Ian P. Temple, Sunil Jit R.J. Logantha, Mais Absi, Yu Zhang, Eleftheria Pervolaraki, Joseph Yanni, Andrew Atkinson, Maria Petkova, Gillian M. Quigley, Simon Castro, Mark Drinkhill, Heiko Schneider, Oliver Monfredi, Elizabeth Cartwright, Min Zi, Tomoko T. Yamanushi, Vaikom S. Mahadevan, Alison M. Gurney, Ed White, Henggui Zhang, George Hart, Mark R. Boyett, Halina Dobrzynski
Circulation: Arrhythmia and Electrophysiology December 2016, 9 (12) e003432; DOI: https://doi.org/10.1161/CIRCEP.115.003432
Ian P. Temple, Sunil Jit R.J. Logantha, Mais Absi, Yu Zhang, Eleftheria Pervolaraki, Joseph Yanni, Andrew Atkinson, Maria Petkova, Gillian M. Quigley, Simon Castro, Mark Drinkhill, Heiko Schneider, Oliver Monfredi, Elizabeth Cartwright, Min Zi, Tomoko T. Yamanushi, Vaikom S. Mahadevan, Alison M. Gurney, Ed White, Henggui Zhang, George Hart, Mark R. Boyett, Halina Dobrzynski
Circulation: Arrhythmia and Electrophysiology December 2016, 9 (12) e003432; DOI: https://doi.org/10.1161/CIRCEP.115.003432
A and B, Echocardiography images (on d 23 following monocrotaline injection) showing development of pulmonary hypertension (PHT). A, Parasternal short-axis view from control (Ai) and monocrotaline-injected (Aii) rats. The left and right ventricles (LV and RV, respectively) are identified by dotted lines (not possible to identify RV in control rat). B, Pulmonary velocity profile from control (Bi) and monocrotaline-injected (Bii) rats. Measurement of pulmonary artery acceleration time (PAAT) and pulmonary artery deceleration (PAD) shown. C, Death of rat with PHT caused by complete heart block 28 d following monocrotaline injection. ECGs recorded by telemetry at different times during final 21 min shown. Ratio of atrial to ventricular beats shown in blue. ECGs shown on different time bases (1 s time marks shown). y axis shows 0.2 mV increments. CHB indicates complete heart block.
Ian P. Temple, Sunil Jit R.J. Logantha, Mais Absi, Yu Zhang, Eleftheria Pervolaraki, Joseph Yanni, Andrew Atkinson, Maria Petkova, Gillian M. Quigley, Simon Castro, Mark Drinkhill, Heiko Schneider, Oliver Monfredi, Elizabeth Cartwright, Min Zi, Tomoko T. Yamanushi, Vaikom S. Mahadevan, Alison M. Gurney, Ed White, Henggui Zhang, George Hart, Mark R. Boyett, Halina Dobrzynski
Circulation: Arrhythmia and Electrophysiology December 2016, 9 (12) e003432; DOI: https://doi.org/10.1161/CIRCEP.115.003432
Ian P. Temple, Sunil Jit R.J. Logantha, Mais Absi, Yu Zhang, Eleftheria Pervolaraki, Joseph Yanni, Andrew Atkinson, Maria Petkova, Gillian M. Quigley, Simon Castro, Mark Drinkhill, Heiko Schneider, Oliver Monfredi, Elizabeth Cartwright, Min Zi, Tomoko T. Yamanushi, Vaikom S. Mahadevan, Alison M. Gurney, Ed White, Henggui Zhang, George Hart, Mark R. Boyett, Halina Dobrzynski
Circulation: Arrhythmia and Electrophysiology December 2016, 9 (12) e003432; DOI: https://doi.org/10.1161/CIRCEP.115.003432
Impaired atrioventricular (AV) node conduction in pulmonary hypertension (PHT) rats. All data collected on day of termination. A, Left, Mean (+SEM) Wenckebach cycle length (WCL), AV node effective refractory period (AVERP), and AV node functional refractory period (AVFRP) in control (black bars) and PHT (red bars) rats (n=10). Recordings made from Langendorff-perfused heart. *P<0.05 (Student t test). A, Right, Typical AV node conduction curves from control and PHT rats showing measurement of AVERP and AVFRP. B, Significant correlation between AVERP and AVFRP and WCL. Each point corresponds to different rat, control (black) or PHT (red). Data are fit by linear regression (AVERP, R2=0.63, P<0.001; AVFRP, R2=0.71, P<0.0001). C, Demonstration of complete heart block in PHT rat. Extracellular potential recordings from region of His bundle of control (Top trace) and PHT (Bottom trace) rats shown. Recordings made from isolated AV node. Atrial (A; marked with green arrow) and His bundle (H; marked with red arrow) signals recorded.
Ian P. Temple, Sunil Jit R.J. Logantha, Mais Absi, Yu Zhang, Eleftheria Pervolaraki, Joseph Yanni, Andrew Atkinson, Maria Petkova, Gillian M. Quigley, Simon Castro, Mark Drinkhill, Heiko Schneider, Oliver Monfredi, Elizabeth Cartwright, Min Zi, Tomoko T. Yamanushi, Vaikom S. Mahadevan, Alison M. Gurney, Ed White, Henggui Zhang, George Hart, Mark R. Boyett, Halina Dobrzynski
Circulation: Arrhythmia and Electrophysiology December 2016, 9 (12) e003432; DOI: https://doi.org/10.1161/CIRCEP.115.003432
Heart block in pulmonary hypertension (PHT) rats explored further. A, Example of atrioventricular (AV) node preparation used for intracellular action potential recording. Tissue was paced at 5 Hz at level of sinus node. B, Intracellular action potentials recorded from compact node showing normal 1:1 conduction in control preparation and complete heart block (as well as ectopic action potentials) in PHT preparation. Sharp deflections, stimulation artifacts. C, Intracellular action potentials recorded along AV conduction axis (transitional tissue, inferior nodal extension/compact node, and penetrating bundle) showing normal conduction in control preparation and decremental conduction in penetrating bundle in PHT preparation.
Ian P. Temple, Sunil Jit R.J. Logantha, Mais Absi, Yu Zhang, Eleftheria Pervolaraki, Joseph Yanni, Andrew Atkinson, Maria Petkova, Gillian M. Quigley, Simon Castro, Mark Drinkhill, Heiko Schneider, Oliver Monfredi, Elizabeth Cartwright, Min Zi, Tomoko T. Yamanushi, Vaikom S. Mahadevan, Alison M. Gurney, Ed White, Henggui Zhang, George Hart, Mark R. Boyett, Halina Dobrzynski
Circulation: Arrhythmia and Electrophysiology December 2016, 9 (12) e003432; DOI: https://doi.org/10.1161/CIRCEP.115.003432
Expression of mRNA for ion channels carrying inward current. Expression shown in atrial muscle (A; A), transitional tissue (TT; B), inferior nodal extension (INE; C), compact node (CN; D), penetrating bundle (PB; E), and ventricular muscle (V; F) from control (black bars) and pulmonary hypertension (PHT; red bars) rats; means (+SEM) shown (n=6–8); bars and asterisks indicate significant differences between control and PHT rats as assessed by the limma test (false discovery rate [FDR]–corrected P<0.2, ie, 20%); for the control tissues only, letters indicate a significant difference from the appropriately lettered region (lower case letters, FDR-corrected P<0.2, ie, 20%; upper case letters, FDR-corrected P<0.05, ie, 5%). Inset, Schematic diagram of AV node (from Greener et al21). CFB indicates central fibrous body; CS, coronary sinus; FO, fossa ovalis; IVC, inferior vena cava; MCT, monocrotaline; and TV, tricuspid valve.
Ian P. Temple, Sunil Jit R.J. Logantha, Mais Absi, Yu Zhang, Eleftheria Pervolaraki, Joseph Yanni, Andrew Atkinson, Maria Petkova, Gillian M. Quigley, Simon Castro, Mark Drinkhill, Heiko Schneider, Oliver Monfredi, Elizabeth Cartwright, Min Zi, Tomoko T. Yamanushi, Vaikom S. Mahadevan, Alison M. Gurney, Ed White, Henggui Zhang, George Hart, Mark R. Boyett, Halina Dobrzynski
Circulation: Arrhythmia and Electrophysiology December 2016, 9 (12) e003432; DOI: https://doi.org/10.1161/CIRCEP.115.003432
Expression of mRNA for voltage-gated K+ channels. Expression shown in atrial muscle (A; A), transitional tissue (TT; B), inferior nodal extension (INE; C), compact node (CN; D), penetrating bundle (PB; E), and ventricular muscle (V; F) from control (black bars) and pulmonary hypertension (PHT; red bars) rats; means (+SEM) shown (n=6–8); bars and asterisks indicate significant differences between control and PHT rats as assessed by the limma test (false discovery rate [FDR]–corrected P<0.2, ie, 20%); for the control tissues only, letters indicate a significant difference from the appropriately lettered region (lower case letters, FDR-corrected P<0.2, ie, 20%; upper case letters, FDR-corrected P<0.05, ie, 5%).
Ian P. Temple, Sunil Jit R.J. Logantha, Mais Absi, Yu Zhang, Eleftheria Pervolaraki, Joseph Yanni, Andrew Atkinson, Maria Petkova, Gillian M. Quigley, Simon Castro, Mark Drinkhill, Heiko Schneider, Oliver Monfredi, Elizabeth Cartwright, Min Zi, Tomoko T. Yamanushi, Vaikom S. Mahadevan, Alison M. Gurney, Ed White, Henggui Zhang, George Hart, Mark R. Boyett, Halina Dobrzynski
Circulation: Arrhythmia and Electrophysiology December 2016, 9 (12) e003432; DOI: https://doi.org/10.1161/CIRCEP.115.003432
Expression of mRNA for inward rectifier K+ channels. Expression shown in atrial muscle (A; A), transitional tissue (TT; B), inferior nodal extension (INE; C), compact node (CN; D), penetrating bundle (PB; E), and ventricular muscle (V; F) from control (black bars) and pulmonary hypertension (PHT; red bars) rats; means (+SEM) shown (n=6–8); bars and asterisks indicate significant differences between control and PHT rats as assessed by the limma test (false discovery rate [FDR]–corrected P<0.2, ie, 20%); for the control tissues only, letters indicate a significant difference from the appropriately lettered region (lower case letters, FDR-corrected P<0.2, ie, 20%; upper case letters, FDR-corrected P<0.05, ie, 5%).
Ian P. Temple, Sunil Jit R.J. Logantha, Mais Absi, Yu Zhang, Eleftheria Pervolaraki, Joseph Yanni, Andrew Atkinson, Maria Petkova, Gillian M. Quigley, Simon Castro, Mark Drinkhill, Heiko Schneider, Oliver Monfredi, Elizabeth Cartwright, Min Zi, Tomoko T. Yamanushi, Vaikom S. Mahadevan, Alison M. Gurney, Ed White, Henggui Zhang, George Hart, Mark R. Boyett, Halina Dobrzynski
Circulation: Arrhythmia and Electrophysiology December 2016, 9 (12) e003432; DOI: https://doi.org/10.1161/CIRCEP.115.003432
Expression of mRNA for Ca2+-handling molecules and connexins. Expression shown in atrial muscle (A; A), transitional tissue (TT; B), inferior nodal extension (INE; C), compact node (CN; D), penetrating bundle (PB; E), and ventricular muscle (V; F) from control (black bars) and pulmonary hypertension (PHT; red bars) rats; means (+SEM) shown (n=6–8); bars and asterisks indicate significant differences between control and PHT rats as assessed by the limma test (false discovery rate [FDR]–corrected P<0.2, ie, 20%); for the control tissues only, letters indicate a significant difference from the appropriately lettered region (lower case letters, FDR-corrected P<0.2, ie, 20%; upper case letters, FDR-corrected P<0.05, ie, 5%).
Ian P. Temple, Sunil Jit R.J. Logantha, Mais Absi, Yu Zhang, Eleftheria Pervolaraki, Joseph Yanni, Andrew Atkinson, Maria Petkova, Gillian M. Quigley, Simon Castro, Mark Drinkhill, Heiko Schneider, Oliver Monfredi, Elizabeth Cartwright, Min Zi, Tomoko T. Yamanushi, Vaikom S. Mahadevan, Alison M. Gurney, Ed White, Henggui Zhang, George Hart, Mark R. Boyett, Halina Dobrzynski
Circulation: Arrhythmia and Electrophysiology December 2016, 9 (12) e003432; DOI: https://doi.org/10.1161/CIRCEP.115.003432
Remodeling of atrioventricular (AV) node predicts heart block in pulmonary hypertension (PHT). A, Simulated conduction along AV conduction axis under control conditions (Top) and in PHT (Bottom). Propagation of 5 consecutive action potentials shown. Membrane potential (color coded) is shown as a function of time and distance. B, Computed conduction velocity (CV) along AV conduction axis under control conditions and in PHT. C, Computed action potential profiles along AV conduction axis under control conditions and in PHT.
