Resuscitative endovascular balloon occlusion of the aorta (REBOA): a scoping review protocol concerning indications—advantages and challenges of implementation in traumatic non-compressible torso haemorrhage

IntroductionHaemorrhage remains the leading cause of preventable death in trauma. Damage control measures applied to patients in extremis in order to control exsanguinating bleeding from non-compressible torso injuries use different techniques to limit blood flow from the aorta to the rest of the body. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is regaining momentum recently as an adjunct measure that can provide the same results using less invasive approaches. This scoping review aims to provide a comprehensive understanding of the existing literature on REBOA. The objective is to analyse evidence and non-evidence-based medical reports and to describe current gaps in the literature about the best indication and implementation strategies for REBOA.Methods and analysisUsing the five-stage framework of Arksey and O’Malley’s scoping review methodology as a guide, we will perform a systematic search in the following databases: MEDLINE, EMBASE, BIOSIS, COCHRANE CENTRAL, PUBMED and SCOPUS from the earliest available publications. The aim is to identify diverse studies related to the topic of REBOA. For a comprehensive search, we will explore organisational websites, key journals and hand-search reference lists of key studies. Data will be charted and sorted using a descriptive analytical approach.Ethics and disseminationEthics approval is not necessary as the data are collected from publicly available sources and there will be no consultative phase. The results will be disseminated through presentations at local, national, clinical and medical education conferences and through publication in a peer-reviewed journal.

What is a pericyte?

Pericytes, spatially isolated contractile cells on capillaries, have been reported to control cerebral blood flow physiologically, and to limit blood flow after ischaemia by constricting capillaries and then dying. Paradoxically, a recent paper dismisses the idea of pericytes controlling cerebral blood flow, despite confirming earlier data showing a role for pericytes. We show that these discrepancies are apparent rather than real, and depend on the new paper defining pericytes differently from previous reports. An objective definition of different sub-classes of pericyte along the capillary bed is needed to develop novel therapeutic approaches for stroke and disorders caused by pericyte malfunction.

Discovery, Engineering and Pre-Clinical Evaluation of an Anti-vWF A1 Domain Aptamer.

Following coronary artery damage, von Willebrand Factor (vWF) multimers adhere to exposed collagen via the vWF A3 domain. Platelets passing through damaged vessels under the conditions of high shear force associated with stenosed arteries will adhere to the vWF A1 domain via GPIb receptors. This initial platelet binding event triggers the formation of a thrombus that can limit blood flow to the myocardium and produce the symptoms of acute coronary syndrome (ACS). Through in vitro selection (SELEX) and subsequent lead optimization, we have generated a nuclease-resistant DNA aptamer that binds to the vWF A1 domain with high affinity. The anti-vWF aptamer inhibits both botrocetin-induced platelet aggregation of platelet rich plasma and shear force-induced platelet aggregation in citrated whole blood. Continuous intravenous infusion of the aptamer in cynomolgus macaques is able to effectively inhibit thrombus formation induced by electrical injury to the carotid artery. Modest effects on template bleeding are observed with the vWF-specific aptamer relative to anti-GPIIb/IIIa therapy. Based upon these results, this aptamer is an excellent candidate for treatment of ACS.

Adrenergic vasoconstriction augments tissue O2 extraction during reductions in O2 delivery

When systemic O2 delivery is reduced, increases in systemic O2 extraction are facilitated by sympathetically mediated increases in vascular resistance that limit blood flow to regions with low metabolic demand. Local metabolic vasodilation competes with this vasoconstriction, thereby effecting a balance between tissue O2 supply and demand. This study examined the role of sympathetically mediated vasoconstriction on the critical level of O2 extraction in hindlimb and whole body during progressive reductions in O2 delivery. In anesthetized dogs, the left hindlimb was vascularly isolated and its O2 delivery was decreased in stages by reducing the speed of an occlusive pump. In a normovolemic group (n = 6), blood volume was maintained to minimize sympathetic tone while flow to the hindlimb was reduced. In a hypovolemic group (n = 6), blood volume was removed in stages to augment sympathetic tone progressively while flow to the limb was reduced simultaneously. A phenoxybenzamine group (n = 6) was identical to the hypovolemic group, except that alpha-adrenergic effects were inhibited with phenoxybenzamine (3 mg/kg). The systemic critical O2 extraction ratio in the phenoxybenzamine group (0.60 +/- 0.06) was less than for the hypovolemic group (0.71 +/- 0.04; P = 0.004). In the hindlimb, critical O2 extractions were significantly less in the normovolemic (0.46 +/- 0.17) and phenoxybenzamine (0.49 +/- 0.10) groups compared with the hypovolemic group (0.72 +/- 0.10; P < or = 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced responses of retinal vessels of the newborn pig to prostaglandins but not to thromboxane

The upper blood pressure limit of retinal blood flow autoregulation is lower in the newborn than in the adult; this suggests an insufficient vasoconstrictor response in the newborn when perfusion pressure is increased. Because prostaglandins (PGs) have an important role in autoregulation of retinal blood flow, we compared the effects of PGE2, PGF2α, carbacyclin (PGI2 analogue), and U46619 (thromboxane analogue), as well as that of agonists for the three different PGE2 receptor subtypes, 17-phenyl trinor PGE2 (EP1), butaprost (EP2), and M&B 28,767 (EP3), on the retinal vasculature of newborn and adult pigs, using isolated eyecup preparations. PGF2α and PGE2 caused a markedly greater constriction of retinal arteries and veins of the adult than of the newborn animals. Further analysis of the response to PGE2, using receptor subtype agonists, revealed that the EP1 receptor agonist, 17-phenyl trinor PGE2, and the EP3 receptor agonist, M&B 28,767, caused a significant constriction of adult arteries and veins but produced minimal effects on newborn vessels; the EP2 receptor agonist, butaprost, caused a small and comparable dilation of newborn and adult arteries and veins. The PGI2 analogue, carbacyclin, caused a greater dilation of the adult than of the newborn arteries, but produced comparable dilation of veins from both newborn and adult animals. In contrast to the effects of PGF2α and PGE2, the thromboxane analogue, U46619, as well as the α1-adrenoceptor agonist, phenylephrine, significantly constricted newborn arteries and veins, and this effect was comparable with that observed on retinal vessels of the adult. Our findings indicate that the retinal vasculature of the newborn responds minimally to prostaglandins, primarily PGF2α and PGE2, compared with the adult, but constricts effectively to thromboxane. Since prostaglandins play an important role in the autoregulation of retinal blood flow, our observations provide an explanation for the inability of the newborn to limit blood flow when perfusion pressure is raised.Key words: retinal vascular responses, prostaglandins, thromboxane, PGE2 receptor subtypes.

Pulmonary interstitial pressure in intact in situ lung: transition to interstitial edema

In anesthetized rabbits (n = 25) subject to slow intravenous saline loading (0.4 ml.min-1.kg-1) for 3 h, we measured pulmonary interstitial pressure (Pip) in intact in situ lungs with glass micropipettes inserted directly into the lung parenchyma via a "pleural window." Measurements were done in apneic animals at the end-expiratory volume with O2 delivered in the trachea. Pip was -10 +/- 1.5 (SD) cmH2O in control and increased to 0.6 +/- 3.8 and 5.7 +/- 3.3 cmH2O at 66 and 180 min, respectively. The wet-to-dry weight ratio (W/D) of the lung was 5.04 +/- 0.2 in the control group and 5.34 +/- 0.7 at 180 min (+6%); the corresponding W/D for intercostal muscles were 3.25 +/- 0.03 and 4.19 +/- 0.5 (+28%). Pulmonary interstitial compliance was 0.47 ml.mmHg-1.100 g wet wt-1. Pulmonary arterial and left atrial pressures were 18.4 +/- 2 and 3 +/- 1 cmH2O in control and increased to 19.5 +/- 2.9 and 4.6 +/- 1.7 cmH2O at 180 min, respectively. Aortic flow (cardiac output) increased from 103 +/- 35 to 131 +/- 26 ml/min; pulmonary resistance fell from 0.17 +/- 0.06 to 0.14 +/- 0.05 cmH2O.min.ml-1 (-18%), suggesting that the increase in Pip did not limit blood flow. The pulmonary capillary-to-interstitium filtration pressure gradient decreased sharply from a control value of 10 cmH2O to 0 cmH2O within 60 min because of the increase in Pip and remained unchanged for < or = 180 min. Data suggest that the pulmonary interstitial matrix can withstand fluid pressures above atmospheric, preventing the development of pulmonary alveolar flooding.