AMRINONE INCREASES VENTRICULAR CONTRACTILITY AND DIASTOLIC COMPLIANCEIN ENDOTOXEMIA

Systolic and diastolic dysfunction occur during human septic shock, an d sensitivity to beta-adrenergic agents is reduced. We sought to deter mine whether amrinone, an inotropic agent independent of beta-receptor s, increases left-ventricular contractility or diastolic compliance af ter endotoxin infusion. We measured left-ventricular volume (using a c onductance catheter) and pressure (using a Millar catheter) before and after administering amrinone (4.5 mg/kg i.v., then 10 mu g/kg/min) to six endotoxemic and seven control pigs. The slope of the end-systolic pressure-volume relationship, E(es) was used as the primary measure o f contractility. Diastolic stiffness was characterized using stiffness parameters taken from pressure-volume relationships (k) and from pres sure-volume strain relationships. Amrinone increased E(es) from a medi an of 10.4 mm Hg/ml (interquartile range, 7.2 to 12.3) to 16.4 (13.7 t o 18.6) (p < 0.05) in the endotoxin group (p < 0.05). Amrinone decreas ed diastolic stiffness (k) in the endotoxin group by 35 +/- 78% (p < 0 .05). Amrinone did not significantly change Ee, or k in the control gr oup. Mean arterial pressure decreased after endotoxin infusion from 11 7 +/- 23 mm Hg to 76.5 +/- 14.9 mm Hg (p < 0.05), and decreased furthe r after amrinone to 62.0 +/- 14.8 mm Hg (p < 0.05). We conclude that i n this model of sepsis, amrinone may beneficially increase systolic co ntractility and diastolic compliance, but may dangerously decrease an already low mean arterial pressure.