• Journal of Chest Surgery
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• v.24 no.4
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• pp.331-337
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• 1991

Recent experimental work indicates latamoxef sodium used as a broadspectrum antibiotics generates oxygen-free radicals. The present study represents an attempt to investigate whether reperfusate containing Shiomarin[85% latamoxef sodium+15% mannitol] might decrease the post-ischemic recovery of cardiac function. In the investigation, twelve isolated rat hearts were subjected to 270 minutes of cold total global ischemia. After the cold total global ischemia, six hearts[KHB group] were reperfused with Krebs-Henseleit buffer solution and the other six hearts[LMS group] with Krebs-Henseleit buffer solution containing latamoxef sodium[200ug /L]. Postischemic recovery rate of heart rate, aortic systolic pressure, aortic flow, coronary flow and cardiac output at 20 minutes reperfusion was 100.66$\pm$10.38, 85.25$\pm$7.61, 78.95$\pm$6. 02, 78.85$\pm$8.86 and 79.11$\pm$6.54 percent respectively in the KHB group and 97.96$\pm$4.19, 87. 72$\pm$4.37, 81.74$\pm$6.80, 82.69$\pm$10.01 and 81.90$\pm$6.67 percent respectively in the LMS group. The hemodynamic data revealed no significant difference in the post-ischemic recovery rate of the two groups. This finding suggests that reperfusate containing Shiomarin[latamoxef sodium, 200ug /L] does not affect the cardiac functional recovery after cold total global ischemia.

• Journal of Chest Surgery
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• v.26 no.6
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• pp.427-440
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• 1993

The paucity of donor hearts for transplantation can be remedied by distant heart procurement. Prolonging donor heart preservation is essential for successful clinical cardiac transplantation. Thirty-two isolated rat hearts were perfused with Krebs-Henseleit buffer solution for 15 minutes, arrested and preserved at 4 oC for 4 hours, and then reperfused for 25 minutes. The following three groups were prepared and hemodynamic changes, creatine kinase-MB isoenzyme levels and ultrastructural changes of the myocardium were analysed before and after cardiac arrest. ; Group I : the heart was arrested with the cardioplegic solution [Plegisol, potassium : 16 mM, sodium : 120 mM] and then stored in a solution with ionic compositions of the extracellular fluid [Hartman, potassium : 4 mM, sodium : 130 mM] ; Group II : the heart was arrested with the cardioplegic solution and stored in a solution with ionic compositions of the intracellular fluid [Modified Euro-Collins, potassium : 108 mM, sodium : 10 mM] ; Group III : the heart was arrested with the cardioplegic solution containing adenosine 20 uM, and then stored in a solution with ionic compositions of the intracellular fluid [Modified University of Wisconsin solution, potassium : 119 mM, sodium: 23 mM]. Left ventricular developed pressure at 20 minutes of the reperfusion was significantly higher in group III [64.3 $\pm$ 3.12 mmHg, p<0.01] and group II [58.3 $\pm$ 1.55 mmHg, p<0.05] as compared with group I [51.4$\pm$ 2.78 mmHg]. The time to induce cardiac arrest after infusion of cardioplegic solution with adenosine 20 uM [5.3 $\pm$ 0.30 second, p<0.005] was significantly shorter than without adenosine [10.6$\pm$ 0.55 second]. Coronary flow at 20 minutes of the reperfusion was augmented significantly in group III [9.6$\pm$ 0.50 ml/min, p<0.05, p<0.05] as compared with group I [8.0 $\pm$ 0.41 ml/min] and group II [8.1$\pm$ 0.51 ml/min]. Percentage recovery of left ventricular developed pressure at 20 minutes of the reperfusion was significantly higher in group III [94.6$\pm$ 2.51 %, p<0.005] as compared with group II and in group II [83.1 $\pm$ 1.22 %, p<0.005] as compared with group I [69.9 $\pm$ 1.73 %], and also percentage recovery of coronary flow at 20 minutes of the reperfusion was significantly higher in group III [82.3 $\pm$ 3.86 %, p<0.05] as compared with group II [71.4 $\pm$ 3.46 %] but there was no significant difference between group I and group II. Measured level of creatine kinase-MB isoenzyme at 15 minutes of the reperfusion was significantly lower in group III [1.23 $\pm$ 0.16 ng/ml, p<0.025] and group II [1.42$\pm$ 0.10 ng/ml, p<0.05] as compared with group I [1.79 0.14 ng/ml]. In the semiquantitative evaluation of the ultrastructural changes of the myocardium, mitochondrial score was lower in group III [0.7 $\pm$ 0.21] than in group I [3.1$\pm$ 0.28] and group II [1.7 $\pm$ 0.19], and also the other structural score was lower in group III [2.7$\pm$ 0.99] than in group I [7.9 $\pm$ 0.89] and group II [5.0 $\pm$ 1.22]. In conclusion, the solution with ionic compositions of the intracellular fluid is appropriate for prolonged cardiac preservation, and it appears to be better preserving method for distant procurement when the donor heart is rapidly arrested with cardioplegic solution containing adenosine 20 uM, and then stored with Modified University of Wisconsin solution.

• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.53-61
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• 1995

The experiments were performed to determine whether the cardiac depressant action of lidocaine is directly associated with the utilization of endogenous substrates in isolated rat atria, by using citrate and bicarbonate-free medium known as potent inhibitors of phosphofructokinases (PFK) enzyme step. Citrate and bicarbonate-free medium produced negative inotropic action of isolated rat atria incubated in normal Krebs-Ringer bicarbonate glucose medium. Pyruvate and acetate increased the force of contraction of atria depressed by citrate or bicarbonate-free medium, whereas fructose was without effect indicating the inhibitory effect of citrate and bicarbonate-free medium at some point in the glycolytic pathway such as the PFK step in atria. In the absence of exogenous substrate, citrate and bicarbonate-free medium produced a marked depression of the force of substrate-depleted atria indicating that utilization of endogenous substrate above the PFK step, probably cardiac glycogen, is also impaired by citrate or bicarbonate-free medium. Lidocaine produced further depression of the contractile force of atria depressed by citrate. These results argue strongly for an additional mechanism of cardiac depression caused by lidocaine involving the sites below the PFK.

• Journal of Chest Surgery
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• v.21 no.5
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• pp.803-815
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• 1988

The present experiments were performed to confirm the hypothesis that xanthine oxidase[XOD], as a source and mechanism of oxygen radical production, plays an important role in the genesis of the reperfusion injury of ischemic myocardium. The experimental ischemic-reperfusion injury was induced in isolated, Langendorff preparations of rat hearts by 60 min. Of global ischemia with aortic clamping followed by 20 min. of reperfusion with oxygenated Krebs-Henseleit solution[pH 7.4, 37*C]. The results were as follows: 1. The releases of creatine phosphokinase and a lipid peroxidation product, malondialdehyde[MDA] into the coronary effluent were abruptly increased upon reperfusion of ischemic hearts. The increases of the enzyme and MDA were suppressed significantly in the hearts removed from rats pretreated with allopurinol, a specific XOD inhibitor[20mg/kg, oral, 24 hrs and 2 hrs before study]. This effect of allopurinol was comparable to that of oxygen radical scavengers, superoxide dismutase[5, 000U] and catalase[12, 500 U]. 2. The increased SOD-inhibitable reduction of ferricytochrome C, which was infused to the hearts starting with reperfusion, was significantly suppressed in allopurinol pretreated hearts. 3. Activities of myocardial XOD were compared in the normal control hearts and the ischemic ones. Total enzyme activities were not different in both hearts. However, comparing with the control, the ischemic ones showed higher activity in 0-form and lower activities in D-form and D/O-form. 4. In the ischemic hearts, phenylmethylsulfonyl fluoride, a serine protease inhibitor, prevented significantly the increase of 0-form and the decreases of D and D/O-form, while thiol reagents did not affect the changes of the enzyme. 5. The increase of 0-form and the decreases of D and D/0-form were not significant in both calcium-free perfused and pimozide, a calmodulin inhibitor, treated ischemic hearts. 6. The SOD-inhibitable reduction of ferricytochrome C were suppressed by PMSF and pimozide treatment as well as by calcium-free perfusion. It is suggested from these results that in the ischemic rat myocardium, xanthine oxidase is converted to oxygen radical producing 0-form by calcium, calmodulin-dependent proteolysis and plays a contributing role in the genesis of ischemic-reperfusion injury by producing oxygen free radicals.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.5
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• pp.507-512
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• 1999

Contribution of prostaglandins $D_2,\;E_2\;and\;I_2\;(PGD_2,\;PGE_2\;and\;PGI_2)$ on the regulation of ATP-sensitive $K^+$ channel $(K_{ATP}\;channel)$ was investigated in isolated single rat ventricular cardiac myocytes using the patch clamp technique. $PGD_2,\;PGE_2\;and\; PGI_2$ did not affect $K_{ATP}$ channel activity in the inside-out patch, but increased channel activity in a dose-dependent manner when the channel activities were attenuated by the administration of 100 ${\mu}M$ ATP to the internal solution in the inside-out patch. Channel activations by the prostaglandins were abolished by 50 ${\mu}M$ glibenclamide, a $K_{ATP}$ channel blocker. Dose-response curves of relative channel activity against the ATP concentrations of internal solution in the inside-out patch were shifted to the right in the presence of those three prostaglandins. The rank order of the channel stimulatory potencies $(as\;IC_{50}\;for\;ATP)$ calculated from the dose-response curves were $PGI_2\;>\;PGD_2\;>\;PGE_2.$ Conductance of the channel was not changed by those three prostaglandins. In conclusion, we suggest that prostaglandins $D_2,\;E_2\;and\;I_2$ are involved in the regulation of $K_{ATP}$ channel activity in certain circumstances, and that those three prostaglandins may cause myocardial relaxation by opening $K_{ATP}$ channels, thus protecting the heart from ischema.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.6
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• pp.469-478
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• 2022

WNT signaling plays an important role in cardiac development, but abnormal activity is often associated with cardiac hypertrophy, myocardial infarction, remodeling, and heart failure. The effect of WNT signaling on regulation of atrial natriuretic peptide (ANP) secretion is unclear. Therefore, the purpose of this study was to investigate the effect of Wnt agonist 1 (Wnta1) on ANP secretion and mechanical dynamics in beating rat atria. Wnta1 treatment significantly increased atrial ANP secretion and pulse pressure; these effects were blocked by U73122, an antagonist of phospholipase C. U73122 also abolished the effects of Wnta1-mediated upregulation of protein kinase C (PKC) β and γ expression, and the PKC antagonist Go 6983 eliminated Wnta1-induced secretion of ANP. In addition, Wnta1 upregulated levels of phospho-transforming growth factor-β activated kinase 1 (p-TAK1), TAK1 banding 1 (TAB1) and phospho-activating transcription factor 2 (p-ATF2); these effects were blocked by both U73122 and Go 6983. Wnta1-induced ATF2 was abrogated by inhibition of TAK1. Furthermore, Wnta1 upregulated the expression of T cell factor (TCF) 3, TCF4, and lymphoid enhancer factor 1 (LEF1), and these effects were blocked by U73122 and Go 6983. Tak1 inhibition abolished the Wnta1-induced expression of TCF3, TCF4, and LEF1 and Wnta1-mediated ANP secretion and changes in mechanical dynamics. These results suggest that Wnta1 increased the secretion of ANP and mechanical dynamics in beating rat atria by activation of PKC-TAK1-ATF2-TCF3/LEF1 and TCF4/LEF1 signaling mainly via the WNT/Ca²⁺ pathway. It is also suggested that WNT-ANP signaling is implicated in cardiac physiology and pathophysiology.

• Toxicological Research
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• v.4 no.1
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• pp.23-35
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• 1988

The role of calcium in the production of oxygen radical which causes reperfusion damage of ischemic heart has been examined. The reperfusion damage was indrced in isolated Langendorff perfused rat hearts by aortic clamping for 60 min followed by reperfusion with oxygenated Krebs-Henseleit solution with or without 1.25 mM $CaCl_2.$ On reperfusion of the ischemic hearts with the calcium containing solution, the release of cytosolic enzymes (LDH and CPK) increased abruptly. These increased release of enzymes were significantly inhibited by additions of oxygen radical scavengers (SOD, 5,000 U; catalase, 12,500 U) into the reperfusion solution. In the hearts isolated from rats pretreated with allopurinol(20 mg/kg orally, 24 hr and 2 hr prior to the experiments), the levels of enzymes being released during reperfusion were significantly lower than that of the control. However, in the hearts perfused with the calcium-free but oxygenated solution, the increase in the release of cytosolic enzymes during reperfusion was neither inhibited by oxygen radical scavengers nor by allopurinol pretreatment. For providing the evidence of oxygen radical generation during the reperfusion of ischemic hearts in situ, the SOD-inhibitable reduction of exogenously administered ferricytochrome C was measured. In the hearts perfused with the calcium containing solution, the SOD-inhibitable ferricytochrome C reduction increased within the first minute of reperfusion, and was almost completely inhibited by allopurinol pretreatment. When the heart was perfused with the calcium free solution, however, the reduction of ferricytochrome C was not only less than that in the calcium containing condition, but also was not so completely inhibited by allopurinol pretreatment. By ischemia, xanthine oxidase (XOD) in the ventricular tissue was changed qualitatively, but not quantitatively. In the heart made ischemic with the calcium containing condition, the oxygen radical producing O-form of XOD increased, while the D- and D/O-form decreased. However, in the ischemic heart reperfused with the calcium free condition, the D/O-form of XOD was elevated without significant increase in O-form of the enzyme. It is suggested from these results that the calclum may play a contributing role in the genesis of reperfusion damage by promoting the conversion of xanthine oxidase from the D/O-form to the oxygen radical producing O-form in the ischemic myocardium.

• Journal of Chest Surgery
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• v.21 no.6
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• pp.970-978
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• 1988

There is tendency of increasing number and decreasing age of patients who are indicated for Rastelli operation for their cyanotic congenital heart disease. So there is the need to find the criterion which saves the patients from early postoperative hemodynamic disturbances. We reviewed the 26 patients who had been performed Rastelli operation at Seoul national University Hospital from January 1981 to June 1988. mean age of the patients was 7.8*3.4 years[range 2.5-15years], mean body surface area[BSA] 0.79*0.25m2[range 0.49-1.51m2] and mean hematocrit 57.95*12%[range 48-80%]. We divided these patients into survived group and died group before postoperative 72 hours, and analyzed preoperative arterial oxygen saturation[SaO2], the ratio of diameter of right pulmonary artery to ascending aorta[RPA/AA], the ratio of both right and left pulmonary artery diameter to descending thoracic aorta[RPA+LPA/DTA], pulmonary artery index[PA index], cardiopulmonary bypass time, aorta cross-clamping time, postoperative perfusion state and total amount of dopamine infused postoperatively. The results showed that RPA+LPA/DTA and PA index were statistically significant factors to influence early postoperative cardiac death rate[P< 0.05]. Especially there were good linear correlations between PA index[X] and peripheral perfusion index[Y][Y= - 1.15+0.02 X, r=0.86, P<0.01]and between PA index[X] and total amount of dopamine infused before postoperative 72 hours[mg/kg, Y][Y=61.94 - 0.15 X, r=-0.80, P < 0.01]. Also there were tendencies that the higher RPA+LPA/DTA[Y], the better peripheral perfusion [X] and the lower need of dopamine[X], but no statistical significance.[Y=0.78+1.60 X, r =0. 49, P >0.05] And the discriminate analysis showed that patients with PA index over 221 mm2/BSA could undergo correction with 25 per cent of error rate. In conclusion, early postoperative hemodynamic states could be predicted by preoperatively measured PA index, and which can be used as a criterion for Rastelli operation performed on cyanotic congenital heart disease.

• YAKHAK HOEJI
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• v.33 no.3
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• pp.167-174
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• 1989

KR-1008 and KR-30006 are 1,4-dihydropyridine derivatives, new vasodilatory calcium antagonists from KRICT. Calcium antagonistic properties of the compounds were studied in the isolated heart (Langendorff preparation), pulmonary artery (vasodilation), and in the papillary muscle (negative inotropic effect) of the guinea pig. Antihypertensive effect were also investigated after i.v. or oral administration in the SHR (spontaneously hypertensive rat). They produced a sigificant inhibition of Ca-induced contraction in the guinea pig pulmonary artery at the concentrations of above $10^{-8}M$. The negative inotropic effect of the electrically stimulated papillary muscle appeared from the concentration of $10^{-6}M$, which is about hundred times higer than the concentration of vasodilation effect. Left ventricular pressure also decreased from the concentration of $3\;{\times}\;10^{-6}M$ in KR-1008 and KR-3006 in the Langendorff heart preparations. Coronary flow rate increased from $10^{-6}M$ in KR-1008 and nicardipine and appeared no change in KR-30006. The antihypertensive effect of KR-1008 (EC 20: $2.9\;{\mu}g/kg$) was potent more than nicardipine (EC 20: $3.4\;{\mu}g/kg$) and than Kr-30006 (EC 20: $6.8\;{\mu}g/kg$) was, after i.v. bolus injection in the anesthetized SHR. The antihypertensive effect in the conscious SHR appeared 30 minutes after oral administration of 10 mg/kg and persisted 4 hrs in KR-1008 and 12 hrs in KR-30006. Heart rate tended to increase for 0.5-1 hr after oral administration of the test compounds.

• Journal of Chest Surgery
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• v.37 no.2
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• pp.119-130
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• 2004

Decrease in cardiac function after open heart surgery is due to an ischemia induced myocardial damage during surgery, and ischemic preconditioning, a condition in which the myocardial damage does not accumulate after repeated episodes of ischemia but protects itself from damage after prolonged ischemia due to myocytes tolerating the ischemia, is known to diminish myocardial damage, which also helps the recovery of myocardium after reperfusion, and decreases incidences of arrythmia. Our study is performed to display the ischemic preconditioning and show the myocardial protective effect by applying cardioplegic solution to the heart removed from rat. Material and Method: Sprague-Dawley male rats were used, They were fixed on a modified isolated working heart model after cannulation. The reperfusion process was according to non-working and working heart methods and the working method was executed for 20 minutes in which the heart rate, aortic pressure, aortic flow and coronary flow were measured and recorded. The control group is the group which the extracted heart was fixed on the isolated working heart model, recovered by reperfusion 60 minutes after infusion and preserved in the cardioplegic solution 20 minutes after the working heart perfusion and aortic cross clamp, The thesis groups were divided into group I, which ischemic hearts that were hypoxia induced were perfused by cardioplegic solution and preserved for 60 minutes; group II, the cardioplegic solution was infused 45 seconds (II-1), 1 minutes (II-2), 3 minutes (II-3), after the ischemia induction, 20 minutes after working heart perfusion and aortic cross clamp; and group III, hearts were executed on working heart perfusion for 20 minutes and aortic cross clamp was performed for 45 seconds (III-1), 1minute (III-2), 3 minutes (III-3), reperfused for 2 minutes to recover the heart, and then aortic cross clamping was repeated for reperfusion, all the groups were compared based on hemodynamic performance after reperfusion of the heart after preservation for 60 minutes. Result: The recovery time until spontaneous heart beat was longer in groups I, II-3, III-2 and III-3 to control group (p<0.01). Group III-1 (p<0.05) had better results in terms of recovery in number of heart rates compared to control group, and recovered better compared to II-1 (p<0.05). The recovery of aortic blood pressure favored group III-1 (p<0.05) and had better outcomes compared with II-1 (p<0.01). Group III-1 also showed best results in terms of cardiac output (p<0.05) and group III-2 was better compared to II-2 (p<0.05). Group I (p<0.01) and II-3 (p<0.05) showed more cardiac edema than control group. Conclusion: When the effects of other organs are dismissed, protecting the heart by infusion of cardioplegic solution after enforcing ischemia for a short period of time before the onset of abnormal heart beats for preconditioning has a better recovery effect in the cardioplegic group with preconditioning compared to the cardioplegic solution itself. we believe that further study is needed to find a more effective method of preconditioning.