Micro-circulating hyperdynamic blood flow as a key pathogenic factor in early sepsis

Objective Human research on sepsis has continually deepened over the years, entering the fields of molecular biology and genomics in the modern day. However, the pathogenesis of sepsis is yet unclear; and even its definition is still controversial. As specified in “International Consensus on Sepsis (3.0)” published in the Journal of the American Medical Association (2016), defining sepsis and septic shock can be a challenge; it is necessary to know the pathogenesis of sepsis more accurately, to accurately define it. As we have recently found in clinical practice, a sublingual micro-circulating and hyperdynamic blood flow is present in the early stages of sepsis. In our study, the necessity and universality of this phenomenon in different mammals was analyzed; a detoxifying mechanism and the Feng-Bernoulli warm shock mechanism were proposed for sepsis, and the pathogenesis of sepsis was inferred. Methods Through the intravenous injection of lipopolysaccharide (LPS), sepsis infection models were established for Bama miniature pigs and Japanese white rabbits respectively. Before and after the modeling, the variation and progress of blood flow rate in the same-branch sublingual capillaries were measured. Through cecum ligation and puncture (CLP) surgery, a sheep septic shock model was also established; and the correlation between micro-circulating hyperdynamic blood flow generation and macro-hemodynamic indices were analyzed. Through LPS injections of different doses into caudal veins, a mild injection and serious injection model was established for SD rats respectively, validating that the hyperdynamic blood flow in animal bodies as the manifestation for immune detoxifying mechanisms is necessary and universal. Results Before and after the modeling, blood flow rate in same-branch capillaries was separately 302 μm/s and 958 μm/s in Bama minipigs. Before modeling, mean blood flow rate in sublingual micro-circulating was 539 μm/s in Japanese white rabbits; in the early period after LPS injection, blood flow was accelerated to generate a hyperdynamic blood flow of mean >1000 μm/s. In the sheep CLP sepsis model, sublingual micro-circulating blood flow acceleration was present before the variation of cardiac index and cardiac output, Under the conditions of either mild infection or serious infection, hyperdynamic blood flow occurred in sublingual micro-circulating of rats; under the condition of mild infection, rats entered semi-sleep state after generation of hyperdynamic blood flow, which could be recovered by themselves; under the condition of serious infection, blood flow was stagnant after the generation of sublingual micro-circulating hyperdynamic blood flow, and rats died if there was no intervention. Conclusion In different mammals and different sepsis models, the phenomenon of micro-circulating blood flow acceleration occurs in the early period, which is necessarily universal. The phenomenon of sublingual micro-circulating blood flow acceleration comes before the variation of cardiac output, which should be key reasons for cardiac output variation. The blood flow acceleration can also accelerate the detoxifying effect, which is the process of immune defense reaction. However, the hyperdynamic blood flow and subsequent cardiac output increase will cause an oxygen exchange disorder, thus inducing warm shock. We have named the effect the Feng-Bernoulli warm shock mechanism, which is actually the primary pathogenesis for early sepsis or distributive shock. ### Competing Interest Statement X. H. Feng is the Technical Director of Xuzhou Lihua Electronic Technology Development Co., Ltd. The other authors declare that there is no conflict of interest.