Microcirculatory dysfunction and tissue oxygenation in critical illness.

Severe sepsis is defined by organ failure, often of the kidneys, heart, and brain. It has been proposed that inadequate delivery of oxygen, or insufficient extraction of oxygen in tissue, may explain organ failure. Despite adequate maintenance of systemic oxygen delivery in septic patients, their morbidity and mortality remain high. The assumption that tissue oxygenation can be preserved by maintaining its blood supply follows from physiological models that only apply to tissue with uniformly perfused capillaries. In sepsis, the microcirculation is profoundly disturbed, and the blood supply of individual organs may therefore no longer reflect their access to oxygen. We review how capillary flow patterns affect oxygen extraction efficacy in tissue, and how the regulation of tissue blood flow must be adjusted to meet the metabolic needs of the tissue as capillary flows become disturbed as observed in critical illness. Using the brain, heart, and kidney as examples, we discuss whether disturbed capillary flow patterns might explain the apparent mismatch between organ blood flow and organ function in sepsis. Finally, we discuss diagnostic means of detecting capillary flow disturbance in animal models and in critically ill patients, and address therapeutic strategies that might improve tissue oxygenation by modifying capillary flow patterns.

Does mean arterial blood pressure scale with body mass in mammals? Effects of measurement of blood pressure.

For at least the last 30 years, it has been discussed whether mean arterial blood pressure (MAP) is independent of body mass or whether it increases in accordance with the vertical height between the heart and the brain. The debate has centred on the most appropriate mathematical models for analysing allometric scaling and phylogenetic relationships; there has been previously little focus on evaluating the validity of underlying physiological data. Currently, the 2 most comprehensive scaling analyses are based on data from 47 species of mammals, based on 114 references. We reviewed all available references to determine under which physiological conditions MAP had been recorded. In 44 (38.6%) of the cited references, MAP was measured in anaesthetized animals. Data from conscious animals were reported in 59 (51.8%) of references; of these, 3 (2.6%) were radiotelemetric studies. In 5 species, data were reported from both anaesthetized and conscious animals, and the mean difference in the MAP between these settings was 20 ± 29 mm Hg. From a literature search, we identified MAP measurements performed by radiotelemetry in 11 of the 47 species included in the meta-analyses. A Bland-Altman analysis showed a bias of 1 mm Hg with 95% confidence interval (from -35 to 36 mm Hg); that is, the limits of agreement between radiotelemetric studies and studies in restrained animals were double the supposed difference in the MAP between the mouse and elephant. In conclusion, the existing literature does not provide evidence for either a positive or neutral scaling of arterial pressure to body mass across taxa.

The role of nitric oxide in the cardiovascular response to chronic and acute hypoxia in White Leghorn chicken (Gallus domesticus).

AIM: Prenatal hypoxia due to placental insufficiency results in deleterious phenotypes and compensatory mechanisms including increased sympathetic tone. Utilizing the embryonic chicken model, we investigated (i) changes in nitric oxide (NO)-mediated tone in response to chronic hypoxic development and (ii) the in vivo role of NO-mediated tone during acute hypoxic exposure, which has not been previously studied. We hypothesized that NO tone on the cardiovascular system would be unaffected by chronic hypoxic incubation in White Leghorn chicken (Gallus domesticus) embryos. METHODS: We measured arterial pressure, heart rate and femoral blood flow (via a Doppler flow probe) in response to acute hypoxia (10% O2 ) and pharmacological manipulations in normoxic- and hypoxic (15% O2 )-incubated embryos. This was performed at 70 and 90% of total incubation time (21 days). At 70% of incubation (day 15), blood volume and chorioallantoic membrane development are maximal; 90% of incubation (day 19) is 1 day prior to lung ventilation. RESULTS: Acute hypoxic exposure decreased femoral flow in both 90% groups, but increased femoral artery resistance in the hypoxic group. NO tone increased during development, but was not affected by hypoxic incubation. Inhibition of NO production by L-NAME (100 mg kg(-1) ) revealed that NO plays a significant role in the flow response to hypoxia. CONCLUSION: Chronic hypoxic incubation has no effect on cardiovascular NO tone during White Leghorn chicken development. In the intact animal, NO function during acute hypoxic stress is suppressed by hypoxic incubation, indicating that chronic hypoxic stress dampens the NO contribution.

Intravascular infusion of PEGylated Au nanoparticles affects cardiovascular function in healthy mice.

Recent advances of nanotechnology in clinical settings have spurred the development of various complex engineered nanoparticles (NPs). NPs share characteristics with ultrafine particles (UFPs; <1 µm) that can cross the pulmonary epithelium and disturb cardiovascular functions. Since these particles are injected directly into the blood stream, it is imperative to clarify whether NPs disrupt cardiovascular functions similar to UFPs. Therefore, we investigated whether engineered polyethylene glycol (PEG)-coated aluminum NPs for biomedical uses disturb cardiovascular functions in healthy mice. Mean arterial blood pressure (MAP) was measured in mice chronically instrumented with telemetric blood pressure transducers, and NPs were administered intravenously (10 mg kg(-1)). The NPs caused a prolonged lowering of MAP 7 days after injection (119.3 ± 3.3 vs. 97.4 ± 7.5 min(-1)), with no effect on the endothelial function as revealed by normal endothelial function of small vessels mounted in a myograph.