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.