Evaluation of blood flow parameters in addition to blood pressure and electrocardiogram in the conscious telemetered beagle dog.
BACKGROUND
The objective of this study was to evaluate a model for measuring blood flow parameters in addition to blood pressure, heart rate and electrocardiogram (ECG) in conscious telemetered restrained and unrestrained beagle dogs.


METHODS
Male beagle dogs were instrumented with fully implantable ITS radio telemetry devices for the measurement of blood pressure and ECG. In addition, the dogs were instrumented with a probe around the pulmonary artery for the measurement of blood flow by ultrasound. Dobutamine at 5, 10 and 20 mug/kg/min, given intravenously to sling restrained animals (n=4), and minoxidil at 2 mg/kg, given orally to unrestrained animals (n=4), were selected as test compounds known to cause changes in the cardiovascular parameters of interest in this work.


RESULTS
Dobutamine produced a small increase in mean (9%) and systolic blood pressure (5%), and an increase in pulse pressure (37%) and heart rate (30%). The additional blood flow parameters showed that dobutamine also increased stroke volume (21%) and cardiac output (58%) and reduced total peripheral resistance (52%). Minoxidil treatment resulted in a prolonged reduction in mean, systolic and diastolic blood pressure (up to 24%). Additionally, a prolonged increase in heart rate (169%) and cardiac output (120%) were observed along with a reduction in total peripheral resistance (62%). The effects of both compounds were consistent with their known pharmacology.


CONCLUSIONS
The results show that measurement of blood flow parameters can be successfully added to the standard telemetered cardiovascular dog model to provide valuable additional information on the effects of compounds on the cardiovascular system.
Taylor
Gemma L
GL
Safety Pharmacology, GlaxoSmithKline, The Frythe, Welwyn, Herts, AL6 9AR, UK. Gemma.L.Taylor@gsk.com
Patel
Bela
B
Sullivan
Andrew T
AT
D000284:Administration, Oral; D058665:Adrenergic beta-1 Receptor Agonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001795:Blood Pressure Determination / Q000379:methods*; D003243:Consciousness; D004280:Dobutamine / Q000008:administration & dosage / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004562:Electrocardiography / Q000379:methods*; D006339:Heart Rate / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D008914:Minoxidil / Q000008:administration & dosage / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D013318:Stroke Volume / Q000187:drug effects; D017180:Tachycardia, Ventricular / Q000139:chemically induced / Q000175:diagnosis / Q000503:physiopathology; D013686:Telemetry / Q000295:instrumentation / Q000379:methods*; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology
D058665:Adrenergic beta-1 Receptor Agonists; D014665:Vasodilator Agents; D004280:Dobutamine; D008914:Minoxidil