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<p>Microcirculatory dysfunction is a defining feature of septic shock and is strongly associated with mortality, yet its relationship to macrocirculatory haemodynamics remains poorly understood. In particular, the persistence of heterogeneous capillary perfusion despite restoration of blood pressure and cardiac output (termed haemodynamic incoherence) lacks a coherent mechanistic explanation. I developed a conceptual and computational model of the microcirculation in which network behaviour is constrained by three interacting variables: cardiac output, vasomotor state, and shear stress regulation. A network of one million parallel arterioles was simulated using physiologically plausible distributions of vessel radius. For each vessel, flow requirements were determined by an apparent shear target, reflecting endothelial sensing of shear rather than absolute physical values. Total cardiac output required to maintain network-wide shear was calculated as the sum of individual vessel demands. The model demonstrates that, for a given shear target, total flow requirements increase in proportion to the sum of vessel radii cubed, such that even modest global vasodilation produces a substantial increase in required cardiac output. Increasing the apparent shear target further amplifies this demand. When cardiac output is insufficient to meet these requirements, vessels experience low shear and undergo functional derecruitment, reducing total flow demand but resulting in marked heterogeneity and reduced functional capillary density. These behaviours reproduce key features of septic physiology, including the hyperdynamic circulation and microvascular shunting observed in severe sepsis. The model provides a unifying framework in which microcirculatory dysfunction emerges as an inevitable consequence of the interaction between vasodilation, flow limitation, and shear regulation, rather than as an independent pathological process. It further predicts that therapies which reduce global vasodilation or lower the apparent shear target may restore microvascular coherence without requiring supranormal cardiac output. This framework generates testable hypotheses and offers a physiologically grounded basis for reinterpreting haemodynamic management in septic shock.</p>

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On the inevitability of microvascular failure in septic shock and other vasodilatory conditions

  • 期刊论文

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  • 发表日期：

    2026年6月24日

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  • Ivor Popovich

摘要

Microcirculatory dysfunction is a defining feature of septic shock and is strongly associated with mortality, yet its relationship to macrocirculatory haemodynamics remains poorly understood. In particular, the persistence of heterogeneous capillary perfusion despite restoration of blood pressure and cardiac output (termed haemodynamic incoherence) lacks a coherent mechanistic explanation. I developed a conceptual and computational model of the microcirculation in which network behaviour is constrained by three interacting variables: cardiac output, vasomotor state, and shear stress regulation. A network of one million parallel arterioles was simulated using physiologically plausible distributions of vessel radius. For each vessel, flow requirements were determined by an apparent shear target, reflecting endothelial sensing of shear rather than absolute physical values. Total cardiac output required to maintain network-wide shear was calculated as the sum of individual vessel demands. The model demonstrates that, for a given shear target, total flow requirements increase in proportion to the sum of vessel radii cubed, such that even modest global vasodilation produces a substantial increase in required cardiac output. Increasing the apparent shear target further amplifies this demand. When cardiac output is insufficient to meet these requirements, vessels experience low shear and undergo functional derecruitment, reducing total flow demand but resulting in marked heterogeneity and reduced functional capillary density. These behaviours reproduce key features of septic physiology, including the hyperdynamic circulation and microvascular shunting observed in severe sepsis. The model provides a unifying framework in which microcirculatory dysfunction emerges as an inevitable consequence of the interaction between vasodilation, flow limitation, and shear regulation, rather than as an independent pathological process. It further predicts that therapies which reduce global vasodilation or lower the apparent shear target may restore microvascular coherence without requiring supranormal cardiac output. This framework generates testable hypotheses and offers a physiologically grounded basis for reinterpreting haemodynamic management in septic shock.