title: Echocardiography, a non-invasive method for the investigation of heart morphology and function in laboratory dogs: 2. Effects of minoxidil and quinidine on the left ventricle function.
abstract: We used echocardiography to investigate the changes in the cardiac function of dogs treated with minoxidil (a vasodilator, administered at doses which can produce mild lesions in the myocardium of the left ventricle) and quinidine (an antiarrhythmic at doses up to 8 times the upper limit of the therapeutic range in dogs). Groups of three beagles received a single administration of minoxidil at doses of 0.5 or 2 mg/kg. Two groups of two dogs received a single administration of quinidine at doses of 80 or 160 mg/kg. Two groups of three control dogs were treated concurrently with the vehicle alone. M-mode echocardiography was performed under two-dimensional echocardiography guidance on three occasions the day before treatment, immediately before dosing and 1, 3 and 24 h after dosing. We measured or calculated end diastolic, end systolic, and stroke volumes (EDV, ESV and SV), fractional shortening (FS), ejection fraction (EF), the percentage of thickening of the septum and of the left ventricle posterior wall (PST and PWT), and the mean and maximal velocities of the left ventricle posterior wall (PWVm and PWVM). At the same time as echocardiography recording, heart rate was measured by cardiac auscultation. Minoxidil produced a marked tachycardia. Less marked increases in heart rate occurred after quinidine. Both compounds were associated with a decrease in ESV and with marked increases in FS, EF, PWVm and PWVM which, in comparison with data for controls, are indicative of an increase in the amplitude and velocity of cardiac contraction. Both drugs also produced a decrease in EDV and consequently there was no increase in SV despite the increased amplitude of ventricular contraction. Cardiac output increased in proportion to the increase in heart rate. Overall, the effects were dose-related and are consistent with the pharmacological properties of the compounds. However, to date these effects have been demonstrated only by invasive methods. To conclude, we have shown that echocardiography allows a non-invasive investigation of the cardiac effects of suprapharmacological doses of antiarrhythmics and of the changes in heart function induced by vasodilators known to cause left ventricular lesions in dogs.
authors.affiliation: PFIZER Research Centre, Amboise, France.
authors.forename: G
authors.initials: G
authors.lastname: Hanton
authors.forename: A
authors.initials: A
authors.lastname: Lodola
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D004285:Dogs; D004452:Echocardiography / Q000379:methods / Q000662:veterinary*; D005260:Female; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D008914:Minoxidil / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D011802:Quinidine / Q000494:pharmacology*; D013318:Stroke Volume / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D000889:Anti-Arrhythmia Agents; D014665:Vasodilator Agents; D008914:Minoxidil; D011802:Quinidine