Unlike adult mammals, newborn mice can regenerate a functional heart after myocardial infarction; however, the precise origin of the newly formed cardiomyocytes and whether the distal part of the conduction system (the Purkinje fiber (PF) network) is properly formed in regenerated hearts remains unclear. PFs, as well as subendocardial contractile cardiomyocytes, are derived from trabeculae, transient myocardial ridges on the inner ventricular surface. Here, using connexin 40-driven genetic tracing, we uncover a substantial participation of the trabecular lineage in myocardial regeneration through dedifferentiation and proliferation. Concomitantly, regeneration disrupted PF network maturation, resulting in permanent PF hyperplasia and impaired ventricular conduction. Proliferation assays, genetic impairment of PF recruitment, lineage tracing and clonal analysis revealed that PF network hyperplasia results from excessive recruitment of PFs due to increased trabecular fate plasticity. These data indicate that PF network hyperplasia is a consequence of trabeculae participation in myocardial regeneration.
- MeSH
- buněčný rodokmen MeSH
- hyperplazie patologie MeSH
- kardiomyocyty patologie fyziologie MeSH
- myši transgenní MeSH
- myši MeSH
- novorozená zvířata * MeSH
- proliferace buněk MeSH
- Purkyňova vlákna * patofyziologie fyziologie patologie MeSH
- regenerace * fyziologie MeSH
- srdeční komory * patologie patofyziologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The mammalian ventricular myocardium forms a functional syncytium due to flow of electrical current mediated in part by gap junctions localized within intercalated disks. The connexin (Cx) subunit of gap junctions have direct and indirect roles in conduction of electrical impulse from the cardiac pacemaker via the cardiac conduction system (CCS) to working myocytes. Cx43 is the dominant isoform in these channels. We have studied the distribution of Cx43 junctions between the CCS and working myocytes in a transgenic mouse model, which had the His-Purkinje portion of the CCS labeled with green fluorescence protein. The highest number of such connections was found in a region about one-third of ventricular length above the apex, and it correlated with the peak proportion of Purkinje fibers (PFs) to the ventricular myocardium. At this location, on the septal surface of the left ventricle, the insulated left bundle branch split into the uninsulated network of PFs that continued to the free wall anteriorly and posteriorly. The second peak of PF abundance was present in the ventricular apex. Epicardial activation maps correspondingly placed the site of the first activation in the apical region, while some hearts presented more highly located breakthrough sites. Taken together, these results increase our understanding of the physiological pattern of ventricular activation and its morphological underpinning through detailed CCS anatomy and distribution of its gap junctional coupling to the working myocardium.
- MeSH
- konexin 43 fyziologie MeSH
- mezerový spoj fyziologie MeSH
- mezibuněčná komunikace * MeSH
- myši MeSH
- perikard cytologie fyziologie MeSH
- Purkyňova vlákna cytologie fyziologie MeSH
- srdeční komory patologie MeSH
- svalové buňky cytologie fyziologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Ventricular fibrillation (VF) storm after myocardial infarction (MI) is a life-threatening condition that necessitates multiple defibrillations. Catheter ablation is a potentially effective treatment strategy for VF storm refractory to optimal medical treatment. However, its impact on patient survival has not been verified in a large population. METHODS: We conducted a multicenter, retrospective observational study involving consecutive patients who underwent catheter ablation of post-MI refractory VF storm without preceding monomorphic ventricular tachycardia. The target of ablation was the Purkinje-related ventricular extrasystoles triggering VF. The primary outcome was in-hospital and long-term mortalities. Univariate logistic regression and Cox proportional-hazards analysis were used to evaluate clinical characteristics associated with in-hospital and long-term mortalities, respectively. RESULTS: One hundred ten patients were enrolled (age, 65±11years; 92 men; left ventricular ejection fraction, 31±10%). VF storm occurred at the acute phase of MI (4.5±2.5 days after the onset of MI during the index hospitalization for MI) in 43 patients (39%), the subacute phase (>1 week) in 48 (44%), and the remote phase (>6 months) in 19 (17%). The focal triggers were found to originate from the scar border zone in 88 patients (80%). During in-hospital stay after ablation, VF storm subsided in 92 patients (84%). Overall, 30 (27%) in-hospital deaths occurred. The duration from the VF occurrence to the ablation procedure was associated with in-hospital mortality (odds ratio for each 1-day increase, 1.11 [95% CI, 1.03-1.20]; P=0.008). During follow-up after discharge from hospital, only 1 patient developed recurrent VF storm. However, 29 patients (36%) died, with a median survival time of 2.2 years (interquartile range, 1.2-5.5 years). Long-term mortality was associated with left ventricular ejection fraction <30% (hazard ratio, 2.54 [95% CI, 1.21-5.32]; P=0.014), New York Heart Association class ≥III (hazard ratio, 2.68 [95% CI, 1.16-6.19]; P=0.021), a history of atrial fibrillation (hazard ratio, 3.89 [95% CI, 1.42-10.67]; P=0.008), and chronic kidney disease (hazard ratio, 2.74 [95% CI, 1.15-6.49]; P=0.023). CONCLUSIONS: In patients with MI presenting with focally triggered VF storm, catheter ablation of culprit triggers is lifesaving and appears to be associated with short- and long-term freedom from recurrent VF storm. Mortality over the long-term follow-up is associated with the severity of underlying cardiovascular disease and comorbidities in this specific patient population.
- MeSH
- analýza přežití MeSH
- fibrilace komor etiologie mortalita patofyziologie terapie MeSH
- infarkt myokardu komplikace MeSH
- katetrizační ablace metody MeSH
- komorové extrasystoly komplikace patofyziologie terapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mortalita v nemocnicích MeSH
- následné studie MeSH
- proporcionální rizikové modely MeSH
- Purkyňova vlákna patofyziologie MeSH
- recidiva MeSH
- retrospektivní studie MeSH
- senioři MeSH
- tepový objem MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
Mammals and birds have a specialized cardiac atrioventricular conduction system enabling rapid activation of both ventricles. This system may have evolved together with high heart rates to support their endothermic state (warm-bloodedness) and is seemingly lacking in ectothermic vertebrates from which first mammals then birds independently evolved. Here, we studied the conduction system in crocodiles (Alligator mississippiensis), the only ectothermic vertebrates with a full ventricular septum. We identified homologues of mammalian conduction system markers (Tbx3-Tbx5, Scn5a, Gja5, Nppa-Nppb) and show the presence of a functional atrioventricular bundle. The ventricular Purkinje network, however, was absent and slow ventricular conduction relied on trabecular myocardium, as it does in other ectothermic vertebrates. We propose the evolution of the atrioventricular bundle followed full ventricular septum formation prior to the development of high heart rates and endothermy. In contrast, the evolution of the ventricular Purkinje network is strongly associated with high heart rates and endothermy.
- MeSH
- aligátoři a krokodýli embryologie genetika fyziologie MeSH
- embryo nesavčí metabolismus MeSH
- Hisův svazek embryologie metabolismus fyziologie MeSH
- hybridizace in situ MeSH
- mezikomorová přepážka embryologie metabolismus fyziologie MeSH
- modely kardiovaskulární MeSH
- převodní systém srdeční embryologie fyziologie MeSH
- proteiny T-boxu genetika metabolismus MeSH
- Purkyňova vlákna embryologie metabolismus fyziologie MeSH
- srdce embryologie fyziologie MeSH
- srdeční frekvence genetika fyziologie MeSH
- srdeční komory embryologie metabolismus MeSH
- vývojová regulace genové exprese MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- dějiny lékařství * MeSH
- lidé MeSH
- převodní systém srdeční * MeSH
- Purkyňova vlákna * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- historické články MeSH
- O autorovi
- Purkyně, Jan Evangelista, 1787-1869 Autorita
- MeSH
- fyziologie * dějiny MeSH
- histologie dějiny MeSH
- mikroskopie dějiny MeSH
- patologie MeSH
- Purkyňova vlákna MeSH
- Purkyňovy buňky MeSH
- Publikační typ
- biografie MeSH
- O autorovi
- Purkyně, Jan Evangelista, 1787-1869 Autorita
- MeSH
- fyziologie * dějiny MeSH
- převodní systém srdeční * MeSH
- Purkyňova vlákna MeSH
- Publikační typ
- biografie MeSH
- historické články MeSH
- O autorovi
- Purkyně, Jan Evangelista, 1787-1869 Autorita
Převodní systém srdeční byl ve formě přítomné u teplokrevných obratlovců úplně popsán před 110 lety. Navzdory tomu bylo v poslední době získáno množství poznatků o jeho specifikaci a vývoji, jež mají význam pro jeho funkci při tvorbě a vedení vzruchu srdcem. Poruchy převodního systému jsou spojovány s arytmiemi, z nichž některé mají vývojový podklad. Evoluční pohled na tuto problematiku je užitečný zejména pro lepší pochopení přestavby síňokomorového kanálu.
Cardiac conduction system was described in its complete form in homeotherm vertebrates 110 years ago. Despite this fact, many new findings concerning its specification and development that have an impact on its pacemaking and conducting function appeared in the past decade. Conduction system disorders are associated with arrhythmias, and some of which have a developmental origin. Evolutionary view on this area is particularly useful for better understanding of the atrioventricular canal remodelling.
- Klíčová slova
- Purkyňův zárodečný měchýřek,
- MeSH
- anatomie * dějiny MeSH
- dějiny lékařství MeSH
- lidé MeSH
- Purkyňova vlákna anatomie a histologie MeSH
- Purkyňovy buňky * cytologie MeSH
- terminologie jako téma MeSH
- významné osobnosti MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- biografie MeSH
- historické články MeSH
- O autorovi
- Purkyně, Jan Evangelista 1787-1869
