DESIGN: Prospective experimental study.
SUBJECTS: Fourteen landrace pigs.
INTERVENTIONS: All animals were anesthetized and catheterized for measurement of central and pulmonary hemodynamics. Ultrasonic flow probes were placed around the renal artery and portal vein to measure blood flow. A tonometer was placed in the ileum to measure mucosal pH.
Levosimendan was given to six animals as a bolus (200 microg x kg(-1)) followed by a continuous infusion (200 microg x kg(-1) x hr(-1)). Thirty minutes after onset of
levosimendan treatment, all animals received
endotoxin (20 microg x kg(-1) x hr(-1) for 3 hrs).
MEASUREMENTS AND MAIN RESULTS: At baseline,
levosimendan induced a systemic vasodilation with a reduction in blood pressure and an increase in heart rate. A tendency to an increase in cardiac index did not reach statistical significance (p =.055). Cardiac index and systemic
oxygen delivery were markedly improved in the
levosimendan group during
endotoxemia. Systemic vascular resistance and blood pressure were reduced in the
levosimendan group. The latter parameter, however, was only different from the control group during the initial phase of
endotoxin shock but not at the late, most pronounced phase of
shock.
Levosimendan also efficiently attenuated
endotoxin-induced
pulmonary hypertension. Portal venous blood flow and gut
oxygen delivery were improved, but no concomitant reduction in
endotoxin-induced intestinal mucosal
acidosis was observed. Renal blood flow was unaffected, as was the
endotoxin-induced increase in plasma endothelin-1-like immunoreactivity. These findings support previous reports of
calcium desensitization as a potential component in septic myocardial depression. Furthermore, the vasodilatory properties of this
drug were well tolerated in the current model of hypodynamic
endotoxin shock, and they may have contributed to improved regional blood flow as seen in the gut as well as improved systemic perfusion by means of reduced biventricular afterload.
CONCLUSION: