Aims During the first 6–12 h of intensive care unit (ICU) stay, post-cardiac arrest (CA) patients treated with a mean arterial pressure (MAP) 65 mmHg target experience a drop of the cerebral oxygenation that may cause additional cerebral damage. Therefore, we investigated whether an early goal directed haemodynamic optimization strategy (EGDHO) (MAP 85–100 mmHg, SVO2 65–75%) is safe and could improve cerebral oxygenation, reduce anoxic brain damage, and improve outcome when compared with a MAP 65 mmHg strategy. Methods and results A total of 112 out-of-hospital CA patients were randomly assigned to EGDHO or MAP 65 mmHg strategies during the first 36 h of ICU stay. The primary outcome was the extent of anoxic brain damage as quantified by the percentage of voxels below an apparent diffusion coefficient (ADC) score of 650.10−6 mm2/s on diffusion weighted magnetic resonance imaging (at day 5 ± 2 post-CA). Main secondary outcome was favourable neurological outcome (CPC score 1–2) at 180 days. In patients assigned to EGDHO, MAP (P < 0.001), and cerebral oxygenation during the first 12 h of ICU stay (P = 0.04) were higher. However, the percentage of voxels below an ADC score of 650.10−6 mm2/s did not differ between both groups [16% vs. 12%, odds ratio 1.37, 95% confidence interval (CI) 0.95–0.98; P = 0.09]. Also, the number of patients with favourable neurological outcome at 180 days was similar (40% vs. 38%, odds ratio 0.98, 95% CI 0.41–2.33; P = 0.96). The number of serious adverse events was lower in patients assigned to EGDHO (P = 0.02). Conclusion Targeting a higher MAP in post-CA patients was safe and improved cerebral oxygenation but did not improve the extent of anoxic brain damage or neurological outcome.

Extracellular vesicles (EVs) are small bilayer lipid membrane vesicles that can be released by most cell types and detected in most body fluids. EVs exert key functions for intercellular communication via transferring their bioactive cargos to recipient cells or activating signaling pathways in target cells. Increasing evidence has shown the important regulatory effects of EVs in cardiovascular diseases (CVDs). EVs secreted by cardiomyocytes, endothelial cells, fibroblasts, and stem cells play essential roles in pathophysiological processes such as cardiac hypertrophy, cardiomyocyte survival and apoptosis, cardiac fibrosis, and angiogenesis in relation to CVDs. In this review, we will first outline the current knowledge about the physical characteristics, biological contents, and isolation methods of EVs. We will then focus on the functional roles of cardiovascular EVs and their pathophysiological effects in CVDs, as well as summarize the potential of EVs as therapeutic agents and biomarkers for CVDs. Finally, we will discuss the specific application of EVs as a novel drug delivery system and the utility of EVs in the field of regenerative medicine.

This is the first prospective study for the management of patients on NOACs undergoing dental extraction. Our pragmatic approach, omitting only a single morning dose, can guide clinical practice. Both patients and physicians should be aware of the increased delayed bleeding risk.

Optimal healing after myocardial infarction requires not only the induction of inflammation, but also its timely resolution. In patients, 30 days post myocardial infarction, circulating monocytes have increased expression of Semaphorin3A (Sema3A) as compared to directly after admission. This increased expression coincides with increased expression of Cx3CR1—a marker of non-classical monocytes that are important for immune resolution hence proper wound healing. In mice, the expression of Sema3A also increases in response to myocardial ischemia being expressed by infiltrating leukocytes. Comparing Sema3A heterozygote (HZ) and wild type (WT) mice post myocardial infarction, revealed increased presence of leukocytes in the cardiac tissues of HZ mice as compared to WT, with no differences in capillary density, collagen deposition, cardiomyocyte surface area, chemokine—or adhesion molecules expression. Whilst infarct sizes were similar 14 days after myocardial infarction in both genotypes, Sema3A HZ mice had thinner infarcts and reduced cardiac function as compared to their WT littermates. In vitro experiments were conducted to study the role of Sema3A in inflammation and resolution of inflammation as a potential explanation for the differences in leukocyte recruitment and cardiac function observed in our in vivo experiments. Here, recombinant Sema3A protein was able to affect the pro-inflammatory state of cultured bone marrow derived macrophages. First, the pro-inflammatory state was altered by the induced apoptosis of classical macrophages in the presence of Sema3A. Second, Sema3A promoted the polarization of classical macrophages to resolution-phase macrophages and enhanced their efferocytotic ability, findings that were reflected in the infarcted cardiac tissue of the Sema3A HZ mice. Finally, we demonstrated that besides promoting resolution of inflammation, Sema3A was also able to retard the migration of monocytes to the myocardium. Collectively our data demonstrate that Sema3A reduces cardiac inflammation and improves cardiac function after myocardial infarction by promoting the resolution of inflammation.Electronic supplementary materialThe online version of this article (doi:10.1007/s00395-017-0630-5) contains supplementary material, which is available to authorized users.

Supplemental Digital Content is available in the text.