Verification of a canine model of transient exercise induced myocardial dysfunction: antianginal effects of flestolol, an ultra short acting beta adrenoceptor antagonist.
STUDY OBJECTIVE - The aim of the study was to verify the reproducibility of a canine model of treadmill exercise induced regional myocardial dysfunction designed to mimic exertional angina pectoris in man. DESIGN - Dogs trained to run on a treadmill were chronically instrumented with a microtip manometer in the left ventricle, a hydraulic occluder around the circumflex branch of the left coronary artery, two pairs of crystals for sonomicrometry, and arterial and venous catheters. Experiments were started 10 d after surgery, when the animals were submitted to seven treadmill exercise cycles, each of 3 min, with a 7 min recovery period. Ischaemia was adjusted so as not to impair regional function at rest but to produce progressive dysfunction with increasing work load. Flestolol (1 microgram.kg-1.min-1) was infused intravenously during the third and fourth exercise cycle. SUBJECTS - Six mongrel dogs, 13.5-29.5 kg, were used. MEASUREMENTS and RESULTS - Flestolol caused a marked reduction in the exercise induced increase in left ventricular positive dP/dtmax, and minor reductions in heart rate and systolic blood pressure, resulting in a decrease in myocardial oxygen demand and an improvement in regional function in the circumflex area of the left coronary artery. The functional improvement was transient and disappeared entirely after termination of flestolol infusion. CONCLUSIONS - The results show that flestolol is beneficial in conditions of limited coronary reserve and exercise induced myocardial dysfunction. The fact that the extent of regional myocardial dysfunction was comparable before and after flestolol infusion confirms the stability and usefulness of this experimental model in the evaluation of antianginal drugs.
Fischer
G
G
University of Vienna, Department of Cardiovascular Pharmacology, Austria.
Grohs
J G
JG
Raberger
G
G
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000787:Angina Pectoris / Q000188:drug therapy* / Q000209:etiology; D000818:Animals; D001794:Blood Pressure; D004195:Disease Models, Animal; D004285:Dogs; D005464:Fluorobenzenes; D006339:Heart Rate; D009203:Myocardial Infarction / Q000503:physiopathology; D005082:Physical Exertion; D011412:Propanolamines / Q000627:therapeutic use*; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D005464:Fluorobenzenes; D011412:Propanolamines; C047847:flestolol