The aim of our study was to characterize resistance to ischemia/reperfusion (I/R) injury in Langendorff-perfused rat hearts and effectivity of ischemic preconditioning (PC) under condition of simulated acute hyperglycemia (SAHG) by perfusion of the hearts with Krebs-Henseleit (KH) solution with elevated glucose concentration (22 mmol/l). I/R injury was induced by 30-min coronary occlusion followed by 120-min reperfusion and PC by two cycles of 5-min occlusion/5-min reperfusion, prior to I/R. The severity of I/R injury was characterized by determination of the size of infarction (IS, expressed in % of area at risk size) and the amount of heart-type fatty acid binding protein (h-FABP, a marker of cell injury) released from the hearts to the effluent. Significantly smaller IS (8.8+/-1 %) and lower total amount of released h-FABP (1808+/-660 pmol) in PC group compared with IS 17.1+/-1.2 % (p<0.01) and amount of h-FABP (8803+/-2415 pmol, p<0.05) in the non-PC control hearts perfused with standard KH solution (glucose 11 mmol/l) confirmed protective effects of PC. In contrast, in SAHG groups, PC enhanced IS (21.4+/-2.2 vs. 14.3+/-1.3 %, p<0.05) and increased total amount of h-FABP (5541+/-229 vs. 3458+/-283 pmol, p<0.05) compared with respective non-PC controls. Results suggest that PC has negative effect on resistance of the hearts to I/R injury under conditions of elevated glucose in vitro.

• MeSH
• časové faktory MeSH
• funkce levé komory srdeční MeSH
• glukosa metabolismus   MeSH
• hyperglykemie komplikace   metabolismus   MeSH
• infarkt myokardu etiologie   metabolismus   patologie   patofyziologie   prevence a kontrola   MeSH
• ischemické přivykání * MeSH
• komorový tlak (srdce) MeSH
• modely nemocí na zvířatech MeSH
• myokard metabolismus   patologie   MeSH
• potkani Wistar MeSH
• proteiny vázající mastné kyseliny metabolismus   MeSH
• reperfuzní poškození myokardu etiologie   metabolismus   patologie   patofyziologie   prevence a kontrola   MeSH
• stupeň závažnosti nemoci MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: During heart development, it has been hypothesized that apoptosis of atrioventricular canal myocardium and replacement by fibrous tissue derived from the epicardium are imperative to develop a mature atrioventricular conduction. To test this, apoptosis was blocked using an established caspase inhibitor and epicardial growth was delayed using the experimental epicardial inhibition model, both in chick embryonic hearts. RESULTS: Chicken embryonic hearts were either treated with the peptide caspase inhibitor zVAD-fmk by intrapericardial injection in ovo (ED4) or underwent epicardial inhibition (ED2.5). Spontaneously beating embryonic hearts isolated (ED7-ED8) were then stained with voltage-sensitive dye Di-4-ANEPPS and imaged at 0.5-1 kHz. Apoptotic cells were quantified (ED5-ED7) by whole-mount LysoTracker Red and anti-active caspase 3 staining. zVAD-treated hearts showed a significantly increased proportion of immature (base to apex) activation patterns at ED8, including ventricular activation originating from the right atrioventricular junction, a pattern never observed in control hearts. zVAD-treated hearts showed decreased numbers of apoptotic cells in the atrioventricular canal myocardium at ED7. Hearts with delayed epicardial outgrowth showed also increased immature activation patterns at ED7.5 and ED8.5. However, the ventricular activation always originated from the left atrioventricular junction. Histological examination showed no changes in apoptosis rates, but a diminished presence of atrioventricular sulcus tissue compared with controls. CONCLUSIONS: Apoptosis in the atrioventricular canal myocardium and controlled replacement of this myocardium by epicardially derived HCN4-/Trop1- sulcus tissue are essential determinants of mature ventricular activation pattern. Disruption can lead to persistence of accessory atrioventricular connections, forming a morphological substrate for ventricular pre-excitation. Developmental Dynamics 247:1033-1042, 2018. © 2018 Wiley Periodicals, Inc.

• MeSH
• adhezní molekula epiteliálních buněk MeSH
• apoptóza * MeSH
• hyperpolarizační iontové kanály řízené cyklickými nukleotidy MeSH
• kuřecí embryo MeSH
• perikard * MeSH
• preexcitační syndromy etiologie   MeSH
• převodní systém srdeční patofyziologie   MeSH
• remodelace komor * MeSH
• remodelace síní * MeSH
• zvířata MeSH
• Check Tag
• kuřecí embryo MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH