Pre-treatment with 1668-thioate attenuated cardiac hypertrophy following pressure overload, possibly by modifying the hypertrophy-induced inflammatory response, thereby reducing cardiac growth and fibrosis as well as delaying loss of cardiac function.

The aim of the study was to investigate whether pre-conditioning with CpG-oligodeoxynucleotides (CpG-ODN) may change cardiac ischemia/reperfusion (I/R)-dependent inflammation and modulates infarct size and cardiac performance. WT and TLR9-deficient mice were pre-treated with 1668-, 1612- and H154-thioate or D-Gal as control. Priming with 1668-thioate significantly induced inflammatory mediators in the serum and a concomitant increase of immune cells in the blood and spleen of WT mice. Furthermore, it induced myocardial pattern recognition receptors and pro-inflammatory cytokines peaking 2 h after priming and a continuous increase of IL-10. 16 h after pre-conditioning, myocardial ischemia was induced for 1 h. Infarct size determined after 24 h of I/R was reduced by 75 % due to pre-conditioning with 1668-thioate but not in the other groups. During reperfusion, cytokine expression in 1668-thioate primed mice increased further with IL-10 exceeding the other mediators by far. These changes were observed neither in animals pre-treated with 1612- or H154-thioate nor in TLR9-deficient mice. The 1668-thioate-dependent increase of IL-10 was further supported by results of a micro-array analysis 3 h after begin of reperfusion. Block of IL-10 signaling increased I/R size and prevented influence of priming. In the group pre-treated with 1668-thioate, cardiac function was preserved 24 h, 14 days and 28 days after I/R, whereas animals without pre-conditioning exhibited impaired heart function 24 h and 14 days after I/R. The excessive 1668-thioate-dependent IL-10 up-regulation during pre-conditioning and after I/R seems to be the key factor for reducing infarct size and improving cardiac function. This is in agreement with the finding that IL-10 block prevents cardioprotection by pre-conditioning.Electronic supplementary materialThe online version of this article (doi:10.1007/s00395-013-0376-7) contains supplementary material, which is available to authorized users.

BackgroundUnresolved inflammation resulting in capillary leakage with endothelial barrier dysfunction is a major contributor to postoperative morbidity and mortality after coronary artery bypass graft (CABG). Angiopoietins (ANGs) are vascular growth factors, also mediating inflammation and disruption of the endothelium, thus inducing capillary leakage. We hypothesized that changes in the relative serum levels of ANG1 and ANG2 influence endothelial barrier function and perioperative morbidity after CABG.MethodsAfter approval and informed consent, serum samples (n = 28) were collected pre CABG surgery, 1, 6, and 24 h after aortic de-clamping. ANG1, ANG2, soluble ANG receptor TIE2 (sTIE2), and IL-6 serum concentrations were analyzed by ELISA. Human pulmonary microvascular endothelial cells (HPMECs) were incubated with patient serum and FITC-dextran permeability was assessed. Furthermore, ANG2 secretion of HPMECs was analyzed after incubation with IL-6-containing patient serum.ResultsCABG induced an early and sustained increase of ANG2/ANG1 ratio (5-fold after 24 h compared to pre-surgery). These changes correlated with elevated serum lactate levels, fluid balance, as well as the duration of mechanical ventilation. Permeability of HPMECs significantly increased after incubation with post-surgery serum showing a marked shift of ANG2/ANG1 balance (18-fold) compared to serum with a less pronounced increase (6-fold). Furthermore, CABG resulted in increased IL-6 serum content. Pre-incubation with serum containing high levels of IL-6 amplified the ANG2 secretion by HPMECs; however, this was not influenced by blocking IL-6.ConclusionsCABG affects the balance between ANG1 and ANG2 towards a dominance of the barrier-disruptive ANG2. Our data suggest that this ANG2/ANG1 imbalance contributes to an increased postoperative endothelial permeability, likewise being reflected by the clinical course. The results strongly suggest a biological effect of altered angiopoietin balance during cardiac surgery on endothelial permeability.

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We are the first to demonstrate vendor and time effects on the murine fecal microbiota influencing sepsis models of intraabdominal stool contamination. The intestinal microbiota must be defined and standardized when designing and interpreting past and future studies using murine abdominal sepsis models.

Background Our objective was to evaluate if changes in on-pump cerebral blood flow, relative to the pre-bypass baseline, are associated with the risk for postoperative delirium (POD) following cardiac surgery. Methods In 47 consecutive adult patients, right middle cerebral artery blood flow velocity (MCAV) was assessed using transcranial Doppler sonography. Individual values, measured during cardiopulmonary bypass (CPB), were normalized to the pre-bypass baseline value and termed MCAV rel . An MCAV rel > 100% was defined as cerebral hyperperfusion. Prevalence of POD was assessed using the Confusion Assessment Method for the Intensive Care Unit. Results Overall prevalence of POD was 27%. In the subgroup without POD, 32% of patients had experienced relative cerebral hyperperfusion during CPB, compared to 67% in the subgroup with POD ( p < 0.05). The mean averaged MCAV rel was 90 (±21) % in the no-POD group vs. 112 (±32) % in the POD group (p < 0.05), and patients developing delirium experienced cerebral hyperperfusion during CPB for about 39 (±35) min, compared to 6 (±11) min in the group without POD ( p < 0.001). In a subcohort with pre-bypass baseline MCAV (MCAV bas ) below the median MCAV bas of the whole cohort, prevalence of POD was 17% when MCAV rel during CPB was kept below 100%, but increased to 53% when these patients actually experienced relative cerebral hyperperfusion. Conclusions Our results suggest a critical role for cerebral hyperperfusion in the pathogenesis of POD following on-pump open-heart surgery, recommending a more individualized hemodynamic management, especially in the population at risk. Electronic supplementary material The online version of this article (10.1186/s12871-019-0705-y) contains supplementary material, which is available to authorized users.

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BackgroundIn case of intravascular fluid depletion, large veins react to volume expansion with dilation. Little is known about the reaction of arterial vessels. We herein report on the effect of a standardized fluid bolus on the diameter of the common carotid artery (CCA) and its association with hemodynamic parameters, assessed in 20 mechanically ventilated patients after cardiac surgery. CCA was visualized using ultrasound, and the percentage increase in diastolic diameter was calculated by measuring before and after administration of crystalloid infusion solution. Invasive arterial blood pressure and pulse pressure variation (PPV) were assessed in parallel.ResultsMedian diastolic CCA diameter was 6.2 (Q1–Q3: 5.4–7.1) mm, and it significantly increased to 6.7 (5.8–7.3) mm upon fluid administration [5.0 (1.9–10.5) % increase]. Mean arterial blood (MAP) pressure likewise increased from 68 (70–73) to 85 (71–100) mmHg, whereas PPV was significantly reduced from 17.6 (16.8–23.9) to 13.2 (6.7–18.1) %. There was a significant association between the change in CCA diameter and the hemodynamic response (delta-MAP: r = 0.53, delta-PPV: r = 0.56; p < 0.05). Furthermore, carotid diameter measured before volume expansion significantly correlated with the delta-PPV upon fluid administration (r = −0.5; p = 0.02).ConclusionsDiameter of the CCA increases in response to intravascular volume expansion. Additional studies on the interplay between carotid geometry and intravascular fluid status are necessary.