Moretti Eduardo H, Rodrigues Abner C, Marques Bruno V, Totola Leonardo T, Ferreira Caroline B, Brito Camila F, Matos Caroline M, da Silva Filipe A, Santos Robson A S, Lopes Luciana B, Moreira Thiago S, Akamine Eliana H, Baccala Luiz A, Fujita André, Steiner Alexandre A
Departamento de Imunologia, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo, Av. Prof. Lineu Prestes, 1730, Sao Paulo, SP 05508-000, Brazil.
Instituto Internacional de Neurociencias Edmond e Lily Safra, Instituto de Ensino e Pesquisa Alberto Santos Dumont, Macaiba, RN 59288-899, Brazil.
PNAS Nexus. 2023 Jan 21;2(2):pgad014. doi: 10.1093/pnasnexus/pgad014. eCollection 2023 Feb.
Uncontrolled vasodilation is known to account for hypotension in the advanced stages of sepsis and other systemic inflammatory conditions, but the mechanisms of hypotension in earlier stages of such conditions are not clear. By monitoring hemodynamics with the highest temporal resolution in unanesthetized rats, in combination with ex-vivo assessment of vascular function, we found that early development of hypotension following injection of bacterial lipopolysaccharide is brought about by a fall in vascular resistance when arterioles are still fully responsive to vasoactive agents. This approach further uncovered that the early development of hypotension stabilized blood flow. We thus hypothesized that prioritization of the local mechanisms of blood flow regulation (tissue autoregulation) over the brain-driven mechanisms of pressure regulation (baroreflex) underscored the early development of hypotension in this model. Consistent with this hypothesis, an assessment of squared coherence and partial-directed coherence revealed that, at the onset of hypotension, the flow-pressure relationship was strengthened at frequencies (<0.2 Hz) known to be associated with autoregulation. The autoregulatory escape to phenylephrine-induced vasoconstriction, another proxy of autoregulation, was also strengthened in this phase. The competitive demand that drives prioritization of flow over pressure regulation could be edema-associated hypovolemia, as this became detectable at the onset of hypotension. Accordingly, blood transfusion aimed at preventing hypovolemia brought the autoregulation proxies back to normal and prevented the fall in vascular resistance. This novel hypothesis opens a new avenue of investigation into the mechanisms that can drive hypotension in systemic inflammation.
已知不受控制的血管舒张是脓毒症和其他全身性炎症疾病晚期低血压的原因，但这些疾病早期低血压的机制尚不清楚。通过在未麻醉大鼠中以最高时间分辨率监测血流动力学，并结合血管功能的体外评估，我们发现注射细菌脂多糖后低血压的早期发展是由于小动脉对血管活性药物仍有充分反应时血管阻力下降所致。这种方法进一步揭示，低血压的早期发展稳定了血流。因此，我们假设，在该模型中，血流调节的局部机制（组织自身调节）优先于大脑驱动的压力调节机制（压力反射），突出了低血压的早期发展。与这一假设一致，对平方相干性和部分定向相干性的评估表明，在低血压开始时，已知与自身调节相关的频率（<0.2Hz）下的血流-压力关系得到了加强。在此阶段，对去氧肾上腺素诱导的血管收缩的自身调节逃逸（另一种自身调节指标）也得到了加强。驱动血流优先于压力调节的竞争性需求可能是与水肿相关的血容量减少，因为这在低血压开始时就可以检测到。因此，旨在预防血容量减少的输血使自身调节指标恢复正常，并防止了血管阻力的下降。这一新假设为研究全身性炎症中导致低血压的机制开辟了一条新途径。
