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.

• Keywords
• cardiac conduction system, connexin, immunohistochemistry, myocardium, optical mapping,
• MeSH
• Connexin 43 physiology   MeSH
• Gap Junctions physiology   MeSH
• Cell Communication * MeSH
• Mice MeSH
• Pericardium cytology   physiology   MeSH
• Purkinje Fibers cytology   physiology   MeSH
• Heart Ventricles pathology   MeSH
• Muscle Cells cytology   physiology   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• GJA1 protein, mouse MeSH Browser
• Connexin 43 MeSH

This study investigates the impact of reduced transmural conduction velocity (TCV) on output parameters of the human heart. In a healthy heart, the TCV contributes to synchronization of the onset of contraction in individual layers of the left ventricle (LV). However, it is unclear whether the clinically observed decrease of TCV contributes significantly to a reduction of LV contractility. The applied three-dimensional finite element model of isovolumic contraction of the human LV incorporates transmural gradients in electromechanical delay and myocyte shortening velocity and evaluates the impact of TCV reduction on pressure rise (namely, (dP/dt)max) and on isovolumic contraction duration (IVCD) in a healthy LV. The model outputs are further exploited in the lumped "Windkessel" model of the human cardiovascular system (based on electrohydrodynamic analogy of respective differential equations) to simulate the impact of changes of (dP/dt)max and IVCD on chosen systemic parameters (ejection fraction, LV power, cardiac output, and blood pressure). The simulations have shown that a 50% decrease in TCV prolongs substantially the isovolumic contraction, decelerates slightly the LV pressure rise, increases the LV energy consumption, and reduces the LV power. These negative effects increase progressively with further reduction of TCV. In conclusion, these results suggest that the pumping efficacy of the human LV decreases with lower TCV due to a higher energy consumption and lower LV power. Although the changes induced by the clinically relevant reduction of TCV are not critical for a healthy heart, they may represent an important factor limiting the heart function under disease conditions.

• MeSH
• Atrial Fibrillation physiopathology   MeSH
• Hemodynamics physiology   MeSH
• Humans MeSH
• Models, Cardiovascular * MeSH
• Computer Simulation * MeSH
• Heart Conduction System physiology   MeSH
• Ventricular Function physiology   MeSH
• Heart Ventricles physiopathology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

Recent studies have shown that left ventricle (LV) exhibits considerable transmural differences in active mechanical properties induced by transmural differences in electrical activity, excitation-contraction coupling, and contractile properties of individual myocytes. It was shown that the time between electrical and mechanical activation of myocytes (electromechanical delay: EMD) decreases from subendocardium to subepicardium and, on the contrary, the myocyte shortening velocity (MSV) increases in the same direction. To investigate the physiological importance of this inhomogeneity, we developed a new finite element model of LV incorporating the observed transmural gradients in EMD and MSV. Comparative simulations with the model showed that when EMD or MSV or both were set constant across the LV wall, the LV contractility during isovolumic contraction (IVC) decreased significantly ((dp/dt)max⁡ was reduced by 2 to 38% and IVC was prolonged by 18 to 73%). This was accompanied by an increase of transmural differences in wall stress. These results suggest that the transmural differences in EMD and MSV play an important role in physiological contractility of LV by synchronising the contraction of individual layers of ventricular wall during the systole. Reduction or enhancement of these differences may therefore impair the function of LV and contribute to heart failure.

• MeSH
• Myocardial Contraction physiology   MeSH
• Humans MeSH
• Models, Cardiovascular * MeSH
• Computer Simulation * MeSH
• Ventricular Function physiology   MeSH
• Heart Ventricles * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

December 2017 was the 230th anniversary of Jan Evangelista Purkinje's birth, which prompted us to review the life of this remarkable man who established the world's first department of physiology in Wroclaw and whose name is immortalized in the cardiologic eponym, Purkinje fibers. This paper offers an overview of Purkinje's life, legacy, and numerous scientific discoveries.

• Keywords
• Cardiology/history, Czech Republic, Poland, Purkinje JE, Purkinje fibers, historical article, history, 19th century, physiology/history,
• MeSH
• Biomedical Research history   MeSH
• History, 18th Century MeSH
• History, 19th Century MeSH
• Physiology history   MeSH
• Cardiology history   MeSH
• Check Tag
• History, 18th Century MeSH
• History, 19th Century MeSH
• Publication type
• Biography MeSH
• Journal Article MeSH
• Historical Article MeSH
• Portrait MeSH
• Geographicals
• Czech Republic MeSH

• About
• Purkinje, Jan Evangelosta

Most embryonic ventricular cardiomyocytes are quite uniform, in contrast to the adult heart, where the specialized ventricular conduction system is molecularly and functionally distinct from the working myocardium. We thus hypothesized that the preferential conduction pathway within the embryonic ventricle could be dictated by trabecular geometry. Mouse embryonic hearts of the Nkx2.5:eGFP strain between ED9.5 and ED14.5 were cleared and imaged whole mount by confocal microscopy, and reconstructed in 3D at 3.4 μm isotropic voxel size. The local orientation of the trabeculae, responsible for the anisotropic spreading of the signal, was characterized using spatially homogenized tensors (3 × 3 matrices) calculated from the trabecular skeleton. Activation maps were simulated assuming constant speed of spreading along the trabeculae. The results were compared with experimentally obtained epicardial activation maps generated by optical mapping with a voltage-sensitive dye. Simulated impulse propagation starting from the top of interventricular septum revealed the first epicardial breakthrough at the interventricular grove, similar to experimentally obtained activation maps. Likewise, ectopic activation from the left ventricular base perpendicular to dominant trabecular orientation resulted in isotropic and slower impulse spreading on the ventricular surface in both simulated and experimental conditions. We conclude that in the embryonic pre-septation heart, the geometry of the A-V connections and trabecular network is sufficient to explain impulse propagation and ventricular activation patterns.

• Keywords
• cardiac conduction, mathematical modeling, mouse embryo, optical mapping, trabeculation,
• Publication type
• Journal Article MeSH