AS conceived the study design, selected studies, extracted and checked data and helped to write the manuscript. who already have compromised perfusion of vital organs. Due to the inaccessibility of vital organs in humans, vasoconstrictive effects of hyperoxia have primarily been studied in animal models. However, the results of these studies vary substantially. Here, we investigate the variation in magnitude of the hyperoxia effect among studies and explore possible sources of heterogeneity, such as vascular region and animal species. Method Pubmed and Embase were searched for eligible studies up to November 2017. In vivo and ex vivo animal studies reporting on vascular Mouse monoclonal to CEA tone changes induced by local or systemic normobaric hyperoxia were included. Experiments with co-interventions (e.g. disease or endothelium removal) or studies focusing on lung, brain or fetal vasculature or the ductus arteriosus were not included. We extracted data pertaining Ozagrel hydrochloride to species, vascular region, blood vessel characteristics and method of hyperoxia induction. Overall effect sizes were estimated with a standardized mean difference (SMD) random effects model. Results We identified a total of 60 studies, which reported data on 67 in vivo and 18 ex vivo experiments. In the in vivo studies, hyperoxia caused vasoconstriction with an SMD of ??1.42 (95% CI ??1.65 to ??1.19). Ex vivo, the overall effect size was SMD ??0.56 (95% CI ??1.09 to ??0.03). Between-study heterogeneity (linear, sigmoidal etc.) . The Akaike information criteria (AIC) was used to determine the optimal number of knots and their position . For each subgroup a minimum of five data sets, from three unique studies, had to be present. Sources of heterogeneity were investigated using meta-regression, by first performing an overall test for interaction, and if the values were adjusted with the Holms-Bonferroni method. The likelihood of publication bias was assessed using the trim and fill method . Because SE-based precision estimates cause distortion of SMD funnel plots we used 1/n as the precision estimate in the trim and fill analysis . Results Search and study selection A flow chart of the study selection process is shown in Fig.?1. After exclusion based on title and abstract, we identified 319 articles investigating the relation between oxygen and vascular tone: 261 studies were excluded based on predefined exclusion criteria. From the 60 included studies, 42 were performed in live animals and 18 studies used isolated arteries and arterioles. One study performed both eligible in vivo and ex vivo experiments . Studies were performed between 1974 Ozagrel hydrochloride and 2017 and the majority (64%) was published between 1980 and 2000. Characteristics of the included studies are presented in Tables?1 (in vivo studies) and ?and22 (ex vivo studies). Open in a separate window Fig. 1 Flowchart describing the inclusion and exclusion of studies. n?=?number of studies, e?=?number of experiments described (either with or without data), k?=?number of data sets, which are the responses accompanied by data suitable for meta-analysis Table 1 In vivo studies New Zealand White, Sprague Dawley, Wistar, Landrace Yorkshire, muscle chamber, wire myograph, pressure myograph, not reported *Effect as reported by the original paper, arrows indicate the direction of the change in diameter **A value suffixed with a % symbol indicates the percentage of oxygen used to oxygenate the physiological salt solution; other values indicate the fraction of inspired oxygen #Not included in the meta-analysis due to a small number of observations or because no data was shown (?) Table 2 Ex vivo studies New Zealand White, Sprague Dawley, Wistar, Landrace Yorkshire, muscle Ozagrel hydrochloride chamber, wire myograph, pressure myograph, not reported *Effect as reported by the original paper; arrows indicate the direction of the effective change in diameter **A value suffixed with a % symbol indicates the percentage of oxygen used to oxygenate the physiological salt solution, other values indicate the oxygen tension in mmHg ?Not included in the meta-analysis because no data was shown or values could not be recalculated (#). For diameters, values are presented as range or average diameter Study characteristics In vivo studiesThe 42 in vivo studies were carried out in rats (values for further pairwise comparisons were adjusted with the Holms-Bonferroni method. Moderators that increased the effect size of hyperoxic constriction were the cremaster as a vascular region () in the overall effect. A smaller response was seen in studies in which the dorsal skin (values are corrected for multiple testing with the Holm-Bonferroni method. ND, not determined; k, data sets Open in a separate window Fig. 6 Relationship between artery diameter and effect size. Increased constriction was seen in the range of 15C25?m. The relationship between the standardized mean difference (SMD) and artery diameter explained 16% of the observed.