Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Stark, G; Stark, U; Samonigg, H; Kasparek, K; Lueger, A; Nagl, S; Bertuch, H; Pilger, E; Tritthart, HA.
Comparison of acute effects of anthracyclines on cardiac electrophysiological parameters of isolated guinea-pig hearts.
Cancer Chemother Pharmacol. 1990; 26(6):415-418
Doi: 10.1007/BF02994091
Web of Science
PubMed
FullText
FullText_MUG
Google Scholar
- Co-Autor*innen der Med Uni Graz
- Kasparek Anne-Katrin
- Pilger Ernst
- Samonigg Hellmut
- Tritthart Helmut
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- This study was performed to evaluate the acute effects of two anthracycline derivatives, doxorubicin and 4'O-tetrahydropyranyl-doxorubicin [(THP)-doxorubicin], on the conduction intervals, heart rate and refractoriness of isolated spontaneously beating guinea-pig hearts using a high-resolution ECG recording technique (SST-ECG). Doxorubicin as well as (THP)-doxorubicin were added to the perfusate in increasing concentrations of 0.1, 1 and 10 microM. Doxorubicin did not significantly alter the heart rate or conduction intervals. Only the rate-dependent QT interval was significantly shortened under the influence of 10 microM doxorubicin. In contrast, 10 microM (THP)-doxorubicin led to a significant reduction in the heart rate (-13% +/- 3%; P less than 0.01, n = 7) and to a prolongation of atrioventricular conduction time (24% +/- 10%; P less than 0.05, n = 7). The rate-dependent repolarization period (QT interval) was only insignificantly shortened in the presence of 10 microM (THP)-doxorubicin. The maximal following frequencies of each part of the conduction system were not changed by 10 microM doxorubicin. In the presence of (THP)-doxorubicin, the maximal following frequency of the ventricular myocardium was increased by as much as 36% +/- 8% (P less than 0.01, n = 7), indicating a shortening of the effective refractory period of the ventricular myocardium (V-ERP). These results show that the activation of (THP)-doxorubicin resembles the effects of Ca-antagonistic compounds on the heart (i.e. decrease in the spontaneous sinus rate and prolongation of the AV-nodal conduction interval). Changes in the QT interval exerted by doxorubicin and the shortening of the ventricular effective refractory period by (THP)-doxorubicin may indicate an alteration of the K(+)-conductance of the membrane. As the acute electrophysiological effects of doxorubicin and (THP)-doxorubicin are modest and occur only at excessive concentrations (10 microM), a direct influence on the generation of arrhythmias in healthy hearts is unlikely.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Antibiotics, Antineoplastic - pharmacology
- Cardiac Pacing, Artificial - pharmacology
- Dose-Response Relationship, Drug - pharmacology
- Doxorubicin - analogs and derivatives
- Electrocardiography - drug effects
- Electrophysiology - drug effects
- Female - drug effects
- Guinea Pigs - drug effects
- Heart - drug effects
- Heart Rate - drug effects
- Male - drug effects
- Time Factors - drug effects