Tissue oxygen monitoring in rodent models of shock

Abstract

Tissue Po(2) (tPo(2)) reflects the balance between local O(2) supply and demand and, thus, could be a useful monitoring modality. However, the consistency and amplitude of the tPo(2) response in different organs during different cardiorespiratory insults is unknown. Therefore, we investigated the effects of endotoxemia, hemorrhage, and hypoxemia on tPo(2) measured in deep and peripheral organ beds. We compared arterial pressure, blood gas and lactate levels, descending aortic and renal blood flow, and tPo(2) in skeletal muscle, bladder epithelium, liver, and renal cortex during 1) LPS infusion (10 mg/kg), 2) sequential removal of 10% of circulating blood volume, and 3) reductions in inspired O(2) concentration in an anesthetized Wistar rat model with values measured in sham-operated animals. Different patterns were seen in each of the shock states, with condition-specific variations in the degree of acidemia, lactatemia, and tissue O(2) responses between organs. Endotoxemia resulted in a rise in bladder tPo(2) and an early fall in liver tPo(2) but no significant change in muscle and renal cortical tPo(2). Progressive hemorrhage, however, produced proportional declines in liver, muscle, and bladder tPo(2), but renal cortical tPo(2) was maintained until profound blood loss had occurred. By contrast, progressive hypoxemia resulted in proportional decreases in tPo(2) in all organ beds. This study highlights the heterogeneity of responses in different organ beds during different shock states that are likely related to local changes in O(2) supply and utilization. Whole body monitoring is not generally reflective of these changes.

The Role of Altered Lipid Metabolism in Septic Myocardial Dysfunction

“…Currently the cause of hyperlactatemia is considered to be the increased expression of Hypoxia-inducible factor1 (HIF-1)-and of cytokines activating PDHK4, an enzyme inhibiting PDH (pyruvate dehydrogenase) through phosphorylation so preventing the transformation of pyruvate into acetyl-CoA and its oxidation through the TCA (Tricarboxilic acid Cycle); the excess of pyruvate is transformed into lactate by Lactate dehydrogenase (LDH) through a process called accelerated aerobic glycolysis [35][36][37][38]. The plasma levels of lactate seems to be related to the outcome [35].…”

“…Short-term metabolic inhibition of PDHK4 is affected by pyruvate while its activation is affected by acetyl CoA and NADH. The long-term regulation is determined by many conditions characterized by insulin deficiency (diabetes) or resistance (starvation, high-fat diet, and hyperthyroidism) that increase PDHK expression, while insulin suppresses its production [35,36,38].…”

“…The absence of relevant cell death by apoptosis or necrosis in parenchymatous organs and the ability also of the tissues with less regenerative capacity to recover led to think that multiple organ dysfunction syndrome (MODS) were related mainly to a functional compromise mediated by endocrine and metabolic alterations and provided with a protective role [144][145][146]. In sepsis a paradoxical increase has been observed, in some tissue, in blood oxygen saturation [147], related to outcome and linked to an altered mitochondrial oxygen utilization (cytopathic hypoxia) [148], which has been attributed to nitric oxide (NO) overproduction by mitochondrial nitric oxide synthase (mtNOS) [149,150] or other NOS isoforms: NO competitively inhibits oxygen binding to cytochrome c oxydase (COX) determining a tonic inhibition of mitochondrial oxygen consumption, reversible on inhibiting its excessive production [151]. The exact role of NO inhibition by COX in vivo in physiologic and pathologic conditions is however an unsettled problem [152].…”

“…SIRT1 is rapidly deactivated by the reduced function of AMPK, the decreased NAD + levels due to the activation of PARP and by the increased expression of miR199a [66]. The stimulation of this enzyme in sepsis was first showed by Fink [148]; recently Zhang and colleagues, after LPS administration in mice, observed that the plasma levels of ATP, SIRT1 and AMPK decline precipitously after 10' and remain below the detection level for up to 12 h while HIF-1 increases contemporarily along with an increase in mitochondrial autophagy. Importantly all these effects are absent in wild type mice treated with resveratrol but not in Sirt1 liver knockout mice [164].…”

Manipulación del transporte y consumo de oxígeno en la sepsis

“…La ausencia de muerte celular significativa en la mayoría de los órganos disfuncionantes 39,48 , a excepción del sistema inmune y del epitelio gastrointestinal; la recuperabilidad funcional de los órganos; y la presencia de presiones tisulares de oxígeno normales o incluso elevadas en aquellos órganos disfuncionantes [49][50][51][52][53][54] , sugieren una disfunción metabólico-celular por sobre una deuda persistente de oxígeno tisular en la sepsis reanimada.…”