Fig. 1

Pathophysiology of vasoplegia. Physiologic contraction of vascular smooth muscle occurs in response to intracellular calcium, which cause myosin phosphorylation leading to myosin-actin filament crosslinking and vasoconstriction. Cytoplasmic calcium is increased through alpha-1 adrenergic receptor, vasopressin-1 receptor, and angiotensin type-1 receptor activation. Inflammatory mediators released during cardiopulmonary bypass can lead to adrenoreceptor desensitization, an immediate increase in vasoconstrictive mediators with subsequent depletion, and the production of nitric oxide (NO). NO leads to an increase in cGMP, which inhibits calcium into cells, leading to muscle relaxation. NO also activates ATP-sensitive potassium channels (KATP), leading to hyperpolarization and inhibited vasoconstriction