The acute effect of a new positive inotropic agent (AR-L 115 BS) on cardiac hemodynamics and contractility in patients with severe chronic congestive heart failure.
The hemodynamic effect of 2-[(2-methoxy-4-methylsulfinyl)phenyl]- 1H-imidazo[4,5-b]pyridine (AR-L 115 BS), a new positive-inotropic substance, was studied in 10 Patients with chronic congestive heart failure after i.v. infusion of increasing does of 1.8 mg/min, 2.7 mg/min and 3.6 mg/min over a period of 40 min each. Prior to each infusion an i.v. bolus of 16 mg was given. The hemodynamic changes were measured by means of a Swan Ganz balloon tipped catheter and by echocardiography. The heart rate remained unchanged whereas systolic, diastolic and mean arterial pressures fell slightly by about 5%. The mean and diastolic pulmonary pressures decreased by 30% with a concomitant increase in cardiac output of 15%. The total peripheral and pulmonary resistance was reduced by 20% and 40%, respectively. The echocardiographically measured fraction of systolic fiber shortening of the left ventricle was increased by 15%. In parallel the ratio of PEP/LVET decreased by 10%. While the increase of the infusion dose from 1.8 mg/min to 2.7 mg/min was followed by an increase in the hemodynamic changes, no further alterations were observed after the dose was increased from 2.7 mg/min to 3.6 mg/min despite a marked increase in the blood level of AR-L 115 BS. The effect was still present 75 min after the infusion had been stopped. The blood level at that time had returned to the level achieved with the dose of 2.7 mg/min. The results are consistent with findings in animals which have shown that AR-L 115 BS exerts not only a positive-inotropic action on the heart, but also exhibits a vasodilating effect, predominantly in the capacitance vessels. As the substance can also be administered orally it could prove to be a useful agent in the management of severe cases of heart failure.
D000328:Adult; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000494:pharmacology*; D002908:Chronic Disease; D003326:Coronary Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*
D002316:Cardiotonic Agents; D007093:Imidazoles; C029758:sulmazole