Am. J. Respir. Crit. Care Med., Vol 152, No. 2, 08 1995, 496-503.
Amrinone increases ventricular contractility and diastolic compliance in endotoxemia
HA Werner, MJ Herbertson and KR Walley
Pulmonary Research Laboratory, St. Paul's Hospital, University of British Columbia, Vancouver, Canada.
Systolic and diastolic dysfunction occur during human septic shock, and
sensitivity to beta-adrenergic agents is reduced. We sought to determine
whether amrinone, an inotropic agent independent of beta- receptors,
increases left-ventricular contractility or diastolic compliance after
endotoxin infusion. We measured left-ventricular volume (using a
conductance catheter) and pressure (using a Millar catheter) before and
after administering amrinone (4.5 mg/kg i.v., then 10 micrograms/kg/min) to
six endotoxemic and seven control pigs. The slope of the end-systolic
pressure-volume relationship, Ees, was used as the primary measure of
contractility. Diastolic stiffness was characterized using stiffness
parameters taken from pressure-volume relationships (k) and from
pressure-volume strain relationships. Amrinone increased Ees from a median
of 10.4 mm Hg/ml (interquartile range, 7.2 to 12.3) to 16.4 (13.7 to 18.6)
(p < 0.05) in the endotoxin group (p < 0.05). Amrinone decreased
diastolic stiffness (k) in the endotoxin group by 35 +/- 18% (p < 0.05).
Amrinone did not significantly change Ees or k in the control group. Mean
arterial pressure decreased after endotoxin infusion from 117 +/- 23 mm Hg
to 76.5 +/- 14.9 mm Hg (p < 0.05), and decreased further after amrinone
to 62.0 +/- 14.8 mm Hg (p < 0.05). We conclude that in this model of
sepsis, amrinone may beneficially increase systolic contractility and
diastolic compliance, but may dangerously decrease an already low mean
arterial pressure.
