Genesis of Antibiotic Resistance (AR) LXXI: Turbulence Modeling of Hemodynamics in Simplified Severe Sepsis Protocol‐2 (SSSP‐2) ‐ NCT01663701: Activated E‐Oligomer Complex Elicit Rapid Leucocyte‐Platelets‐Erythrocytes (LPE) Aggregation and Occlusion of Capillary by Impairing Energy Cascading and Starling Forces (Net Filtration Pressure)

Abstract

Here we present a rationale for the fluid overload-induced accelerated LPE aggregates to occlude the arterial end of the capillary bed resulting in critical closing pressure (CCP). It is known that native purine/pyrimidine receptors have yet to be purified to homogeneity and characterization of receptor-ligand kinetics. Recombinant purine/pyrimidine receptors knockout genotype mice are not embryonic lethal, while its characterization in vivo is dependent of multifactorial factors of epigenetic origin namely (post-translational modification, lineage-specific developmental and hemodynamic heterogeneity; ex: meaning age, gender, morphological attribute(s) of the platelet(s), viscosity, and hematocrit). Every attempt to purify Ca2+ /Mg2+ ecto-ATPase (EC 3.6.1.15) to homogeneity, showed co-purification of CD36, PMID: 9925363); cell-CAM105 (PMID: 1637321 PMCID: PMC1132742, PMID: 8387753, PMID: 1985902); mmCGM1a (PMID: 1633107); PECAM-1,(PMID: 19558578); CBATP, (PMID: 9218468); BgP (PMID: 2527235); caldesmon (PMID: 1930128); NCAM (PMID: 8262246, PMID: 7804134); Ig gene superfamily (PMID: 2141577), Cadherin (PMID: 8489264); and chicken gizzard ecto-ATPase amino acid similarity to CD39 (PMID: 8995405). The fact remain that native CD39 has never been tested for mM [Ca2+] or [Mg2+] ecto-ATPase (EC 3.6.1.15) or E-NTPDase (NTPDase1) (EC 3.6.1.6) (PMID: 1672348, PMID: 1721639). Further, neither CAM nor CD39 knockout genotype is embryonic lethal. Experimental evidence shows that differential regulation of CD38, integrin's (CD11), and CD39 in the liver allograft, implicit of interdependency in host immune response (PMID: 31511354). We have obtained evidence that the phylogenetic tree analysis, neighbor-joining tree without distance correlation among CD36, CD38, CD39, CAM, P2Y/P2, and corona #2, receptors. The cladogram show a marked evolutionary conservancy between CD39 & P2X, CD36 & Corona virus-2, CAM & P2Y &cadherin, with a possibility of existence as an oligomer (ECpx). Taken together, it is hypothesized that nucleotide receptors (P2Y/P2X), CAM, and ectonucleotidases family of a protein complex (E-Cpx) could possibly exist as a membrane-bound oligomer. Subsequent activation of E-Cpx on LPE, aggregation, and rapid occlusion of the capillary by forming T-S waves, 3D distortion of T-S waves, in phase arrays of hairpin K-type vortices, turbulent spot formation, merging of turbulent spot formation, without energy cascading among the LPE aggregates and adherence to the damaged endothelial cells at the arterial end of the capillary, Refer Fig: 3.4, 3.5, 3.6 3.8; (ISBN: 978-0-13-127498-3), a robust anaerobic /aerobic persister (s) colonization eliciting CCP. In turn, a progressive hypotensive state induced endothelial damage and abrupt collapse of interstitial space would result in CCP ensuing hypoxia. Such a scenario may have been the cause for exacerbated mortality among the sepsis cohort in NCT01663701-SSSP-2 (PMID: 28973227).