Pathological Changes in the Sinoatrial Node Tissues of Rats Caused by Pulsed Microwave Exposure

To observe microwave induced dynamic pathological changes in the sinus nodes, wistar rats were exposed to 0, 5, 10, 50 mW/cm^2 microwave. In 10 and 50 mW/cm^2 groups, disorganized sinoatrial node cells, cell swelling, cytoplasmic condensation, nuclear pyknosis, and anachromasis, swollen, and empty mitochondria, and blurred and focally dissolved myofibrils could be detected from 1 to 28 d, while reduced parenchymal cells, increased collagen fibers, and extracellular matrix remodeling of interstitial cells were observed from 6 to 12 months. In conclusion, 10 and 50 mW/cm^2 microwave could cause structural damages in the sinoatrial node and extracellular matrix remodeling in rats.

Effect of simulated ischemia-reperfusion on I_f in sinoatrial node cells and the intervention of KATP channel opener

Objective: To study the effect of simulated ischemia-reperfusion (I/R) on If of sinoatrial node (SAN) cells and the intervention of KATP channel opener Pinacidil. Methods: The SAN cells of the neonatal rats were detached and purified 2 d before the experiment. The experimental animals were randomly divided into the control group, group of simulated I/R, group intervened with KATP channel opener Pinacidil (P+ I/R) and group intervened with KATP channel blocking agent 5-HD (5-HD + P + I/R & 5-HD + I/R). The If density of each group was measured by technique of routine whole cell patch clamp and multiple-catheter perfusion system and the If activated curve in each group was drawn. Results: ①Under different directive potentials, the If density of the SAN cells in I/R group increased significantly, compared with that in the control group ( P < 0.01); that in P + I/R group decreased significantly, compared with that in I/R group ( P < 0.01); the If density values in 5-HD + P + I/R group and 5-HD + I/R group increased significantly, compared with that in P + I/R group, but showed no significant difference with that in I/R group. ②Compared with that in the control group, the If activated curve of the SAN cells moved rightwards under ultimate activating potential, half of which was from - 108.0 ± 12.4 to - 89.5 ± 7.2 mV ( P <0.01); compared with that in I/R group, If activated curve of the SAN cells moved leftwards under ultimate activating potential, half of which was the range from -99.5± 10.8 mV (P<0.05); KATP channel blocking agent 5-HD could block the effect of Pinacdil on If activated curve. Conclusion: KATP channel opener Pinacidil can antagonize the effect of simulated I/R on the If of SAN cells, which may be beneficial to the maintenance of the relative stability of ion steady state and electrophysiological activities under condition of simulated I/R.

Junctional Pacemaker May Replace the Sinoatrial Node

Junctional rhythm is usually seen in the clinic with different causes.We report a case of bicuspid aortic valve accompa-nied by sinoatrial node dysfunction.The junctional escape beat could accelerate with physiological needs and provided for the normal needs of daily life when dysfunction of the sinoatrial node occurred,which provides a new way for the treatment of sinoatrial node dysfunction.Our fi ndings could be potentially signifi cant for identifying causes and choos-ing appropriate treatment strategies by using ECG monitoring in the clinic in the future.

Protective effect and mechanism of K_(ATp) channel opener on the sinoatrial node cells of neonatal rat cultured in simulated ischemia-reperfusion

Objective: To study the effect of KATp channel opener and its possible mechanism on the sinoatrial node cells of neonatal rats which were cultured under simulated ischemia-reperfusion. Methods: Freshly isolated sinoatrial node (SAN) cells of neonatal rats were purified and cultured for 2 d, and then they were randomly divided into the control, simulated ischemia-reperfusion group (I/R group) , group intervened with KATp channel opener pinacidil (P + I/R group), KATP Channel blocking agent 5-HD (5-HD + I/R group) , and group with the 2 agents at same time (5-HD + P + I/R group) . The survival rate of cells was measured by flow cytometry and the content of intracellular calcium in the cells of each group was detected with laser confocal microscopy. Results: ① The survival rate of SAN cells in I/R group [ (51. 79±6. 28)% ] was remarkably significantly lower than in control [ (95. 08±10. 48)% ] (P < 0.001), and very significantly lower than in P + I/R group [ (63. 77±5. 35) % ] (P<0.01), however, those of 5-HD + P + I/R group [(52. 88±6. 25)% ] and 5-HD+I/R group [ (53. 16±5. 35)% ] was significantly lower compared with that in P + I/R group (P <0. 01) ; ② When the average fluorescence intensity of sinoatrial node cells in the control was regarded as 100% , the relative fluorescence intensities of each group were: ( 374±52) % in I/R group, significantly higher than that of control (P <0. 01) ; ( 162±20)% in P + I/R group, declining significantly than that of I/R group (P<0.01); (385?6)% in 5-HD+ P + I/R group and (379±44)% in 5-HD + I/R group, increasing significantly than that of I/R group (P<0.01). Conclusion: ① Simulated ischemia-reperfusion can significantly reduce the survival rate of SAN cells, and can also lead to the overload of intracellular calcium in them.② KATp channel opener, pinacidil, exerts protective effect on the cells under simulated ischemia-reperfusion, which may be associated with the decrease of intracellular calcium loading in them.

Effects of external stimuli on the pacemaker function of the sinoatrial node in sodium channel gene mutations models

Loss of function and gain of function mutations of the sodium channel were investigated using an intact two-dimensional rabbit sinoatrial node (SAN) and atrial cell model. The effects of three external stimuli (acetylcholine secretion by the vagal nerve, acid-base concentration, and tissue temperature) on cardiac pacemaker function and conduction were studied. Our results show that these two groups of mutations have different effects on pacemaker function and conduction. Furthermore, we found that the negative effects of these mutations could be altered by external stimuli. The bradycardic effects of mutations were magnified by an increase in acetylcholine level. Changes in acid-base concentration and tissue temperature increased the ability of the SAN to recover its pacemaker function. The results of this study increase our understanding of sodium channel disorders, and help to advance research on the treatment of these conditions.

Effects of Chinese Herbal Medicine Serum on the Apoptosis of Sinoatrial Node Cells Induced by Simulated Ischemia-reperfusion

Objective:To study the effect of Chinese herbal medicine Kangxin Fumai Granule(康心复脉颗粒 Granule for heart diseases) serum on the primary cultured sinoatrial node(SAN) cell apoptosis induced by simulated ischemia-reperfusion(IR).Methods:The SAN cells removed from SAN tissue of neonatal Wistar rats were cultured and purified with differential attachment and 5'-bromodeoxyuridine(BrdU) treatment.Simulated IR model was adopted.The obtained cells were morphologically observed with inverted microscopy.By using the method of serum pharmacology,the cell apoptosis was measured with TUNEL staining qualitatively and with flow cytometry quantitatively.Results:Three kinds of cells were observed in the cultured SAN cells:spindle,triangle and irregular.The spindle cells comprised the greatest proportion.The SAN cells in the model group showed moderate positive brown staining in the nucleus,and the apoptosis rate increased significantly compared to that in the control group(P<0.01).While the SAN cells in the Kangxin Fumai Granule high-dose group did not demonstrated positive staining in the nucleus,and the apoptosis rate decreased significantly compared to that in the model group(P<0.05).Conclusion:Of the cells cultured from SAN,the spindle cells were pacemaker cells of SAN in rats.Blockade and/or inhibition of the SAN cell apoptosis might be one of the important mechanisms of Kangxin Fumai Granule in preventing and treating sinoatrial injury induced by simulated IR.

Effect of Qiangxin Fumai Granule(强心复脉颗粒) on Electrophysiological Functions of the Sinoatrial Node during Ischemia-reperfusion of the Right Coronary Artery in Rabbits

Objective： To study the effect of the Chinese medicine Qiangxin Fumai Granule （强心复脉颗粒, QFG） on electrophysiological functions of the sinoatrial node during ischemia-reperfusion （IR） of the right coronary artery in rabbits. Methods： The right coronary artery IR model in rabbits was adopted. The modeled rabbits were randomly divided into 4 groups： the model group, the atropine group, the highdose QFG group, and the low-dose QFG group, with 8 animals in each group. In addition, twelve rabbits were selected for the sham-operative group. The drugs were administered once via duodenal perfusion after modeling had been stabilized for 10 min. The changes in AA interval, the sinoatrial conduction time （SACT）, the sinus node recovery time （SNRT）, the corrected sinus node recovery time （CSNRT） and the index of sinus node recovery time （ISNRT） at different time points during ischemia and reperfusion were measured. Results： The AA interval was prolonged for more than 40 ms in the model group during ischemia. Compared with the model group, the four electrophysiological parameters abovementioned in the high-dose QFG group and the low-dose QFG group were decreased to different extents at each time point （P〈0.01 or P〈0.05）, and no statistically significant differences were found between the QFG groups and the atropine group （P〉0.05）. Conclusion： QFG is beneficial for accelerating the recovery of sinus node autorhythmicity and conduction function, so as to protect electrophysiological functions of the sinoatrial node. Accelerating the recovery of autorhythmicity and conduction function in the sinus node is considered its electrophysiological mechanism in the treatment of sinoatrial node injury induced by ischemia.

Primary culture and identification of sinoatrial node cells from newborn rat

Objective To establish a reliable approach to primary culture and identification of sinoatrial node (SAN) cells. Methods The SAN cells were cultured from SAN tissue removed from neonatal Wistar rats and purified with differential attachment and 5'-bromodeoxyuridine (BrdU) treatment. The obtained cells were morphologically observed with inverted microscopy and transmission electron microscopy. Its action potential was recorded using electrophysiological methods.Results Three distinctly different cells were observed in the cultured SAN cells: spindle, triangle and irregular. Of these, the spindle cells comprised the greatest proportion, with their shape, structure and electrophysiological characteristics consistent with those of the pacemaker cells of SAN. The triangle cells were similar in features to the similarly shaped myocytes located in the atrial myocardium. Conclusions The culture method of differential attachment combined with BrdU treatment is a reliable approach to growing SAN cells. Of the cells cultured from SAN, the spindle cells appear to function as pacemaker cells.

Sinoatrial node pacemaker cells share dominant biological properties with glutamatergic neurons

Activation of the heart normally begins in the sinoatrial node(SAN).Electrical impulses spontaneously released by SAN pacemaker cells(SANPCs)trigger the contraction of the heart.However,the cellular nature of SANPCs remains controversial.Here,we report that SANPCs exhibit glutamatergic neuron-like properties.By comparing the single-cell transcriptome of SANPCs with that of cells from primary visual cortex in mouse,we found that SANPCs co-clustered with cortical neurons.Tissue and cellular imaging confirmed that SANPCs contained key elements of glutamatergic neurotransmitter system,expressing genes encoding glutamate synthesis pathway(G/s),ionotropic and metabotropic glutamate receptors(Grina,Gria3,Grm1 and Grm5)t and glutamate transporters(Slc17a7).SANPCs highly expressed cell markers of glutamatergic neurons(Snap25 and S/-c17a7)t whereas Gad1,a marker of GABAergic neurons,was negative.Functional studies revealed that inhibition of glutamate receptors or transporters reduced spontaneous pacing frequency of isolated SAN tissues and spontaneous Ca2+transients frequency in single SANPC.Collectively,our work suggests that SANPCs share dominant biological properties with glutamatergic neurons,and the glutamatergic neurotransmitter system may act as an intrinsic regulation module of heart rhythm,which provides a potential intervention target for pacemaker cell-associated arrhythmias.

Cardiac conductive system excitation maps using intracardiac tissue Doppler imaging

OBJECTIVE: To precisely visualize cardiac anatomic structures and simultaneously depict electro-mechanical events for the purpose of precise underblood intervention. METHODS: Intracardiac high-resolution tissue Doppler imaging was used to map real time myocardial contractions in response to electrical activation within the anatomic structure of the cardiac conductive system using a canine open-chest model. RESULTS: The detailed inner anatomic structure of the cardiac conductive system at different sites (i.e., sino-atrial, atrial wall, atrial-ventricular node and ventricular wall) with the inside onset and propagation of myocardial velocity and acceleration induced by electrical activation was clearly visualized and quantitatively evaluated. CONCLUSION: The simultaneous single modality visualization of the anatomy, function and electrical events of the cardiac conductive system will foster target pacing and precision ablation.