• Journal of Chest Surgery
• /
• v.32 no.9
• /
• pp.773-780
• /
• 1999

Background: It has been demonstrated that brief periods of calcium depletion and repletion (calcium-free preconditioning, CP) have cardioprotective effects as seen in ischemic preconditioning(IP) which enhances the recovery of post-ischemic contractile dysfunction and reduces the incidence of reperfusion-induced arrhythmia or infarct size after a prolonged ischemia. In the present study, we tested this paradoxical phenomenon in isolated rabbit hearts. Material and Method: Hearts isolated from New Zealand white rabbits(1.5∼2.0 Kg body weight) were perfused with Tyrode solution using the Langendorff technique. After stabilizing the baseline hemodynamics, the hearts were subjected to 45 minutes of global ischemia followed by 120 minutes of reperfusion with IP(IP group, n=7) or without IP (ischemic control group, n=7). IP was induced by a single episode of 5 minutes global ischemia and 10 minutes reperfusion. In the CP group(n=7), the hearts were subjected to perfusion with Tyrode solution with calcium depletion for 5 minutes and repletion for 10 minutes, and 45 minutes of ischemia and 120 minutes of reperfusion. Left ventricular function including developed pressure, dP/dt, heart rate, left ventricular end-diastolic pressure and coronary flow was measured. Infarct size was determined by staining with 1% triphenyltetrazolium chloride and planimetry. Data were analyzed by a one-way analysis of variance and Tukey's post-hoc test. Result: In comparison with the ischemic control group, IP significantly enhanced the recovery of the left ventricular function including the left ventricular developed pressure, contractility, and coronary flow; in contrast, these functional parameters of the CP group tended to be lower than those of the ischemic control group. However, the infarct size was significantly reduced by IP or CP(p<0.05). Conclusion: These results suggest that in isolated Langendorff-perfused rabbit heart model, CP(induced by single episode of 5 minutes calcium depletion and 10 minutes repletion) could not improve the post-ischemic contractile dysfunction(after a 45-minute global ischemia) but it has an infarct size-limiting effect.

• Journal of Chest Surgery
• /
• v.13 no.4
• /
• pp.321-337
• /
• 1980

The increasing use of cardioplegic solution for the reduction of ischemic tissue injury requires that all cardiplegic solution be carefully assessed for any protective or damaging properties. This study describes functional, enzymatic and structural assessment of the efficiency of three cardioplegic solutions (Young & GIK, Bretschneider, and $K^{+}$ Albumin solution) in a Modified Isolated Rat Heart Model of cardiopulmonary bypass and ischemic arrest. Isolated rat heart were subjected to a 2-minute period of coronary infusion with a cold cardioplegic or a noncardioplegic solution immediately before and also at the midpoint of a 60-minute period of hypothermic ($10{\pm}1$. C) ischemic cardiac arrest. The results of this study were as follow: 1. Spontaneous heart beat after ischemic arrest occured 16 seconds later after Langendorff reperfusion in the Young & GIK group (n=6), and 40 second later in the Bretschneider group (n=6) and 6 minute later in the $K^{+}$ Albumin group (n=6), and 16 minute later in the control group (non-cardioplegia). A good recovery state of spontaneous heart beat was shown in the Young & GIK and Bretschneider groups. 2. The percentage of recorveries of heart function at 30 minute after postischemic working heart perfusion were : heart rate $91.6{\pm}3.1$% (P<0.01)m oeaj airtuc oressyre $83{\pm}3$% (P<0.01), coronary flow $70{\pm}8$% (P<0.05) and aortic flow flow rate $39{\pm}9.3$% (P<0.05) in the Young & GIK group. This percentage of recoveries of the Young & GIK group was significantly greater than the control group. In the Bretschneider group, the percentage of recoveries were : heart rate $87.8{\pm}7.5$%(P<0.05), peak aortic pressure $71{\pm}2.3$% (P<0.05) and aortic flow rate $33.2{\pm}6.6$%(P<0.05). hte percentage of recoveries were significantly greater than in the control group. In the $K^{+}$ Albumin group, recoveries of heart function were poor. 3. Total CPK leakage was $131.2{\pm}12.75$IU/30 min/gm. dry weight in the control group, $50.65{\pm}12.75$IU in the Young & GIK gruop, $69.40{\pm}32.21$Iu in Bretschneider group, and $103.65{\pm}15.47$IU in the $K^{+}$ Albumin group during the 30 minute postischemic Langendorff reperfusion. Total CPK leakage was significantly less (P<0.001) in the Young & GIK group, than in the control group. 4. Direct correlatin between percentage recovery of aortic flow rate and total amount of CPK leakage from Myocardium was noticed.(Correlation Coefficient r = 0.76, P<0.001). 5. Mild perivascular edema was the only finding of light microscopic study of myocardium after 60 minute ischemic arrest with cold cardioplegic solutions and hypothermla.

• The Korean Journal of Pharmacology
• /
• v.28 no.2
• /
• pp.163-170
• /
• 1992

The present study was attempted to investigate the effect of cyclobuxine (a steroidal alkaloid) on generation of reactive oxygen metablite and myocardial damage promoted by an exogenous administeration of arachidonate in ischemic-reperfused hearts. Langendorff preparation of the isolated rat heart was made ischemic condition by reducing the flow rate to 0.5 ml/min for 45 min, and then followed by normal reperfusion (7 ml/min) for 5 min. The generation of superoxide anion was estimated by measuring the SOD-inhibitable ferricytochrome C reduction. The degree of lipid peroxidation in myocardial tissue was estimated from the tissue malondialdehyde (MDA) concentration using thiobarbituric acid method. The myocardial cell damage was observed by measuring LDH released into the coronary effluent. Sodium arachidonate $(0.1\;and\;1.0\;{\mu}g/ml)$ infused during the period of oxygenated reperfusion stimulated superoxide anion production dose-dependently. The rate of arachidonate-induced superoxide anion generation was markedly inhibited by cyclobuxine $(1.0\;and\;10\;{\mu}g/ml)$. The production of malondialdehyde was increased by infusion of arachidonate. This increase was prevented by superoxide dismutase (300 U/ml) and cyclobuxine $(1.0\;and\;10\;{\mu}g/ml)$. The release of LDH was increased by sodium arachidonate was also inhibited by superoxide dismutase and cyclobuxine. In conclusion, the present results suggest that cyclobuxine inhibits the production of reactive oxygen metabolite and myocardial damages which were promoted by an administeration of arachidonate during reperfusion of ischemic hearts.

• Journal of Chest Surgery
• /
• v.35 no.5
• /
• pp.336-342
• /
• 2002

Background: Recently, cell transplantation has been extensively investigated to improve heart function in dysfunctional heart. This study was designed to compare the effects of smooth muscle cells (SMC) and heart cells (HC) transplantation in dilated cardiomyopathic hamsters. Material and Method: HC and SMC were isolated from heart and ductus deferens of BIO 53.58 hamsters, and cultured for transplantation. HC and SMC or culture medium were transplanted into the left ventricle of 17 weeks old adult hamsters in HC transplanted (HCTx), SMC transplantation (SMCTX), and control groups (Con) (N = 10 each). Cyclosporine (5 mg/Kg) was administered subcutaneously for HCTx. Sham operated hamsters (N=10) underwent the surgery but did not receive an injection. At 4 weeks after transplantation, heart function was evaluated in all groups using a Langendorff perfusion apparatus. Result: Histology showed severe focal myocardial necrosis in all groups. HCTx and SMCTx formed huge muscle tissue in dilated myocardium. SMCTx and HCTx had better heart function than Con and sham (p<0.01). And SMCTx had better peak systolic pressure (p<0.05) antral developed pressure (p<0.05) than HCTx. But sham and Con did not any statistical make difference. Conclusion: SMCTx and HCTx formed muscle tissue and improved ventricular function in hamsters with dilated cardiomyopathy And SMCTx showed better heart function in peak systolic pressure and developed pressure than HCTx.

• The Korean Journal of Pharmacology
• /
• v.32 no.1
• /
• pp.31-37
• /
• 1996

The protective effect of 'ischemic preconditioning (IP)'on ischemia-reperfusion injury of heart has been reported in various animal species, but the mechanism is unclear. In an attempt to elucidate the mechanism of IP, we examined the effects of blockers against adenosine and protein kinase C in preconditioned heart of rat. The hearts perfused with oxygen-saturated Krebs-Henseleit solution by Langendorff method were exposed to 30 min global ischemia followed by 20 min reperfusion. IP was performed with three episodes of 5 min ischcmia and 5 min reperfusion just before ischemia-reperfusion. IP prevented the depression of contractile function and the myocardial contracture in the ischemic-reperfused heart and reduced the release of lactate dehydrogenase during the reperfusion period. Polymyxin B, chelerythrine and colchicine, PKC inhibitors, attenuated almost completely the anti-ischemic effect of IP, while adenosine receptor antagonists did not. These results indicate that PKC may be a crucial intracellular mediator in anti-ischemic action of IP in ischemic-reperfused rat heart, while adenosine may not be involved in the mechanism of IP.

• The Journal of Internal Korean Medicine
• /
• v.18 no.2
• /
• pp.220-228
• /
• 1997

Background The stenosis of the coronary artery may decrease myocardial oxygen supply and occur myocardial ischemia or infarction. Soojeomsan, one of analgesics is generally regarded to have the effect of vitalizing blood, expelling blood stasis and alleviation cardiac pain. Methods The purpose of this experimental study is to find the influence of Soojeomsan on cardiac enzyme (CPK, Na-K ATPase) of ischemic and reperfused rat hearts which are isolated under the Langendorff apparatus. Ischemia was induced In isolated hearts of Sprague-Dawley rats by ceasing the perfusion for 20 minutes. The experiments were divided into a normal saline orally administered group(control group), a Soojeomsan orally 20ml administered group(sample A) and a Soojeomsan orally 30ml administered group(sample B). The CPK (creatinine phosphokinase) and Na-K ATPase activity of this three group were measured and compared in order to assess the influence of Soojeomsan on protection of isolated rat hearts from ischemia. Results 1. CPK was significantly reduced in Sample A group and Sample B group in comparison with control group in reperfusion(P<0.01), and there were no significant difference between Sample A and B. 2. Na-K ATPase activity was significantly increased in Sample A group and Sample B group in comparison with control group in ischemia(P<0.001), and the activity was significantly higher in Sample B then in Sample A.(P<0.01) 3. There were no significant difference in Na-K ATPase activity of the three groups after reperfusion. Conclusion Soojeomsan has effects to decrease CPK activity and activate Na pump. This result in protection of the myocardium of isolated rat hearts from ischemia.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.16 no.1
• /
• pp.160-164
• /
• 2002

The water extract of Sophorae radix was tested for its preventive effects against cardiovascular anaphylaxis elicited in experimental animals. H₂O and ethyl acetate fractionation of Sophorae radix water extract improved anaphylactic cardiac dysfunction in passively sensitized isolated guinea hearts: improvement was noted in the maximal contractile force, post-challenge contractile force, post-challenge coronary flow and creatine kinase change elevation. These results suggest that H₂O and ethyl acute fractionation of Sophorae radix water extract possesses anti-anaphylactic effect in cardiovascular system.

• Biomolecules & Therapeutics
• /
• v.7 no.4
• /
• pp.354-361
• /
• 1999

In this study, the effects of tauroursodeoxycholic acid (TUDCA) on ischemia/ reperfusion injury were investigated on isolated heart perfusion models. Hezrts were perfused with oxygenated Krebs-henseleit solution (pH 7.4, $37^{\cire}C$) on a Langendorff apparatus. After equilibration, isolated hearts were treated with TUDCA 100 and 200 $\mu\textrm{M}$ or vehicle (0.02% DMSO) for 10 min before the onset of ischemia in single treatment group. In 7 day pretreatment group. TUDCA 50, 100 and 200 mg/kg body weight were given orally for 7 days before operation. After global ischemia (30 min), ischemic hearts were reperfused for 30 min. The physiological (i.e. heart rate, left ventricdular developed pressure, coronary flow, double product, time to contracture formation) and biochemical (lactate dehydrogenase; LDH) parameters were evaluated. In vehicle-treated group, time to contracture formation was 810 sec during ischemia, LVDP was 34.0 mmHg at the endpoint of reperfusion and LDH activity in total reperfusion effluent was 34.3 U/L. Single treatment with TUDCA did not change the postischemic recovery of cardiac function, LDH and time to contractur compared with ischemic control group. TUDCA pretreatment showed the tendency to decrease LDH release and to increase time to contracture and coronary flow. Our findings suggest that TUDCA does not ameliorate ischemia/reperfusion-reduced myocardial damage.

• Applied Microscopy
• /
• v.20 no.1
• /
• pp.65-76
• /
• 1990

The effect of calcium-free reperfusion for 5, 10, and 15 minutes, respectively, followed by continuous reperfusion with normal Tyrode solution containing 1.0mM calcium chloride, after global ischemia in the isolated perfused guinea pig heart by Langendorff techniques was examined with transmission electron microscope. Compared to the nomal Tyrode solution-perfused control hearts, the 5 minute calcium-free-reperfused hearts showed loss or thickening of Z lines, focal sarcolemmal disruption, mitochondrial swelling, clumping of chroma-tin, intracellular fluid accumulation, and some separation of cell junctions, especially the fasciae adherentes. These changes became more severe in the hearts of 10 minute calcium-free reperfusion. Subsarcolemmal larger bleb and near complete separation of cell junctions were noticed. In the 15 minute calcium-free-reperfused hearts, irreversible ultrastructural changes including contraction bands, biazrre mitochondria, and sarcolemmal destruction were widely distributed. The severity of myocardial changes were in accordance with the duration of calcium-free reperfusion. These changes indicate that calcium-free reperfusion regardless of its duration could not salvage the post-ischemic myocardium probably due to development of calcium paradox.

• Journal of Chest Surgery
• /
• v.23 no.6
• /
• pp.1074-1083
• /
• 1990

This study was evaluated the metabolic, physiologic and histologic effects of myocardial protection of verapamil[isoveratril]on isolated rat hearts to 90 minutes of ischemic arrest. Heart was perfused with a modified Kreb’s Henseleit bicarbonate buffer with glucose and arrested with retrograde coronary perfusion by glucose insulin[GI], potassium and verapamil. Mean aortic systolic pressure, heart rate, coronary flows were measured and morphologic changes were examined during working heart perfusion. Perfusion and arrest were controlled four groups subjected 60 isolated rat hearts. Four groups hearts reperfused during 40 minutes after 90 minutes global ischemia for physiologic recovery. 15 hearts of four groups were assayed to histological morphologic changes. GI treated hearts recovered less than 28% of function and changed more than 80% of mitochondria of control group. Verapamil hearts[0.2, 0.1 gm/kg] recovered more than 88% of function and permitted the maintenance of continuous cellular level of Serum Glutamic Oxalaxetate Transaminase[SGOT], but declined 28% of Phosphate Kinase[CP], GI treated heart showed widespread evidence of extensive damage of mitochondria. The damage was that interstitial huge edema are present and there was contraction band formation within the swollen cells. The verapamil and potassium group were not found morphologic change compared with control group. Their functions were shown that metabolic and physiologic action of verapamil-group lasted 20 minutes longer than potassium group.