• The Korean Journal of Physiology and Pharmacology
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• v.1 no.6
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• pp.731-739
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• 1997

The aim of present study is to investigate the effects of cGMP on hyperpolarization activated inward current ($I_f$), pacemaker current of the heart, in rabbit sino-atrial node cells using the whole-cell patch clamp technique. When sodium nitroprusside (SNP, $80{\mu}M$), which is known to activate guanylyl cyclase, was added, $I_f$ amplitude was increased and its activation was accelerated. However, when $I_f$ was prestimulated by isopreterenol (ISO, $1{\mu}M$), SNP reversed the effect of ISO. In the absence of ISO, SNP shifted activation curve rightward. On the contrary in the presence of ISO, SNP shifted activation curve in opposite direction. $8Br-cGMP(100\;{\mu}M)$, more potent PKG activator and worse PDE activator than cGMP, also increased basal $I_f$ but did not reverse stimulatory effect of ISO. It was probable that PKG activation seemed to be involved in SNP-induced basal $I_f$ increase. The fact that SNP inhibited ISO-stimulated $I_f$ suggested cGMP antagonize cAMP action via the activation of PDE. This possibility was supported by experiment using 3-isobutyl-1-methylxanthine (IBMX), non-specific PDE inhibitor. SNP did not affect $I_f$ when $I_f$ was stimulated by $20{\mu}M$ IBMX. Therefore, cGMP reversed the stimulatory effect of cAMP via cAMP breakdown by activating cGMP-stimulated PDE. These results suggest that PKG and PDE are involved in the modulation of $I_f$ by cGMP: PKG may facilitate $I_f$ and cGMP-stimulated PDE can counteract the stimulatory action of cAMP.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.4
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• pp.173-181
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• 2002

The sinoatrial (SA) node is a complex and inhomogeneous tissue in terms of cell morphology and electrical activity. There are two models of the cellular organisation of the sinoatrial node: the gradient and mosaic models. According to the gradient model there is a gradual transition in morphology and electrical properties of SA node cells from the centre to the periphery of the SA node. In the mosaic model, there is a variable mix of atrial and sinoatrial node cells from the centre to the periphery. This review focuses on the cellular organisation of the rabbit sinoatrial node in terms of the expression of connexin (Cx40, Cx43 and Cx45), L-type $Ca^{2+}$ channel and $Na^+-Ca^{2+}$ exchanger proteins. These immunocytochemical data, together with morphological and electrophysiological data, obtained from the intact sinoatrial node and isolated sinoatrial node cells support the gradient model of the cellular organisation of the SA node. The complex organisation of the sinoatrial node is important for the normal functioning of the sinoatrial node: (i) it allows the sinoatrial node to drive the surrounding hyperpolarized atrial muscle without being suppressed by it; (ii) it helps the pacemaker activity of the sinoatrial node continue under a wide range of physiological and pathophysiological conditions; (iii) it helps protect the sinoatrial node from reentrant arrhythmias.

• Anatomy and Cell Biology
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• v.56 no.4
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• pp.428-434
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• 2023

Pulmonary veins (PVs) and their myocardial sleeves play an important role in the development of atrial fibrillation. Hence, detailed knowledge of PV anatomy is required to improve the procedural success rate and prevent complications during cardiac procedures. The aim of this study was to evaluate the PV anatomy along with anatomical variations in the Indian population. Total 100 formalin fixed cadaveric hearts were examined. The number and pattern of the PVs were observed along with the measurement of their horizontal and vertical diameters. The ovality index for each PV was calculated. Classical PV pattern was observed in 62% cases. Variant pattern like additional right middle PV pattern and left common PV pattern were found in 20% and 10% cases respectively. A separate pattern with presence of both right middle PV and left common PV was observed in 6% cases. In the classical pattern right superior PV was the largest followed by right inferior, left superior and left inferior PV. The additional right middle PV had the smallest diameter whereas the left common PV had the largest diameter. Almost all the veins had greater vertical diameters in comparison to horizontal diameters. The variant PVs were oval and had greater ovality index compared to the normal PVs. In classical pattern 54.8% hearts whereas in variant pattern 79% hearts had one or more oval PV. The given data can help clinicians for planning and execution of various interventional and electrophysiological procedures involving PVs.

• Biomolecules & Therapeutics
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• v.22 no.6
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• pp.553-557
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• 2014

Verapamil is used in the treatment of hypertension, angina pectoris, and atrial fibrillation. Recently, several studies have demonstrated that verapamil increased the optic nerve head blood flow and improved the retrobulbar circulation. All these show that verapamil is potentially useful for ophthalmic treatment. Thus, the aim of this study is to investigate whether verapamil could protect human lens epithelial cell (HLEC) from oxidative stress induced by $H_2O_2$ and the cellular mechanism underlying this protective function. The viability of HLEC was determined by the MTT assay and apoptotic cell death was analyzed by Hoechst 33258 staining. Moreover, Caspase-3 expression was detected by immunocytochemistry and flow cytometry analysis. We also detected Caspase-3 mRNA expression by reverse-transcription-polymerase chain reaction and the GSH content in cell culture. The results showed that oxidative stress produced significant cell apoptotic death and it was reduced by previous treatment with the verapamil. Verapamil was effective in reducing HLEC death mainly through reducing the expression level of apoptosis-related proteins, caspase-3, and increasing glutathione content. Therefore, it was suggested that verapamil was effective in reducing HLEC apoptosis induced by $H_2O_2$.

• Journal of Chest Surgery
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• v.22 no.4
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• pp.548-561
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• 1989

In single atrial cells isolated from the rabbit the properties of inward current of Na-Ca exchange were investigated using the whole cell voltage clamp technique. The current was recorded during repolarization following brief 2 ms depolarizing pulse to +40 mV from a holding potential of * 70 mV. Followings are the results obtained: 1. When stimulated every 30 seconds, the inward currents were activated and reached peak values 6-12 ms after the beginning of depolarizing pulse. The mean current amplitude was 342 pA/cell. 2. The current decayed spontaneously from the peak activation and the time course of the relaxation showed two different phases fast and slow phase. The time constants were 10-18 ms and 60-140 ms, respectively. 3. The recovery of inward current was tested by paired pulse of various intervals. The peak current recovered exponentially with time constant of 140 ms and 1 p M isoprenaline accelerated the recovery process. 4. Relaxation time course was also affected by pulse interval and time constant of the fast phase was reduced almost linearly according to the decrease of pulse interval between 30 sec and 1 sec. 5. The peak activation was increased in magnitude by long prepulse stimulation, 5 p M Bay K, 1 p M isoprenaline or internal and external application of c-AMP. 6. The relaxation time constant of the fast phase was prolonged by 5 p M Bay K or c-AMP, and shortened by isoprenaline. However the time course of the slow relaxation phase was not so much changed. From the above results, it could be concluded that increase of the calcium current by Bay K or c-AMP results in the potentiation and prolongation of intracellular calcium transient, and the facilitation of Ca uptake by SR might be a mechanism of shortening the time constant of current relaxation by short interval stimulation or isoprenaline.

• Proceedings of the KSAR Conference
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• 2003.06a
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• pp.76-76
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• 2003

Pluripotent embryonic stem cells can differentiate into beating cardiomyocytes with proper culture conditions and stimulants via embryo-like aggregates. We describe here the use of mouse embryonic stem (mES03) cells as a reproducible differentiation system for cardiomyocyte. mES03 cells growing in colonies were dissociated and allowed to re-aggregated in suspension [embryoid body (EB) formation〕. To induce cardiomyocytic differentiation, cells were exposed to 0.75% dimethyl sulfoxide (DMSO) during EB formation for 4 days and then another 4 days without DMSO (4+/4-). Thus treated EB was plated onto gelatin-coated dishes for differentiation. Spontaneously contracting colonies which appeared in approximately 4~5 days upon differentiation were mechanically dissected, enzymatically dispersed, plated onto coverslips, and then incubated for another 48~72 hrs. By RT-PCR, robust expression of cardiac myosin heavy chain $\alpha$, cardiac muscle heavy polypeptide 7 $\beta$($\beta$-MHC), cardiac transcription factor GATA4, and skeletal muscle-specific $\alpha$$_1$-subunit of the L-type calcium channel ($\alpha$$_1$CaC $h_{sm}$ ) were detected as early as 8 days after EB formation, but message of cardiac muscle-specific $\alpha$$_1$-subunit of the L-type calcium channel ($\alpha$$_1$CaCh) were reveled at a low level. In contrast, expression of myosin light chain (MLC-2V) and atrial natriuretic factor (ANF) were not detected during EB formation for 8 days. However, a strong expression of the atrial-specific ANF gene was expressed from day 8 onward, which were remained constant in EB. (cardiac specialization and terminal differentiation stage). Electrophysiological examination of spontaneously contracting cells showed ventricle-like action potential 17 days after the EB formation. This study indicates that mES03 cell-derived cardiomyocytes via 4+/4- protocol displayed biochemical and electrophysiological properties of subpopulation of cardiomyocytes.

• Korean Journal of Veterinary Research
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• v.27 no.1
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• pp.27-34
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• 1987

To verify the direct effects of the thyroid hormone ($T_3$) on the rabbit heart, $T_3$-Tyrode solution in vitro was perfused on the normal atrial muscles and enzymatically isolated ventricular myocytes of the rabbit. All the experimental procedures were conducted at $35^{\circ}C$ and the same procedures were repeated after Ca. 120 minutes from the beginning of $T_3$-Tyrode perfusion. Compared to the state between the normal Tyrode solution and $T_3$-Tyrode solution, results were observed on the same cells by electrophysiological methods (conventional intracellular recording and whole cell patch clamping) as soon as possible. The results obtained were as follows : 1. Action potential duration (APD) on the left atrial muscle was reduced under the perfusion of $T_3$-Tyrode. 2. Absolute refractory Period was shortened by $T_3$-Tryrode perfusion. (117 msec./114 msec., 90 msec./78 msec.) 3. Maximal Ca currents ($i_{Ca}$) were decreased in single: ventricular myocytes under the $T_3$-Tyrode (2.98 nA) than under the normal Tyrode (6.65 nA) 4. On I-V relation, reversal potential was shifted to lower membrane potential and membrane potential showing maximal $i_{Ca}$was lowered from +10mV to -20mV by $T_3$ effect. 5. Above results were likely to explain that tachycardia in the hyperthyroid state was caused in part by the reduced repolarization phase and the reduced refractory period due to the decrease of the Ca current.

• Korean Journal of Plant Resources
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• v.25 no.6
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• pp.693-699
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• 2012

This study was conducted to investigate the effects of Woohwangcheungsimweun (ox bezoar), deer antlers, and wild ginseng on induction of cardiomyocyte differentiation using the established mouse embryonic stem (ES) cells. The expression of atrial natriuretic peptide (ANP) was highest in Woohwangcheungsimweun treatment group. The expression of rabbit anti-GATA-4(GATA-4) and troponin (TnI) were highest in wild ginseng and Woohwangcheungsimweun treatment groups, respectively. Fluorescence activated cell sorting (FACS) analysis showed that the expression of ANP was highest in Dimethyl sulfoxide(DMSO) and Woohwangcheungsimweun treatment groups. The expression of GATA-4 was relatively high in wild ginseng treatment group. The expression of TnI was highest in Woohwangcheungsimweun treatment group. In the gene expression analysis, DMSO greatly inhibited GATA-4 expression to 25% of control. Woohwangcheungsimweun treatment caused to increase cTnI and cardiac ANP expression significantly. Wild ginseng extract upregulated GATA-4 gene expression. In conclusion, DMSO widely used as cardiomyocyte differentiation inducer did not show significant effects on the expression of ANP, GATA-4 and TnI in this study. Woohwangcheungsimweun showed upregulation of ANP and TnI expression. Wild ginseng extract showed greater effects than DMSO on GATA-4 expression. These results might suggest that the combination of Woohwangcheungsimweun and wild ginseng extract treatment can be expected to increase expressions of all three genes.

• Journal of Chest Surgery
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• v.22 no.2
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• pp.179-190
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• 1989

The experimental study for extracorporeal preservation of the heart-lung preparation by autoperfusion system was performed in 10 dogs. Under intravenous Pentothal endotracheal anesthesia bilateral thoracotomies were performed. A 24F cannula connected to a plastic reservoir bag located 100 cm above the level of the heart was introduced into the aortic arch. Left subclavian, innominate artery, and descending aorta were ligated and divided. Both vena cavae were ligated and divided after the bag was half filled with blood. A 24F catheter inserted into right atrium and connected to the plastic bag in order to keep constant the preload. The thoracic trachea was intubated and the lungs were ventilated. The heart-lung preparations were removed en bloc and floated in a $34^{\circ}C$ bath of Hartmann solution. The preparations were observed for from 2 hours to 8 hours, with the average of 5.2 hours. Hemodynamic and hematologic variables were measured during preharvest and autoperfusion. The pH revealed severe respiratory alkalosis due to very low $PaCO_2$ during autoperfusion ; $PaO_2$ remained constant for 130-140 mmHg; $A-aDO_2$ increased markedly. The static inspiratory pressure [SIP] at late autoperfusion [6hr] increased significantly as compared with at early autoperfusion [2hr]. There was no difference between white blood cell counts from right atrium and those of left atrium. Heart rates remained constant for 110-120/min; cardiac outputs maintained to approximately 0.6L/min; mean aortic pressures, 75 mmHg; mean pulmonary arterial pressures, 15-18 mmHg; mean right atrial pressures, 9-13 mmHg; mean left atrial pressures, 12 mmHg lower than those of right atrium. Serum Na maintained with normal range during autoperfusion; K increased significantly; Ca decreased progressively. Hemoglobin and hematocrit decreased significantly during autoperfusion. The study demonstrated that stable hemodynamics could be maintained throughout the experiment and the preparation of the lung seemed to be inadequate, especially after 3-4 hours, such as high $A-aDO_2$, increased SIP, and scattered atelectasis and edema in their gross appearances.

• Journal of Chest Surgery
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• v.28 no.7
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• pp.649-657
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• 1995

From December 1993 to April 1994, to investigate complement activation and pulmonary leukostasis, thirty adult patients were studied during cardiopulmonary bypass[CPB for cardiac surgery in Department of Cardiovascular & Thoracic Surgery, Pusan Paik Hospital, Inje University. Total patients were divided into group I and II according to the purpose of study ; Group I was 15 patients undergoing CPB with bubble oxygenator, Group II was 15 patients undergoing CPB with membrane oxygenator. The results of study were summarized as follows.1. The decrease of C3 and C4 levels were observed within few minutes of beginning of CPB in all patients[P<0.05 , and this decrease was proved to be due to complement activation, not by the influence of hemodilution.2. In the correlation between the change of C3 and C4, group I showed linear correlation each other suggesting complement activation occurred through the classical pathway, group II showed a correlation at only partial sampling times suggesting complement activation via both classical and alternative pathway, however there was no significant statistical difference at the change of C3 and C4 concentrations in two groups[P>0.05 .3. After switching to partial CPB, a few difference between right atrial and left atrial WBC count was observed, but statistically not significant and median cell count difference between group I and II was not significant, too [P>0.05 . With the above result, we concluded that CPB itself contributes to the activation of complement system, but bubble oxygenator does not activate always complement system more than membrane oxygenator.