Gastrointestinal injury in cardiopulmonary bypass: current insights and future directions

FIGURE 1. Schematic illustration of the mechanisms underlying gastrointestinal injury during CPB. CPB initiates multiple pathophysiological processes that compromise intestinal integrity. Non-pulsatile flow, hypothermia, mechanical compression, decreased cardiac output, inflammatory response, and vasoactive medications collectively lead to visceral hypoperfusion, characterized by impaired mesenteric blood flow autoregulation and reduced splanchnic circulation. This hypoperfusion subsequently triggers gastrointestinal IRI, resulting in intestinal barrier dysfunction, microbiota dysbiosis, and bacterial translocation. These pathological alterations ultimately contribute to multiple organ dysfunction, affecting the heart, lungs, liver, and kidneys.

FIGURE 2. Integrated mechanisms of gastrointestinal injury following ischemia-reperfusion. This schematic diagram illustrates the pathophysiological cascade of gastrointestinal injury with emphasis on three interconnected components. The upper section depicts overall gastrointestinal injury as represented by affected intestinal and gastric organs. The left lower panel demonstrates two critical consequences of ischemia-reperfusion injury (IRI): intestinal barrier dysfunction, characterized by disruption of tight junctions between enterocytes (indicated by red stars), and gut microbiota dysbiosis, shown as altered microbial composition within the intestinal lumen. The right lower panel details the cellular and molecular mechanisms of IRI: initial ischemia triggers anaerobic glycolysis, lactate accumulation, and pH reduction. Upon reperfusion, paradoxical exacerbation of injury occurs through several pathways: (1) mitochondrial dysfunction with impaired ATP production and oxidative phosphorylation, (2) intracellular calcium (Ca2+) overload, (3) generation of reactive oxygen species (ROS), and (4) release of damage-associated molecular patterns (DAMPs). These events promote chemokine…

FIGURE 3. Comprehensive landscape of preclinical and clinical research on CPB-associated gastrointestinal injury. This schematic illustration presents a holistic view of both preclinical studies (left panel) and clinical research domains (right panel) investigating gastrointestinal injury following cardiopulmonary bypass (CPB). The preclinical studies encompass multiple animal models: Human/mouse studies demonstrate significant correlations between microbiota metabolites and post-operative outcomes, with lactobacillus murinus showing protective effects through TLR2-mediated pathways. Rat models reveal protective interventions including κ-opioid receptor agonists targeting NF-κB/HIF-1α pathways, penehyclidine hydrochloride, and α7nAChR activation, while highlighting the role of mast cells and CIRBP in intestinal barrier maintenance. Porcine studies, representing a substantial proportion of research, evaluate various CPB techniques and therapeutic strategies, particularly emphasizing microcirculatory alterations and benefits of interventions such as dopexamine and selective visceral perfusion. Additional species studies provide complementary insights: rabbit models validate preconditioning…