BACKGROUND: Right ventricular outflow tract (RVOT) is a common source of ventricular tachycardia, which often requires ablation. However, the mechanisms underlying the RVOT's unique arrhythmia susceptibility remain poorly understood due to lack of detailed electrophysiological and molecular studies of the human RVOT. METHODS: We conducted optical mapping studies in 16 nondiseased donor human RVOT preparations subjected to pharmacologically induced adrenergic and cholinergic stimulation to evaluate susceptibility to arrhythmias and characterize arrhythmia dynamics. RESULTS: We found that under control conditions, RVOT has shorter action potential duration at 80% repolarization relative to the right ventricular apical region. Treatment with isoproterenol (100 nM) shortened action potential duration at 80% repolarization and increased incidence of premature ventricular contractions (=0.003), whereas acetylcholine (100 μM) stimulation alone had no effect on action potential duration at 80% repolarization or premature ventricular contractions. However, acetylcholine treatment after isoproterenol stimulation reduced the incidence of premature ventricular contractions (=0.034) and partially reversed action potential duration at 80% repolarization shortening (=0.029). Immunolabeling of RVOT (n=4) confirmed the presence of cholinergic marker VAChT (vesicular acetylcholine transporter) in the region. Rapid pacing revealed RVOT susceptibility to both concordant and discordant alternans. Investigation into transmural arrhythmia dynamics showed that arrhythmia wave fronts and phase singularities (rotors) were relatively more organized in the endocardium than in the epicardium (=0.006). Moreover, there was a weak but positive spatiotemporal autocorrelation between epicardial and endocardial arrhythmic wave fronts and rotors. Transcriptome analysis (n=10 hearts) suggests a trend that MAPK (mitogen-activated protein kinase) signaling, calcium signaling, and cGMP-PKG (protein kinase G) signaling are among the pathways that may be enriched in the male RVOT, whereas pathways of neurodegeneration may be enriched in the female RVOT. CONCLUSIONS: Human RVOT electrophysiology is characterized by shorter action potential duration relative to the right ventricular apical region. Cholinergic right ventricular stimulation attenuates the arrhythmogenic effects of adrenergic stimulation, including increase in frequency of premature ventricular contractions and shortening of wavelength. Right ventricular arrhythmia is characterized by positive spatial-temporal autocorrelation between epicardial-endocardial arrhythmic wave fronts and rotors that are relatively more organized in the endocardium.

<p>Ishemijska bolest srca najče&scaron;će nastaje kao posledica razvoja aterosklerotskih promena na koronarnim krvnim sudovima koji dovode do suženja lumena i posledičnog pada protoka arterijske krvi u području vaskularizacije. Akutni oblik koronarne bolesti koji zahteva hitnu primenu reperfuzione terapije je ST elevirani infarkt miokarda. EKG ima veliki značaj u postavljanju dijagnoze ali i u proceni uspe&scaron;nosti same reperfuzije. &Scaron;irina QRS kompleksa jedan je od EKG parametara čija dinamika promena može ukazati na uspe&scaron;nost pPKI i veličinu infarktne zone. Evaluacija &scaron;irine QRS kompleksa kao prediktora veličine infarkta miokarda i reperfuzije nakon pPKI kod pacijenata sa STEMI. Ispitivanje je sprovedeno kao prospektivna, opservaciona klinička studija na Klinici za kardiologiju, Instituta za kardiovaskularne bolesti Vojvodine u periodu od januara 2016. do decembra 2018. godine. U isptivanje je uključeno 200 pacijenata sa STEMI kod kojih je urađena pPKI. Na osnovu dužine trajanja tegoba formirane su dve grupe od po 100 pacijenata. Grupa A kod kojih je totalno ishemijsko vreme bilo &lt;6h i grupa B kod kojih je totalno ishemijsko vreme između 6 i 12h. . Sprovedeno je EKG praćenje radi procene &scaron;irine QRS kompleksa intrahospitalno (pre procedure, odmah nakon pPKI kao i posle 1h i 72h) i na dve vizite ambulantno tokom &scaron;estomesečnog praćenja (nakon mesec dana i &scaron;est meseci). Ehokardiografija je urađena kod svih pacijenata intrahospitalno i na &scaron;estomesečnom ambulantnom pregledu. &Scaron;irine QRS kompleksa su korelirane sa rezultatima interventne procedure procenjene TIMI protokom i TMPG, dinamikom kardiospecifičnih enzima i ehokardiografskim nalazima. U istraživanje je uključeno 71% mu&scaron;karaca i 29% žena, prosečna starost uzorka iznosila je 60.6&plusmn;11.39. Dužina trajanja tegoba značajno se razlikovala između grupa. U grupi A tegobe su trajale prosečno 120 minuta (90-180), dok su u grupi B trajale 420 minuta (360-600) (p&lt;0.0005). DTB nije se značajno razlikovao, 42 minuta (31-54.5) u odnosu na 40.5 minuta (34.5-55) (p=0.818). Prosečna &scaron;irina QRS kompeksa na EKG-u pre pPKI nije se značajno razlikovala između grupa, 100 msec (90-110) u odnosu na 100 msec (93-110) (p=0.308). Nakon reperfuzije uočena je značajna razlika u &scaron;irini QRS kompleksa između grupa na svim intrahospitalnim kao i EKG-ima načinjenim tokom perioda praćenja. QRS kompleks je &scaron;iri kod pacijenata iz grupe B (p&lt;0.0005). Pacijenti iz grupe A koji su imali prohodnu infarktnu arteriju sa TIMI 3 protokom pre implantacije stenta imali su značajno uži QRS kompleks na incijilanom EKG-u u odnosu na pacijente kod kojih je IRA bila sub/okludirana sa TIMI protokom &le;2 (p=0.001). U grupi B prohodna infarktna arterija sa TIMI 3 protokom nije značajno uticala na &scaron;irinu QRS kompleksa na inicijalnom EKG-u (p=0.144). Na EKG-ima nakon procedure QRS kompleks bio je značajno &scaron;iri kod pacijenata kod kojih je TIMI protok &le;2, ali samo za grupu pacijenata koja se javila unutar 6h od početka tegoba (p=0.001). QRS kompleks kod pacijenata koji su se javili nakon 6h od početka tegoba jeste bio uži, ali bez statistički značajne razlike (p=0.336). Pearsonovim testom registrovano je postojanje negativne korelacije &scaron;irine QRS kompleksa i istisne frakcije leve komore, ali i pozitivne korelacije sa WMSI i indeksiranim end sistolnim i end dijastolnim volumenom. ROC analizom pokazano je da ukoliko je QRS kompleks &scaron;iri od 89 msec nakon mesec dana, 8.5 puta je veći rizik od snižene EF na &scaron;estomesečnoj kontroli (p&lt;0.0005, AUC=0.808, cut-off=89msec.). ROC analiza pokazala je i da ukoliko je QRS kompleks &scaron;iri od 99msec 1h nakon procedure, 5 puta je veći rizik od pojave MACE (p&lt;0.0005, AUC=0.744, cut-off=99msec). Izvedena su dva matematička modela zasnovana na &scaron;irini QRS kompleksa koja vr&scaron;e predikciju snižene EF i pojave MACE tokom perioda praćenja. &Scaron;irina QRS kompleksa je pokazatelj reperfuzije kod pacijenata sa STEMI kod kojih se načini revaskularizacija unutar 6h od nastanka tegoba. &Scaron;irina QRS kompleksa mesec dana nakon STEMI predstavlja nezavisni prediktor snižene EF. Pro&scaron;irenje preko 89msec 8.5 povećava rizik od snižene EF. &Scaron;irina QRS kompleksa jedan sat nakon pPKI predstavlja nezavisni prediktor za MACE. Pro&scaron;irenje preko 99msec 5 puta povećava rizik od neželjenog kardiolo&scaron;kog događaja. Izvedena su dva matematička modela koja koriste &scaron;irinu QRS kompleksa i sa visokom precizno&scaron;ću vr&scaron;e predikciju MACE-a, odnosno snižene EF nakon &scaron;est meseci.&nbsp;</p> / <p>Ischemic heart disease most commonly occurs as a result of the atherosclerotic changes in the coronary vessels that lead to the narrowing of the lumen and consequent fall in arterial blood flow in the vascularization area. An acute form of coronary artery disease requiring immediate reperfusion therapy is ST-elevation myocardial infarction. The ECG is of great importance not only in making the diagnosis but also in evaluating the success of the reperfusion itself. The duration of the QRS complex is one of the ECG parameters whose change in dynamics can indicate the success of pPCI as well as the size of the infarct zone. Evaluation of the width of the QRS complex as a predictor of myocardial infarction size and reperfusion after pPCI in patients with STEMI. The study was conducted as a prospective, observational clinical study at the Cardiology Clinic of the Institute of Cardiovascular Diseases of Vojvodina between January 2016 and December 2018. The study included 200 patients with STEMI in whom pPCI was performed. Based on the length of discomforts two groups with 100 patients were formed. Group A had a total ischemic time &lt;6h and the total ischemic time in group B was between 6-12h. To assess the duration of the QRS complex, the ECG monitoring was performed intrahospital (before the procedure, immediately after pPCI as well as 1h and 72h after the procedure) and on two outpatient visits during the six-month follow-up period (after one month and six months). Echocardiography was performed in all patients intrahospital and at a six-month outpatient visit. The duration of the QRS complex correlated with the results of the interventional procedure that was evaluated by the TIMI flow and TMPG, the dynamics of cardiospecific enzymes and echocardiography findings. The survey included 71% of men and 29% of women with an average age of 60.6 &plusmn; 11.39. The duration of the discomforts varied significantly between the groups. In group A the discomforts lasted 120 minutes in an average (90-180), while they lasted 420 minutes in group B (360-600) (p &lt;0.0005). DTB did not differ significantly, 42 minutes (31-54.5) versus 40.5 minutes (34.5-55) (p = 0.818). The average duration of the QRS complex on the ECG before pPCI did not differ significantly between the groups, 100 msec (90-110) versus 100 msec (93-110) (p = 0.308). After the reperfusion, a significant difference in the duration of the QRS complex was observed between the groups at all intrahospital ECGs and the ECGs performed during the follow-up period. The QRS complex was broader in group B patients (p &lt;0.0005). Group A patients who had a patent infarct artery with TIMI 3 flow before the stent implantation had a significantly narrower QRS complex on the initial ECG compared to the patients whose IRA was sub / occluded with TIMI flow &le;2 (p = 0.001). In group B, the patent infarct artery with TIMI 3 flow did not significantly affect the duration of the QRS complex at the initial ECG. (p = 0.144). At the post-procedural ECGs the QRS complex was significantly broader in patients with TIMI flow &le;2, but only in the group of patients who arrived within 6 h from the onset of discomforts (p = 0.001). The QRS complex in patients who arrived 6 h after the onset of discomforts was narrower but without statistically significant difference (p = 0.336). The Pearson test registered the existence of a negative correlation of the QRS complex width and the left ventricular ejection fraction, but also a positive correlation with the WMSI and index end-systolic and end-diastolic volumes. The ROC analysis showed that if the QRS complex was wider than 89 msec after one month, there was an 8.5 times higher risk of decreased EF at the six-month control examination (p &lt;0.0005, AUC = 0.808, cut-off = 89msec.). The ROC analysis also showed that if the QRS complex was wider than 99msec 1h after the procedure, there was a 5 times higher risk of MACE (p &lt;0.0005, AUC = 0.744, cut-off = 99msec). Two mathematical models based on the width of the QRS complex were derived that predicted the lowered EF and the occurrence of MACE during the monitored period. The width of the QRS complex is an indicator of reperfusion in patients with STEMI who undergo revascularization within 6 hours from the onset of discomforts. The width of the QRS complex one month after STEMI is an independent predictor of decreased EF. Broadening over 89msec increases the risk of lowered EF for 8.5 times. The width of the QRS complex one hour after pPCI represents an independent predictor of MACE. Broadening over 99msec increases the risk of an adverse cardiac event 5 times. Two mathematical models have derived that use the width of the QRS complex and predict MACE with high precision as well as reduced EF after six months.</p>