• The Korean Journal of Physiology
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• v.23 no.2
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• pp.329-337
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• 1989

Cardiac muscles show stimulation frequency-dependent tension changes i.e. Bowditch phenomenon and Woodworth phenomenon, the former is an increase of tension with the increase of stimulation frequency, whereas the latter is an increase of tension with a decrease of stimulation frequency. Bowditch phenomenon is seen in the range of frequency 1.0 cps and above, and Woodworth phenomenon below the frequency 1.0 cps in the most of mammalian cardiac atrium. To throw some light on the possible mechanism of both phenomena in rat atrium, influences of drugs affecting $Ca^{2+}$ influx through the plasma membrane $(verapamil,\;La^{3+},\;norepinephrine)$ and $Ca^{2+}$ release from sarcoplasmic reticulum (SR) on frequency-tension curve were studied. The results obtained are summarized as follows: 1) At low temperature $(27.5^{\circ}C)$, both Bowditch and Woodworth phenomenon were demonstrated. But Bowditch phenomenon disappeared at the temperature above $(32.5^{\circ}C)$. 2) At $(27.5^{\circ}C)$, in the presence of verapamil, a $Ca^{2+}$ channel blocker, a time course of change in the frequency-tension was studied. It was found that Bowditch phenomenon was affected before the Woodworth phenomenon, then the former was completely disappeared. At $(32.5^{\circ}C)$, where no Bow-ditch is seen in normal atrial muscle, Bowditch phenomenon was reappeared by an administration of norepinephrine suggesting again that slow inward current of such as $Ca^{2+}$ channel is closely related to Bowditch phenomenon. 3) At $27.5^{\circ}C$, in the presence of $La^{3+}$, although tensions were decreased at all stimulation frequencies, Bowditch and Woodworth phenomenon were still demonstrated. However in the presence of both $La^{3+}$ and verapamil, Bowditch phenomena was disappeared suggesting that $La^{3+}$ is less effective in blocking $Ca^{2+}$ channel than verapamil. 4) At $27.5^{\circ}C$, in the presence of ryanodine, an inhibitor of calcium release from SR, Woodworth phenomenon was disappeared, which was consistent with previous reports of others, suggesting that $Ca^{2+}$ release from SR is closely related to Woodworth phenomenon. From the above findings, it may be concluded that Bowditch phenomenon is dependent on the magnitude of $Ca^{2+}$ influx through slow channel and Woodworth phenomenon is dependent on the amount of $Ca^{2+}$ stored in SR.

• Journal of Chest Surgery
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• v.31 no.4
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• pp.393-397
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• 1998

A 25-year-old man with viral cardiomyopathy and chronic active hepatitis successfully underwent dynamic cardiomyoplasty for the first time in Korea on July 30, 1996. The patient had been intermittently dyspneic for 5 years and was admitted to our center twice because of heart failure. For the past 2 years, he was NYHA functional class III status with a left ventricular ejection fraction(LVEF) of around 30%. The patient was born with scoliosis and showed a short stature. The liver function showed elevated liver enzymes, and hepatitis B antigen was positive. The liver biopsy revealed chronic active hepatitis. The preoperative echocardiogram showed decreased left ventricular function with grade II mitral and grade II tricuspid regurgitation with dilated left and right atrium. Recently his symptoms worsened and we decided to perform a dynamic cardiomyoplasty. The left latissmus dorsi muscle(LDM) was mobilized and tested with lead placement on his right lateral decubitus position. The patient was positioned into supine and, after median sternotomy, the heart was wrapped with the mobilized muscle. The Russian made cardiomyostimulator(EKS-445) and leads (Myocardial PEMB for heart and PEMP-1 for LDM) were used. The total operation time was 8 hours and there were no perioperative episodes. Postoperatively the LDM had been trained for a 10 week period and currently the stimulation ratio is maintained at 1:4. The postoperative LVEF did not increase with the value of 30-35%. However, the patient feels better postoperatively with slightly increased activity.

• Journal of Chest Surgery
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• v.21 no.3
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• pp.425-446
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• 1988

After 24 hours of preservation under 15 mmHg perfusion pressure the recovery rates of isolated canine hearts were determined. Preservation was performed in a cold room maintained at 4*C with 4 different types of perfusates bubbled with a mixture of 95% 0y and 5% CO~ using a modified perfusion unit designed in our institute. The perfusates used were as follows; Group 1: Krebs-Henseleit solution, Group 2: Krebs solution added by albumin and PGE1. Group 3: Modified Wicomb*s solution, Group 4: Modified Collin*s solution. The extent of myocardial recovery was evaluated using a modified isolated carmine perfusion model by measuring heart rate, systolic arterial pressure, left atrial pressure[LAP] and cardiac output. In addition to the above hemodynamic parameters, biochemical and enzymatic assays from perfusates and electron microscopic changes of the myocardium were also studied. The results were as follows; 1] The heart recovery rates were 41.6%, 53.4% and 108.9% in groups 1, 2 and 3, respectively, and group 3 elicited the best result[p< 0.001]. The heart beat was never recovered in group 4. 2] Recovered systolic arterial pressures[mmHg] were 63.3% in group 1, 94.9% in group 2 and 94.3% in group 3. 3] LAPs[mmHg] were 20 in group 1, 13.5 in group 2 and 11.2 in group 3, which suggested that the best myocardial preservation was elicited in group 3[p< 0.05]. 4] Cardiac output, the sum of aortic stroke volume and coronary leakage, were 69.1% in group 2, and 90.7% in group 3, but these were not statistically significant[p=0.24]. No aortic stroke output was measured in group 1 and 4. 5] The degree of myocardial edema increase was 17.5` in group 1, 24.6% in group 2, 20.9% in group 3 and 55.3% in group 4. But there were no statistical differences in each group[p= 0.08]. 6] CPK-MB[U/L] levels were increased 750% and 332%[p< 0.05], glucose levels[mg/dl] 60.5% and 78.2% and SGOT[U/L] levels 523% and 333%, in groups 2 and 3, respectively. Biochemical and enzymatic assays could not be performed in group 1 and group 4, because of poor recovery of heart beat. 7] Electron microscopic findings in the myocardium of most groups revealed slight to moderate muscle cell and mitochondrial edema. But all these findings were within the limits of reversible change. From these above results, it is suggested that modified Wicomb*s solution seems to be the most useful physiologic salt solution for preservation of the heart. We propose that after further study and improvement, our portable continuous hypothermic perfusion system will contribute to the development of a better preservation method for donor hearts for human heart transplantation.

• Journal of Life Science
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• v.31 no.10
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• pp.913-921
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• 2021

Limb-girdle muscular dystrophy (LGMD) which is characterized by progressive muscle weakening of the hip and shoulder shows both dominant and recessive inheritances with many pathogenic genes including TTN. This study performed to identify genetic causes of a male patient with late onset (45 years old) autosomal recessive LGMD and atrial flutter. By application of the whole exome sequencing, we identified bi-allelic variants of TTN gene in the patient. One allele had a single missense variant of [c.24124G>T (p.V8042F)], while the other allele consisted of three missense variants of [c.29222G>C (p.R9741P) + c.67490A>G (p.H22497R) + c.75376C>T (p.R25126C)]. The p.V8042F allele was transmitted from his mother, while the other haplotype allele was putatively transmitted from his father. His two unaffected sons had only the p.R9741P. These variants have been not reported or rarely reported in the public human genome databases (1,000 Genome, gnomAD, and KRGDB). Most variants were located in the highly conserved immunoglobulin or fibronectin domains and were predicted to be pathogenic by the in silico analyses. The TTN giant protein plays a key role in muscle assembly, force transmission at the Z-line, and maintenance of resting tension in the I-band. In conclusion, we think that these bi-allelic compound heterozygous mutations may play a role as the genetic causes of the LGMD phenotype.

• The Korean Journal of Pharmacology
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• v.20 no.1 s.34
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• pp.55-65
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• 1984

Comparative effects of $PGF_{2{\alpha}}$ and ouabain on the isolated rat(Sprague-Dowley) atria were studied. The isolated rat atria were prepared for isometric myography in the isolated organ bath containing Feigen's solution perfused with 95% $O_2$ and 5% $CO_2$, and the pH of the medium was maintained at 7.4. The cumulative concentration-response relationship revealed the positive inotropic effects of both drugs with the higher potency of $PGF_{2{\alpha}}$ and the higher efficacy of ouabain. $PGF_{2{\alpha}}$ showed a positive chronotropic effect, but ouabain showed a tendency of increasing the contraction rate. In low-Ca(1.4 mM) medium, the positive inotropic and chronotropic effect of $PGF_{2{\alpha}}$(by $3{\times}10^{-8}M$) were preponderant $(p<0.05{\sim}p<0.005)$ over those of ouabain(by $3{\times}10^{-3}M$). $Ca^{++}$-addition(cumulative, to 2.8, 4.2, 5.6, and 7.0 mM) into the medium evoked the more sensitive response in the $PGF_{2{\alpha}}$ group than in the ouabain group. In low-K(2.8 mM) medium, the $PGF_{2{\alpha}}a(3{\times}10^{-8}M)$ group and the ouabain$(3{\times}10^{-3}M)$ group showed similar tensions(DT and RT) and contraction rates. And both group showed significantly(p<0.05p<0.01) higher tensions and contraction rates than those of the control group. By the cumulative addition of the $K^+$(to 4.2, 5.6, 7.0 and 8.4 mM), only the DT of the $PGF_{2{\alpha}}$ group was sustained at signifcantly$(p<0.05{\sim}p<0.01)$ higher level than the DT of the control group. The $K^+$-addition inhibited the positive inotropic effect of ouabain significantly (p<0.05). The cumulative addition of lidocaine in high concentrations $(1{\times}10^{-5}\;to\;1{\times}10^{-3}M)$ evoked no significant influence on the intropic activities of $PGF_{2{\alpha}}$ and ouabain, but significant ${\beta}$-blockade with propranolol could not inhibit the positive intropic and chronotropic effect of $PGF_{2{\alpha}}$. In conclusion, it is presumed that $PGF_{2{\alpha}}$ may have some more active mechanism of accelerating the influx of $Ca^{++}$ across the cell membrane of the isolated rat atria as compared with ouabain, and the action site may be located at the cell membrane. As a supposition which needs further investigations, it is presumed that $PGF_{2{\alpha}}$ may have its specific membrane receptors on the atrial muscle or sinus node cells.

• Journal of Chest Surgery
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• v.38 no.10 s.255
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• pp.680-684
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• 2005

Background: With the increasing age of the population, coronary artery bypass grafting in the elderly patients is becoming common. Off-pump coronary artery bypass grafting (OPCAB) has been proven to be less morbidity and to facilitate early recovery. The elderly patients may have benefits by avoiding the adverse effects of the cardiopulmonary bypass. The purpose of this study is to evaluate our results of OPCAB in elderly patients. Material and Method: A retrospective chart review was carried out for 12 patients aged over 80 years who underwent isolated OPCAB from January 2001 and March 2004. Data were collected risk factors for disease, extent of coronary disease, and in-hospital outcomes. Postoperative graft patiency was evaluated in 9 patients by multi-slice computed tomography. Result: Eleven patients had triple vessel disease or left main disease. Four patients were suffered from preoperative CVA, and 4 patients had chronic obstructive pulmonary disease. Two patients had myocardial infarction (MI), among them 1 patient was suffered from pulmonary edema after preoperative MI. There was no perioperative death, perioperative MI, and no ventricular arrhythmia. Also there was no perioperative stroke and renal failure. But there was one deep sternal infection who recovered by treating of muscle flap. Atrial fibrillation was newly developed in 1 patient, but was well controlled by medication. Mean intubation time was $15.9\pm4.4(8\~20hrs)$ hrs and mean ICU stay was $2.9\pm0.8(2\~4 days)$ days. Mean hospital day was $21.6\pm14.3(13\~56 days)$ days. Postoperative mean CK-MS was $11.3\pm14.1\;ng/mL$. Early postoperative graft patency rate was $100\%(24/24)$. Follow-up was completed in all patients. In this time, there was no patients with angina or death. Conclusion: The results of this study suggest that OPCAB reduces morbidity and favors hospital outcomes. Therefore, OPCAB is safe, reasonable and might be preferable operative strategy in elderly patients.

• Journal of Chest Surgery
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• v.42 no.3
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• pp.292-298
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• 2009

Background: Surgery for mitral valve disease in children carries both technical and clinical difficulties that are due to both the wide spectrum of morphologic abnormalities and the high incidence of associated cardiac anomalies. The purpose of this study is to assess the outcome of mitral valve surgery for treating congenital mitral regurgitation in children. Material and Method: From 1997 to 2007, 22 children (mean age: 5.4 years) who had congenital mitral regurgitation underwent mitral valve repair. The median age of the patients was 5.4 years old and four patients (18%) were under 12 months of age. 15 patients (68%) had cardiac anomalies. There were 13 cases of ventricular septal defect, 1 case of atrial septal defect and 1 case of supravalvar aortic stenosis. The grade of the preoperative mitral valve regurgitation was II in 4 patients, III in 15 patients and IV in 3. The regurgitation was due to leaflet prolapse in 12 patients, annular dilatation in 4 patients and restrictive leaflet motion in 5 patients. The preoperative MV Z-value and the regurgitation grade were compared with those obtained at follow-up. Result: MV repair was possible in all the patients. 19 patients required reduction annuloplasty and 18 patients required valvuloplasty that included shortening of the chordae, papillary muscle splitting, artificial chordae insertion and cleft closure. There were no early or late deaths. The mitral valve regurgitation after surgery was improved in all patients (absent=10, grade I=5, II=5, III=2). MV repair resulted in reduction of the mitral valve Z-value ($2.2{\pm}2.1$ vs. $0.7{\pm}2.3$, respectively, p<0.01). During the mid-term follow-up period of 3.68 years, reoperation was done in three patients (one with repair and two with replacement) and three patients showed mild progression of their mitral reguration. Conclusion: our experience indicates that mitral valve repair in children with congenital mitral valve regurgitation is an effective and reliable surgical method with a low reoperation rate. A good postoperative outcome can be obtained by preoperatively recognizing the intrinsic mitral valve pathophysiology detected on echocardiography and with the well-designed, aggressive application of the various reconstruction techniques.

• Journal of Chest Surgery
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• v.31 no.8
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• pp.749-755
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• 1998

Background: Twelve patients with acyanotic tetralogy of Fallot(TOF), characterized by the combination of a malaligned ventricular septal defect(VSD) and infundibular pulmonic stenosis with the clinical finding of acyanosis at rest, underwent surgical correction between January 1988 and July 1997. Materials and methods: 9.92% of patients with the diagnosis of TOF were acyanotic TOF in the same period. Ages ranged from 12 to 42 months(mean 25.2 months). 2D-echocardiographic studies, cardiac catheterization, and angiocardiograms were performed in all patients before operation. The preoperative mean systemic arterial oxygen saturation was 93.5%. According to the 2D-echocardiographic analysis, there was Lt-to-Rt shunt through VSD in 4 patients, bidirectional shunt in 2 patients, and no shunt in 6 patients. Results: The preoperative mean right ventricle to pulmonary artery(RV-PA) pressure gradients were 52.3 mmHg on 2D- echocardiogram and 48.4 mmHg on cardiac catheterization. The repair of ventricular septal defect was performed through a right atrial approach and the hypertrophic infundibular muscle bundles were resected by the transatrial and transpulmonary approach. Six patients(50%) received a transannular patch. The mean cardiopulmonary bypass time was 135.0 minutes, and the aortic crossclamp time was 87.8 minutes. Postoperative complications included bleeding necessitating reentry in one and chylothorax in one. No patient died after operation and there were no late deaths. Postoperative 2D-echocardiograms revealed tiny patch dehiscence in 5 cases and a moderate RV-PA pressure gradients(mean 15.3 mmHg). All patients were in New York Heart Association functional class 1 after operation. Conclusions: acyanotic TOF is the uncommon form of TOF, and acyanotic TOF can be repaired with a good outcome.

• The Korean Journal of Pharmacology
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• v.13 no.2
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• pp.1-9
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• 1977

The effects of extracellular calcium concentrations and several concentration of Aconiti tuber butanol fraction, norepinephrine, ouabain on the force of isometric contraction of isolated atrial preparations obtained from rabbits were determined at $11{\sim}14$ different frequencies of contraction. Qualitatively similar results were obtained in all preparations. In most preparations, rested-state contraction was induced at the range of $120{\sim}400$ seconds stimulation interval. Over the range of intervals from 120 to 10 seconds negative inotropic effect of activation (NIEA) was predominant, so the steady-state contractile force progressively declined. At the intervals of 3 seconds, changes in the cumulated negative and positive isotropic effect of activation (PIEA) practically cancelled each other under steady-state conditions. At the interval from 3 seconds to 0.25 seconds, the additional cumulation of PIEA was greater than that of the NIEA. When the intervals between contractions were shorter than 0.25 seconds, the cumulation of the NIEA was again predominant. The positive inotropic effect of cardiac glycoside resulted at least in large part from increase in the rested-state contraction. No significant effect on the PIEA was found. The decay of the NIEA was apparently greatly accelerated in the presence of high concentration of ouabain, but this may also be a reflection of their action on the state determining the strength of the rested-state contraction. In the case of extracellular calcium concentration increment, the similar results with the ouabain treatment were obtained. Norepinephrine produced more powerful inotropic effect at shorter stimulation interval than long. The rested-state contraction and the decay of the NIEA were not significantly altered in the presence of norepinephrine, but cumulated PIEA and the amount of PIEA produced by each contraction were significantly increased. Aconiti tuber butanol fraction showed similar results with that of norepinephrine. The increment of contractile force at various contraction frequency were dose-responsive in the presence of Aconiti tuber butanol fraction. It is suggested that the positive inotropic effect of Aconiti tuber butanol fraction at various contraction frequency may be due to increase of the cumulation of PIEA and the amount of PIEA produced by each beat.

• Journal of Chest Surgery
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• v.32 no.6
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• pp.495-503
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• 1999

Background: We tested the technical feasibility of fetal cardiac bypass and collected baseline data on the fetal hemodynamics and placental functions related to the cardiopulmonary bypass in the fetal lamb model. Material and Method: Eleven fetuses at 120 to 150 days of gestation were subjected to bypass via trans-sternal approach with a 12 G pulmonary arterial cannula and 14 to 18 F venous cannula for 30 minutes. All ewes received general anesthesia with ketamine. In all the fetuses, no anesthetic agents were used except muscle relaxant. Eight served as a group in which placenta was excluded from the extracorporeal circulation by clamping the umbilical cord during the bypass(the oxygenator group) and in the remaining three, the placenta worked as the only source of oxygen supply(the placenta group). Observations were made every 10 minute during a 30-minute bypass and 30-minute post bypass period. No prostaglandin inhibitors were used both in ewes and in fetuses. Result: Weights of the fetuses ranged from 1.9 to 5.2 kg. In the oxygenator group, means of arterial pressure, PaO2, atrial pressure, heart rate, and bypass flow rate ranged 69.8 to 82.6 mmHg, 201.7 to 220.9 mmHg, 4.1 to 4.3 mmHg, 169 to 182/min, and 140.3 to 164.0 ml/kg/min, respectively during bypass, but rapid deterioration of the fetal cardiac functions and the placental gas exchange was observed after the cessation of bypass. In the placenta group, means of arterial pressure decreased from 44.7 to 14.4 mmHg and means of PaCO2 increased from 61.9 to 129.6 mmHg during bypass. Flow rate was suboptimal(74.3 to 97.0 ml/kg/min) during bypass. All hearts fibrillated immediately after the discontinuation of bypass. Conclusion: In this study, the technical feasibility of fetal cardiopulmonary bypass was confirmed in the fetal lamb model. However, further studies with modifications of the bypass including an addition of prostaglandin inhibitor, an application of the total spinal anesthesia on the fetus, a creation of more concise bypass circuit, and a use of active pump are mandatory to improve the outcome.