Hold your horses: External factors that influence circadian rhythms in horses

October 5, 2021Isabella L. Bean, PharmD Candidate

A recent webinar delivered by Barbara Murphy, PhD, BSc, uncovered how light, temperature, and exercise impact equine circadian rhythms and fertility, plus she outlined what future research is needed.

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Light is the primary regulator of circadian rhythms and it governs physical, mental, and behavioral changes in most living things. A circadian rhythm is a natural, internal process that lasts approximately 24 hours and exists under constant conditions.1 Barbara Murphy, PhD, BSc, the equine programme director and head of subject for equine science at the University College Dublin, presented how light, exercise, and temperature affect circadian rhythm and fertility in horses during a recent webinar for the University of Connecticut.

To understand the regulation of equine activity rhythms, Murphy cited researchers who recorded 6 mares’ activity patterns for 2 weeks at a time. Horses spent 2 weeks in the pasture, in the stables with light and dark cycles, then in the stables in complete darkness. This study revealed that circadian rhythms with strong ultradian components regulate equine activity patterns.1 Ultradian rhythms are biological cycles that occur within 24 hours, and they include heart rate, pulse, and blinking. This study also showed that equines contain endogenous circadian rhythms in the absence of environmental stimuli.1 These findings suggest that humans who implement management regimens that capitalize on these findings can strengthen equine circadian behavioral outputs.1

Another study Murphy noted tried to identify the time of day when horses would experience optimal exercise performance. Handlers exercised 6 sedentary young thoroughbred mares for 8 weeks using an automated high speed horse exerciser. Researchers then collected muscle biopsies over a 24-hour period. Researchers analyzed equine skeletal muscle and discovered that exercise synchronizes gene expression. This study implies that optimal performance is found at the time of day that coincides with training.1

Circannual rhythms (processes that occur over approximately 1 year) regulate equine reproduction. Circannual rhythms can be manipulated by external signals such as light, food, and temperature. Extending the daylight allows for a longer breeding season whereas the cold weather and waiting for the grass to grow in the spring slows breeding.1 Increasing the light stimulates reproductive activity, growth, and lactation.1 Researchers placed blue light masks on pregnant mares to see the effects on gestation. The study discovered that delivering blue light to a single eye can reduce gestation length, increase foal birth weights, and reduce hair coat length of the post-foaling mare.1

Current research describes how light, temperature, and exercise influence the circadian and circannual rhythms that horses exhibit. Future research should evaluate what stable lighting is optimal for supporting equine biological and physiological rhythms.

Reference

  1. Murphy B. Biological rhythms in horses: Implications for breeding and performance? Webinar; September 24, 2021.

Gastric dilatation-volvulus (GDV) is a common life-threatening emergency for which immediate recognition, stabilization, and surgical intervention remain the only option for therapy. Despite numerous advances in emergency and critical care, the exact etiology of this condition remains elusive. GDV is most common in large and giant purebred dogs but can occur in any size and breed of dog as well as in human and nonhuman primates, cats,1 guinea pigs, and other species.

Advances have been made in identifying genetic predisposition in breeds such as the Great Dane, leading to the possibility of eliminating predisposed dogs from the breeding population.2 Despite this, other risk factors including large thoracic depth to width ratios, advanced age,3 stretched hepatosplenic ligaments, barometric pressure change, dietary fat content, meal and dry particle food size, foreign body ingestion,4 patient temperament, prior splenectomy,5-8 raising or lowering food bowls, and postprandial activity have also been implicated as potential causes for GDV; however, studies have shown conflicting results.9

Pathophysiology

Independent of risk factors, GDV is a process in which instability of the gastric fundus, along with delayed gastric emptying and gas or fluid distension, results in 180° to 270° rotation of the stomach around its mesenteric vascular axis.10 Some dogs may experience intermittent rotation and repositioning, but in the majority of cases, once mispositioned the dilated, rotated stomach compresses the caudal vena cava and diminishes venous return to the right heart, ultimately affecting cardiac preload and output.11Lack of perfusion to the stomach, along with decreased cardiac output, rapidly results in clinical signs associated with distributive and cardiogenic shock. Prompt recognition and early intervention are required to improve chances of a successful outcome.

Clinical signs and diagnostic testing

Characteristic clinical signs of GDV include unproductive retching, ptyalism, abdominal distension, restlessness, and stretching. For confirmation, the right lateral abdominal radiograph is the most rewarding to demonstrate a classic appearance of dorsocranial displacement of the pylorus with gas distension of the gastric fundus and compartmentalization. In some instances, the presence of fluid or 360° rotation can make a diagnosis of GDV more challenging. In such instances, evaluation of contralateral and ventrodorsal abdominal radiographs may be required. Thoracic radiographs often reveal dilation of the esophagus with a small caudal vena cava and microcardia. Because of the lack of cardiac preload, the cardiac silhouette may be elevated from the sternum.12

In the patient with GDV, a minimum database should be obtained, consisting of a PCV/TS, venous electrolytes, acid-base status, and lactate concentration. Although the initial PCV/TS is not prognostic, patients with GDV can have rupture of the short gastric vessels or concurrent splenic torsion, resulting in absolute or relative anemia that may require transfusion of red blood cell products. Additional information gained by the animal’s acid-base status and lactate concentration is also important and can be prognostic. Plasma lactate levels greater than 7 to 9 mmol/L have been associated with the presence of gastric necrosis and may be prognostic of survival in initial studies.13-14 Lactate clearance, or a drop in lactate to less than 40% to 50% of baseline, or by more than 4 mmol/L with therapy, has more accurately been predictive of survival.15-17 Serum spec cPL (canine pancreatic lipase) immunoreactivity may also be elevated in dogs with GDV, suggesting simultaneous pancreatic injury.18 Prolonged coagulation times, an elevated D-dimer level, and lower fibrinogen concentration as well as Protein C and antithrombin activity have all been noted in dogs that do not survive postoperatively.17

Stabilization and preop care

Once a diagnosis of GDV is made, timing is critical in providing supportive care and initiating immediate surgical intervention. Placement of large bore intravenous catheters into the cephalic or lateral saphenous veins allows administration of crystalloid fluids. Isotonic crystalloids (Normosol-R, Plasma-Lyte A, 0.9% saline) should be administered in incremental boluses, starting with a quarter of the patient’s calculated shock volume. In dogs, this is roughly 22 mL/kg (or take the patient’s body weight in pounds and add a zero for the quarter shock volume) and should be administered as rapidly as possible. Once the calculated volume has been infused, reevaluation of the patient’s perfusion parameters (heart rate, blood pressure, capillary refill time, mucous membrane color) should be performed to determine whether to continue additional fluid boluses or to add a colloid such as hydroxyethyl starch (5-10 mL/kg) for additional vascular support. Gastric decompression by trocarisation or orogastric tube placement should be performed to alleviate gastric dilation and improve cardiac preload.19 Many dogs with GDV are bacteremic at the time of diagnosis due to bacterial translocation.20 Preoperative administration of a first-generation cephalosporin (Cefazolin 22 mg/kg IV) is indicated, along with maropitant (1 mg/kg IV) to decrease the risk of postoperative vomiting and subsequent aspiration pneumonia.

Analgesia and anesthesia

Analgesia in the form of a pure mu opioid such as methadone (0.1-0.2 mg/kg IV, IM) or fentanyl (2-3 µg/kg IV) can be administered prior to anesthetic induction. Opioids such as morphine and hydromorphone have potent emetic properties and so ideally should be avoided. Although the partial agonist buprenorphine may be beneficial at providing analgesia, its avid binding to the mu receptors may compete with more potent mu agonists such as fentanyl, which may be required intraoperatively or postoperatively, so its administration is not ideal.

Drug choices for anesthetic induction should be chosen based on the patient’s degree of instability. In stable patients with functional reserves of adrenal norepinephrine, ketamine (0.5 mg/kg IV) and midazolam/diazepam (0.1-0.2 mg/kg IV) may be chosen, because ketamine results in the adrenal release of norepinephrine and an increase in cardiac output. Propofol (4-7 mg/kg IV) with or without a benzodiazepine (midazolam/diazepam) can be used during simultaneous preoxygenation and administration of an intravenous crystalloid fluid bolus to prevent vasodilator-induced hypotension. In the least stable patients, a combination of fentanyl (5-10 µg/kg IV) with a benzodiazepine (midazolam/diazepam) or etomidate (0.2-4 mg/kg IV) with a benzodiazepine can be performed. Once the animal is anesthetized and intubated, a constant rate infusion of fentanyl (10-20 µg/kg/hour) can be administered to reduce the level of gas anesthesia.

Cardiac dysrhythmias

The presence of preoperative, intraoperative, and postoperative cardiac dysrhythmias is common. Sinus tachycardia can be associated with relative hypovolemia from lack of cardiac preload, blood loss, discomfort, or vasodilation from gas anesthesia or inflammatory cytokines and reperfusion injury. Treatment of sinus tachycardia consists of intravenous crystalloid and colloid boluses, blood products when needed to address blood loss and anemia, and provision of adequate analgesia and anesthesia during surgery. Even in the absence of ventricular dysrhythmias in the preoperative period, early preemptive intervention with lidocaine (2 mg/kg IV, followed by 50 µg/kg/min constant rate infusion) has been shown to decrease the incidence of postoperative ventricular dysrhythmias, acute kidney injury, and hospitalization time.21

Ventricular dysrhythmias in the form of unifocal or multifocal ventricular premature contractions (VPCs), ventricular tachycardia, and R-on-T are common and should be addressed whenever they occur during anesthesia. During the postoperative period, lidocaine should be continued for its antiarrhythmic properties as well as provision of analgesia and treatment of reperfusion injury.

Surgical intervention

At the time of surgery, the stomach should be untwisted into its normal anatomic location. Next, the abdomen should be systematically explored. The spleen and its vascular supply should be carefully evaluated to determine whether torsion or thrombosis are present, necessitating splenectomy. Once a complete exploration of the abdomen has been performed, the stomach should be visualized and palpated for integrity and the presence of necrosis or perforation. When present, small areas of necrosis should be removed, resected, and not invaginated. The need for gastric resection, with or without concurrent splenectomy, has been demonstrated to be a negative prognostic indicator for survival.22 Multiple gastropexy techniques have been described, including the right paracostal incisional, belt-loop, modified belt-loop, and circumcostal.23-26 The technique chosen should depend on surgeon preference. Independent of the gastropexy performed, GDV recurrence is rare (<5% chance of recurrence) when the technique is performed properly.27 Possible causes of recurrence include too small an area of gastropexy (<4 cm) or breakdown of the gastropexy site. Placement of the gastropexy too close to the pylorus also can result in the postoperative complication of delayed gastric emptying.

Postoperative care

Postoperative care involves provision of adequate analgesia, ongoing maintenance of fluid balance, treatment of cardiac dysrhythmias, and monitoring for postoperative complications such as ileus, gastrointestinal reflux and feeding intolerance, and disseminated intravascular coagulation.27 Standard analgesia consists of administration of a pure mu opioid (methadone, fentanyl, hydromorphone) or administration of the partial mu agonist buprenorphine. These can then be transitioned to gabapentin (1.25-4 mg/kg po tid-qd) when administration of oral medication is possible. Because opioid drugs can contribute to postoperative ileus, early transition to other analgesia such as gabapentin is preferred. Intravenous crystalloids, with or without a constant rate infusion of metoclopramide (1-2 mg/kg/day), should be administered to maintain hydration and perfusion. Gastroprotectant therapy in the form of antiemetics (maropitant 1 mg/kg SQ, IV or 2 mg/kg po qd ondansetron 0.1-1 mg/kg IV, po bid-tid) or acid reduction (famotidine 0.5-1 mg/kg IV, po bid; pantoprazole 1 mg/kg IV bid or omeprazole 1 mg/kg po bid can be administered. Sucralfate (0.5-1 g per dog po tid – qid) and cisapride (0.1-0.5 mg/kg po tid) can be administered in the event of postoperative regurgitation. Careful attention to an animal’s acid-base and electrolyte status is warranted, because hypokalemia can predispose a patient to cardiac dysrhythmias. Continuous ECG monitoring for a minimum of 24 hours postoperatively should be performed. If ventricular tachycardia is greater than 160 beats per minute, if there are multifocal VPCs or R-on-T beats present, or if the dysrhythmia is causing hypotension, lidocaine should be administered as previously described. If the ventricular dysrhythmias continue after the patient has been transitioned to oral medications, sotalol (1-2 mg/kg po bid) can be administered at the time of discharge and continued for 2 weeks until the time of staple/suture removal. In the most complicated cases involving partial gastrectomy, patients should have coagulation tests and a daily platelet estimate on a blood smear performed daily to investigate for disseminated intravascular coagulation (DIC). If DIC is suspected and coagulation times are prolonged, administration of fresh frozen plasma (5-20 mL/kg) should be considered.

Prognosis

The overall survival for a patient with GDV ranges from 70% to 80% following surgical correction in most studies. Negative prognostic indicators include persistent elevations in lactate that do not drop by at least 40% of baseline following treatment, the need for lidocaine administration,28,29 and the need for partial gastrectomy with or without concurrent splenectomy.22

Prevention

The best method of preventing GDV and its complications is to educate pet owners about prophylactic gastropexy in predisposed large-, giant-, or deep-chested breeds.24,30-32 Prophylactic gastropexy can be performed as an elective procedure at the same time as a spay or neuter. Midline celiotomy approach as well as laparoscopic and laparoscopic-assisted gastropexy can be performed depending on the resources available, experience, and preference.30-32 Although minor complications such as incisional infection are possible, the prognosis for recovery and prevention of future GDV is good.32

References

  1. Leary ML, Sinnott-Stutzman V. Spontaneous gastric dilatation-volvulus in two cats. J Vet Emerg Crit Care (San Antonio). 2018;28(4):346-355. doi:10.1111/vec.12734
  2. Harkey MA, Villagran AM, Venkataraman GM, Leisenring WM, Hullar MAJ, Torok-Storb BJ. Associations between gastric dilatation-volvulus in Great Danes and specific alleles of the canine immune-system genes DLA88, DRB1, and TLR5. Am J Vet Res. 2017;78(8):934-945. doi:10.2460/ajvr.78.8.934
  3. O’Neill DG, Case J, Boag AK, et al. Gastric dilation-volvulus in dogs attending UK emergency-care veterinary practices: prevalence, risk factors and survival. J Small Anim Pract. 2017;58(11):629-638. doi:10.1111/jsap.12723
  4. de Battisti A, Toscano MJ, Formaggini L. Gastric foreign body as a risk factor for gastric dilatation and volvulus in dogs. J Am Vet Med Assoc. 2012;241(9):1190-1193. doi:10.2460/javma.241.9.1190
  5. Sartor AJ, Bentley AM, Brown DC. Association between previous splenectomy and gastric dilatation-volvulus in dogs: 453 cases (2004-2009). J Am Vet Med Assoc. 2013;242(10):1381-1384. doi:10.2460/javma.242.10.1381
  6. Maki LC, Males KN, Byrnes MJ, El-Saad AA, Coronado GS. Incidence of gastric dilatation-volvulus following a splenectomy in 238 dogs. Can Vet J. 2017;58(12):1275-1280.
  7. Grange AM, Clough W, Casale SA. Evaluation of splenectomy as a risk factor for gastric dilatation-volvulus. J Am Vet Med Assoc. 2012;241(4):461-466. doi:10.2460/javma.241.4.461
  8. Goldhammer MA, Haining H, Milne EM, Shaw DJ, Yool DA. Assessment of the incidence of GDV following splenectomy in dogs. J Small Anim Pract. 2010;51(1):23-28.
    doi:10.1111/j.1748-5827.2009.00844.x
  9. Bell JS. Inherited and predisposing factors in the development of gastric dilatation volvulus in dogs. Top Companion Anim Med. 2014;29(3):60-63. doi:10.1053/j.tcam.2014.09.002
  10. Czajkowski PS, Hallman RM. Diagnosis of chronic gastric instability using computed tomography in a Great Dane that progressed to gastric dilatation and volvulus: a literature review and case report. Open Vet J. 2018;8(2):219-223. doi:10.4314/ovj.v8i2.18
  11. Sharp CR, Rozanski EA. Cardiovascular and systemic effects of gastric dilatation and volvulus in dogs. Top Companion Anim Med. 2014;29(3):67-70. doi:10.1053/j.tcam.2014.09.007
  12. Green JL, Cimino Brown D, Agnello KA. Preoperative thoracic radiographic findings in dogs presenting for gastric dilatation-volvulus (2000-2010): 101 cases. J Vet Emerg Crit Care (San Antonio). 2012;22(5):595-600. doi:10.1111/j.1476-4431.2012.00802.x
  13. Zacher LA, Berg J, Shaw SP, Kudej RK. Association between outcome and changes in plasma lactate concentration during presurgical treatment in dogs with gastric dilatation-volvulus: 64 cases (2002-2008). J Am Vet Med Assoc. 2010;236(8):892-897. doi:10.2460/javma.236.8.892
  14. Beer KA, Syring RS, Drobatz KJ. Evaluation of plasma lactate concentration and base excess at the time of hospital admission as predictors of gastric necrosis and outcome and correlation between those variables in dogs with gastric dilatation-volvulus: 78 cases (2004-2009).
    J Am Vet Med Assoc. 2013;242(1):54-58. doi:10.2460/javma.242.1.54
  15. Mooney E, Raw C, Hughes D. Plasma lactate concentration as a prognostic biomarker in dogs with gastric dilation and volvulus. Top Companion Anim Med. 2014;29(3):71-76. doi:10.1053/j.tcam.2014.09.005
  16. Green TI, Tonozzi CC, Kirby R, Rudloff E. Evaluation of initial plasma lactate values as a predictor of gastric necrosis and initial and subsequent plasma lactate values as a predictor of survival in dogs with gastric dilatation-volvulus: 84 dogs (2003-2007). J Vet Emerg Crit Care (San Antonio). 2011;21(1):36-44. doi:10.1111/j.1476-4431.2010.00599.x
  17. Verschoof J, Moritz A, Kramer M, Bauer N. Hemostatic variables, plasma lactate concentration, and inflammatory biomarkers in dogs with gastric dilatation-volvulus. Tierarztl Prax Ausg K Kleintiere Heimtiere. 2015;43(6):389-398. doi:10.15654/TPK-150284
  18. Spinella G, Dondi F, Grassato L, et al. Prognostic value of canine pancreatic lipase immunoreactivity and lipase activity in dogs with gastric dilatation-volvulus. PLoS One. 2018;13(9):e0204216. doi:10.1371/journal.pone.0204216
  19. Goodrich ZJ, Powell LL, Hulting KJ. Assessment of two methods of gastric decompression for the initial management of gastric dilatation-volvulus. J Small Anim Pract. 2013;54(2):75-79. doi:10.1111/jsap.12019
  20. Winkler KP, Greenfield CL, Schaeffer DJ. Bacteremia and bacterial translocation in the naturally occurring canine gastric dilatation-volvulus patient. J Am Anim Hosp Assoc. 2003;39(4):361-368. doi:10.5326/0390361
  21. Bruchim Y, Itay S, Shira BH, et al. Evaluation of lidocaine treatment on frequency of cardiac arrhythmias, acute kidney injury, and hospitalization time in dogs with gastric dilatation volvulus. J Vet Emerg Crit Care (San Antonio). 2012;22(4):419-427. doi:10.1111/j.1476-4431.2012.00779.x
  22. Beck JJ, Staatz AJ, Pelsue DH, et al. Risk factors associated with short-term outcome and development of perioperative complications in dogs undergoing surgery because of gastric dilatation-volvulus: 166 cases (1992-2003). J Am Vet Med Assoc. 2006;229(12):1934-1939. doi:10.2460/javma.229.12.1934
  23. Allen P, Paul A. Gastropexy for prevention of gastric dilatation-volvulus in dogs: history and techniques. Top Companion Anim Med. 2014;29(3):77-80. doi:10.1053/j.tcam.2014.09.001
  24. Benitez ME, Schmiedt CW, Radlinsky MG, Cornell KK. Efficacy of incisional gastropexy for prevention of GDV in dogs. J Am Anim Hosp Assoc. 2013;49(3):185-189.
    doi:10.5326/JAAHA-MS-5849
  25. Formaggini L, Degna MT. A prospective evaluation of a modified belt-loop gastropexy in 100 dogs with gastric dilatation-volvulus. J Am Anim Hosp Assoc. 2018;54(5):239-245. doi:10.5326/JAAHA-MS-6596
  26. Przywara JF, Abel SB, Peacock JT, Shott S. Occurrence and recurrence of gastric dilatation with or without volvulus after incisional gastropexy. Can Vet J. 2014;55(10):981-984.
  27. Bruchim Y, Kelmer E. Postoperative management of dogs with gastric dilatation and volvulus. Top Companion Anim Med. 2014;29(3):81-85. doi:10.1053/j.tcam.2014.09.003
  28. Buber T, Saragusty J, Ranen E, Epstein A, Bdolah-Abram T, Bruchim Y. Evaluation of lidocaine treatment and risk factors for death associated with gastric dilatation and volvulus in dogs: 112 cases (1997-2005). J Am Vet Med Assoc. 2007;230(9):1334-1339. doi:10.2460/javma.230.9.1334
  29. Mackenzie G, Barnhart M, Kennedy S, DeHoff W, Schertel E. A retrospective study of factors influencing survival following surgery for gastric dilatation-volvulus syndrome in 306 dogs. J Am Anim Hosp Assoc. 2010;46(2):97-102. doi:10.5326/0460097
  30. Rivier P, Furneaux R, Viguier E. Combined laparoscopic ovariectomy and laparoscopic-assisted gastropexy in dogs susceptible to gastric dilatation-volvulus. Can Vet J. 2011;52(1):62-66.
  31. Loy Son NK, Singh A, Amsellem P, et al. Long-term outcome and complications following prophylactic laparoscopic-assisted gastropexy in dogs. Vet Surg. 2016;45(S1):O77-O83. doi:10.1111/vsu.12568
  32. Coleman KA, Boscan P, Ferguson L, Twedt D, Monnet E. Evaluation of gastric motility in nine dogs before and after prophylactic laparoscopic gastropexy: a pilot study. Aust Vet J. 2019;97(7):225-230. doi:10.1111/avj.12829