current knowledge on the 5-HT₇ receptor in equine duodenum, ileum and pelvic flexure by studying its expression throughout the intestine and its role in modulating contractility in vitro by immunofluorescence and organ bath experiments, respectively.5-HT₇ immunoreactivity was demonstrated in both smooth muscle layers, particularly in the circular one, and within the myenteric plexus. Interstitial cells of Cajal (ICC), identified by c-Kit labeling, show a staining pattern similar to that of 5-HT₇ immunoreactivity.The selective 5-HT₇ receptor antagonist SB-269970 increased the amplitude of contractions in spontaneous contracting specimens of the ileum and in electrical field-stimulated specimens of the pelvic flexure concentration-dependently.Our in vitro experiments suggest an involvement of the 5-HT₇ receptor subtype in contractility of equine intestine. While the 5-HT₇ receptor has been established to be constitutively active and inhibits smooth muscle contractility, our experiments demonstrate an increase in contractility by the 5-HT₇ receptor ligand SB-269970, suggesting it exerting inverse agonist properties.     

In vitro investigation of the effect of prostaglandins and nonsteroidal anti-inflammatory drugs on contractile activity of the equine smooth muscle of the dorsal colon, ventral colon, and pelvic flexure

OBJECTIVES: To determine the in vitro effect of prostaglandin E2 (PGE2), PGF2alpha, PGI2; and nonsteroidal anti-inflammatory drugs (NSAID; ie, flunixin meglumine, ketoprofen, carprofen, and phenylbutazone) on contractile activity of the equine dorsal colon, ventral colon, and pelvic flexure circular and longitudinal smooth muscle. ANIMALS: 26 healthy horses. PROCEDURE: Tissue collected from the ventral colon, dorsal colon, and pelvic flexure was cut into strips and mounted in a tissue bath system where contractile strength was determined. Incremental doses of PGE2, PGF2alpha,, PGI2, flunixin meglumine, carprofen, ketoprofen, and phenylbutazone were added to the baths, and the contractile activity was recorded for each location and orientation of smooth muscle. RESULTS: In substance P-stimulated tissues, PGE2 and PGF2alpha enhanced contractility in the longitudinal smooth muscle with a decrease or no effect on circular smooth muscle activity. Prostaglandin I2 inhibited the circular smooth muscle response with no effect on the longitudinal muscle. The activity of NSAID was predominantly inhibitory regardless of location or muscle orientation. CONCLUSIONS AND CLINICAL RELEVANCE: In the equine large intestine, exogenous prostaglandins had a variable effect on contractile activity, depending on the location in the colon and orientation of the smooth muscle. The administration of NSAID inhibited contractility, with flunixin meglumine generally inducing the most profound inhibition relative to the other NSAID evaluated in substance P-stimulated smooth muscle of the large intestine. The results of this study indicate that prolonged use of NSAID may potentially predispose horses to develop gastrointestinal tract stasis and subsequent impaction.     

In vitro effects of bethanechol on smooth muscle preparations from abomasal fundus, corpus, and antrum of dairy cows

Abomasal displacement has been associated with gastric hypomotility. The supply of prokinetic drugs available to address this problem is insufficient. The goal of the study was to investigate the effect of the muscarinic agonist bethanechol (BeCh) on contractility parameters of smooth muscle preparations from several regions of the bovine abomasum (fundus, corpus, and antrum). Cumulative concentration-response curves were constructed using BeCh in vitro with and without pre-incubation with antagonists targeted at M(2) and M(3) muscarinic acetylcholine receptor (mAChR) subtypes. In all preparations investigated, BeCh induced a significant and concentration-dependent increase in all contractility parameters investigated. The maximal attainable effect (V(max)) was more pronounced in circular specimens, and V(max) of antral specimens in circular orientation were significantly lower when compared to the other preparations. Both antagonists caused a rightward shift of the concentration-response curve, suggesting that the effect of BeCh is mediated at least partly by M(2) and M(3) AChRs.     

Effect of sodium butyric acid, sodium valerianic acid, and osmolarity on contractility of specimens of intestinal wall obtained from the cecum and spiral colon of healthy cows

OBJECTIVE: To compare the effect of various concentrations of sodium butyric acid and sodium valerianic acid, as well as various osmolarities, on contractility of ex-vivo intestinal wall specimens obtained from the cecum and spiral colon of each of several healthy cows. SAMPLE POPULATION: Full-thickness preparations of intestinal wall, dissected parallel to the longitudinal smooth muscle layers, harvested from freshly slaughtered healthy cows. PROCEDURE: Specimens of intestinal wall were incubated for 5 minutes with various concentrations of sodium butyric acid and sodium valerianic acid as well as various osmolar concentrations of NaCl, using a crossover design. Isometric contractions were induced 7 times with carbachol (CH; 5 X 10(-6) mol/L). Contractility was defined as the maximum amplitude of contraction and the amplitude of contraction 2 minutes after addition of CH. RESULTS: Repeated addition of CH did not result in a significant effect on contractility of specimens from the cecum and spiral colon. Contractility after addition of CH was not significantly affected by prior incubation with various concentrations of sodium butyric acid or sodium valerianic acid or after an increase of osmolarity. Maximum amplitude of contraction was significantly higher in specimens from the spiral colon, compared with specimens from the cecum. CONCLUSIONS: Increases in concentrations of sodium butyric acid or sodium valerianic acid and increases in osmolarity did not inhibit contractility of intestinal wall specimens from the cecum and spiral colon of a group of healthy cows.     

In vitro investigation of the effects of nonsteroidal anti-inflammatory drugs, prostaglandin E2, and prostaglandin F2alpha on contractile activity of the third compartment of the stomach of llamas

OBJECTIVE: To determine the in vitro effect of prostaglandin (PG) E2, PGF2alpha, and the nonsteroidal anti-inflammatory drugs (NSAIDs) indomethacin, ketoprofen, and nabumetone on the contractile strength of the circular smooth muscle layer of the third compartment of the stomach of llamas. SAMPLE POPULATION: Specimens of the third compartment obtained from 5 healthy adult llamas. PROCEDURE: Full-thickness tissue samples were collected from the third compartment immediately after euthanasia. Specimens were cut into strips oriented along the circular muscle layer and mounted in a tissue bath system. Incremental amounts of ketoprofen, nabumetone, indomethacin, PGE2, and PGF2alpha were added, and contractile strength (amplitude of contractions) was recorded. RESULTS: Generally, PGE2 reduced contractile strength of the circular smooth layer of the third compartment, whereas PGF2alpha, increased the strength of contractions. The activity of the NSAIDs was generally excitatory in a concentration-dependent manner, although significant changes were induced only by administration of indomethacin. CONCLUSIONS AND CLINICAL RELEVANCE: On isolated smooth muscle strips of the third compartment of llamas, exogenous PGE2 and PGF2alpha had a variable effect on contractile strength. Administration of the NSAIDs did not inhibit contractility and would not be likely to induce stasis of the third compartment in the absence of an underlying disease process.     

Effects of rosiglitazone, a PPAR-γ agonist, on the contractility of bovine uterus in vitro

Rosiglitazone is a drug used in human medicine for treating type II diabetes mellitus. It activates Peroxisome Proliferators-Activated Receptors gamma (PPAR-γ), which regulate energetic metabolism. We aimed to evaluate the effects of rosiglitazone on bovine myometrial contractility in vitro . Myometrial strips were collected from uteri of cows in estrus, diestrus, and pregnancy. Contractions were recorded using an isometric force transducer. After the equilibration period, rosiglitazone (1 × 10⁻⁶) was added to the bath. Its effects on the amplitude and frequency of spontaneous contractions were evaluated. Data were analyzed using an ANOVA and Student's t -test and were considered significant at P  < 0.05. Rosiglitazone increased the mean amplitude during estrus ( P  < 0.01), diestrus ( P  < 0.05), and pregnancy ( P  < 0.01); the frequency of contractions in both pregnancy ( P  < 0.05) and diestrus ( P  < 0.05) increased as well. These effects are likely due, in our opinion, to an increase in intracellular calcium concentrations, as well as enhanced uptake of glucose from the Krebs' solution. The differences observed according in the different phases are ascribable to the different hormonal milieu. Our study indicates that rosiglitazone affects bovine myometrial contractility. It may be considered a starting point for further studies on the application of this drug in veterinary obstetrics.     

Tissue Doppler Imaging and Two-Dimensional Speckle Tracking of Left Ventricular Function in Healthy Horses After Clenbuterol Application

The cardiac effects of high dosages of the ß²-adrenergic agent clenbuterol have been the focus of several histological, biochemical and echocardiographic studies in the past. Possible effects of a therapeutic dosage on myocardial contractility and velocities have not been evaluated using tissue Doppler imaging (TDI) and two-dimensional speckle tracking (2DST) in equine medicine. Twenty-five healthy horses were treated over 14 days with clenbuterol in a normal dosage (0.8 μg/kg every 12 hours). Before and after the treatment, an echocardiographic examination was performed using B-mode, M-mode, color flow Doppler, and tissue Doppler imaging (TDI). In all horses, the radial and circumferential myocardial functions were recorded in the right parasternal short-axis view (SAX). Pulsed-wave (PW) and color TDI were used for evaluation of peak and mean myocardial velocities; myocardial deformation was documented in 2DST. An improvement of diastolic function after clenbuterol treatment was demonstrated by a significant increase of the early diastolic radial wall motion velocity (E_m) in all myocardial sections except the right ventricular free wall (RVFW) in TDI, as well as an increase of the E/A quotient in the left ventricular free wall (LVFW) and the interventricular septum (IVS). Shortened time intervals, in particular in the LVFW and a tendency of increase of all deformation parameters showed improved relaxation characteristics of the cardiac muscle after treatment. The results can be interpreted as beginning physiologic cardiac hypertrophy due to clenbuterol treatment. No signs of increased rigidity or reduced compliance of the heart muscle could be found at the applied dosage. This study demonstrates the sensitivity of TDI and 2DST in equine cardiology to detect myocardial remodeling before the appearance of obvious findings in conventional echocardiographic techniques. This technique can be used to detect pharmacologic effects on myocardial function.     

In vitro effects of cisapride, metoclopramide and bethanechol on smooth muscle preparations from abomasal antrum and duodenum of dairy cows

The objective of this study was to investigate the effects of cisapride (CIS), metoclopramide (MET) and bethanechol (BET) on contractility parameters from smooth muscle preparations of the abomasal antrum and proximal duodenum of cows. Smooth muscle preparations were harvested shortly post-mortem from 42 healthy dairy cows, and concentration-response curves were performed by cumulative application of the drugs. Cisapride and MET did not have any significant effect on the contractility parameters studied, while BET induced a significant, concentration-dependent increase in basal tone (BT), mean amplitude (Amean), and area under the curve (AUC) in smooth muscle preparations from the abomasal antrum, but not from the duodenum. The effect of BET on BT was more pronounced in specimens with longitudinal orientation while the maximal obtainable effect (Vm) in Amean was more pronounced in circular-oriented preparations. Atropine (1 x 10-5 m) significantly inhibited the effect of BET, whereas pre-incubation with hexamethonium or tetrodotoxin (TTX) had no effect, suggesting that the effect was mediated by cholinergic receptors on the smooth muscle. The results may be relevant to diseases or disorders associated with gastric emptying and gastric hypomotility. Further investigations are warranted to investigate the potential ability of BET to enhance abomasal emptying of adult dairy cows.     

Quantitative motor unit action potential analysis of skeletal muscles in the Warmblood horse

Motor unit action potential (MUP) analysis in human medicine is a valuable and important diagnostic technique enabling discrimination between myogenic and neurogenic problems. This study establishes normative data in subclavian, triceps and lateral vastus muscles for clinical application of MUP analysis in the Warmblood horse, and examines whether muscle differences are present. Electromyographic (EMG) needle examination and MUP analysis were performed of the triceps, lateral vastus and subclavian muscles in 7 awake, nonsedated, Warmblood horses age 4-10 years. The amplitude, duration, number of phases and turns were calculated from the recorded superimposed MUPs together with intramuscular and rectal temperatures. No significant differences were found in duration of insertional activity between the 3 muscles. The mean +/- s.d. duration of the insertional activity was 526 +/- 1483 ms. The MUP amplitude of all 3 muscles differed significantly, with the highest amplitude (427 +/- 3.20 microV) in the triceps and the lowest (220 +/- 2.08 microV) in the subclavian muscle. The number of turns of the lateral vastus (3.0 +/- 1.22) was significantly higher than that of the triceps muscle (2.7 +/- 1.51). No differences were found in MUP duration (5.9-6.4 ms).     

Calcium regulation by skeletal muscle membranes of horses with recurrent exertional rhabdomyolysis

OBJECTIVE: To determine whether an alteration in calcium regulation by skeletal muscle sarcoplasmic reticulum, similar to known defects that cause malignant hyperthermia (MH), could be identified in membrane vesicles isolated from the muscles of Thoroughbreds with recurrent exertional rhabdomyolysis (RER). SAMPLE POPULATION: Muscle biopsy specimens from 6 Thoroughbreds with RER and 6 healthy (control) horses. PROCEDURES: RER was diagnosed on the basis of a history of > 3 episodes of exertional rhabdomyolysis confirmed by increases in serum creatine kinase (CK) activity. Skeletal muscle membrane vesicles, prepared by differential centrifugation of muscle tissue homogenates obtained from the horses, were characterized for sarcoplasmic reticulum (SR) activities, including the Ca2+ release rate for the ryanodine receptor-Ca2+ release channel, [3H]ryanodine binding activities, and rate of SR Ca2+-ATPase activity and its activation by Ca2+. RESULTS: Time course of SR Ca2+-induced Ca2+ release and [3H]ryanodine binding to the ryanodine receptor after incubation with varying concentrations of ryanodine, caffeine, and ionized calcium did not differ between muscle membranes obtained from control and RER horses. Furthermore, the maximal rate of SR Ca2+-ATPase activity and its affinity for Ca2+ did not differ between muscle membranes from control horses and horses with RER. CONCLUSIONS AND CLINICAL RELEVANCE: Despite clinical and physiologic similarities between RER and MH, we concluded that RER in Thoroughbreds does not resemble the SR ryanodine receptor defect responsible for MH and may represent a novel defect in muscle excitation-contraction coupling, calcium regulation, or contractility.     

The effect of cholecystokinin peptides on ovine duodeno-jejunal slow waves with and without pretreatment with proglumide

Cholecystokinin exerts a composite influence on gastrointestinal motility but little is known about its effect on small-intestinal slow waves. Thus, six rams were implanted with four bipolar serosal electrodes onto the duodeno-jejunal wall. In the course of chronic experiments the myoelectric activity was continuously recorded in the non-fasted animals. After recording of the full normal migrating myoelectric complex (MMC), 0.15 M NaCl or CCK peptides were injected intravenously during various phases of the next MMC cycle. Five ml of saline was injected over 30 s during phases 1, 2a, or 2b of the MMC. Cerulein was administered at doses of 1 (over 30 s), 10 (over 30 or 60 s), or 100 ng/kg (over 30, 60, 120 or 300 s) and cholecystokinin octapeptide (CCK-OP) at doses 20 times higher. CCK peptides were applied during early or late phase 1 of the MMC and during phases 2a and 2b of the MMC. In the course of additional experiments, saline and hormone administration was directly preceded by infusion of proglumide, an unspecific CCK receptor antagonist, at a dose of 10 mg/kg. The myoelectric recordings were continued until the arrival of a subsequent regular phase 3 of the MMC. In the duodenal bulb, slow waves were occasionally observed. In the duodenum the slow-wave frequency oscillated between 20 and 24 cpm and in the jejunum between 19 and 22 cpm before or after CCK peptides and proglumide. In the duodenum the slow-wave amplitude increased significantly after all doses of cerulein injected during phase 2b of the MMC. After administration of CCK-OP changes in duodenal slow-wave amplitude were not significant but exhibited a tendency similar to those after cerulein. In the jejunum, injection of cerulein and CCK-OP during phase 2 of the MMC increased the slow-wave amplitude significantly and the duration of these changes was longer than in the duodenum. After infusion of proglumide, administration of cerulein at the low dose over 30 s and at the high dose over 300 s in the course of late phase 1 and phases 2a and 2b of the MMC, significantly increased the duodenal slow-wave amplitude. Cerulein injection during phase 2b of the MMC at the high dose over 30 and 60 s, preceded by proglumide infusion, significantly inhibited the duodenal slow-wave amplitude. In the jejunum these changes were even more pronounced and their duration was much longer. It is concluded that CCK peptides affect slow-wave amplitude in the duodeno-jejunum in non-fasted sheep. This effect is stronger in the jejunum and is altered but not abolished by pretreatment with proglumide. Cerulein evokes more pronounced alterations in the slow-wave amplitude than CCK-OP in conscious sheep.     

Adrenergic, cholinergic, and nonadrenergic-noncholinergic intrinsic innervation of the jejunum in horses.

OBJECTIVE: To determine the major neurotransmitters that regulate contractile activity in the jejunum of horses. SAMPLE POPULATION: Jejunal specimens from 65 horses without gastrointestinal tract lesions. PROCEDURE: Jejunal smooth muscle strips, oriented in the plane of the circular or longitudinal muscular layer, were suspended isometrically in muscle baths. Neurotransmitter release was induced by electrical field stimulation (EFS) delivered at 30 and 70 V intensities and at various frequencies on muscle strips maintained at low or high muscle tone. To detect residual nonadrenergic-noncholinergic neurotransmission, the response of muscle to EFS in the presence of adrenergic and cholinergic blockade was compared with the response in the presence of tetrodotoxin. RESULTS: Atropine (ATR) decreased the contractile response of muscle strips to EFS under most conditions. However, ATR increased the contractile response of high-tone circular muscle. Adrenergic blockade generally increased the muscle responses to 30 V EFS and in high-tone longitudinal muscle but decreased contractile responses in high-tone circular muscle. Tetrodotoxin significantly altered the responses to EFS, compared with adrenergic and cholinergic receptor blockade. CONCLUSIONS: Acetylcholine and norepinephrine appear to be important neurotransmitters regulating smooth muscle contractility in the equine jejunum. They induce contraction and relaxation, respectively, in most muscle preparations, although they may cause opposite effects under certain conditions. In addition, nonadrenergic-noncholinergic excitatory and inhibitory influences were detected. CLINICAL RELEVANCE: Acetylcholine or norepinephrine release within the myenteric plexus of horses may alter gastrointestinal motility.     

Sedative, analgesic and cardiorespiratory effects of romifidine in cats

OBJECTIVE: To evaluate the sedative, analgesic, and cardiorespiratory effects of intramascular (IM) romifidine in cats. STUDY DESIGN: Prospective, randomized experimental trial. ANIMALS: Ten healthy adult cats. METHODS: Romifidine (100, 200, and 400 microg kg(-1)) or xylazine (1 mg kg(-1)) was given IM in a cross-over study design. Heart rate (HR), respiratory rate (RR), rectal temperature (RT), hemoglobin saturation, oscillometric arterial pressure, and scores for sedation, muscle relaxation, position, auditory response, and analgesia were determined before and after drug administration. Time to recumbency, duration of recumbency, and time to recover from sedation were determined. Subjective evaluation and cardiorespiratory variables were recorded before and at regular intervals for 60 minutes after drug administration. RESULTS: Bradycardia developed in all cats that were given romifidine or xylazine. No other significant differences in physiologic parameters were observed from baseline values or between treatments. Increasing the dose of romifidine did not result in increased sedation or muscle relaxation. Cats given xylazine showed higher sedation and muscle relaxation scores over time. Analgesia scores were significantly higher after administration of romifidine (400 microg kg(-1)) and xylazine (1 mg kg(-1)) than after romifidine at 100 or 200 microg kg(-1). Duration of lateral recumbency was not significantly different between treatments; however, cats took longer to recover after administration of 400 micro g kg(-1) romifidine. CONCLUSIONS AND CLINICAL RELEVANCE: Bradycardia is the most important adverse effect after IM administration of romifidine at doses ranging from 100 to 400 microg kg(-1) or 1 mg kg(-1) of xylazine in cats. The sedative effects of romifidine at 200 microg kg(-1) are comparable to those of 1 mg kg(-1) of xylazine, although muscle relaxation and analgesia were significantly less with romifidine than with xylazine.     

Anovulation and plasma hormone concentrations after administration of dexamethasone during the middle of the luteal phase in sows undergoing estrous cycles

The effect of glucocorticoids on early follicular growth in sows undergoing normal estrous cycles was evaluated by administration of dexamethasone during the middle of the luteal phase. Plasma specimens were obtained for measurement of luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone, and estradiol-17 beta concentrations. Fifteen sows were used. Control sows (n = 5) were given physiologic saline solution twice daily from day 9 to day 14 of the estrous cycle. Sows of the second group (n = 5) were given dexamethasone (30 micrograms/kg of body weight, IM) similarly, and those of the third group (n = 5) were given dexamethasone plus gonadotropin-releasing hormone (GnRH; 50 micrograms at 6-hour intervals, IV). Plasma specimens, obtained twice daily from day 8 through day 26, indicated that progesterone production and luteal regression were not inhibited by any of the 3 treatment regimens. Although preovulatory plasma estradiol concentration increased in control sows, such was not observed in the sows treated with dexamethasone or dexamethasone plus GnRH (P less than 0.01). Ovulation, with formation of corpora lutea, occurred in gilts given saline solution. Dexamethasone administration resulted in persistence of 19 to 41 follicles/ovary (2 to 4 mm in diameter), and dexamethasone-plus-GnRH treatment resulted in 6 to 18 follicles/ovary (5 to 6 mm in diameter). Plasma was obtained at 15-minute intervals for 12 hours to compare the effect of treatment on hormone concentrations on day 12 of the estrous cycle with the values on day 8.(ABSTRACT TRUNCATED AT 250 WORDS)     

In vitro effects of bethanechol on specimens of intestinal smooth muscle obtained from the duodenum and jejunum of healthy dairy cows

OBJECTIVE: To describe the in vitro effects of bethanechol on contractility of smooth muscle preparations from the small intestines of healthy cows and define the muscarinic receptor subtypes involved in mediating contraction. SAMPLE POPULATION: Tissue samples from the duodenum and jejunum collected immediately after slaughter of 40 healthy cows. PROCEDURES: Cumulative concentration-response curves were determined for the muscarinic receptor agonist bethanechol with or without prior incubation with subtype-specific receptor antagonists in an organ bath. Effects of bethanechol and antagonists and the influence of intestinal location on basal tone, maximal amplitude (A(max)), and area under the curve (AUC) were evaluated. RESULTS: Bethanechol induced a significant, concentration-dependent increase in all preparations and variables. The effect of bethanechol was more pronounced in jejunal than in duodenal samples and in circular than in longitudinal preparations. Significant inhibition of the effects of bethanechol was observed after prior incubation with muscarinic receptor subtype M(3) antagonists (more commonly for basal tone than for A(max) and AUC). The M(2) receptor antagonists partly inhibited the response to bethanechol, especially for basal tone. The M(3) receptor antagonists were generally more potent than the M(2) receptor antagonists. In a protection experiment, an M(3) receptor antagonist was less potent than when used in combination with an M(2) receptor antagonist. Receptor antagonists for M(1) and M(4) did not affect contractility variables. CONCLUSIONS AND CLINICAL RELEVANCE: Bethanechol acting on muscarinic receptor sub-types M(2) and M(3) may be of clinical use as a prokinetic drug for motility disorders of the duodenum and jejunum in dairy cows.     

Evaluation of substance P as a neurotransmitter in equine jejunum

OBJECTIVE: To determine whether substance P (SP) functions as a neurotransmitter in equine jejunum. SAMPLE POPULATION: Samples of jejunum obtained from horses that did not have lesions in the gastrointestinal tract. PROCEDURE: Jejunal smooth muscle strips, oriented in the plane of the circular or longitudinal muscle, were suspended isometrically in muscle baths. Neurotransmitter release was induced by electrical field stimulation (EFS) delivered at 2 intensities (30 and 70 V) and various frequencies on muscle strips that were maintained at low tension or were under contraction. A neurokinin-1 receptor blocker (CP-96,345) was added to baths prior to EFS to interrupt SP neurotransmission. Additionally, direct effects of SP on muscle strips were evaluated, and SP-like immunoreactivity was localized in intestinal tissues, using indirect immunofluorescence testing. RESULTS: Substance P contracted circularly and longitudinally oriented muscle strips. Prior treatment with CP-96,345 altered muscle responses to SP and EFS, suggesting that SP was released from depolarized myenteric neurons. Depending on orientation of muscle strips and stimulation variables used, CP-96,345 increased or decreased the contractile response to EFS. Substance P-like immunoreactivity was detected in the myenteric plexus and circular muscle layers. CONCLUSIONS AND CLINICAL RELEVANCE: Substance P appears to function as a neurotransmitter in equine jejunum. It apparently modulates smooth muscle contractility, depending on preexisting conditions. Effects of SP may be altered in some forms of intestinal dysfunction. Altering SP neurotransmission in the jejunum may provide a therapeutic option for motility disorders of horses that are unresponsive to adrenergic and cholinergic drugs.     

In vitro effects of erythromycin, lidocaine, and metoclopramide on smooth muscle from the pyloric antrum, proximal portion of the duodenum, and middle portion of the jejunum of horses

OBJECTIVE: To evaluate effects of erythromycin, lidocaine, and metoclopramide on smooth muscle of the pyloric antrum (PA), proximal portion of the duodenum (PD), and middle portion of the jejunum (MJ) of horses. Sample Population-Strips of smooth muscle from 7 horses. PROCEDURE: Isolated muscle strips were suspended in a bath and attached to isometric force transducers. Once stable spontaneous contractions were observed, agents were added. Isometric stress responses were compared with the amplitude of spontaneous contractions. RESULTS: A single dose of erythromycin to the PA increased contractile amplitude (CA) for the longitudinal smooth muscle (mean +/- SEM, 76+/-16 g/cm2) but decreased CA for circular smooth muscle (-79+/-23 g/cm2). The inhibitory effect was decreased by tetrodotoxin, N(G)-nitro-L-arginine methyl ester, and a vasoactive intestinal peptide antagonist. Erythromycin increased CA for the MJ, which was maximal at 10(-4)M (171+/-36 g/cm2). Lidocaine increased CA for the PD, which was maximal at 10(-4) M (60+/-5 g/cm2). Metoclopramide increased the CA, which was maximal at 10(-4) M for the PA (75+/-26 g/cm2), PD (279+/-33 g/cm2), and MJ (456+/-59 g/cm2). CONCLUSIONS: Regional differences in responses to erythromycin, lidocaine, and metoclopramide were evident in the gastrointestinal tract of horses. Metoclopramide increased CA in all tissues used, whereas erythromycin inhibited CA in circular smooth muscle but stimulated CA in longitudinal smooth muscle from the PA. Inhibition is caused by stimulation of inhibitory nerves and is mediated, in part, by nitric oxide and vasoactive intestinal peptide.