In conclusion, a predictive index combining clinical and hematological parameters measured at an intermediate step on the way to the top may provide information on impending AMS.

These findings show for the first time the possible role of thrombin generation within the complex activation of inflammatory response in causing hemodynamic instability in the early postoperative period after AAA surgery.

Although angiotensin (Ang)II-induced Janus-activated kinase (JAK)2 phosphorylation was reported to be enhanced in failing human cardiomyocytes, the downstream balance between cardio-protective (signal transducer and activator of transcription-STAT3) and the pro-inflammatory (STAT2 and STAT5) response remains unexplored. Therefore STATs phosphorylation and putative genes overexpression following JAK2 activation were investigated in isolated cardiomyocytes obtained from failing human hearts (n = 16), and from non-failing(NF) hearts of humans (putative donors, n = 6) or adult rats. In NF myocytes Ang II-induced JAK2 activation was followed by STAT3 phosphorylation (186 AE 45% at 30 min), with no STAT2 or STAT5 response. The associated B cell lymphoma (Bcl)-xL overexpression (1.05 AE 0.39 fold) was abolished by both JAK2 and extracellular signal-regulated kinase (ERK)1/2 inhibitors (AG490, 10 mM, and PD98059, 30 mM, respectively), whereas Fas ligand (Fas-L) response (0.91 AE 0.21 fold) was inhibited only by p38MAPK antagonism (SB203580, 10 mM). In failing myocytes Ang II-induced JAK2 activation was followed by STAT2 (237 AE 38%) and STAT5 (222 AE 31%) phosphorylation, with no STAT3 response. No changes in Bcl-xL expression were observed, and the associated Fas-L gene overexpression (1.14 AE 0.27 fold) being abolished by p38 mitogen-activated protein kinase (MAPK) antagonism. The altered JAK2 induced STATs response in human failing cardiomyocytes may be of relevance for the progression of cardiac dysfunction in heart failure.

Abstract:Previous investigations have shown that the signal transducers and activators of transcription (STATs) signaling pathway play an important role in the modulation of apoptosis after ischemia and reperfusion. The mechanism for this enhanced cardioprotection is unknown, but we believe that alterations STATs may play a role.To investigate this hypothesis, we examined the effects of angiotension II type 1 (AT1) and angiotension II type 2 (AT2) receptor antagonist added to cardioplegia on the downstream response of different STATs, connected with proinflammatory pathways (STAT2, STAT5) and prohypertrophic and antiapoptotic pathways (STAT3). Isolated, nonworking hearts (n = 3 per group) from neonatal rats were perfused aerobically (4°C) for 20 min in the Langendorff mode with the modified St. Thomas' Hospital no. 2 (MSTH2) cardioplegic solution (Group 1), the MSTH2 cardioplegic solution + AT1 receptor antagonist (Group 2), and MSTH2 cardioplegic solution + AT2 receptor antagonist (Group 3). Thus, myocytes were isolated by enzymatic digestion, and STAT2, STAT3, and STAT5 were investigated in Western blot studies. Times to arrest after cardioplegia were 8-12 s for all groups. Total cardioplegia delivery volume was about 300 mL for the 20 min. Perfusion with the MSTH2 cardioplegic solution supplemented with AT1 receptor antagonist (Group 2) induced a significant reduction in STAT2 and STAT5 tyrosine phosphorylation (-58 and -63%, respectively, vs. Group 1, P < 0.05). Conversely, STAT2 and STAT5 activation were unaffected by perfusion with the MSTH2 cardioplegic solution supplemented with AT2 receptor antagonist (Group 3). The decreased activation of STAT2 and STAT5 observed in Group 2 was accompanied by reduction of interleukin-1b (-57% in Group 2 vs. Group 1, P < 0.05). There were no significant differences in STAT3 phosphorylation among all groups. Only the addition of AT1 receptor antagonist to MSTH2 cardioplegia significantly decreases the inflammatory response of the neonatal rat cardiomyocytes without affecting antiapoptotic influence provided by tyrosine phosphorylation of STAT3. AT1 receptor antagonist added to cardioplegia represents an additional modality for enhancing myocardial protection during cardiac surgery and could contribute to optimize the ischemia tolerance of the pediatric heart. Key Words: Rat myocardiumCardioplegia-Angiotensin II antagonist-ValsartanSignal transducers and activators of transcription.Although the tolerance of immature myocardium to ischemia is greater than that of mature myocardium, inadequate protection by crystalloid cardioplegia(s) for immature myocardium has been cited as one of the major reasons for postoperative complications and deaths in children (1).The interpretation of studies of cardioplegic efficacy in the immature myocardium is complicated by the variety of animal species, the range of different cardioplegic solutions used, and different hypothermias. Therefore, a considerable controversy surrounds the ability of cardioplegic solutions to protect the immature ...

a b s t r a c tAlthough optical reading systems are important tools to transfer data from a paper form to electronic databases, the impact of system fine-tuning on the final error rate is not usually considered. At the end of a multi-step process involving paper form design training of operators, and fine-tuning procedure, the final rate of error can be reduced from 0.65% to 0.05%. Fine-tuning should be introduced as a standard procedure while using optical reading systems.