H. Miyano et al., Acute effect of tumor necrosis factor-alpha is minimal on mechanics but significant on energetics in blood-perfused canine left ventricles, CRIT CARE M, 27(1), 1999, pp. 168-176
Objectives: We hypothesized that tumor necrosis factor-alpha (TNF-alpha) ac
utely alters left ventricular mechanoenergetics in blood-perfused hearts. T
o test this hypothesis, we examined the relation between left ventricular m
echanics and energetics, both before and after infusion of TNF-alpha.
Design: Prospective, experimental study.
Setting: Research laboratory.
Subjects: Nine isolated, blood-perfosed canine hearts.
Interventions: Recombinant human TNF-alpha (90 mu g/min) was infused into t
he coronary circulation of the isolated hearts for 20 mins.
Measurements and Main Results: In the isolated, cross circulated, blood per
fused canine left ventricles, left ventricular contractility was assessed t
hrough measurement of end-systolic elastance (Ees). Energetics were examine
d in terms of the end systolic pressure volume area-myocardial oxygen consu
mption (MVo(2)) relation. TNF-alpha concentration in coronary venous blood
was >1000 ng/mL throughout the experiments. Nevertheless, infusion of TNF-a
lpha barely affected contractility acutely, i.e., there was a minimal decre
ase during the infusion (8.1 +/- 2.8% at 10 mins, p<.01) and a minimal incr
ease after the infusion (11.2 +/- 2.5% at 10 mins, p<.01). Neither did the
TNF-alpha infusion affect the slope of the end-systolic pressure-volume are
a MVo(2) relation. This finding indicated that the chemomechanical conversi
on efficiency remained unchanged. However, TNF-alpha infusion significantly
increased the oxygen cost of contractility by 40% (1.25 +/- 0.13 vs. 1.75
+/- 0.24 mt oxygen.mL/mm Hg/beat, p<.05), indicating that MVo(2) for the ex
citation-contraction coupling increased.
Conclusions: TNF-alpha minimally alters left ventricular mechanics, but sig
nificantly changes energetics. The latter effect may result from changes in
intracellular calcium handling.