Presence of negative inotropic agents in canine plasma during positive end-expiratory pressure

Application of positive end-expiratory pressure (PEEP) will reduce cardiac output (CO). Humoral mediation of this event by circulating negative inotropic agents was examined using a rat papillary muscle bioassay. Twenty-seven dogs were anesthetized with an iv pentobarbital infusion. Plasma was obtained before and after 30 minutes of PEEP. The plasma was oxygenated in a small (4.5-ml) papillary muscle chamber using a diffusion membrane. An average PO2 of 416 mm Hg was achieved. PEEP plasma reduced developed tension (Tpd) from 2.16 +/- 1.0 to 1.90 +/- 1.05 g (P less than 0.0001). A fall in Tpd was observed whether or not CO was maintained constant with fluid infusion. Resting tension was unchanged. The percent reduction in Tpd correlated with the fall in CO (r = 0.63, P less than 0.01) when fluid was not infused to maintain CO. Reapplication of control plasma restored Tpd. Barbiturate levels in anesthetized dogs rose from 17.3 to 19.4 microns/ml during PEEP (P less than 0.1). Addition of pentobarbital to normal plasma led to a slight decrease in Tpd only when the concentration exceeded 99 microns/ml. In three experiments on ex vivo perfused hearts, application of PEEP led to lowering of peak systolic pressure (PSP) within 5 minutes. Removal of PEEP restored PSP in a similar time. The results support the hypothesis that the decline in CO with PEEP is mediated in part by a circulating negative inotropic agent.