K. Kroll et al., OPEN-SYSTEM KINETICS OF MYOCARDIAL PHOSPHOENERGETICS DURING CORONARY UNDERPERFUSION, American journal of physiology. Heart and circulatory physiology, 41(6), 1997, pp. 2563-2576
A novel hypothesis is proposed and tested describing open-system kinet
ics for myocardial phosphoenergetics. The hypothesis is that during se
vere coronary underperfusion there is precise matching of the rates of
ATP synthesis and hydrolysis, but despite the precise balance of ATP
rates, there is a decrease in the concentration of ATP and an increase
in the concentration of phosphocreatine (PCr) caused by the hydrolysi
s of AMP to adenosine. Isolated rabbit hearts were perfused using a cr
ystalloid medium, and coronary flow was reduced by 95% from baseline f
or 45 min followed by reperfusion. Phosphorus nuclear magnetic resonan
ce spectroscopy showed a rapid decrease in PCr concentration to 25% of
baseline at the onset of underperfusion followed by a gradual increas
e in PCr to 42% of baseline, while ATP decreased continuously to 65% o
f baseline. The kinetics of PCr and ATP could only be described by the
precise matching of the rates of ATP synthesis and ATP hydrolysis and
an open adenylate system that included the decrease in cytosolic AMP
concentration via the production and efflux of adenosine. To confirm t
he hypothesis of open-system kinetics, two independent predictions wer
e tested in separate experiments: 1) total coronary venous purine effl
ux (adenosine + inosine + hypoxanthine) during underperfusion was equa
l to the decrease in ATP concentration, and 2) there was no increase i
n PCr during moderate coronary underperfusion (80% flow reduction). In
conclusion, the open nature of the myocardial adenylate system causes
mass action effects that exert novel control over PCr and ATP concent
rations during coronary underperfusion. The open-system kinetics cause
ATP to decrease and PCr to increase, even though there is precise mat
ching of the rates of ATP synthesis and hydrolysis. Finally, the hydro
lysis of AMP to adenosine may benefit tissue survival during ischemia
by improving the free energy of ATP hydrolysis, thereby delaying or pr
eventing calcium overload.