Systemic inflammatory responses in patients undergoing extracorporeal membrane oxygenation (ECMO) contribute significantly to ECMO-associated morbidity and mortality. In recent years, the number of type 2 diabetes mellitus patients has increased, and the number of these patients undergoing ECMO has also increased. Type 2 diabetes mellitus is a high-risk factor for complications during ECMO. We studied the effects of ECMO on inflammatory response in a diabetic rat ECMO model. Twenty-eight rats were divided into 4 groups: normal SHAM group (normal rats: n = 7), diabetic SHAM group (diabetic rats: n = 7), normal ECMO group (normal rats: n = 7), and diabetic ECMO group (diabetic rats: n = 7). We measured the plasma levels of cytokines, tumor necrosis factor-α, and interleukin-6. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), creatinine (Cr), and liver-type fatty acid binding protein (L-FABP) were examined in the rat cardiopulmonary bypass model to ascertain organ damage. In addition, the lung wet-to-dry weight (W/D) ratio was measured as an index of pulmonary tissue edema. A pathologic evaluation of kidneys was conducted by hematoxylin-eosin (HE) and periodic-acid-methenamine-silver (PAM) staining. In the diabetic ECMO group, levels of cytokines, AST, ALT, LDH, and L-FABP increased significantly, reaching a maximum at the end of ECMO in comparison with other groups (p < 0.05). In addition, hematoxylin-eosin and periodic acid-methenamine-silver staining of renal tissues showed marked injury in the ECMO group (normal ECMO and diabetic ECMO groups). Furthermore, when the normal ECMO and diabetic ECMO groups were compared, severe organ injury was seen in the diabetic ECMO group. There was remarkable organ injury in the diabetic ECMO group. These data demonstrate that diabetes enhances proinflammatory cytokine release, renal damage, and pulmonary edema during ECMO in an animal model.

(1) Background: Extracorporeal circulation (ECC) is indispensable for cardiac surgery. Despite the fact that ECC causes non-physiological damage to blood components, its pathophysiology has not been fully elucidated. In our previous study, we constructed a rat ECC system and observed a systemic inflammatory response during and after blood tests assessing ECC, while the damage per organ localization caused by ECC was not examined. In this study, we used a rat model to assess the gene expression of inflammatory cytokines in major organs during ECC. (2) Methods: The ECC system consisted of a membranous oxygenator, tubing line, and a small roller pump. Rats were divided into a SHAM (which received surgical preparation only, without ECC) group and an ECC group. Proinflammatory cytokines were measured using real-time PCR in major organs after ECC to evaluate local inflammatory responses in the organs. (3) Results: Interleukin (IL)-6 levels were significantly elevated in the ECC group compared to the SHAM group, especially in the heart and lungs. (4) Conclusions: This study suggests that ECC promotes organ damage and the inflammatory response, but the degree of gene expression of proinflammatory cytokines varies from organ to organ, suggesting that it does not uniformly cause organ damage.

Extracorporeal membrane oxygenation (ECMO) is increasingly used in intensive care units; however, ECMO can modify drug pharmacokinetics (PK), leading to underexposure and associated treatment failure. The aim of the present study was to determine the effect of ECMO on the PK of dexmedetomidine (DEX). In vivo rat models were developed, both of which involved a bolus injection of DEX and concentration monitoring. In the in vivo model experiment, rats which underwent ECMO were compared with a control group. PK analysis of in vivo data (noncompartmental analysis and nonlinear mixed-effects modelling) was carried out to determine the effect of ECMO. In vivo PK exploration showed that ECMO induced a decrease in DEX clearance. Because the effect of ECMO on the PK of DEX is not clinically significant, normal DEX dosing for critically ill patients should be effective for patients undergoing ECMO.

In recent years, venovenous extracorporeal membrane oxygenation (VV ECMO) has been used to support patients with severe lung disease. Active use of VV ECMO was also recommended for severe respiratory failure due to COVID-19. However, VV ECMO is also known to cause various complications due to extracorporeal circulation. Although we conducted ECMO research using rats, we have not been able to establish whether double-lumen single-cannulation VV ECMO models in rats have been described previously. The purpose of this study was to establish a simple, stable, and maintainable miniature double-lumen single-canulation VV ECMO model in rats. A double-lumen catheter used as a plain central venous catheter (SMAC plus Seldinger type; Covidien Japan Co., Tokyo, Japan) was passed through the right external jugular vein and advanced into the right atrium as a conduit for venous uptake. The VV ECMO system comprised a roller pump, miniature membrane oxygenator, and polyvinyl chloride tubing line. During VV ECMO, blood pressure and hemodilution rate were maintained at around 80 mmHg and 30%, respectively. Hemoglobin was kept at >9 g/dL, no serious hemolysis was observed, and VV ECMO was maintained without blood transfusion. Oxygenation and removal of carbon dioxide from the blood were confirmed and pH was adequately maintained. This miniature VV ECMO model appears very useful for studying the mechanisms of biological reactions during VV ECMO.

The stress reaction of trainees is an issue in the practices of medical-related examinations that involve real-time decision making based on the examiner–subject interactions. The Goldmann perimetry (GP) test is one of these examinations. To evaluate the students’ stress reactions in the practice of the GP test, the stress-related substances and heart rate variability were measured in forty students enrolled in the practice. While there was no significant increase in stress-related substances during the practice, significantly increased sympathetic activities were observed at the beginning of the tests. Moreover, the plasma cortisol measured before the tests showed a significant positive correlation to the students’ self-confidence scores, indicating the students, especially those with higher self-confidence scores, were anxious for upcoming tests with unfamiliar subjects. Once the tests began, they felt relieved in the procedures they had learned repeatedly. On the other hand, while the average plasma ACTH decreased significantly during the test, the ACTH secretion correlated positively to the test duration, indicating that the skillful participants had less stress during the test. In the medical-related practices, pre-training on how to deal with unfamiliar subjects may be helpful for reducing the stress of the trainees, in addition to the procedure itself.