Calcium-dependent changes of the myocardial contractile function at chronic adriamycin treatment.
The contractile function of hearts and atria isolated from rats treated with adriamycin (ADM, total cumulative dose 16-20 mg/kg for 8-10 weeks) was moderately lower as compared to control preparations. However, the former exhibited a relatively higher positive inotropic response to an elevation of Ca++ concentration in the perfusate of isolated hearts or paired pulse stimulation of atria so that maximally attainable values were similar in both groups. On the contrary, the depression of ADM-treated atrial contractile amplitude became even more prominent at moderate increase in stimulation rate and was associated with the apparent incomplete relaxation. Chemically skinned fibers from ADM-treated hearts began to develop force at lower Ca++ concentration and exhibited higher Ca++-sensitivity in pCA range 5.8-5.4. Results suggest that long-term ADM-treatment may be associated with a functional deficiency of Ca++-transporting mechanisms in myocardial cells which may contribute to the depression of the cardiac contractile function.
Kapelko
V I
VI
Institute of Experimental Cardiology, USSR Cardiology Research Center, Moscow.
Veksler
V I
VI
Gorina
M S
MS
Golikov
M A
MA
D000818:Animals; D016275:Atrial Function; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D051381:Rats; D012016:Reference Values; D013318:Stroke Volume / Q000187:drug effects
D004317:Doxorubicin; D002118:Calcium