• The Korean Journal of Physiology and Pharmacology
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• v.4 no.6
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• pp.515-523
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• 2000

Polymorphonuclear leukocytes (PMNs) play an important role in myocardial ischemia/reperfusion (MI/R) injury. Moreover, platelets are also important blood cells that can aggravate myocardial ischemic injury. This study was designed to test the effects of PMNs and platelets separately and together in provoking cardiac dysfunction in isolated perfused rat hearts following ischemia and reperfusion. Additional control rat hearts were perfused with $75{\times}10^6$ PMNs, with $75{\times}10^6$ platelets, or with $75{\times}10^6\;PMNs+75{\times}10^6$ platelets over a five minute perfusion followed by a 75 min observation period. No significant reduction in coronary flow (CF), left ventricular developed pressure (LVDP), or the first derivative of LVDP (dP/dt max) was observed at the end of the observation period in any non-ischemic group. Similarly, global ischemia (I) for 20 min followed by 45 minutes of reperfusion (R) produced no sustained effects on the final recovery of any of these parameters in any group of hearts perfused in the absence of blood cells. However, I/R hearts perfused with either PMNs or platelets alone exhibited decreases in these variables of $5{\sim}10%$ (p＜0.05 from control). Furthermore, I/R hearts perfused with both PMNs and platelets exhibited decreases of 50 to 60% in all measurements of cardiac function (p＜0.01). These dual cell perfused I/R hearts also exhibited marked increases in cardiac myeloperoxidase (MPO) activity indicating a significant PMN infiltration, and enhanced P-selectin expression on the coronary microvascular endothelium. All cardiaodynamic effects as well as PMN accumulation and P-selectin expression were markedly attenuated by a recombinant soluble PSGL-1 which inhibits selectin mediated cell adhesion. These results provide evidence that platelets and PMNs act synergistically in provoking post-reperfusion cardiac dysfunction, and that this may be largely due to cell to cell interactions mediated by P-selectin. These results also demonstrate that a recombinant soluble PSGL-1 reduces myocardial reperfusion injury by platelet and PMNs interaction.

• 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 Korean Neurosurgical Society
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• v.59 no.2
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• pp.154-157
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• 2016

A continuous electroencephalography (cEEG) can be helpful in detecting vasospasm and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage (SAH). We describe a patient with an aneurysmal SAH whose symptomatic vasospasm was detected promptly by using a real-time cEEG. Patient was immediately treated by intraarterial vasodilator therapy. A 50-year-old woman without any significant medical history presented with a severe bifrontal headache due to acute SAH with a ruptured aneurysm on the anterior communicating artery (Fisher grade 3). On bleed day 6, she developed a sudden onset of global aphasia and left hemiparesis preceded by cEEG changes consistent with vasospasm. A stat chemical dilator therapy was performed and she recovered without significant neurological deficits. A real-time and protocol-based cEEG can be utilized in order to avoid any delay in detection of vasospasm in aneurysmal SAH and thereby improve clinical outcomes.

• Korean Journal of Clinical Pharmacy
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• v.7 no.1
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• pp.33-39
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• 1997

Cardiac and antihypertensive effects of BMS-180448, a cardiac-selective ATP-sensitive potassium channel opener, and its newly synthesized derivatives KR-31281, KR-31282 and KR-31299 were evaluated in isolated perfused rat hearts (25 min global ischemia/30 min reperfusion) and conscious rats. Three new compounds $(10\;{\mu}M)$ induced positive inotropism as evidenced by increased LVDP (left ventricular developed pressure) and RPP (Rate-Pressure Product) in nonischemic rat heart. HR-31299 increased CF (coronary flow) and HR (heart rate) but the other two had no effects. KR-31282, KR-31281 and HR-31299 had a tendency to increase reperfusion LVDP and RPP compared with vehicle, while the latter two significantly reduced reperfusion EDP with a tendency to inclose TTC (time to contracture). All three KR-compounds had very weak effects on MBP and HR in conscious rats. These results indicate that KR-31281 and HR-31299 may have some cardioprotective effects, although weaker than BMS-180448, and their mode of action different from that of BMS-180448, despite the similarity in major structural moeity.

• Korean Journal of Veterinary Service
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• v.29 no.4
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• pp.469-482
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• 2006

The term 'heat shock protein (Hsps)' was derived from the fact that these proteins were initially discovered to be induced by hyperthermic conditions. In response to a range of stressful stimuli, including hyperthermia, immobilization, UV radiation, amino acid analogues, arsenite, various chemicals, and drugs the mammalian brain demonstrates a rapid and intense induction of the heat shock protein. Moreover, Hsps were expressed on the various pathological conditions including trauma, focal or global ischemia, hypoxia, infarction, infections, starvation, and anoxia. Especially, Hsp25 has a protective activity, facilitated by the ability of the protein to decrease the intracellular levels of reactive oxygen species (ROS) as well as its chaperone activity, which favors the degradation of oxidized proteins. Recently, it has clearly demonstrated that Hsp25 is constitutively expressed in the adult mouse cerebellum by parasagittal bands of purkinje cells in three distinct regions, the central zone (lobule VI-VII) and nodular zone (lobule IX-X), and paraflocculus. The Mongolian gerbil has been introduced into stroke study model because of its unique brain vasculature. There are no significant connections between the basilarvertebral system and the carotid system. This anatomy feature renders the mongolian gerbil susceptible to forebrain ischemia-induced seizure. The present study is designed to examine the pattern of Hsp25 expression in the cerebellum of this animal in comparison with that in mouse.

• Journal of Chest Surgery
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• v.32 no.7
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• pp.603-612
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• 1999

Background : It has been documented that brief repetitive periods of ischemia and reperfusion (ischemic preconditioning, IP) enhances the recovery of post-ischemic contractile function and reduces infarct size after a longer period of ischemia. Many mechanisms have been proposed to explain this process. Recent studies have suggested that transient increase in the intracellular calcium may have triggered the activation of protein kinase C(PKC); however, there are still many controversies. Accordingly, the author performed the present study to test the hypothesis that preconditioning with high concentration of calcium before sustained subsequent ischemia(calcium preconditioning) mimics IP by PKC activation. Material and Method : The isolated hearts from the New Zealand White rabbits(1.5∼2.0 kg body weight) Method: The isolated hearts from the New Zealand White rabbits(1.5∼2.0 kg body weight) were perfused with Tyrode solution by Langendorff technique. After stabilization of baseline hemodynamics, the hearts were subjected to 45-minute global ischemia followed by a 120-minute reperfusion with IP(IP group, n=13) or without IP(ischemic control, n=10). IP was induced by single episode of 5-minute global ischemia and 10-minute reperfusion. In the Ca2+ preconditioned group, perfusate containing 10(n=10) or 20 mM(n=11) CaCl2 was perfused for 10 minutes after 5-minute ischemia followed by a 45-minute global ischemia and a 120-minute reperfusion. Baseline PKC was measured after 50-minute perfusion without any treatment(n=5). Left ventricular function including developed pressure(LVDP), dP/dt, heart rate, left ventricular end-diastolic pressure(LVEDP) and coronary flow(CF) was measured. Myo car ial cytosolic and membrane PKC activities were measured by 32P-${\gamma}$-ATP incorporation into PKC-specific pepetide. The infarct size was determined using the TTC (tetrazolium salt) staining and planimetry. Data were analyzed using one-way analysis of variance(ANOVA) variance(ANOVA) and Tukey's post-hoc test. Result: IP increased the functional recovery including LVDP, dP/dt and CF(p<0.05) and lowered the ascending range of LVEDP(p<0.05); it also reduced the infarct size from 38% to 20%(p<0.05). In both of the Ca2+ preconditioned group, functional recovery was not significantly different in comparison with the ischemic control, however, the infarct size was reduced to 19∼23%(p<0.05). In comparison with the baseline(7.31 0.31 nmol/g tissue), the activities of the cytosolic PKC tended to decrease in both the IP and Ca2+ preconditioned groups, particularly in the 10 mM Ca2+ preconditioned group(4.19 0.39 nmol/g tissue, p<0.01); the activity of membrane PKC was significantly increased in both IP and 10 mM Ca2+ preconditioned group (p<0.05; 1.84 0.21, 4.00 0.14, and 4.02 0.70 nmol/g tissue in the baseline, IP, and 10 mM Ca2+ preconditioned group, respectively). However, the activity of both PKC fractions were not significantly different between the baseline and the ischemic control. Conclusion: These results indicate that in isolated Langendorff-perfused rabbit heart model, calcium preconditioning with high concentration of calcium does not improve post-ischemic functional recovery. However, it does have an effect of limiting(reducing) the infart size by ischemic preconditioning, and this cardioprotective effect, at least in part, may have resulted from the activation of PKC by calcium which acts as a messenger(or trigger) to activate membrane PKC.

• Journal of Oriental Neuropsychiatry
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• v.21 no.1
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• pp.59-69
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• 2010

Objectives: The study aims to look into how the application of EA(Electro-acupuncture) in the initial step of ischemic brain injury affects the changes in Bax and Caspase-3 expression among forebrain apoptosis. Methods: It caused GI by using common carotid artery occlusion and conducted the test by dividing into the no applied EA group after 6 hours and 12 hours, the LI 4 EA group that applied EA to LI4, and GV 20 EA group that was applied to GV 20. After that, the following results were obtained by comparing Bax and Caspase-3 expression, which were apoptosis-related factors, with its application time through immunohistochemical staining after extracting brain of each group. Results: According to each group's Bax expression by the application time, the order of expression increase after 6 hours is shown to be the no applied EA group, LI 4 group, and GV 20 group. The stimulation after 12 hours was most lowly expressed in the GV 20 group, and the no applied EA group and LI 4 group showed similar level. Conclusions: EA stimulation in the initial step after ischemia seems to affect positively Bax and Caspase-3 expression that are index of forebrain apoptosis.

• Journal of Chest Surgery
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• v.33 no.7
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• pp.531-540
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• 2000

Baclgrpimd; Recent studies have suggested that the cardioprotective effect of ischemic preconditioning(IP) is closely related to glycogen depletion and attenuation of intracellular acidosis. In the present study, the authors tested this hypothesis by perfusion isolated rabbit hearts with glucose(G) is closely related to glycogen depletion and attenuation of intracellular acidosis. In the present study, the authors tested this hypothesis by perfusion isolated rabbit hearts with glucose(G)-free perfusate. Material and Method; Hearts isolated from New Zealand white rabbits(1.5~2.0 kg body weight) were perfused with Tyrode solution by Langendorff technique. After stabilization of baseline hemodynamics, the hearts were subjected to 45 min global ischemia followed by 120 min reperfusion with IP(IP group, n=13) or without IP(ischemic control group, n=10). IP was induced by single episode of 5 min global ischemia and 10 min reperfusion. In the G-free preconditioned group(n=12), G depletion was induced by perfusionwith G-free Tyrode solution for 5 min and then perfused with G-containing Tyrode solution for 10 min; and 45 min ischemia and 120 min reperfusion. Left ventricular functionincluding developed pressure(LVDP), dP/dt, heart rate, left ventricular end-distolic pressure(LVEDP) and coronary flow (CF) were measured. Myocardial cytosolic and membrane PKC activities were measured by 32P-${\gamma}$-ATP incorporation into PKC-specific peptide and PKC isozymes were analyzed by Western blot with monoclonal antibodies. Infarct size was determined by staining with TTC(tetrazolium salt) and planimetry. Data were analyzed by one-way analysis of variance (ANOVA) and Turkey's post-hoc test. Result ; In comparison with the ischemic control group, IP significantly enhanced functional recovery of the left ventricle; in contrast, functional significantly enhanced functional recovery of the left ventricle; in contrast, functional recovery were not significantly different between the G-free preconditioned and the ischemic control groups. However, the infarct size was significantly reduced by IP or G-free preconditioning(39$\pm$2.7% in the ischemic control, 19$\pm$1.2% in the IP, and 15$\pm$3.9% in the G-free preconditioned, p<0.05). Membrane PKC activities were increased significantly after IP (119%), IP and 45 min ischemia(145%), G-free [recpmdotopmomg (150%), and G-free preconditioning and 45 min ischemia(127%); expression of membrane PKC isozymes, $\alpha$ and $\varepsilon$, tended to be increased after IP or G-free preconditioning. Conclusion; These results suggest that in isolated Langendorff-perfused rabbit heart model, G-free preconditioning (induced by single episode of 5 min G depletion and 10 min repletion) colud not improve post-ischemic contractile dysfunction(after 45-minute global ischemia); however, it has an infarct size-limiting effect.

• Journal of Chest Surgery
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• v.29 no.8
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• pp.807-815
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• 1996

The protective effect of'ischemic preconditioning'on ischemid-reperfusion injury of heart has been reported in various animal species. but without known mechAnism in detail, In An attempt to investigate the cardioprotective mechanism of ischemic preconditioning, we examined the effects of nitric oxide(UO) synthesis in preconditioned heart of rat The isolated hearts perfused by Langendorfr's method were ex- posed to 30min global ischemia followed by 30min reperfusion with oxygenated Krebs-Henseleit(K-H) sol- ution. Ischemic preconditioning was performed with three episodes of Sm n ischemia and Smin repeyfusion before the induction of prolong ischemia(30min)-reperfusion(30min). Ischemic preconditioning prevented the depression of cardiac function(left ventricular pressure .K heart rate) observed in the ischemia- reperfusion hearts and reduced the release of lactate dehydrogenase during the reperfusion period. On electromicroscopic pictures, myocardial ultrastructures wore relatively well preserved in isthemic preconditioned hearts. N6_nitro-L-arginine methyl ester(L-NAME) an inhibitor of L-arginine citric oxide pathway, was infused at a rate O.Smllmin In a dose of 10mg kg-1 before the initial ischemic preconditioning. neither the protection of cardiac function nor the reduction of LDH releAse in ischemic preconditioning hearts was altered in the presence of added L-NAME On ultrastructural finding, the preservation of morphology in ischemic preconditioning heart was not change by the pretreatment of L-UAME. The failure of the WO synthesis inhibitor to reduce t e effect of ischemic preconditioning may be related to be species specific in that NO may allot be the trigger for ischemic preconditioning in rats.

• Journal of Chest Surgery
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• v.31 no.2
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• pp.95-101
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• 1998

Ischemic preconditioning is known to have protective effect on myocardial function at prolonged ischemic insult but the mechanism of the effect is not clearly known. The effect of the preconditioning on the global ischemia using cardioplegic solution is not well known. To evaluate the effect of global myocardial preconditioning on the functional recovery after cardioplegic arrest and two hours of hypothermic storage, we used the isolated rat heart and two hours cardioplegic arrest time at $0^{\circ}C$. In the experimental group(n=10), after baseline functional data was obtained, ischemic preconditioning was induced with 1 min of global normothermic ischemia for three times before the arrest period. In the control group(n=10), hearts underwent no ischemic precondi- tioning. After 2 hrs of cardioplegic arrest and storage in the $0^{\circ}C$ cardioplegic solution reperfusion was done and hemodynamic data were collected at post-reperfusion 20 min. Heart with ischemic preconditioning showed improved functional recovery at post reperfusion 20 min in peak developed pressure and dP/dT. In percent change of the peak pressure, preconditioning group showed 93.20$\pm$15.7% recovery rate compared to baseline data, and control group showed 67.3$\pm$15.6% recovery rate. In percent change of the dP/dT, control group showed 54.7$\pm$18.2% recovery rate and preconditioning group showed 78.1$\pm$15.1% recovery rate. Percent changes in heart rate and coronary flow showed no significant difference between two groups and there was no significant differences in amount of cardioplegic delivery between groups. Our data suggest ischemic preconditioning may have protective effect on recovery state after cardioplegic arrest and 2 hr ischemic storage of isolated rat heart and its mechanism is not related to the amount of the cardioplegic delivery amount.