• The Korean Journal of Physiology and Pharmacology
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• 제4권6호
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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.

• The Korean Journal of Physiology and Pharmacology
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• 제3권6호
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• pp.579-586
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• 1999

Complement-mediated neutrophil activation has been hypothesized to be an important mechanism of reperfusion injury. It has been proposed that C1 esterase inhibitor (C1 INH) may prevent the complement- dependent activation of polymorphonuclear leukocytes (PMNs) that occurs within postischemic myocardium. Therefore, The effect of C1 INH was examined in neutrophil dependent isolated perfused rat heart model of ischemia (I) (20 min) and reperfusion (R) (45 min). Administration of C1 INH (5 mg/Kg) to I/R hearts in the presence of PMNs $(100{\times}10^6)$ and homologous plasma improved coronary flow and preserved cardiac contractile function (p＜0.001) in comparison to those I/R hearts receiving only vehicle. In addition, C1 INH significantly (p＜0.001) reduced PMN accumulation in the ischemic myocardium as evidenced by an attenuation in myeloperoxidase activity. These findings demonstrate the C1 INH is a potent and effective cardioprotective agent inhibits leukocyte-endothelial interaction and preserves cardiac contractile function and coronary perfusion following myocardial ischemia and reperfusion.

• Journal of Chest Surgery
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• 제31권5호
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• pp.481-487
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• 1998

하행대동맥의 급성박리에 대한 외과적 치료에 대해서는 논란이 많다. 하행대동맥의 급성 박리병변이 수술적응이 될 경우 대동맥 차단시간은 30분 이상 소요될 수 있으므로 척수손상을 예방하기 위해 대동맥 차단부위 하방에 혈류를 유지하기 위한 여러 방법이 소개되었다. 저자들은 파열(혈흉) 및 쇼크의 합병증을 동반한 하행 대동맥의 급성 박리증 8예를 체외순환법을 이용하여 수술하고 그 방법에 대한 안전성과 효용성을 찾고자 하였다. 체외순환방법에 있어서는 대동맥병변의 상하에 2개의 동맥카뉼라를 넣어 대동맥 차단으로 수술 도중 상하체의 혈류공급을 동시에 이루어지도록 하였고, 산화기로 정맥혈의 환류를 위해 우심방이나 좌대퇴정맥에 정맥관을 삽입하였다. 비교적 장시간의 대동맥 차단에도 불구하고 수술후 8예 모두에서 척수손상은 없었다. 2예(25%)의 병원사망(각각 술후 31일과 41일)은 비교적 고령에서 지연성 합병증인 폐농양, 호흡부전증 등에 의해 발생했다. 주위조직의 부종 및 연약함 때문에 수술시간이 연장될 수 있는 급성 하행동맥 박리증에서 체외 순환방법하의 인공혈관 대치술은 대동맥 차단시간의 연장에 의한 척수 허혈손상을 피할 수 있는 안전하고 효과적인 외과적 치료방법이 될 수 있을 것으로 사료된다.

• Journal of Korean Neurosurgical Society
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• 제67권4호
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• pp.442-450
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• 2024

Objective : Cerebral hyperperfusion syndrome (CHS) manifests as a collection of symptoms brought on by heightened focal cerebral blood flow (CBF), afflicting nearly 30% of patients who have undergone superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis. The aim of this study was to investigate whether the amalgamation of magnetic resonance imaging (MRI) fluid-attenuated inversion recovery (FLAIR) and apparent diffusion coefficient (ADC) imaging via MRI can discern cerebral hyperemia after STA-MCA anastomosis surgery. Methods : A retrospective study was performed of patients who underwent STA-MCA anastomosis due to Moyamoya disease or atherosclerotic steno-occlusive disease. A protocol aimed at preventing CHS was instituted, leveraging the use of MRI FLAIR. Patients underwent MRI diffusion with FLAIR imaging 24 hours after STA-MCA anastomosis. A high signal on FLAIR images signified the presence of hyperemia at the bypass site, triggering a protocol of hyperemia care. All patients underwent hemodynamic evaluations, including perfusion MRI, single-photon emission computed tomography (SPECT), and digital subtraction angiography, both before and after the surgery. If a high signal intensity is observed on MRI FLAIR within 24 hours of the surgery, a repeat MRI is performed to confirm the presence of hyperemia. Patients with confirmed hyperemia are managed according to a protocol aimed at preventing further progression. Results : Out of a total of 162 patients, 24 individuals (comprising 16 women and 8 men) exhibited hyperemia on their MRI FLAIR scans following the procedure. SPECT was conducted on 23 patients, and 11 of them yielded positive results. All 24 patients underwent perfusion MRI, but nine of them showed no significant findings. Among the patients, 10 displayed elevations in both CBF and cerebral blood volume (CBV), three only showed elevation in CBF, and two only showed elevation in CBV. Follow-up MRI FLAIR scans conducted 6 months later on these patients revealed complete normalization of the previously observed high signal intensity, with no evidence of ischemic injury. Conclusion : The study determined that the use of MRI FLAIR and ADC mapping is a competent means of early detection of hyperemia after STA-MCA anastomosis surgery. The protocol established can be adopted by other neurosurgical institutions to enhance patient outcomes and mitigate the hazard of permanent cerebral injury caused by cerebral hyperemia.

• Journal of Chest Surgery
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• 제30권2호
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• pp.119-124
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• 1997

저자들은 흰쥐의 적출된 심장을 이용하여 Verapamil이 허혈성 심근에 대하여 심근보호효과가 있는지를 관찰하였다 흰쥐의 적출된 심장은 허혈상태에서 심근온도가 $25^{\circ}C$가 되게 유지하였다. 24마리의 흰쥐로부터 적출된 심장을 Krebs-Henseleit완충액을 사용하여 30분간의 비작업성 역관류로 안정시킨 후 $25^{\circ}C$의 심정지액 (St. Thomas' Hospital Cardioplegic Solution)에 60분 동안 저장하였다. 허혈성 심정지를 유도하기 전에 적출된 심장을 저온의 심정지액으로 처리한 군을 대조군(n=12)으로 하고, Verapamil 이 첨가된 저온의 심정지액으로 처리한 군을 실험군(n=12)으로 하였다. 60분 동안의 허혈성 심정지후 심정지전에 측정했던 혈역학적 및 생화학적 지표인 심박동수, 좌심실압, +dpfdt max, 관상관류량과 CPK치를 재관류후 30분에 재측정하여 심정지전과 비교하여 심기능 회복 정도를 관찰하였다. Verapamil이 첨가된 저온의 심정지액을 사용한 실험군이 심박동수, 좌심실압, +dp/dt max, 관상관류량과 CPK치에서 대조군에 비하여 유의하게 높은 회복율을 나타내었다(p <0.05).

• The Korean Journal of Physiology and Pharmacology
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• 제2권6호
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• pp.753-761
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• 1998

Preconditioning of a heart with small doses of catecholamines induces a tolerance against the subsequent lethal ischemia. The present study was performed to find a specific receptor pathway involved with the catecholamine preconditioning and to test if adenosine plays a role in this cardioprotective effect. Isolated rat hearts, pretreated with small doses of ${\alpha}-\;or\;{\beta}-adrenergic$ agonists/antagonists, were subjected to 20 minutes ischemia and 20 minutes reperfusion by Langendorff perfusion method. Cardiac mechanical functions, lactate dehydrogenase and adenosine release from the hearts were measured before and after the drug treatments and ischemia. In another series of experiments, adenosine $A_1\;or\;A_2$ receptor blockers were treated prior to administration of adrenergic agonists. Pretreatments of a ${\beta}-agonist,\;isoproterenol(10^{-9}{\sim}10^{-7}\;M)$ markedly improved the post-ischemic mechanical function and reduced the lactate dehydrogenase release. Similar cardioprotective effect was observed with an ?-agonist, phenylephrine pretreatment, but much higher $concentration(10^{-4}\;M)$ was needed to achieve the same degree of cardioprotection. The cardioprotective effects of isoproterenol and phenylephrine pretreatments were blocked by a ${\beta}_1-adrenergic$ receptor antagonist, atenolol, but not by an ${\alpha}_1-antagonist,$ prazosin. Adenosine release from the heart was increased by isoproterenol, and the increase was also blocked by atenolol, but not by prazosin. A selective $A_1-adenosine$ receptor antagonist, 1,3-dipropyl-8-cyclopentyl xanthine (DPCPX) blocked the cardioprotection by isoproterenol pretreatment. These results suggest that catecholamine pretreatment protects rat myocardium against ischemia and reperfusion injury by mediation of ${\beta}_1-adrenergic$ receptor pathway, and that adenosine is involved in this cardioprotective effect.

• Journal of Chest Surgery
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• 제33권5호
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• pp.377-384
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• 2000

Background: Numerous studies of safe, long term preservation for lung transplantation have been performed using ex vivo models or in vivo single lung transplantation models. However, a safe preservation time which is applicable for clinical use is difficult to determine. We prepared LPDG solution for lung preservation study. In this study we examined the efficacy of LPDG(low potassium dextran glucose) solution in 24-hour lung preservation by using a sequential bilateral canine lung allotransplant model. Material and Method: Seven bilateral lung transplant procedures were performed using weight-matched pairs(24 to 25kg) of adult mongrel dogs. The donor lungs were flushed with LPDG solution and maintained hyperinflated with 100% oxygen at 1$0^{\circ}C$ for a planned ischemic time of 24 hours for the lung implanted first. After sequential bilateral lung transplantation, dogs were maintained on ventilators for 3 hours: arterial resistance were determined if the recipients hourly after bilateral reperfusion and compared with pretransplant-recipient values, which were used as controls. After 2hours of reperfusion, the chest X-ray, computed tomogram and lung perfusion scan were performed for assessmint of early graft lung function. Pathological examinations for ultrastructural findings of alveolar structure and endothelial structure of pulmonary artery were performed. Result: Five of seven experiments successfully finished the whole assessments after bilateral reperfusion for three hours. Arterial oxygen tension in the recipients was markedly decrased in immediate reperfusion period but gradually recovered after reperfusion for three hours. The pulmonary artery and pulmonary vascular resistance showed singificant elevation(p<0.05 versus control values) but also recovered after reperfusion for three hours(p<0.05 versus immediate period value). The ultrastructural findings of alveolar structure and endothelial structure of pulmonary artery showed reversible mild injury in 24 hours of lung perservation and reperfusion. Conclusion : This study suggests that LPDG solution provides excellent preservation in a canine model in which the dog is completely dependent on the function of the transplanted lung.

• Journal of Chest Surgery
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• 제31권9호
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• pp.845-854
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• 1998

Background: S-2-(3 aminoprophlamino) ethylphosphorothioic acid(WR-2721) is one of the radical scavenging thiols. We tested its protective effects in the reperfused heart. Material and Method: The experimental setup was the constant pressure Langendorffs perfusion system. We investigated the radical scavenging properties of this compound in isolated rat hearts which were exposed to 20 minutes ischemia and 20 minutes reperfusion. Four experimental groups were used:group I, control, Amifostine 50 mg(1 mL) peritoneal injection 30 minutes before ischemia(group II), Amifostine 10 mg(0.2 mL) injection during ischemia through coronary artery(group III),and Amifostine 50 mg(1 mL) peritoneal injection 2 hrs before ischemia(group IV). The experimental parameters were the levels of latate, CK-MB, and adenosine deaminase(ADA) in frozen myocardium, the quantity of coronary flow,and left ventricular developed pressure, and it's dp/dt. Statistical analysis was performed using repeated measured analysis of variance and student t-test. Result: The coronary flow of group II and IV were less than group I and III at equilibrium state but recovery of coronary flow at reperfusion state of group II, III, and IV were more increased compared with group I. The change of systolic left ventricular devoloping pressure of group II and IV were less than control group at equilibrium state, which seemed to be the influence of the pharmacological hypotensive effect of amifostine. But it was higher compared with group I at reperfusion state. The lactic acid contents of group II were less than control group in frozen myocardium.(Group I was 0.20 0.29 mM/g vs Group II, which was 0.10 0.11 mM/g). The quantity of CK-MB in myocardial tissue was highest in group IV (P=0.026 I: 120.0 97.8 U/L vs IV: 242.2 79.15 U/L). The adenosine deaminase contents in the coronary flow and frozen myocardium were not significantly different among each group. Conclusion: Amifostine seemed to have significant cardioprotective effect during ischemia and reperfusion injuries of myocardium.

• Childhood Kidney Diseases
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• 제2권2호
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• pp.138-144
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• 1998

목 적 : 면역억제제로 사용되는 cyclosporine과 항암제로 사용되는 mitomycin의 신장에 미치는 직접적인 독성여부를 확인하고 이들 약제의 사용으로 초래되는 신장병변의 발생기전을 알아보고자 본 연구를 시행하였다. 대상 및 방법 : 실험동물은 체중 250-300gm의 Sprague-Dawley계 흰쥐를 암수 구별없이 사용하였으며 약물 투여는 Hoyer등이 기술한 방법을 다소 변형한 일측성 신관류 방법을 사용하여 좌측 신장을 대동맥과 대정맥의 혈류로부터 차단하고 좌측 신동맥을 통하여 좌측신을 관류시켰다. Cyclosporine은 4 mL에 2.5 mg, mitomycin은 4 mL에 1.6mg의 농도로 하였고 대조군은 생리적 식염수를 .사용하였으며 혈관 clamping으로부터 감자제거까지 소요된 총 ischemic time은 15분을 초과하지 않았다. 약제 투여후 48시간에 실험 동물을 도살하고 좌측 신장을 적출하여 광학 및 전자 현미경 검사를 시행하였다. 결 과 : Cyclosporine투여군에서는 사구체 내피세포 및 상피세포의 심한 종창이 있었으며 간질내 모세혈관의 내피세포도 심한 종창을 보였다. Mitomycin투여군에서는 사구체 내피세포 및 상피세포의 심한 종창을 보였으며 일부의 모세 혈관에는 혈소판의 응집, 종창 및 탈과립 현상과 섬유소 물질도 포함된 혈전성 미세혈관 병변의 소견을 보였다. 결 론 : Cyclosporine과 mitomycin은 신장 내피세포에 직접적인 손상을 초래하며 그러므로 이들 약제 사용으로 인한 혈전성 미세혈관 병변 (용혈성 요독증)의 발생 기전에는 이들 약제의 신장 내피세포에의 직접적인 손상이 중요한 시발점이 되는 것으로 생각된다.($41.4\%$)이 신초음파에서 이상소견을 보였다. 방광요관역류가 있었던 32명(53역류신장)은 역류정도에따라 Grade $I:25.0\%,\;II:44.5\%,\;III:64.3\%,;IV:92.9\%,\;V:100\%$에서 초기 DMSA 신주사상 이상소견을 보였다. 53역류신장중 전체적으로 DMSA신주사에서 36신장($68.0\%$), 신초음파에서 26신장($49.1\%$)이 이상소견을 보여 유의한 차이를 보였으며(P<0.05). 특히 Grade IV 역류신장에서 유의한 차이가 있었다(P<0.05). 결 론 : DMSA신주사를 이용한 급성신우신염의 진단은 신초음파검사 보다 유용하며, 초기 DMSA신주사 소견상 이상소견을 보인 경우 약 8-12주 후 추적검사를 시행하여 변화를 관찰하고 섭취결손 부분이 남아있는 경우에는 향후 새로운 병소의 출현 혹은 정상화 여부를 보기 위한 추적검사가 필요하리라 사료된다. 방광요관역류 환아에서 DMSA신주사소견은 방광요관역류의 정도가 심할수록 이상소견을 보일 확률이 높으며 신초음파 검사보다 민감도가 높은 것을 알 수 있었다.이는 혈압을 조절시키지 못하였고 저단백식이 항고혈압제투여군은 저단백식이 단독투여군보다 혈압조절 및 단백뇨의 감소 소견은 유의한 차이를 보였으나, mesangial matrix expansion score,대상성 사구체비대는 통계적으로 유의한 차이를 보이지 않았다. 그러므로 만성신부전의 진행을 지연시키는데 있어서 저단백식이와 함께 항고혈압제를 추가하였을 때 항고혈압제에 의한 추가적인 지연 효과는 관찰되지 않았다.학생이 남학생보다 높고, 물리치료과를 타의로