title: The effects of housing conditions on baseline cardiovascular parameters and the sensitivity to detect changes in contractility in telemetry-implanted dogs.
abstract: BACKGROUND
  There is a growing weight of evidence to suggest that myocardial contractility is an important parameter to assess as part of IND enabling studies in addition to standard assessments as per the ICH S7A and S7B guidelines. Historically, assessments of contractility have been limited to snap-shot echocardiography or single housed telemetry assessments of left ventricular pressure. There is a growing number of studies showing that social housing conditions in large animals are beneficial, do not impact the integrity of the data collected and improve animal welfare. With current advances in cardiovascular technology it is now feasible to conduct cardiovascular assessments under group housing conditions. Therefore, the purpose of this study was to evaluate baseline hemodynamic parameters, within a group housed environment, and to demonstrate that the model retains the sensitivity of the traditional assessments.
  
  
  METHODS
  Four animals were instrumented with DSI HD-L21 implants for continuous 24-hour assessment of systemic arterial pressures, left ventricular pressures, heart rate and electrocardiogram intervals in group housed conditions. The animals were administered either Atenolol (0.3, 1 and 3mg/kg), a known negative inotrope, or Pimobendan (0.1, 0.3 and 1mg/kg), a known positive inotrope.
  
  
  RESULTS
  The results showed that group housing had no influence on baseline hemodynamic assessments as compared to historical data from single housed animals. The administration of Atenolol and Pimobendan induced the expected changes in cardiovascular parameters.
  
  
  CONCLUSIONS
  The baseline hemodynamic parameters remained within physiological ranges and were not influenced by group housing conditions. The model retained sensitivity to detect the expected changes in contractility in line with known effects of Atenolol and Pimobendan in dogs. In conclusion, the use of social housing conditions in dogs provides an enriched environment, compliant with animal welfare recommendations, and is in line with the ICH S7A safety pharmacology guidelines, while retaining sensitivity to detect changes in myocardial contractility.
authors.affiliation: Charles River Laboratories, 22022 Transcanadienne, Senneville, Quebec, H9X 3R3, Canada. Electronic address: nataliya.sadekova@crl.com.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Sadekova
authors.affiliation: Charles River Laboratories, 22022 Transcanadienne, Senneville, Quebec, H9X 3R3, Canada.
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Boudreau
authors.affiliation: Charles River Laboratories, 22022 Transcanadienne, Senneville, Quebec, H9X 3R3, Canada.
authors.forename: Benoit
authors.initials: B
authors.lastname: Jalbert
authors.affiliation: Charles River Laboratories, 22022 Transcanadienne, Senneville, Quebec, H9X 3R3, Canada.
authors.forename: Kevin
authors.initials: K
authors.lastname: Norton
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001262:Atenolol / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology; D002319:Cardiovascular System / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006799:Housing, Animal / Q000592:standards*; D008297:Male; D008954:Models, Biological; D009200:Myocardial Contraction / Q000187:drug effects*; D011724:Pyridazines / Q000494:pharmacology; D012931:Social Environment; D013686:Telemetry; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D002316:Cardiotonic Agents; D011724:Pyridazines; C041648:pimobendan; D001262:Atenolol
keywords: Beagle dog; Contractility; Left ventricular pressure; Methods; Social housing; Telemetry