AN OVINE MODEL OF HYPERDYNAMIC ENDOTOXEMIA AND VITAL ORGAN METABOLISM

作者：Byrne Liam; Obonyo Nchafatso G; Diab Sara; Dunster Kimble; Passmore Margaret; Boon Ai Ching; Hoe Louise See; Hay Karen; Van Haren Frank; Tung John Paul; Cullen Louise; Shekar Kiran; Maitland Kathryn; Fraser John F

来源：Shock, 2018, 49(1): 99-107.

DOI：10.1097/SHK.0000000000000904

• Endotoxemia
• hemodynamic monitoring
• microdialysis
• resuscitation
• sepsis

Background: Animal models of endotoxemia are frequently used to understand the pathophysiology of sepsis and test new therapies. However, important differences exist between commonly used experimental models of endotoxemia and clinical sepsis. Animal models of endotoxemia frequently produce hypodynamic shock in contrast to clinical hyperdynamic shock. This difference may exaggerate the importance of hypoperfusion as a causative factor in organ dysfunction. This study sought to develop an ovine model of hyperdynamic endotoxemia and assess if there is evidence of impaired oxidative metabolism in the vital organs. Methods: Eight sheep had microdialysis catheters implanted into the brain, heart, liver, kidney, and arterial circulation. Shock was induced with a 4 h escalating dose infusion of endotoxin. After 3 h vasopressor support was initiated with noradrenaline and vasopressin. Animals were monitored for 12 h after endotoxemia. Blood samples were recovered for hemoglobin, white blood cell count, creatinine, and proinflammatory cytokines (IL-1Beta, IL-6, and IL-8). Results: The endotoxin infusion was successful in producing distributive shock with the mean arterial pressure decreasing from 84.5 +/- 12.8mm Hg to 49 +/- 8.03mm Hg (P < 0.001). Cardiac index remained within the normal range decreasing from 3.33 +/- 0.56 L/min/m(2) to 2.89I +/- 0.36 L/min/m(2) (P = 0.0845). Lactate/pyruvate ratios were not significantly abnormal in the heart, brain, kidney, or arterial circulation. Liver microdialysis samples demonstrated persistently high lactate/pyruvate ratios (mean 37.9 +/- 3.3). Conclusions: An escalating dose endotoxin infusion was successful in producing hyperdynamic shock. There was evidence of impaired oxidative metabolism in the liver suggesting impaired splanchnic perfusion. This may be a modifiable factor in the progression to multiple organ dysfunction and death.

• 出版日期2018-1