Effects of intracoronary caffeine on left ventricular mechanoenergetics in Ca2+ overload failing rat hearts.
How different the effects of caffeine on cardiac mechanoenergetics in failing hearts are from those of normal hearts remains to be fully elucidated. First we successfully instituted a new experimental model of acute mild heart failure in the rat by 0.005 mM Ca2+ Tyrode perfusion. These failing hearts neither decreased left ventricular end-systolic pressure nor increased left ventricular end-diastolic pressure, indicating unchanged left ventricular mechanics. However, their myocardial mitochondrial respiratory function examined by respiratory control index (RCI) and oxygen consumption rate in state III (State III O2) was significantly depressed compared with normal hearts. From these results, we judged that this Ca2+ protocol could make mild Ca2+ overload acute failing hearts and that this model would be appropriate for comparing the effects of caffeine on cardiac mechanoenergetics between normal hearts and these failing hearts. We investigated the effects of caffeine on cardiac mechanoenergetics above a concentration of 0.05 mM that corresponds to the maximum blood concentration after a healthy human subject drinks a cup of coffee or tea. We obtained results indicating that caffeine depressed left ventricular systolic and diastolic functions and decreased a measure of total mechanical energy per beat in terms of systolic pressure-volume area (PVA) more severely in these failing hearts at concentrations (20-fold higher than the concentration in a cup of coffee) lower than those in normal hearts. This result implies that these acute failing hearts are Ca2+ overloaded.
Fujii
W
W
Mimasaka Women's Junior College, Tsuyama, 708-8511, Japan.
Takaki
M
M
Yoshida
A
A
Ishidate
H
H
Ito
H
H
Suga
H
H
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002110:Caffeine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D002118:Calcium / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000187:drug effects; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000502:physiology
D002110:Caffeine; D002118:Calcium