Inhalative and intravenous stimulation of soluble guanylate cyclase reduces pulmonary vascular resistance and increases cardiac output in experimental septic shock

Abstract

The effects of inhaled and intravenous application of a guanylate cyclase stimulator (BAY 41-8543) on pulmonary vascular resistance (PVR) and cardiac output (CO) were investigated in an experimental model of septic shock. Following induction of septic shock, anaesthetized pigs (n=31) were randomly place into two groups receiving different interventions. Animals in the first group received intravenous BAY 41-8543 (0.6 mg), inhalative BAY 41-8543 (6 mg) or a placebo. In the second group, the dosage of BAY 41-8543 was increased two-fold or combined with inhalation of nitric oxide (iNO). Intravenous and inhaled administration of BAY 41-8543 resulted in a significantly (P<0.05) reduced PVR and increased CO compared with the placebo. Increasing the dosage of BAY 41-8543 or combining it with iNO did not further decrease PVR. The results of the present study indicate that BAY 41-8543 effectively reduces PVR and increases CO in septic shock, through inhaled or intravenous routes of administration.