Effect of erythromycin and gentamicin on abomasal emptying rate in suckling calves

BACKGROUND: Commonly used dosage protocols for antimicrobial agents may alter the rate of gastric emptying. HYPOTHESIS: Parenteral administration of erythromycin increases and gentamicin decreases the rate of abomasal emptying. ANIMALS: Five male Holstein-Friesian calves (8-15 days of age). METHODS: Calves received each of the following 4 IM treatments in random order: control, 2 mL of 0.9% NaCl; erythromycin, 8.8 mg/kg; low-dose gentamicin, 4.4 mg/kg; high-dose gentamicin, 6.6 mg/kg. Abomasal emptying rate was assessed by acetaminophen and glucose absorption. Calves were fed 2 L of cow's milk containing acetaminophen (50 mg/kg body weight) 30 minutes after each treatment was administered, and jugular venous blood samples were obtained periodically after suckling. The maximum observed plasma acetaminophen concentration (actual C(max)) and time of actual C(max) (actual T(max)) were determined, and pharmacokinetic modeling was used to calculate model C(max) and model T(max). RESULTS: Erythromycin increased abomasal emptying rate, as indicated by a shorter time to actual T(max) and model T(max) (P < .05). Abomasal emptying rate after injection of low-dose gentamicin was similar to that of control. Administration of high-dose gentamicin resulted in a longer time to actual T(max) (P= .021) but did not change model T(max) (P= .62). CONCLUSIONS AND CLINICAL RELEVANCE: IM injection of erythromycin increased abomasal emptying rate in dairy calves, whereas low-dose and high-dose gentamicin did not alter the rate of abomasal emptying as measured by acetaminophen kinetics and glucose absorption. The clinical relevance of these findings remains to be determined.     

Effect of parenteral administration of erythromycin, tilmicosin, and tylosin on abomasal emptying rate in suckling calves

OBJECTIVE: To determine the effect of parenteral administration of erythromycin, tilmicosin, and tylosin on abomasal emptying rate in suckling calves. ANIMALS: 8 male Holstein-Friesian calves < 35 days old. PROCEDURES: Calves received each of 4 treatments in random order (2 mL of saline [0.9% NaCl] solution, IM [control treatment]; erythromycin, 8.8 mg/kg, IM; tilmicosin, 10 mg/kg, SC; and tylosin, 17.6 mg/kg, IM). Calves were fed 2 L of milk replacer containing acetaminophen (50 mg/kg) 30 minutes later. Jugular venous blood samples and transabdominal ultrasonographic abomasal dimensions were obtained periodically after suckling. Abomasal emptying rate was assessed on the basis of the time to maximal plasma acetaminophen concentration and ultrasonographic determination of the halftime of abomasal emptying. One-tailed Dunnett post tests were conducted whenever the F value for group was significant. RESULTS: Emptying rate was faster for erythromycin, tilimicosin, and tylosin than for the control treatment, as determined on the basis of time to maximal plasma acetaminophen concentration. Ultrasonography indicated that the half-time of abomasal emptying was significantly shorter for erythromycin than for the control treatment. Tylosin and tilmicosin accelerated the abomasal emptying rate, but not significantly, relative to the emptying rate for the control treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of erythromycin, tilmicosin, and tylosin at the label dosage increased abomasal emptying rate in calves. The clinical importance of an increase in abomasal emptying rate in cattle remains to be determined.     

Ultrasonographic measurement of abomasal volume, location, and emptying rate in calves

OBJECTIVE: To develop and validate an ultrasonographic method for measuring abomasal volume, location, and emptying rate in suckling calves. ANIMALS: 9 male Holstein calves < 40 days of age. PROCEDURE: Before and after calves were fed different volumes of milk replacer or 2 L of oral electrolyte solutions, ultrasonographic measurements of abomasal dimensions (width, length, and height) were obtained by applying a 3.5-MHz sector probe to the ventral aspect of the abdomen in the transverse and sagittal planes. Abomasal volume was calculated from the ultrasonographic measurements by modeling the abomasum as an ellipsoid and by use of a power exponential equation to calculate the half-time of abomasal emptying (t1/2). RESULTS: Preprandial abomasal volume was 20 to 137 mL. All 3 abomasal dimensions increased during feeding and after suckling, and the abomasum was symmetrically located about the midline of the ventral aspect of the abdomen. Strong linear relationships were identified between ultrasonographic and suckled volumes, between ultrasonographic and scintigraphic heights, and between ultrasonographic and scintigraphic lengths. Ultrasonographic t1/2 was linearly related to scintigraphic t1/2; the latter is regarded as the gold standard measure of gastric emptying rate. CONCLUSIONS AND CLINICAL RELEVANCE: Ultrasonographic evaluation of the abomasum appears to provide a practical, rapid, noninvasive, and accurate method for determination of abomasal volume, location, and emptying rate in suckling calves.     

Effect of spiramycin and tulathromycin on abomasal emptying rate in milk-fed calves

Impaired abomasal motility is common in cattle with abomasal disorders. The macrolide erythromycin has been demonstrated to be an effective prokinetic agent in healthy calves and in adult cattle with abomasal volvulus or left displaced abomasum. We hypothesized that 2 structurally related macrolides, spiramycin and tulathromycin, would also be effective prokinetic agents in cattle. Six milk-fed, male, Holstein-Friesian calves were administered each of the following 4 treatments: spiramycin, 75 000 IU/kg BW, IM, this dose approximates 25 mg/kg BW, IM; tulathromycin, 2.5 mg/kg BW, SC; 2 mL of 0.9% NaCl (negative control); and erythromycin, 8.8 mg/kg BW, IM (positive control). Calves were fed 2 L of cow’s milk containing acetaminophen (50 mg/kg body weight) 30 min after each treatment was administered and jugular venous blood samples were obtained periodically after the start of sucking. Abomasal emptying rate was assessed by the time to maximal plasma acetaminophen concentration. Spiramycin, tulathromycin, and the positive control erythromycin increased abomasal emptying rate compared to the negative control. We conclude that the labeled antimicrobial dose of spiramycin and tulathromycin increases the abomasal emptying rate in healthy milk-fed calves. Additional studies investigating whether spiramycin and tulathromycin exert a prokinetic effect in adult cattle with abomasal hypomotility appear indicated.     

Effects of wheat protein in milk replacers on abomasal emptying rate in calves

Diarrhoea is a condition with tremendous impact on calf health. Infectious agents play a dominant role; however, non‐infective factors may also contribute to pathogenesis of diarrhoea. One factor, the abomasal emptying rate, is mainly influenced by the composition of feed. The aim of the study was to assess the influence of different protein sources in milk replacers on abomasal emptying rate and clinical parameters. The effect of increasing age of the calves on abomasal emptying was also evaluated. The study compared abomasal emptying rates and clinical parameters in calves, which were fed either milk replacer containing only whey protein or one which partially contained wheat protein. Abomasal emptying rate was estimated by ultrasonography. Ten calves were used in the study over 18 days, and each calf was fed 3 periods of 3 days length using different milk replacers in an alternating crossover design. The abomasum was emptied significantly faster when the wheat protein containing milk replacer was fed (half‐emptying time wheat protein 49.1 ± 4.1 min, half‐emptying time milk protein 59.1 ± 7.4 min); however, clinical parameters and weight gain did not differ between the feeding regimes. Age did not significantly influence abomasal emptying rate. As milk replacers containing wheat proteins increased abomasal emptying rate, they may have a higher potential to initiate diarrhoea, especially if high volumes are fed. Thus, the feeding regimes are likely to be even more important when such milk replacers are used.     

Comparison of two oral electrolyte solutions and route of administration on the abomasal emptying rate of Holstein-Friesian calves

Dehydrated calves with diarrhea are routinely given an oral electrolyte solution (OES) by suckling or esophageal intubation. An important issue related to rehydration therapy is the rate of OES delivery to the small intestine. It is widely assumed that the glucose content of the OES does not impact the speed of resuscitation and that fluid administered by esophageal intubation provides a similar resuscitative response to that obtained by suckling. The aims of this study were to compare the abomasal emptying rate in calves suckling an OES containing a high or low glucose concentration and in calves administered a high-glucose OES by suckling or esophageal intubation. Seven male Holstein-Friesian calves were given the following treatments in random order: 2 L of a commercially available high-glucose OES ([glucose] = 405 mM) by suckling or esophageal intubation or 2 L of a commercially available low-glucose OES ([glucose] = 56 mM) by suckling. Abomasal emptying rate was determined by acetaminophen absorption, ultrasonography, and glucose absorption. High-glucose OES rapidly increased plasma glucose concentration after suckling but produced a slower rate of abomasal emptying than did low-glucose OES. Esophageal intubation of high-glucose OES produced the same initial change in abomasal volume as did suckling, but delayed the rate of OES delivery to the small intestine. Our results suggest that suckling a low-glucose OES provides the fastest rate of abomasal emptying and plasma volume expansion, whereas a high-glucose OES provides the most appropriate oral solution for treating hypoglycemic calves.     

Effects of metoclopramide, clenbuterol and butorphanol on ruminoreticular motility of calves

Rate and amplitude of contractions of the rumen dorsal sac and reticulum of 6 male Holstein calves ages 12 to 20 weeks were monitored with electromyography, strain gauges and an intraruminal pressure catheter. Heart rate and mean arterial pressure were measured with ultrasound. The effects of metoclopramide, a dopamine antagonist, clenbuterol, a beta-2 adrenergic agonist, and butorphanol, a narcotic agonist/antagonist, were observed utilizing dosages bracketing those employed clinically. Metoclopramide significantly decreased the intraruminal pressure peaks associated with cyclical contractions without changing their rate. Clenbuterol had no measurable effect on the ruminoreticulum. Butorphanol totally inhibited ruminoreticular contractions for periods of 6 to greater than 40 min depending on dosage. Only clenbuterol significantly affected cardiovascular function; it increased heart rate and decreased mean arterial pressure. Both metoclopramide and butorphanol produced behavioral changes in the calves.     

Effect of suckling isotonic or hypertonic solutions of sodium bicarbonate or glucose on abomasal emptying rate in calves

OBJECTIVE: To determine and compare the abomasal emptying rates in calves suckling milk replacer or an isotonic or hypertonic solution of NaHCO(3) or glucose. ANIMALS: 5 male Holstein-Friesian calves that were < 30 days of age. PROCEDURES: Calves were fed 2 L of milk replacer or isotonic (300 mOsm/L) or hypertonic (600 mOsm/L) solutions of NaHCO(3) or glucose containing acetaminophen (50 mg/kg). Venous blood samples and transabdominal ultrasonographic abomasal dimensions were obtained periodically after feeding, and abomasal luminal pH was continuously monitored by placement of a luminal pH electrode through an abomasal cannula. Abomasal emptying rate was assessed by the time to maximal plasma acetaminophen concentration, ultrasonographic determination of the half-time of abomasal emptying, and the time for luminal pH to return to within 1 pH unit of the preprandial value. RESULTS: Hypertonic NaHCO(3) solution was emptied slower than an isotonic NaHCO(3) solution, isotonic glucose solution was emptied slower than an isotonic NaHCO(3) solution, and hypertonic glucose solution emptied slower than an isotonic glucose solution. CONCLUSIONS AND CLINICAL RELEVANCE: An electrolyte solution for oral administration with a high osmolarity and glucose concentration may lead to a slower resuscitation of dehydrated diarrheic calves because such solutions decrease the abomasal emptying rate and therefore the rate of solution delivery to the small intestine. Whether slowing of the abomasal emptying rate in dehydrated diarrheic calves suckling an oral electrolyte solution is clinically important remains to be determined.     

Effect of suckling an isotonic solution of sodium acetate, sodium bicarbonate, or sodium chloride on abomasal emptying rate and luminal pH in calves

OBJECTIVES: To compare abomasal emptying rates in calves after suckling milk replacer or 3 common orally administered electrolyte solution components. ANIMALS: 5 male calves < 35 days of age. PROCEDURES: Calves with a cannula fitted in the abomasal body were fed 2 L of milk replacer with or without parenteral administration of atropine (0.01 mg/kg, i.v., then 0.02 mg/ kg, s.c., q 30 min) or isotonic (150 mM) solutions of sodium acetate, NaHCO(3), or NaCl in a randomized crossover design. Abomasal emptying rates were determined via scintigraphy, acetaminophen absorption, ultrasonography, and change in abomasal luminal pH. RESULTS: Scintigraphic half-emptying time, time of maximal plasma acetaminophen concentration, ultrasonographic half-emptying time, and pH return time indicated similar abomasal emptying rates following suckling of isotonic sodium acetate, NaHCO(3), and NaCl solutions, whereas the emptying rate of milk replacer was significantly slower. Mean maximal abomasal luminal pH was highest following suckling of NaHCO(3) (pH(max)=7.85) and lowest following suckling of NaCl (pH(max)=4.52); sodium acetate (pH(max)=6.59) and milk replacer (pH(max)=5.84) yielded intermediate pH values. CONCLUSIONS AND CLINICAL RELEVANCE: Isotonic solutions of sodium acetate, NaHCO(3), and NaCl were rapidly emptied from the abomasum but varied markedly in their ability to alkalinize the abomasum. Sodium bicarbonate-containing orally administered electrolyte solution might increase the frequency of infection or severity of clinical disease in diarrheic calves treated for dehydration by causing prolonged abomasal alkalinization.     

Comparison of abomasal emptying in neonatal calves with a nuclear scintigraphic procedure.

The purpose of the present study was to demonstrate that nuclear medicine technology allows observation of the effect that milk clotting has on abomasal emptying in the living neonatal calf. Scintigraphic evaluation of abomasal emptying was carried out in 6 healthy male Holstein calves. The calves were fed 10% of their body weight daily as whole cow's milk that was divided equally and consumed as 2 feedings via a nipple bottle. One day before the nuclear scintigraphic procedure, the calves were randomly fed whole cow's milk, or an oral rehydration solution (ORS) containing bicarbonate and high levels of soluble fibre was fed for 3 consecutive feedings an hour before the portion of milk. For each calf, both feeding programs were repeated twice at a one-week interval. Immediately following administration of the 99mTC-sulfur-colloid-containing milk, the calves were imaged with the gamma camera positioned lateral and ventral to the abomasum. Additional right lateral and ventral views of the abomasum were collected at 15, 30, 45, 60, 90, 120, 150, 180, 210, and 240 min after administration of the radionuclide. Blood glucose determination were performed at one-hour intervals for 7 h after feeding milk to evaluate milk digestibility in both feeding programs. No significant differences in the results of the glucose absorption test or in the radionuclide counts of the abomasum were found between both feeding programs. Scintigraphic evaluation of abomasal emptying was found to be a useful technique for visualization of milk clotting and to test the effect of an ORS on milk digestibility.     

Ultrasonographic assessment of the reticular motility in cows after administration of different doses of metoclopramide and neostigmine

The aim of the present study was to use of ultrasonography for assessment of reticular motility after administration of various doses of metclopramide and neostigmine in cows. A total of ten Holstein cows were used in six trials in each one single dose of each drug was used. Metoclopramide was used at 0.1, 0.2 and 0.3 mg/kg intramuscularly, whereas neostigmine was used at 0.02, 0.03, and 0.04 mg/kg subcutaneously. Reticular motility was assessed using 3.5 MHz transducer just before drugs administration and every 20 minutes after administration with total time of two hours. At twenty minutes postadministration, metoclopramide at a dose rate of 0.3 mg kg significantly (P<0.01) produced shortening of the interval time between the two biphasic reticular contractions by 25% and significantly (P<0.05) increased the amplitude of the first reticular contraction by 42%, but with mild neurological signs. Neostigmine produced non-significant increase in reticular contraction rate and strength. The results of the present study indicate that metoclopramide and neostigmine at selected doses are not clinically useful agents for increasing reticular contraction rate and strength. The findings of this study in healthy animals may not be extrapolatable to findings in cattle with reticuloruminal hypomotility.     

Effect of preoperative administration of erythromycin or flunixin meglumine on postoperative abomasal emptying rate in dairy cows undergoing surgical correction of left displacement of the abomasum

Objective: To determine whether preoperative administration of erythromycin or flunixin meglumine altered postoperative abomasal emptying rate, rumen contraction rate, or milk production in dairy cattle undergoing surgical correction of left displacement of the abomasum (LDA). DESIGN: Nonrandomized, controlled clinical trial. ANIMALS: 45 lactating Holstein-Friesian cows with LDA. PROCEDURES: Cows were alternately assigned to an erythromycin (10 mg/kg [4.5 mg/lb], IM), flunixin (2.2 mg/kg [1.0 mg/lb], IV), or control group (n = 15/group). Treatments were administered once 1 hour before surgical correction of LDA. D-Xylose solution (50%; 0.5 g/kg [0.23 g/lb]) was injected into the abomasal lumen during surgery, and venous blood samples were periodically obtained to determine time to maximum serum D-xylose concentration. RESULTS: Abomasal emptying rate was significantly faster in cows treated with erythromycin (mean +/- SD time to maximum serum D-xylose concentration, 149 +/- 48 minutes) than in control cows (277 +/- 95 minutes) but was not significantly different between cows treated with flunixin (230 +/- 49 minutes) and control cows. Cows treated with erythromycin had significantly greater milk production, relative to production before surgery, on postoperative days 1 and 2 than did control cows. Cows in the erythromycin and flunixin groups had a significantly higher rumen contraction rate on the first postoperative day than did control cows. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that preoperative administration of a single dose of erythromycin increased abomasal emptying rate, rumen contraction rate, and milk production in the immediate postoperative period in cows undergoing surgical correction of LDA.     

Effects of hypocalcaemia on abomasal motility

Abomasal mechanical and myoelectric activity were measured in two adult Holstein cows. Hypocalcaemia was induced using a constant infusion of disodium EDTA and serum total and diffusible calcium concentrations were measured. Abomasal motility remained normal in the face of declining calcium concentrations until a threshold value was reached (1.2 +/- 0.2 mmol litre-1) below which all mechanical and electrical activity was absent. A similar threshold effect was observed when calcium concentrations were allowed to rise. These data do not support hypocalcaemia as being a clinically important cause of abomasal atony.     

Effects of mosapride citrate, metoclopramide hydrochloride, lidocaine hydrochloride, and cisapride citrate on equine gastric emptying, small intestinal and caecal motility

Objective

Although extensive work has been done to elucidate the beneficial and unfavorable effects of gastrointestinal prokinetic agents in humans, little is known on the effects of these agents in horses. In this study, we compared the effects of mosapride, metoclopramide, cisapride, and lidocaine on equine gastric emptying, jejunal and caecal motility and evaluated these agents’ adverse drug reactions (ADRs).

Animals

Seven healthy adult Thoroughbreds.

Procedure

Mosapride 1.0 mg/kg and 2.0 mg/kg, metoclopramide 0.2 mg/kg, and cisapride 1.0 mg/kg were dissolved in 100 mL distilled water for oral administration. Lidocaine 1.3 mg/kg was mixed with 500 mL saline for a 30-min intravenous infusion. Oral administration of 100 mL distilled water was used as control. Gastric emptying was evaluated using ¹³CO₂ breath test, and jejunal and caecal motility was assessed by electrointestinography.

Results

The present study demonstrates that mosapride at doses of 1.0 mg/kg and 2.0 mg/kg facilitates gastric emptying in horses. Improved jejunal motility was observed following administration of mosapride (1.0 mg/kg and 2.0 mg/kg), metoclopramide (0.2 mg/kg), and cisapride (1.0 mg/kg). Similarly, improved caecal motility was observed following administration of mosapride (2.0 mg/kg).

Conclusions and clinical relevance

This study shows that among the prokinetic agents studied here, only mosapride (2.0 mg/kg) promotes jejunal and caecal motility in horses. Considering mosapride ADRs profile, it is believed that this compound is useful in the treatment of diseases associated with decreased GI motility, including postoperative ileus.     

Isolation of Clostridium perfringens from neonatal calves with ruminal and abomasal tympany, abomasitis, and abomasal ulceration

Eight neonatal calves (2 to 21 days old) with suspected abomasal displacement or intestinal obstruction after acute onset of abdominal tympany, colic, depression, or death were referred to Kansas State University for clinical examination or for necropsy. Results of routine hematologic and serum chemical analyses did not reveal consistent changes. Necropsy revealed abomasal distention, with various degrees of abomasitis, hemorrhage, and ulceration, but did not reveal evidence of displaced abomasum or obstructed intestine. Specimens of ruminal contents collected via stomach tube or at necropsy and abomasal contents collected at necropsy were obtained for anaerobic bacteriologic culture. Clostridium perfringens was isolated from all specimens, and on the basis of toxin neutralization tests in mice, 7 were type A and one was type E. Copper concentrations in serum and tissues were within normal limits. It appeared that the acute abdominal syndrome in these neonatal calves was unrelated to copper deficiency, and that C perfringens, particularly type A, may have had an appreciable contributory role in its pathogenesis.     

Ultrasonographic imaging of abomasal milk clotting and abomasal diameter in healthy and diarrheic calves

In case of diarrhea calves are treated with oral rehydration solutions (ORS), which are known to increase abomasal pH and inhibit milk clotting in vitro. Nevertheless, recent studies have shown that ORS with HCO₃^‐ ≤ 62 mmol/L do not interfere with abomasal milk clotting in healthy calves. However, in diarrheic calves, feeding ORS and milk simultaneously may disturb abomasal curd formation and exacerbate diarrhea due to faster abomasal passage of ingesta. Therefore, the aim of the present study was to ultrasonographically examine abomasal milk clotting and diameter after feeding milk and milk replacer (MR) with and without ORS to healthy and diarrheic calves. Abomasal curd formation and diameter in healthy and diarrheic calves were ultrasonographically imaged before and after feeding milk, MR and ORS prepared in milk or MR. Feeding mixtures of milk or MR with ORS did not cause any remarkable differences in the ultrasonographic images of abomasal content. Moreover, abomasal milk clotting was not disturbed due to diarrhea. Statistically significant differences of abomasal diameter after feeding between healthy and diarrheic calves indicated that abomasal emptying is delayed in diarrheic calves. Hence, further studies are needed to determine reasons for decelerated abomasal passage in calves suffering from diarrhea.