Z. Szilvassy et al., ANTIISCHEMIC EFFECT OF MONOPHOSPHORYL LIPID-A IN CONSCIOUS RABBITS WITH HYPERCHOLESTEROLEMIA AND ATHEROSCLEROSIS, Journal of cardiovascular pharmacology, 32(2), 1998, pp. 206-212
We studied whether monophosphoryl lipid A (MLA), an endotoxin derivati
ve, protected the heart from planned ischemia in hypercholesterolemic
conscious rabbits. Normal and hypercholesterolemic (8-week exposure to
1.5% cholesterol-enriched diet) conscious rabbits with right ventricu
lar electrode and left ventricular polyethylene catheters were subject
ed to ventricular overdrive pacing (VOP, 500 beats/min over 10 min = c
ontrol VOP). The resulting intracavitary ST-segment elevation, increas
e in left ventricular end-diastolic pressure (LVEDP), and a reduction
of ventricular effective refractory period (VERP) were measured. Three
days later the animals were given a single intravenous bolus of 10 or
30 mu g/kg MLA or its solvent or both, and a second VOP (test VOP) wa
s applied 24 h later. MLA decreased ST elevation and LVEDP increase fr
om 2.1 +/- 0.16 to 1.27 +/- 0.25 and 0.97 +/- 0.13 mV and 14.6 +/- 1.2
to 11.1 +/- 1.0 and 12.4 +/- 1.2 mm Hg in normal animals and from 2.5
5 +/-.0.14 to 1.31 +/- 0.12 and 0.96 +/- 0.30 mV and from 21.0 +/- 1.6
to 11.7 +/- 1.3 and 12.4 +/- 1.3 mm Hg in atherosclerotic animals aft
er 10- and 30-mu g/kg doses, respectively (p < 0.001 for each). VOP-in
duced VERP reduction was also significantly alleviated by both MLA dos
es: nevertheless, 30-mu g/kg MLA significantly prolonged resting VERP
with a slight VERP reduction in response to pacing in both normal and
atherosclerotic animals. We conclude that MLA produces a delayed antii
schemic effect in both normal and hypercholesterolemic/atherosclerotic
conscious rabbits.