Microvascular dysfunction following cardiopulmonary bypass plays a central role in postoperative organ dysfunction

Figures

• 

  FIGURE 1. Ischemia-reperfusion injury following cardioplegic arrest may lead to multisystem dysfunction through multiple mechanisms. These mechanisms include endothelial activation and inflammation leading to oxidative stress and altered vasomotor and myogenic tone leading to vasospasm and organ malperfusion.

• 

  FIGURE 2. Ischemia-reperfusion injury is complex and multifactorial. At the cellular level, initial transient hypoxia due to cardiopulmonary bypass (CPB) leads to a switch from mitochondrial oxidative phosphorylation to anaerobic glycolysis, with a marked reduction in ATP yield. In poorly oxygenated tissues, pyruvate (the end-product of glycolysis) is shunted away from mitochondria and instead undergoes conversion to lactate by cytosolic lactate dehydrogenase (LDH). The resulting lactic acidosis in combination with high extracellular potassium and hypothermia due to cold cardioplegia inhibits the activity of Na+/K+-ATPase, an enzyme critical for maintaining physiologic resting membrane potential of cardiomyocytes close to the Nerst equilibrium potential of potassium (approximately –85 to –90 millivolts). Metabolic acidosis dually increases H+/Na+-antiporter activity, resulting in a small but notable increase in intracellular sodium, further exacerbating the sodium “window current” phenomenon during hyperkalemic cardioplegia. These electrochemical events drive the new membrane potential closer to –50 millivolts. The Na+/Ca2+-exchanger begins to operate in reverse, moving three Na+ ions out…

• 

  FIGURE 3. Factors leading to renal dysfunction during and after cardiopulmonary bypass. Perioperative hypotension, renal microvascular inflammation, glomerular fibrin deposition, and cardiopulmonary bypass (CPB) circuit shear forces all act in concert to impair renal perfusion and glomerular filtration rate (GFR), ultimately leading to acute kidney injury. Figure created using BioRender.com.

• 

  FIGURE 4. Factors leading to cerebrovascular dysfunction during and after cardiopulmonary bypass. Inflammation, microemboli, and macroemboli all lead to microvascular dysfunction. This in turn leads to neuronal ischemia and disruption of blood brain barrier integrity, resulting in brain injury. Figure created using BioRender.com.

• 

  FIGURE 5. Factors leading to pulmonary injury during and after cardiopulmonary bypass. Cardiopulmonary bypass (CPB) triggers a pathological series of impaired vasomotor tone, ischemia, and inflammation that drives pulmonary microvascular dysfunction. This in turn can lead to disruption of the alveolar-capillary membranes, pulmonary edema, acute respiratory distress syndrome (ARDS), and atelectasis. In addition, pathologic pulmonary microvascular remodeling can lead to postoperative pulmonary hypertension. Figure created using BioRender.com.