Clinical effect of indolidan in congestive heart failure.
Indolidan (IN) experimentally inhibits type IV phosphodiesterase. It was administered to twelve patients (age 64 +/- 15 years) with New York Heart Association (NYHA) class 2-3 congestive heart failure in which digoxin and diuretic therapy were continued. IN was administered i.v. at 1,180 +/- 340 micrograms (15 micrograms/kg) over two hours. After 24 hours, IN was given p.o. at 231 +/- 44 micrograms. The time course effect of IN i.v. revealed an increase in cardiac index and a decrease in pulmonary capillary wedge pressure and blood pressure. Daily oral administration of IN or placebo was carried out for up to 3 months. There were no significant hemodynamic changes of chronically administered IN. The maximum oxygen uptake increased in placebo relative to IN therapy. IN tended to be arrhythmogenic as evidenced by a general increased frequency of ventricular premature contractions of both single and paired type. Therefore, IN had some hemodynamic efficacy on acute i.v. and p.o. administration but not during chronic therapy, and there was negative safety features of arrhythmias.
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Clinical Pharmacology Division, Oklahoma Medical Research Foundation, Oklahoma City 73104.
Puls
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Wilson
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D000284:Administration, Oral; D000368:Aged; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004077:Digoxin / Q000627:therapeutic use; D004232:Diuretics / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D017079:Exercise Tolerance / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D007275:Injections, Intravenous; D008875:Middle Aged; D000078183:Oxindoles; D010101:Oxygen Consumption; D011724:Pyridazines / Q000494:pharmacology / Q000627:therapeutic use*
D002316:Cardiotonic Agents; D004232:Diuretics; D007211:Indoles; D000078183:Oxindoles; D011724:Pyridazines; C050325:indolidan; D004077:Digoxin