Apoptosis of lymphoid tissues during sepsis is well documented and linked to the pathobiology of organ failure and death. In this study, we evaluated the effect of a single dose of recombinant erythropoietin (EPO) on thymic and splenic apoptosis in an endotoxic sepsis model. Young male Wistar rats were divided into 3 groups and administered intraperitoneally (IP) either normal saline; lipopolysaccharide (LPS) 10 mg/kg; or EPO (5000 U/kg) 30 min before lipopolysaccharide. Six hours following LPS administration animals were sacrificed. Apoptosis was assessed by hematoxylin-eosin staining, terminal deoxynucleotide transferase-mediated fluorescein-dUTP nick end labeling (TUNEL), and caspase-3 immunostaining. When compared with animals given LPS, animals pretreated with EPO displayed reduced splenic and thymic TUNEL positivity of 44±3 (p<0.05) and 1434 (p<0.05) nuclei per high power field (hpf), respectively. Caspase-3 positivity was also significantly reduced in the spleen and thymus, with 31±4 (p<0.05) and 93±3 (p<0.05) positive stained nuclei per hpf, respectively. Serum nitrite levels were elevated in animals given lipopolysaccharide. Pretreatment with EPO attenuated the increase in nitrite levels; however, this did not reach statistical significance. We conclude that a single dose of recombinant erythropoietin can reduce thymic and splenic apoptosis associated with lipopolysaccharide administration.
Limited information is available about selection of the threshold for arterial blood pressure in critically ill patients, particularly in sepsis when normal organ blood flow autoregulation may be altered. The present experimental study investigated whether increasing perfusion pressure using norepinephrine in normotensive hyperdynamic porcine bacteremia affects intestinal macro- and microcirculation. Nine pigs received continuous i.v. administration of Pseudomonas aeruginosa (PSAE) to develop hyperdynamic, normotensive (mean arterial pressure [MAP] 65 mm Hg) sepsis. Norepinephrine was used to achieve 10-15 % increase in MAP. Mesenteric arterial blood flow (Qgut), ileal mucosal microvascular perfusion (LDFgut) and ileal-end-tidal PCO2 gap (PCO2 gap) were measured before norepinephrine, after 60 min of norepinephrine infusion and 60 min after norepinephrine infusion had been discontinued. During a 12 h period of PSAE infusion all pigs developed hyperdynamic circulation with significantly decreased MAP. Although the mesenteric blood flow remained unchanged, infusion of PSAE resulted in a gradual fall of ileal microvascular perfusion, which was associated with progressively rising PCO2 gap. Norepinephrine which induced a 10-15 % increase in perfusion pressure (i.e. titrated to attain near baseline values of MAP) affected neither Qgut nor the intestinal blood flow distribution (Qgut/CO). Similarly, norepinephrine did not change either LDFgut or PCO2 gap. In this hyperdynamic, normotensive porcine bacteremia, norepinephrine-induced increase in perfusion pressure exhibited neither beneficial nor deleterious effects on intestinal macrocirculatory blood flow and ileal mucosal microcirculation. The lack of changes suggests that the gut perfusion was within its autoregulatory range.