Abstract

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.

Highlights

  • Extracorporeal membrane oxygenation (ECMO) is known to cause a variety of complications while saving patients [1,2,3]

  • Our recent study demonstrated that extracorporeal life support (ECLS) causes principal organ damage and a systemic inflammatory response in a small animal ECMO model [6,7,8]

  • Mean arterial pressure (MAP) and Hb were significantly decreased during ECMO in both normal and diabetic ECMO groups

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Summary

Introduction

Extracorporeal membrane oxygenation (ECMO) is known to cause a variety of complications while saving patients [1,2,3]. ECMO has multiple adverse effects with a systemic inflammatory response, mainly caused by blood coming in contact with the artificial foreign surface of the ECMO circuit [1,2,3]. This complex inflammatory chain reaction significantly affects the morbidity and mortality associated with extracorporeal life support (ECLS) [4]. ECMO has been commonly used in the world to support patients with severe pneumonia [9,10,11,12]. The active use of ECMO was recommended for severe pneumonia from COVID-19, which has been rampant since 2020 [13]

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