Xue-Han Ning

Influence of the ph of cardioplegic solutions on cellular energy metabolism and hydrogen ion flux during neonatal hypothermic circulatory arrest and reperfusion: A dynamic 31p nuclear magnetic resonance study in a pig model

OBJECTIVESnThe pH of cardioplegic solutions is postulated to affect myocardial protection during neonatal hypothermic circulatory arrest. Neither optimization of cardioplegic pH nor its influence on intracellular pH during hypothermic circulatory arrest has been previously studied in vivo. Thus we examined the effects of the pH of cardioplegic solutions on postischemic cardiac function in vivo, including two possible operative mechanisms: (1) reduction in adenosine triphosphate use and depletion of high-energy phosphate stores or (2) reduction of H+ flux during reperfusion, or both.nnnMETHODSnDynamic 31P spectroscopy was used to measure rates of adenosine triphosphate use, high-energy phosphate depletion, cytosolic acidification during hypothermic circulatory arrest, and phosphocreatine repletion and realkalinization during reperfusion. Neonatal pigs in three groups (n = 8 each)--group A, acidic cardioplegia (pH = 6.8); group B, basic cardioplegia (pH = 7.8); and group N, no cardioplegia--underwent hypothermia at 20 degrees C with 60 minutes of hypothermic cardioplegia followed by reperfusion.nnnRESULTSnRecoveries of peak elastance, stroke work, and diastolic stiffness were superior in group B. Indices of ischemic adenosine triphosphate use, initial phosphocreatine depletion rate, and tau, the exponential decay half-time, were not different among groups. Peak [H+] in group A (end-ischemia) was significantly elevated over that of group B. The realkalinization rate was reduced in group B compared with that in groups A (p = 0.015) and N (p = 0.035), with no difference between groups A and N (p = 0.3). Cytosolic realkalinization rate was markedly reduced and the half-time of [H+] decay was increased during reperfusion in group B.nnnCONCLUSIONSnSuperior postischemic cardiac function in group B is not related to alterations in ischemic adenosine triphosphate use or high-energy store depletion, but may be due to slowing in H+ efflux during reperfusion, which should reduce Ca++ and Na+ influx.

Circulating miRNAs from Dried Blood Spots are Associated with High Altitude Sickness

Circulating miRNAs isolated from dried blood spots (DBS) were found to be associated with high altitude sickness (HAS) patients in Tibet. HAS arises from two different diseases which are acute (AMS) and chronic (CMS) mountain sickness. Circulating miRNAs differences were found between AMS Han Chinese patients and normal Han controls and between CMS Tibetan Chinese patients and normal Tibetan controls. HAS arises from hypoxia which afflicts some high altitude inhabitants or visitors and not others. The difference results from each individual’s genetic makeup where hypoxia related genes have been shown to be a major contributor to these sicknesses. Several fold changes increases (up regulation) were found in the hypoxia associated miRNAs let-7f-5p, miR-9-5p, miR-19a-3p, miR-23a-3p, miR-98-5p, miR-125a-5p, miR-181b-5p, mir-202-3p, miR-372, miR-381-3p, miR-519d, miR-520d-3p, and miR-656 for both HAS groups compared to their controls. Other miRNAs (miR-19a-3p, 302c-3p and 875-3p) were found to be up regulated in one HAS group and down regulated in the other HAS group indicating the genetic differences between the two sickness groups.

SNPs, linkage disequilibrium, and chronic mountain sickness in Tibetan Chinese

Chronic mountain sickness (CMS) is estimated at 1.2% in Tibetans living at the Qinghai–Tibetan Plateau. Eighteen single-nucleotide polymorphisms (SNPs) from nine nuclear genes that have an association with CMS in Tibetans have been analyzed by using pairwise linkage disequilibrium (LD). The SNPs included are the angiotensin-converting enzyme (rs4340), the angiotensinogen (rs699), and the angiotensin II type 1 receptor (AGTR1) (rs5186) from the renin–angiotensin system. A low-density lipoprotein apolipoprotein B (rs693) SNP was also included. From the hypoxia-inducible factor oxygen signaling pathway, the endothetal Per-Arnt-Sim domain protein 1 (EPAS1) and the egl nine homolog 1 (ENGL1) (rs480902) SNPs were included in the study. SNPs from the vascular endothelial growth factor (VEGF) signaling pathway included are the v-akt murine thymoma viral oncogene homolog 3 (rs4590656 and rs2291409), the endothelial cell nitric oxide synthase 3 (rs1007311 and rs1799983), and the (VEGFA) (rs699947, rs34357231, rs79469752, rs13207351, rs28357093, rs1570360, rs2010963, and rs3025039). An increase in LD occurred in 40 pairwise comparisons, whereas a decrease in LD was found in 55 pairwise comparisons between the controls and CMS patients. These changes were found to occur within and between signaling pathways, which suggests that there is an interaction between SNP alleles from different areas of the genome that affect CMS.