Growing Evidence for LV Unloading in VA ECMO.

Impressively increasing availability of mechanical circulatory/cardiac support systems (MCSs) worldwide, together with the deepening of the knowledge of critical care medical practitioners, has inevitably led to the discussion about further improvements of intensive care associated to MCS. An appealing topic of the left ventricle (LV) overload related to VA ECMO support endangering myocardial recovery is being widely discussed within the scientific community. Unloading of LV leads to the reduction in LV end-diastolic pressure, reduction in pressure in the left atrium, and decrease in the LV thrombus formation risk. Consequently, better conditions for myocardial recovery, with comfortable filling pressures and a better oxygen delivery/demand ratio, are achieved. The combination of VA ECMO and Impella device, also called ECPELLA, seems to be a promising strategy that may bring the improvement of CS mortality rates. The series of presented trials and meta-analyses clearly showed the potential benefits of this strategy. However, the ongoing research has brought a series of new questions, such as whether Impella itself is the only appropriate unloading modality, or any other approach to unload LV would be beneficial in the same way. Benefits and potential risks of LV unloading and its timing are being discussed in this current review.

Update on Anticoagulation Strategies in Patients with ECMO-A Narrative Review.

The use of extracorporeal membrane oxygenation (ECMO) has recently increased exponentially. ECMO has become the preferred mode of organ support in refractory respiratory or circulatory failure. The fragile balance of haemostasis physiology is massively altered by the patient's critical condition and specifically the aetiology of the underlying disease. Furthermore, an application of ECMO conveys another disturbance of haemostasis due to blood-circuit interaction and the presence of an oxygenator. The purpose of this review is to summarise current knowledge on the anticoagulation management in patients undergoing ECMO therapy. The unfractionated heparin modality with monitoring of activated partial thromboplastin tests is considered to be a gold standard for anticoagulation in this specific subgroup of intensive care patients. However, alternative modalities with other agents are comprehensively discussed. Furthermore, other ways of monitoring can represent the actual state of coagulation in a more complex fashion, such as thromboelastometric/graphic methods, and might become more frequent. In conclusion, the coagulation system of patients with ECMO is altered by multiple variables, and there is a significant lack of evidence in this area. Therefore, a highly individualised approach is the best solution today.

Using the national electronic prescription system to determine the primary non-adherence to medication in the Czech Republic.

The primary medication non-adherence occurs when a patient does not collect his or her newly prescribed medication. Various studies give estimates that this occurs between 0.2 percent and 74 percent. Recently, this topic has been researched by analyzing data in national electronic prescription systems. The database of the Czech electronic prescription system was used to obtain the number of all prescriptions issued and collected in 2021 for fifty particular substances (associated with six medication groups). Additionally, a similar query was performed with an additional criterion that the same substance had not been prescribed within the last 365 days. The data were obtained separately in five age categories. The total number of prescriptions analyzed in this study was over 21 million, which represents almost 30 percent of all prescriptions issued in the Czech Republic in 2021. The primary medication non-adherence in the selected substances was 4.56 percent, which negatively correlates (rxy = 0.707) with the age of a patient. There is a higher primary non-adherence in the Psychoanaleptics and Lipid modifying medication groups than in the whole studied sample (p < 0.05). Lipid-modifying medication group and several other particular substances showed a larger difference between primary non-adherence and overall non-adherence, indicating issues in the initiation of these drugs. The results of our study are following earlier studies with similar methodologies from other countries. However, the difference between primary non-adherence and overall non-adherence had not been observed in other studies before. The electronic prescription system proved to be a valuable tool for conducting this type of research.

Anaesthesia for non-cardiac surgical procedures in patients after heart transplantation.

Over the last 5 years, around 75 heart transplantations a year have been performed in the Czech Republic. According to these data and longer survival of these patients, it is obvious that non-cardiac surgical procedures in this particular group of patients are not rare. In the patients after heart transplantation, there is a significantly higher risk of undergoing elective and emergency surgical procedures due to various reasons. Appropriate anaesthesia and perioperative care are fundamentally affected by the knowledge of pathophysiological and pharmacological differences of transplanted heart. An equally important aspect is a lifetime immunosuppressive therapy in these patients.

Quercetin protects jejunal mucosa from experimental intestinal ischemia reperfusion injury by activation of CD68 positive cells.

The aim of our study was to analyse the possible protective effect of quercetin application during the jejunal ischemia-reperfusion injury (IRI) in rats. Quercetin was administered intraperitoneally 30min before 1h ischemia of superior mesenteric artery with following 24h lasting reperfusion period. The male specific pathogen-free (SPF) Charles River Wistar rats were used. In the group with applied quercetin, the significantly increased (p<0.001) levels of anti-inflammatory cytokine IL10 were observed both in the blood serum and jejunal tissue. The improvement of the mucosal tissue morphology and proliferating and DNA repairing cell number measured by PCNA activity were recorded by more than 30% higher in the quercetin group. Simultaneously, significant elongation of the intestinal glands (p<0.001) and increase in the number of CD68-positive cells in the lamina propria mucosae (p<0.001) in comparison with control group were found. Based on our results, the preventive application of quercetin before induction of jejunal IRI stimulates faster jejunal mucosa restoration and it seems to have immunomodulatory and anti-inflammatory effects as well. CD68-positive macrophages could have crucial role in this process since they work as both growth factor and cytokine producers.

Quercetin attenuates the ischemia reperfusion induced COX-2 and MPO expression in the small intestine mucosa.

Quercetin, the active substance of tea, fruits and vegetables, exerts a broad spectrum of pharmacological activities and is considered to have potential therapeutic application. The present study was designed to investigate the beneficial effect of quercetin against experimental ischemia- reperfusion (IR) injury of the small intestine in rats. Quercetin was administrated intraperitoneally 30min before 1h ischemia of superior mesenteric artery with following reperfusion periods lasting 1, 4 and 24h. The male specific pathogen-free Charles River Wistar rats were used (n=45). In acute phase, 4h after start of reperfusion, the quercetin induced a significant decrease in mucosal injury index (p<0.05) accompanied by a significant decrease in cyclooxygenase-2 (COX-2) expression in the epithelial lining of the intestinal villi in comparison with the control group (p<0.01). In the epithelium of the intestinal glands, COX-2 expression resulting from IR injury significantly increased regardless quercetin application (in control group p<0.001; in quercetin group p<0.05), but in quercetin group, significant decrease in it during 24h of reperfusion in a late phase of IR injury was detected (p<0.001). Based on morphology of COX-2 positive cells, the COX-2 positivity was found particularly in goblet cells of the intestinal villi epithelium and enteroendocrine cells respectively, in the glandular epithelium. We concluded that quercetin application attenuated mucosal damage from IR injury by inhibiting neutrophil infiltration which was demonstrated by a lower number of myeloperoxidase positive cells in the lamina propria during both phases of IR injury and the significant decrease in that in a late phase after 24h of reperfusion (p<0.05).

The effect of R-(-)-deprenyl administration on reproductive parameters of rat males.

The aim of the study was to investigate the effect of R-(-)-deprenyl administration on the reproductive parameters of rat males. After 30 days of intraperitoneal administration of saline or 0.0025mg/kg (10(-5)mol/l) of R-(-)-deprenyl dissolved in saline, males were mated with females of the same strain. Subsequently, animals were killed by thiopental, and their blood and sperm were collected. We found that epididymis of males exposed to R-(-)-deprenyl had higher sperm count (P<0.05), and females who mated with these males gave birth to a greater number of offspring (P<0.05) compared to control. The blood of experimental animals contained higher levels of testosterone (P<0.05), FSH (P<0.01), and total antioxidants (P<0.01). We did not detect sperm DNA fragmentation in control or in experimental males. Interestingly, round spermatids were often observed inside seminiferous tubules of experimental animals, but obviously without any negative consequences on male fertility. Our findings could be verified on a sample of human male volunteers treated for infertility, because human organism tolerate higher doses of R-(-)-deprenyl, which is a selective inhibitor of monoamine oxidase B employed in our experiment and used in the therapy of Parkinson׳s disease, rather well.