Damage-associated molecular patterns in resuscitated hemorrhagic shock are mitigated by peritoneal fluid administration

Conventional resuscitation (CR) of hemorrhagic shock (HS), a significant cause of trauma mortality, is intravenous blood and fluids. CR restores central hemodynamics, but vital organ flow can drop, causing hypoperfusion, hypoxia, damage-associated molecular patterns (DAMPs), and remote organ dysfunction (i.e., lung). CR plus direct peritoneal resuscitation (DPR) prevents intestinal and hepatic hypoperfusion. We hypothesized that DPR prevents lung injury in HS/CR by altering DAMPs. Anesthetized male Sprague-Dawley rats were randomized to groups ( n = 8/group) in one of two sets: 1) sham (no HS, CR, or DPR), 2) HS/CR (HS = 40% mean arterial pressure (MAP) for 60 min, CR = shed blood + 2 volumes normal saline), or 3) HS/CR + DPR. The first set underwent whole lung blood flow by colorimetric microspheres. The second set underwent tissue collection for Luminex, ELISAs, and histopathology. Lipopolysaccharide (LPS) and DAMPs were measured in serum and/or lung, including cytokines, hyaluronic acid (HA), high-mobility group box 1 (HMGB1), Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 protein (MYD88), and TIR-domain-containing adapter-inducing interferon-β (TRIF). Statistics were by ANOVA and Tukey-Kramer test with a priori P < 0.05. HS/CR increased serum LPS, HA, HMGB1, and some cytokines [interleukin (IL)-1α, IL-1β, IL-6, and interferon-γ]. Lung TLR4 and MYD88 were increased but not TRIF compared with Shams. HS/CR + DPR decreased LPS, HA, cytokines, HMGB1, TLR4, and MYD88 levels but did not alter TRIF compared with HS/CR. The data suggest that gut-derived DAMPs can be modulated by adjunctive DPR to prevent activation of lung TLR-4-mediated processes. Also, DPR improved lung blood flow and reduced lung tissue injury. Adjunctive DPR in HS/CR potentially improves morbidity and mortality by downregulating the systemic DAMP response.

The influence of gravity on regional lung blood flow in humans: SPECT in the upright and head-down posture

Previous studies in humans have shown that gravity has little influence on the distribution of lung blood flow while changing posture from supine to prone. This study aimed to evaluate the maximal influence of posture by comparison of regional lung blood flow in the upright and head-down posture in 8 healthy volunteers, using a tilt table. Regional lung blood flow was marked by intravenous injection of macroaggregates of human albumin labeled with 99mTc or 113mIn, in the upright and head-down posture, respectively, during tidal breathing. Both radiotracers remain fixed in the lung after administration. The distribution of radioactivity was mapped using quantitative single photon emission computed tomography (SPECT) corrected for attenuation and scatter. All images were obtained supine during tidal breathing. A shift from upright to the head-down posture caused a clear redistribution of blood flow from basal to apical regions. We conclude that posture plays a role for the distribution of lung blood flow in upright humans, and that the influence of posture, and thereby gravity, is much greater in the upright and head-down posture than in horizontal postures. However, the results of the study demonstrate that lung structure is the main determinant of regional blood flow and gravity is a secondary contributor to the distribution of lung blood flow in the upright and head-down positions. NEW & NOTEWORTHY Using a dual-isotope quantitative SPECT method, we demonstrated that although a shift in posture redistributes blood flow in the direction of gravity, the results are also consistent with lung structure being a greater determinant of regional blood flow than gravity. To our knowledge, this is the first study to use modern imaging methods to quantify the shift in regional lung blood flow in humans at a change between the upright and head-down postures.

Case Studies in Physiology: Ventilation and perfusion in a giraffe–does size matter?

The trachea in the giraffe is long but narrow, and dead space ventilation is considered to be of approximately the same size as in other mammals. Less is known about the matching between ventilation and lung blood flow. The lungs in the giraffe are large, up to 1 m high and 0.7 m wide, and this may cause considerable ventilation/perfusion (VA/Q) mismatch due to the influence of gravitational forces, which could lead to hypoxemia. We studied a young giraffe under anesthesia using the multiple inert gas elimination technique to analyze the VA/Q distribution and arterial oxygenation and compared the results with those obtained in other species of different sizes, including humans. VA/Q distribution was broad but unimodal, and the shunt of blood flow through nonventilated lung regions was essentially absent, suggesting no lung collapse. The VA/Q match was as good as in the similarly sized horse and was even comparable to that in smaller sized animals, including rabbit and rat. The match was also similar to that in anesthetized humans. Arterial oxygenation was essentially similar in all studied species. The findings suggest that the efficiency of VA/Q matching is independent of lung size in the studied mammals that vary in weight from less than 1 to more than 400 kg.

No redistribution of lung blood flow by inhaled nitric oxide in endotoxemic piglets pretreated with an endothelin receptor antagonist

Inhaled nitric oxide (INO) improves ventilation-perfusion matching and alleviates pulmonary hypertension in patients with acute respiratory distress syndrome. However, outcome has not yet been shown to improve, and nonresponse is common. A better understanding of the mechanisms by which INO acts may guide in improving treatment with INO in patients with severe respiratory failure. We hypothesized that INO may act not only by vasodilation in ventilated lung regions, but also by causing vasoconstriction via endothelin (ET-1) in atelectatic, nonventilated lung regions. This was studied in 30 anesthetized, mechanically ventilated piglets. The fall in oxygenation and rise in pulmonary artery pressure during a sepsislike condition (infusion of endotoxin) were blunted by INO 40 ppm. Endotoxin infusion increased serum ET-1, and INO almost doubled the ratio between mRNA expression of endothelin receptor A (mediating vasoconstriction) and B (mediating vasodilation and clearance of ET-1) (ET-A/ET-B) in atelectatic lung regions. INO caused a shift in blood flow away from atelectatic lung regions in the endotoxemic piglets, but not during ET receptor antagonism. We conclude that INO in short-term experiments, in addition to causing selective pulmonary vasodilation in ventilated lung regions, increases the ET-A/ET-B mRNA expression ratio in lung tissue. This might augment the vasoconstriction in atelectatic lung regions, enhancing the redistribution of pulmonary blood flow to ventilated lung regions which are reached by INO. Such vasoconstriction may be an important additional factor explaining the effect of INO.

Single Ventricle Physiology

Congenital cardiac abnormalities in which there is functionally only a single ventricle are a heterogeneous group of conditions. These include patients with marked hypoplasia of one ventricle, usually with hypoplasia or atresia of the inflow of the ventricle, such as in hypoplastic left heart syndrome or conditions where surgical separation of the flow to each ventricle is not possible, such as double-inlet left ventricle. The most common pathway for palliating these conditions will be to use cavopulmonary connections to provide lung blood flow direct from systemic venous return (reliant on systemic venous pressure). The single ventricle pumps to the systemic arterial circulation. Many of these patients will be long-term survivors and present with acute surgical conditions unrelated to their cardiac condition. The safe anesthesia management of patients with single ventricle physiology and cavopulmonary connections involves assessing their cardiovascular reserve and understanding the effects of hypovolemia, anesthesia, positive-pressure ventilation, and the procedure itself on their circulation.

Positive End-expiratory Pressure Redistributes Regional Blood Flow and Ventilation Differently in Supine and Prone Humans

Background Animal studies have demonstrated an interaction between posture and the effect of positive end-expiratory pressure (PEEP) on regional ventilation and lung blood flow. The aim of this study was to explore this interaction in humans. Methods Regional lung blood flow and ventilation were compared between mechanical ventilation with and without PEEP in the supine and prone postures. Six normal subjects were studied in each posture. Regional lung blood flow was marked with In-labeled macroaggregates and ventilation with Technegas (Tc). Radiotracer distributions were mapped using quantitative single-photon emission computed tomography. Results In supine subjects, PEEP caused a similar redistribution of both ventilation and blood flow toward dependent (dorsal) lung regions, resulting in little change in the V/Q correlation. In contrast, in prone subjects, the redistribution toward dependent (ventral) regions was much greater for blood flow than for ventilation, causing increased V/Q mismatch. Without PEEP, the vertical ventilation-to-perfusion gradient was less in prone postures than in supine, but with PEEP, the gradient was similar. Conclusions During mechanical ventilation of healthy volunteers, the addition of PEEP, 10 cm H2O, causes redistribution of both lung blood flow and ventilation, and the effect is different between the supine and prone postures. Our results suggest that the addition of PEEP in prone might be less beneficial than in supine and that optimal use of the prone posture requires reevaluation of the applied PEEP.