• Journal of Chest Surgery
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• v.21 no.2
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• pp.231-239
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• 1988

Currently numerous methods are in use for myocardial hypothermia as a myocardial preservation modality for cardiac operation. During cardiac ischemia after crystalloid cardioplegia[4C GIK solution], topical cold saline[Group I, a=9], topical ice slush[Group II, n=9] and topical ice chip[Group III, a=10] have been compared for myocardial surface cooling in the isolated rat heart model of cardiopulmonary bypass. During postischemic period, hemodynamic functions[aortic flow, coronary flow, peak aortic pressure and heart rate], biochemical enzymatic activities and cellular injuries with electron microscope were evaluated in this isolated rat heart perfusion model. Postischemic aortic flow, cardiac output and peak aortic pressure in Group I and Group II recovered better than Group III.[p< 0.05] Postischemic creatine kinase and lactate dehydrogenase leakages in Group II and Group III increased more than Group l and postischemic mitochondrial swelling in Group III was more severe than Group I, and Group II.[p< 0.05] These results suggest that topical cold saline was the better method than topical ice slush or topical ice chip as a myocardial preservation modality in the isolated rat heart model of cardiopulmonary bypass.

• Journal of Chest Surgery
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• v.33 no.8
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• pp.605-612
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• 2000

Background: Ischemic preconditioning enhances the tolerance of myocardium against ischemia/reperfusion injury, with the enhancement of the recovery of post-ischemic myocardial function. This study was disigned to assess whether the protective effect of ischemic preconditioning could provide one additional hour of myocardial preservation in four hour myocardial ischemia in a rate heart. Material and method: Fourty four Spargue-Dawley rats, weighing 300~450gm, were divided into four groups. Group 1(n=7) and group 3(n=12) were subjected to 30 minutes of aerobic Langendorff perfusion without ischemic preconditioning and then preserved in saline solution at 2~4$^{\circ}C$ for 4 hours and 5 respectively. Group 2(n=7) and group 4(n=18) were perfused in the same way for 20 minutes, followed by 3 minutes of global mormothermic ischemia and 10 minutes of perfusion and then preserved in the same cold saline solution for 4 hours and 5 hours respectively. Heart rate, left ventricular developed pressure(LVDP), and coronary flow were measured at 15 minutes during perfusion as baseline. Spontaneous defibrillation time was measured after reperfusion. Heart rate, LVDP, and coronary flow were also recorded at 15 minutes, 30 minutes, and 45 minutes during reperfusion. Samples of the apical left ventricular wall were studied using a transmission electron microscope. Result: Time of spontaneous defibrillation(TSD) was significantly longer in group 4 than in group 1(p<0.001), and TSD in group 1 was significantly longer in comparision to that of group 2(p<0.05). Heart rate at 45 minutes was significantly higher in group 1 than in group 4(p<0.05). Heart rate at 15 min was significantly higher in group 2 than in group 1(p<0.001) and in group 4 than in group 3(p<0.05). Left ventricular developed pressure(LVDP) at 30 minutes and 45 minutes was higher in group 1 than in group 4(p<0.01), LVDP at 45 minutes was higher in group 4 than in group 3(p<0.05). Rate-pressure product(RPP) at 30 minutes and 45 minutes was higher in group 1 than in group 4(p<0.05). RPP at 15 minutes was higher in group 2 than in group 1(p<0.01). RPP at 30 minutes and 45 minutes was higher in group 4 than in group 3(p<0.05). Group 2 showed relatively less sarcoplasmic edema and less nuclear chromatin clearance than group 1. Group 4 showed less myocardial cell damage than group 3, group 4 showed less myocardial cell damage than group 3, group 4 showed more myocardial cell edema than group 1. Conclusion: Ischemic preconditioning enhanced the recovery of postischemic myocardial function after 4 hours and 5 hours preservation. However, it was not demonstrated that ischemic preconditioning could definitely provide one additional hour of myocardial preservation in four hour myocardial ischemia in a rat heart.

• Journal of Chest Surgery
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• v.26 no.2
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• pp.75-79
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• 1993

Myocardial protection against ischemic and reperfusion injuries is still in troublesome eventhough couples of the way of myocardial protection have been applied since 1970's. One of the possibility in myocardial protection is adding Fructose-l,6-diphosphate(FDP) in cardioplegic solution. It is assumed that FDP can promote ATP production under anaerobic condition as well as inhibiting the supressing effect of lactate on phosphofructokinase. We compared the myocardial protecting effects of FDP in crystalloid cardioplegic solution (St. Thomas formula, 10$^{\circ}C$, pH = 7.4) and reperfusate using isolated rat hearts in modified Langendorf apparatus by the parameters of preischemic and post reperfusing heart rate, time to first beat, occurance of arrhythmia, time to stabilization, and the rate of left ventricular pressure developing. Group A (n = 10), containing no FDP in cardioplegic and reperfusing solutions was control. Group B (n = 5), containing FDP in cardioplegic solution, showed statistically significant superiority of postischemic left ventricular pressure development than the control group. Group C (n = 5), containing FDP in reperfusate, showed statistically significant myocardial depressing effect than the controls. Other parameters were unremarkable. The cause is uncertain, but it is assumed that the negative feedback inhibition of FDP in energy metabolism or unknown blocking effect of FDP on certain transmembrane ionic currents is present. In conclusion, 1) FDP in cardioplegic solution has beneficial effect on postischemic left ventricular preservation. 2) FDP is strong acid when is hydrolyzed, so precise acid titration is neccessary. 3) FDP in reperfusate has negative left ventricular preservation, otherwise the mechanism is still uncertain.

• Journal of Chest Surgery
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• v.28 no.6
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• pp.549-556
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• 1995

We investigated the effects of aprotinin, a protease inhibitor, on isolated rat heart subjected to cardioplegia and global ischemia for 4 hours and then reperfused for 40 minutes. Before ischemia, hearts were perfused with either aprotinin 1x105KIU/L[Aprotinin group,n=8 or no aprotinin[control group,n=8 added to Krebs-Henseleite solution for 30 minutes. Hemodynamic and biochemical parameters such as heart rate, LVP, dP/dt, coronary flow and creatine kinase were measured before cardioplegia and after reperfusion 10,20,30,40 minutes. After completion of experiment, wet and dry heart weight were measured for tissue water and water content evaluation. On reperfusion, recovery of LVP of aprotinin group at each time point was significantly better than that of control group[p<0.05 , and of dP/dt at reperfusion 40 minutes[p=0.034 . No statistically significant differences in heart rate, coronary flow and CK were observed between the two groups, but aprotinin group seemed to have better recovery. No significant differences in tissue water and water content were observed between the two group.These results suggest that pretreatment of aprotinin is effective in myocardial preservation in prolonged hypothermic ischemia and reperfusion.

• Journal of Chest Surgery
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• v.30 no.1
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• pp.1-10
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• 1997

The successful cardiac transplantation depends partly on the donor heart preservation by a solution that will ensure recovery of myocardial function. The purpose of this study was to perform the evaluation of various preservation solutions and to accumulate the data on the requisites for ideal preservation solution. The experimental setup was the constant pressure Langendorffs perfusion system. Isolated rabbit hearts were perfused for 20minutes with unarm Krebs-Henseleit solution, stored for 4 hours in cold preservation solution after cardioplegia, and then were reperfused for 20minutes. The 4 experimental groups were prepared Hartmann's solution group (group 1, control), modified Euro-collins solution group(group II. MEC), modified University of Wisconsin group (group n, MUW), and CK solution(made by the author) group (group W, CK). The parameters for assessing the preservation ability were levels of enzymes in freezed myocardial tissues (lactate, creatine kinase-MB and adenosine deaminase), coronary flow. left ventricular developing pressure and dpldt. In conclusion, the ability of preservation for isolated rabbit heart was excellent in CK solution and modified University of Wisconsin solution, and poor in modified Euro-collins solution, compared with Hartmann solution. CK solution has low potassium concentrations(34.2mEq/L) and includes various substrates to be salutary on myocardial preservation. This fact may indicates the necessity of further refinements in selection or composition of electrolytes and substrates.

• Journal of Chest Surgery
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• v.25 no.2
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• pp.131-136
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• 1992

The effect of temperature of cardioplegic solution on myocardial preservation was studied using isolated rat heart perfusion technique. Twenty Sprague-Dawley rats, weighing 120~140gm, were pretreated with intraperitoneal injection of heparin sodium[300u/kg] and then the hearts were excised after cervical herniation 30 minutes later. The hearts were perfused in isolated working heart apparatus with oxygenated modified Tyrode solution at 37oC. After 10 minutes of non working heart perfusion, the hearts were subjected to arrest for 30 minutes by administration of 5cc cardioplegic solution at the temperature of 4oC [Group I ], 15oC [Group II], 25oC [Group III], 37oC[Group IV]. At the same time, the topical cooling of heart was performed using ice saline. After arrest, the hearts were reperfused by non working heart perfusion for 1 hour with modified Tyrode solution at 37oC. The CPK, GOT and LDH in reperfusate were measured at 5,20,40,60 minutes after start of reperfusion. With the values of those, we compared the effect of temperature of cardioplegic solution on myocardial preservation. The results were as follows; 1. The enzyme values in reperfusate were highest at 5 minute and after then declined. 2. At 5 minutes after reperfusion, the enzyme values in Group I were lower than those in other Groups. These results suggest that the cardioplegic solutions using for cardiac arrest and myocardial protection can be working better at 4oC than at any other temperature.

• Journal of Chest Surgery
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• v.23 no.6
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• pp.1090-1106
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• 1990

This study was undertaken to investigate whether adenosine administered during cardioplegic arrest could enhance myocardial protection and improve recovery of function after ischemia. Isolated Langendorff-perfused rat hearts were subjected to 40 minutes of normothermic [37oC] ischemia. Control hearts [n=10] received modified St. Thomas’ cardioplegic solution, and the remaining hearts received modified St. Thomas’ cardioplegic solution with either 20 \ulcornerM [n=10], 200 \ulcornerM [n=10] adenosine. After ischemia of 40 minutes and 30 minutes of reperfusion, left ventricular contractility was superior in all groups of adenosine-treated hearts compared with control hearts. Furthermore, there was a significant incremental increase in functional recovery with increasing dose of adenosine. Post-ischemic diastolic stiffness was significantly better in all adenosine groups compared with controls. No differences were noted in coronary flow or myocardial water content between adenosine-treated and control hearts. These data demonstrate that adenosine administered in these concentrations provides myocardial protection, preservation of myocardial ATP and creatine phosphokinase and improved post-ischemic functional hemodynamic recovery after normothermic ischemia, presumably metabolically by reducing depletion of adenosine triphosphate, inducing rapid cardiac arrest and enabling improved post-ischemic recovery.

• Journal of Chest Surgery
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• v.25 no.3
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• pp.211-219
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• 1992

Hypothermic cardioplegia is a well established method to optimize myocardial preservation during ischemic arrest, and it has been demonstrated that oxygenation of crystalloid cardioplegic solutions markedly enhances myocardial protection, The addition of a small amount of red blood cells to a crystalloid cardioplegic solutions improves capillary perfusion. Considering these results, we changed our cardioplegic solution from cold oxygenated crystalloid[Group 2] to cold oxygenated diluted blood[Group 1]. In this investigation, we examined the effects of two hypothermic potassium cardioplegic solutions on myocardial preservation in 50 patients[30 of Group 1 and 20 of Group 2] of child age group. Factors considered preoperatively included age, sex, body weight, preoperative diagnosis, and they showed no statistical differences, Intraoperative factors considered included duration of cardiopulmonary bypass, duration of aortic occlusion, operative mortality, which also revealed no statistically significant differences, We measured the serum levels of GOT[glutamate oxaloacetate transaminase] and CPK [creatine phosphokinase] during the first two days postoperatively, which, in both groups, showed significantly higher values until postoperative 1 day, and decreasing tendancy thereafter, however we failed to find any significant difference between two groups regarding the serum levels of those enzymes each day. Time for extubation and use of inotropics also revealed no significant differences. Defibrillation was needed less in Group 1 than in Group 2[p<0.05], and one case of supraventricular tachyarrhythmia occured in Group l. We conclude that cold oxygenated diluted blood cardioplegia provides no less preservation than does an oxygenated crystalloid cardioplegic solution in child age group.

• Journal of Chest Surgery
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• v.33 no.2
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• pp.117-124
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• 2000

Background: Nucleoside transport inhibitor(NTI) Keeps AMP, ADP, ATP levels high in myocytes by inhibiting adenosine cataboilsm so that it may preserve the myocardial contractability during ischemia In this study we investigated the effects of cyclic AMP phosphodiesterase inhibor(C-AMP PDSI) and S-P-nitrobenzyl-6 -thioniosine(NBT; a sort of NIT) on myocadial preservation and changes of constituent enzyme. Material and method: Twenty-six isolated rabbit hearts were perfused with Krebs-Henseleit buffer solution for 20 minutes arrested for 20 minutes and ten reperfused for 30 minutes. The following four groups were prepared and hemodynamic changes coronary effluent lactate dehydrogenase (LDH) a-hydroxybutylic accid(a-HBD) levels and myocardial LDH creatine kinase-MB (CK-MB) adenosine deaminase(ADA) a-HBD levels and myocardial LDH creatine kinase-MB (CK-MB) adenosine deaminase(ADA) a-HBD levels were analysed before and after cardiac arest ; Group I(control) ; the heart was only perfused with K-H ; Group II ; the heart was perfused with K-H including C-AMP PDSI(Amrinone 25mg/L); Group III ; the heart was perfused with K-H including NBT(4.19mg/L) ; Group IV ; the heart was perfused with K-H including C-AMP PDSI + NBT. Result : Left venticular developed pressure(LVDP) at 10 minutes of the equilibrium was significantly higher in group III(72.1$\pm$5.3 mmHg p<0.01) and group III(72$\pm$5.6 mmHg P<0.025) as compared with group I (40.8$\pm$4.7mmHg) and LVDP at 20 minutes of the reperfusion was significantly higher in group II(74$\pm$5.3mmHg p<0.01) and group III(72$\pm$5.6mmHg p<0.025) as compared with group I (44.2$\pm$4.6mmHg). Percentage recovery of LVDP at the reperfusion was the highest in group II(123.3%) Percentage recovery of coronary flow at the equilibrium reperfusion were higher in group II(310%, 270%) group III(230%, 290%) group IV(310%, 280%) as compared with group I (100%) respectively. Myocadial LDH level was significant lower in group IV(33495$\pm$1802 IU/gm p<0.04) as compared with group I(48767$\pm$1421 IU/gm) Myocadial CK-MB level was significant higher in group II(74820$\pm$1421 IU/gm) compared with group I (45450$\pm$1737 IU/gm) Myocadial ADA level was significant higher group IV(1215$\pm$8 IU/gm p<0.05) compared with group I(125$\pm$15 IU/gm) but there was no significant difference between group I and group II ,III, IV in changes of coronary effluent LDH, a-HBD levels. Conclusion: C-AMP PDSI solely appears to have a better effect on myocardial preservation after ischemia than NBT but with no synergistic effect and it could keep CK-MB leve high in myocardial tissues.

• 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.