Sustained hemodynamic and clinical effects of a new cardiotonic agent, WIN 47203, in patients with severe congestive heart failure

C. S. Maskin, L. Sinoway, B. Chadwick, E. H. Sonnenblick, T. H. Le Jemtel

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Abstract

The hemodynamic and clinical effects of WIN 47203, a newly synthesized noncatecholamine, nonglycosidic inotropic agent, were studied in 11 patients with severe chronic congestive heart failure. Intravenous WIN 47203 increased cardiac index from 1.93 ± 0.36 to 2.87 ± 0.45 l/min/m2 (p < 0.001) and reduced pulmonary capillary wedge pressure from 27.0 ± 8.4 to 16.3 ± 6.1 mm Hg (p < 0.001). Mean systemic arterial pressure decreased from 75.2 ± 6.7 to 72.4 ± 6.3 mm Hg (p < 0.01) and systemic vascular resistance from 1591 ± 397 to 1071 ± 293 dyn-sec-cm5 (p < 0.001); heart rate was unchanged. Oral WIN 47203 produced similar hemodynamic improvement. Hemodynamic monitoring of six consecutive doses did not demonstrate evidence for attenuation of effectiveness. Chronic therapy with WIN 47203 produced substantial symptomatic improvement and increased maximal oxygen updake at 1 week. Patients were further improved after 4 weeks of WIN 47203, and maximal oxygen uptake increased from 9.0 ± 1.9 to 11.6 ± 2.5 ml/kg/min (p < 0.01 vs control). No overt clinical or laboratory manifestations of toxicity were observed. Withdrawal of WIN 47203 in two patients in whom clinical benefit was not sustained resulted in clinical and hemodynamic deterioration, which was reversed by reinstitution of the drug. Therefore, this study demonstrates the acute and sustained cardiotonic efficacy of WIN 47203 in man. If long-term administration remains well tolerated and without side effects, this drug appears to be very promising for treatment of chronic severe congestive heart failure.

Original languageEnglish (US)
Pages (from-to)1065-1070
Number of pages6
JournalUnknown Journal
Volume67
Issue number5
DOIs
StatePublished - Jan 1 1983

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Cardiotonic Agents
Heart Failure
Hemodynamics
Oxygen
Pulmonary Wedge Pressure
Drug-Related Side Effects and Adverse Reactions
Vascular Resistance
Arterial Pressure
Heart Rate
Therapeutics
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Maskin, C. S. ; Sinoway, L. ; Chadwick, B. ; Sonnenblick, E. H. ; Le Jemtel, T. H. / Sustained hemodynamic and clinical effects of a new cardiotonic agent, WIN 47203, in patients with severe congestive heart failure. In: Unknown Journal. 1983 ; Vol. 67, No. 5. pp. 1065-1070.
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Sustained hemodynamic and clinical effects of a new cardiotonic agent, WIN 47203, in patients with severe congestive heart failure. / Maskin, C. S.; Sinoway, L.; Chadwick, B.; Sonnenblick, E. H.; Le Jemtel, T. H.

In: Unknown Journal, Vol. 67, No. 5, 01.01.1983, p. 1065-1070.

Research output: Contribution to journalArticle

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T1 - Sustained hemodynamic and clinical effects of a new cardiotonic agent, WIN 47203, in patients with severe congestive heart failure

AU - Maskin, C. S.

AU - Sinoway, L.

AU - Chadwick, B.

AU - Sonnenblick, E. H.

AU - Le Jemtel, T. H.

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N2 - The hemodynamic and clinical effects of WIN 47203, a newly synthesized noncatecholamine, nonglycosidic inotropic agent, were studied in 11 patients with severe chronic congestive heart failure. Intravenous WIN 47203 increased cardiac index from 1.93 ± 0.36 to 2.87 ± 0.45 l/min/m2 (p < 0.001) and reduced pulmonary capillary wedge pressure from 27.0 ± 8.4 to 16.3 ± 6.1 mm Hg (p < 0.001). Mean systemic arterial pressure decreased from 75.2 ± 6.7 to 72.4 ± 6.3 mm Hg (p < 0.01) and systemic vascular resistance from 1591 ± 397 to 1071 ± 293 dyn-sec-cm5 (p < 0.001); heart rate was unchanged. Oral WIN 47203 produced similar hemodynamic improvement. Hemodynamic monitoring of six consecutive doses did not demonstrate evidence for attenuation of effectiveness. Chronic therapy with WIN 47203 produced substantial symptomatic improvement and increased maximal oxygen updake at 1 week. Patients were further improved after 4 weeks of WIN 47203, and maximal oxygen uptake increased from 9.0 ± 1.9 to 11.6 ± 2.5 ml/kg/min (p < 0.01 vs control). No overt clinical or laboratory manifestations of toxicity were observed. Withdrawal of WIN 47203 in two patients in whom clinical benefit was not sustained resulted in clinical and hemodynamic deterioration, which was reversed by reinstitution of the drug. Therefore, this study demonstrates the acute and sustained cardiotonic efficacy of WIN 47203 in man. If long-term administration remains well tolerated and without side effects, this drug appears to be very promising for treatment of chronic severe congestive heart failure.

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