F. Nomura et al., EFFECTS OF HYPERCARBIC ACIDOTIC REPERFUSION ON RECOVERY OF MYOCARDIAL-FUNCTION AFTER CARDIOPLEGIC ISCHEMIA IN NEONATAL LAMBS, Circulation, 90(5), 1994, pp. 321-327
Background There is continued controversy over the management of pH du
ring ischemia and reperfusion. Calcium overload is an integral feature
of the injury resulting from ischemia and reperfusion, and hydrogen i
ons are known to blunt Ca2+ influx into cells because H+ inhibits the
Na+-Ca2+ exchange and the slow calcium channels. Hypercarbia is one so
urce of H+, but elevated CO2 level is also known to be a potent corona
ry vasodilator, which may be beneficial during early reperfusion. This
study was designed to explore the effect of respiratory and metabolic
acidosis during the initial phases of reperfusion after hypothermic c
ardioplegic ischemia in the neonatal lamb. Methods and Results Forty i
solated, blood-perfused neonatal lamb hearts underwent 2 hours of cold
cardioplegic ischemia followed by reperfusion with blood with various
pH values. pH was controlled either by altering the FICO2 in the vent
ilating gas to the oxygenator (groups A through D) or by adding HCl to
the reperfusate (group E). pH of the initial reperfusate was 6.8 in g
roup A, 7.1 in group B, 7.5 in group C, and 7.8 in group D. In these g
roups, pH values were maintained for the initial 5 minutes of reperfus
ion and then corrected to 7.4 over 20 minutes by changing the FICO2, t
o the oxygenator. In group E, HCl was added to the reperfusate to give
pH 6.8 (metabolic acidosis). pH was corrected after 5 minutes of repe
rfusion by administration of NaHCO3 and THAM over the next 15 minutes.
At 30 and 60 minutes of reperfusion, left ventricular maximum develop
ed pressure, dP/dt, -dP/dt, maximum developed pressure at V-10 (volume
that gave left ventricular end-diastolic pressure of 10 mm Hg during
baseline measurements), and dP/dt at V-10 were measured. Coronary bloo
d flow and oxygen consumption (MVo(2)) were also measured to evaluate
the metabolic recovery. Group A showed better functional recovery than
groups B, C, or D (maximum dP/dt V-10: group A, 88.3+/-7.7%; group B,
69.3+/-10.8%; group C, 74.6+/-10.3%; group D, 66.1+/-9.4%; and group
E, 73.7+/-13.8% at 30 minutes [P<.05]; group A, 76.1+/-13.6%; group B,
61.9+/-8.6%; group C, 63.8+/-5.4%; group D, 57.9+/-9.4%; and group E,
62.6+/-12.7% at 60 minutes [P<.05]). Coronary blood flow was higher i
n group A than in other groups (A, 177.2+/-29.6%; B, 144.1+/-18.1%; C,
127.3+/-18.5%; D, 150.4+/-24.3%; and E, 106.0+/-20.0% [P<.05]). There
were no significant differences in MVo(2). Conclusions These data ind
icate that hypercarbic reperfusion (pH 6.8) for a short period after i
schemia improved functional recovery after cold cardioplegic ischemia
in neonatal lamb hearts but that metabolic acidosis to an equivalent p
H did not improve postischemic function. Possible mechanisms for this
effect include reduction of calcium loading to the myocardium through
H+ inhibition of calcium uptake or the induction of coronary vasodilat
ion by hypercarbia.