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EXPLORATORY-STUDY OF THE EFFECTS OF SINGLE DOSES OF ISOMAZOLE AN HEMODYNAMICS AND HEART-RATE-VARIABILITY PARAMETERS IN CHRONIC HEART-FAILURE

TUININGA, YS., VANVELDHUISEN, DJ., CRIJNS, HJGM., VANDENBROEK, SAJ., BROUWER, J., HAAKSMA, J., MANINTVELD, AJ. & LIE, KI., Jan-1995, In : Journal of Cardiovascular Pharmacology. 25, 1, p. 81-86 6 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • YS TUININGA
  • DJ VANVELDHUISEN
  • HJGM CRIJNS
  • SAJ VANDENBROEK
  • J BROUWER
  • J HAAKSMA
  • AJ MANINTVELD
  • KI LIE

Ventricular arrhythmias and disturbed autonomic control, as reflected by abnormal heart rate variability (HRV), are related to hemodynamic impairment in chronic heart failure (CHF). We investigated the effects of orally (p.o.) administered isomazole, a new phosphodiesterase (PDE) inhibitor with calcium-sensitizing properties, on hemodynamics, ventricular arrhythmias, and HRV and examined a possible interaction between these parameters. Hemodynamic measurements and ambulatory ECG monitoring were performed in 12 patients with stable CHF class III-IV after single doses of isomazole 5-30 mg. Pulmonary wedge pressure decreased after 5, 10, 20, and 30 mg, but cardiac output, (CO) increased only after the higher doses [20 mg, +20%(p = 0.031)] of isomazole. KR did not change. Mean arterial and pulmonary artery pressure, (MAP, PAP) decreased significantly in the 10-and 20-mg groups [10 mg, -6%(p = 0.035) and -14%(p <0.001) respectively; 20 mg, -13%(p = 0.047) and -31%(p = 0.006), respectively]. Isomazole did not exert a significant effect on ventricular arrhythmias in the subsequent 24 h after acute dosing. Analysis of HRV showed that rMSSD and pNN50 (parameters of vagal tone) tended to increase after isomazole administration. Normalized high-frequency power during the day increased from 17.4 to 22.3 nu (p <0.05), whereas low frequency tended to decrease from 52.7 to 48.2 nu (p = 0.06). Acute isomazole administration improves hemodynamics but has no effect on ventricular arrhythmias. The HRV variability data suggest development of an increase in vagal control of KR, parallel to the acute hemodynamic improvement after isomazole. Withdrawal of vagal control of HR in CHF may be a reversible process.

Original languageEnglish
Pages (from-to)81-86
Number of pages6
JournalJournal of Cardiovascular Pharmacology
Volume25
Issue number1
Publication statusPublished - Jan-1995

    Keywords

  • ISOMAZOLE, HEART FAILURE, HEART RATE VARIABILITY, HEMODYNAMICS, AUTONOMIC NERVOUS SYSTEM, PDE INHIBITOR, MILRINONE, CAPTOPRIL, DIGOXIN

ID: 6410967