Dragan Ivanisevic

Coronary artery bypass grafting (CABG) utilizing cardiopulmonary bypass (CPB) remains a cornerstone of treatment for advanced multivessel coronary artery disease. During the ischemic period, myocardial cells become injured and increasingly depend on anaerobic metabolism. After reperfusion, exposure of blood components to artificial surfaces, combined with ischemia–reperfusion injury, surgical trauma, and gut translocation of endotoxins, triggers a complex systemic inflammatory response syndrome (SIRS). This inflammatory cascade involves a tightly regulated network of humoral cascades (complement, contact, coagulation, and fibrinolytic systems) and cellular effectors (neutrophils, monocytes, endothelial cells, and platelets). Molecular signaling pathways, notably Toll-like receptor 4 (TLR4) activation, nuclear factor kappa B (NF-κB) nuclear translocation, mitogen-activated protein kinase (MAPK) phosphorylation, and NLRP3 inflammasome assembly, drive a cytokine storm characterized by massive releases of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-8 (IL-8). These molecular events lead to endothelial barrier disruption, vasoplegic shock, acute lung injury, myocardial dysfunction, and acute kidney injury. This comprehensive narrative review provides a detailed synthesis of the cellular and molecular mechanisms underlying CPB-induced SIRS, highlights recent advances in neutrophil extracellular trap (NET) dynamics and microvascular injury, and evaluates contemporary pharmacological and bioengineering therapeutic strategies designed to mitigate postoperative organ dysfunction.

Coronary artery bypass grafting (CABG) utilizing cardiopulmonary bypass (CPB) remains a cornerstone of treatment for advanced multivessel coronary artery disease. However, exposure of blood components toDuring the ischemic period, myocardial cells become injured and increasingly depend on anaerobic metabolism. After reperfus artificial surfaces, combined with ischemia-reperfusion injury, surgical trauma, and gut translocation of endotoxins, triggers a complex systemic inflammatory response syndrome (SIRS). This inflammatory cascade involves a tightly regulated network of humoral cascades (complement, contact, coagulation, and fibrinolytic systems) and cellular effectors (neutrophils, monocytes, endothelial cells, and platelets). Molecular signaling pathways, notably Toll-like receptor 4 (TLR4) activation, nuclear factor kappa B (NF-κB) nuclear translocation, mitogen-activated protein kinase (MAPK) phosphorylation, and NLRP3 inflammasome assembly, drive a cytokine storm characterized by massive releases of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-8 (IL-8). These molecular events lead to endothelial barrier disruption, vasoplegic shock, acute lung injury, myocardial dysfunction, and acute kidney injury. This comprehensive narrative review provides a detailed synthesis of the cellular and molecular mechanisms underlying CPB-induced SIRS, highlights recent advances in neutrophil extracellular trap (NET) dynamics and microvascular injury, and evaluates contemporary pharmacological and bioengineering therapeutic strategies designed to mitigate postoperative organ dysfunction.

Coronary artery disease is a leading cause of morbidity and mortality in modern medicine. In contrast, surgical myocardial revascularization via coronary artery bypass grafting (CABG) remains the gold standard of treatment for complex multivessel disease. The great saphenous vein remains the most frequently used conduit due to its availability and technical simplicity, but its long-term patency is significantly inferior to that of arterial grafts. The primary pathological process responsible for vein graft failure is intimal hyperplasia, which represents a complex response of the vascular wall to surgical trauma, vein arterialization, inflammation, and hemodynamic stress. This process is characterized by endothelial dysfunction, inflammatory cell activation, proliferation and migration of vascular smooth muscle cells, and extracellular matrix remodeling. Underpinning these alterations are numerous molecular pathways, including NF-κB, MAPK, PI3K/Akt, TGF-β, and mTOR signaling, as well as substantial contributions from oxidative stress, cytokines, growth factors, and microRNAs. Contemporary research indicates that the phenotypic transformation of vascular smooth muscle cells constitutes the central event in the development of intimal hyperplasia. Understanding the cellular and molecular mechanisms underlying this disease’s onset enables the development of novel therapeutic strategies to preserve long-term graft patency. This review paper aims to provide a systematic overview of current knowledge regarding the molecular and cellular mechanisms of intimal hyperplasia development in vein grafts following CABG.

Coronary artery disease is a leading cause of morbidity and mortality in modern medicine. In contrast, surgical myocardial revascularization via coronary artery bypass grafting (CABG) remains the gold standard of treatment for complex multivessel disease. The great saphenous vein remains the most frequently used conduit due to its availability and technical simplicity, but its long-term patency is significantly inferior to that of arterial grafts. The primary pathological process responsible for vein graft failure is intimal hyperplasia, which represents a complex response of the vascular wall to surgical trauma, vein arterialization, inflammation, and hemodynamic stress. This process is characterized by endothelial dysfunction, inflammatory cell activation, proliferation and migration of vascular smooth muscle cells, and extracellular matrix remodeling. Underpinning these alterations are numerous molecular pathways, including NF-κB, MAPK, PI3K/Akt, TGF-β, and mTOR signaling, as well as substantial contributions from oxidative stress, cytokines, growth factors, and microRNAs. Contemporary research indicates that the phenotypic transformation of vascular smooth muscle cells constitutes the central event in the development of intimal hyperplasia. Understanding the cellular and molecular mechanisms underlying this disease's onset enables the development of novel therapeutic strategies to preserve long-term graft patency. This review paper aims to provide a systematic overview of current knowledge regarding the molecular and cellular mechanisms of intimal hyperplasia development in vein grafts following CABG.

The coarctation of the aorta is a congenital anomaly characterized by a local narrowing of the aortic lumen localized near the ductus arteriosus. Typically diagnosed in childhood, but it can remain until symptoms become evident. This aortic anomaly can also coexist with aortic valve stenosis. In our case report, we present a 46-year-old male with chest pain, dyspnea, and a significant blood pressure gradient between upper and lower extremities. Diagnostic examination included transthoracic echocardiography and computerized tomography. This diagnostic imaging showed narrowing of the aortic lumen with a residual lumen dimension of 3 mm and severe aortic stenosis. The patient underwent a complex surgical procedure, replacement of the aortic valve and reconstruction of the aorta. An extra-anatomic ascending-to-descending aortic bypass was constructed using a 20 mm Dacron graft, combined with mechanical aortic valve replacement. The operation was performed through median sternotomy with two arterial canula in the femoral artery and in the aorta, and one venous canula in the right atrium. Two canulae are placed for the safe performance of cardiopulmonary bypass. The patient was discharged at home without complication. This case highlights that a single surgical procedure may represent a definitive treatment of a complex problem with good short-term results.

The coarctation of the aorta is a congenital anomaly characterized by a local narrowing of the aortic lumen localized near the ductus arteriosus. Typically diagnosed in child-hood, but it can remain until symptoms become evident. This aortic anomaly can also coexist with aortic valve stenosis. In our case report, we present a 46-year-old male with chest pain, dyspnea, and a significant blood pressure gradient between upper and lower extremities. Diagnostic examination included transthoracic echocardiography and computerised tomography. This diagnostic imaging showed narrowing of the aor-tic lumen with a residual lumen dimension of 3 mm and severe aortic stenosis. The pa-tient underwent a complex surgical procedure, replacment of the aortic valve and re-construction of the aorta. An extra-anatomic ascending to descending aortic bypass was constructed using a 20 mm Dacron graft, combined with mechanical aortic valve replacment. The operation was performed through median sternotomy with two arte-rial canula in the femoral artery and in the aorta, and one venous canula in the right atrium. Two canulae are placed for the safe performance of cardiopulmonary bypass. The patient was discharged at home without complication. This case highlights that a single surgical procedure may represent a definitive treatment of a complex problem with good short-term results.

Coronary artery bypass grafting (CABG) remains the gold standard for patients with advanced multivessel coronary artery disease. Optimal myocardial protection versus ischemia during reversible and controlled cardiac arrest is a cornerstone of successful outcomes. Myocardial ischemia represents a state of reduced coronary perfusion with oxygenated blood, insufficient to meet the metabolic demands of the myocardium. Conventional cardioplegic solutions offer controlled and reversible cardiac arrest while actively modulating the molecular and cellular mechanisms that mediate ischemia–reperfusion injury. Cardioplegia dramatically elongates the reversible period of ischemic injury and restricts cardiomyocyte death by shutting down electromechanical activity, lowering metabolic demand, stabilizing ionic homeostasis, protecting mitochondrial integrity, and slowing oxidative stress and inflammatory signaling. During ischemia, cardiomyocytes shift from aerobic to anaerobic metabolism, resulting in adenosine triphosphate (ATP) depletion, loss of ionic homeostasis and calcium overload that activate proteases, phospholipases and membrane damage. Reperfusion restores oxygen supply and prevents irreversible necrosis but paradoxically initiates additional injury in marginally viable myocardium. The reoxygenation phase induces excessive production of reactive oxygen species (ROS), endothelial dysfunction and a strong inflammatory response mediated by neutrophils, platelets and cytokines. Mitochondrial dysfunction and opening of the mitochondrial permeability transition pore (mPTP) further amplify oxidative stress and inflammation, and trigger apoptosis and necroptosis. Understanding these intertwined cellular and molecular mechanisms remains essential for identifying novel therapeutic targets aimed at reducing reperfusion injury and improving myocardial recovery after ischemic events, particularly in coronary surgery.