Adaptation of cardiac contractile function to conditions of chronic energy deficiency.
Left ventricular (LV) contractile function and pump function were depressed in isolated working hearts from rats treated with either guanidinopropionic acid (GPA), an inhibitor of creatine influx, or the anthracycline antibiotic, adriamycin, for 6 and 10 weeks, respectively. In both groups of treated animals myocardial phosphocreatine content was lower than in control hearts, while ATP content was unchanged. Hearts of treated animals exhibited only a minor depression of cardiac output with a submaximal pressure load or during volume overload. However, at maximal pressure load GPA- and adriamycin-treated hearts performed 43% and 37% less pressure-volume work than control hearts. These changes were due both to decreased LV pressure development and diminished cardiac output. LV diastolic stiffness was significantly higher at the submaximal pressure load and the LV filling pressure area, which reflected LV filling, was lower in hearts of both treated groups. The differences in both indices were exaggerated when the maximal pressure load was applied. Limited LV filling due to incomplete myocardial relaxation appeared to represent the underlying cause of cardiac failure when afterload was increased. These results may be explained if adaptation of cardiac contractile function in some chronic cardiac diseases arises from a limited energy supply to the myofibrils.
Kapelko
V I
VI
Institute of Experimental Cardiology, Academy of Medical Sciences, Moscow, USSR.
Saks
V A
VA
Novikova
N A
NA
Golikov
M A
MA
Kupriyanov
V V
VV
Popovich
M I
MI
D000222:Adaptation, Physiological; D000818:Animals; D003401:Creatine / Q000378:metabolism; D004317:Doxorubicin / Q000633:toxicity; D004734:Energy Metabolism / Q000187:drug effects; D006146:Guanidines / Q000633:toxicity; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D011422:Propionates / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains
D006146:Guanidines; D011422:Propionates; D010725:Phosphocreatine; D004317:Doxorubicin; D003401:Creatine; C005775:guanidinopropionic acid