흰쥐의 재관류시킨 심근경색증에 대한 Verapamil 의 영향

김철민(Chul Min Kim),전승석(Seung Sok Chun),노태호(Tai Ho Rho),박인수(In Soo Park),김종상(Chong Sang Kim),김재형(Jae Hyung Kim),최규보(Kyu Bo Choi),홍순조(Soon Jo Hong) 대한내과학회 1990 대한내과학회지 Vol.39 No.1

N/A Calcium channel blockers have proved effective in angina pectoris. However, despite a strong theoretical rationale for their use and promising experimental data, these agents have not reduced infarct size in acute myocardial infarction in the clinical trials performed to date. But treatment of calcium channel blockers before, at the time of, or shortly after the onset of coronary occlusion can increase the quantity of ischemic myocardium tha1 can be salvaged by repertusion. This agent appears to act by delaying cell death and may leave a larger quantity of viable cells which can be rescued by timely repertusion. This study was designed to investigate whether intervention with verapamil in reperfused myocardial infarction might reduce infarct size, infarct expansion and mortality in rats. An experimental model of myocardial infarction was produced in open chest rats by ligation of the left main coronary artery. After 30 minutes of ischemic time, reperfusion was done by cutting the ligated silk. The rats were administered an intraperitoneal injection of 20 mg/kg verapamil 30 minutes before ligation (treatment group 1, Tx 1)and 15 minutes after ligation (treatment group 2, Tx 2) in each treatment group. The control rats were administered an intraperitoneal injection of 8 ml kg 0.9% psaline 30minutes before ligation. On the seventh day, a topographic measurement of the left ventricle was obtained by planimeter. The infarct size was assessed by percetage of the left ventricular tissue area and by percentage of the left ventricular circumference of myocardial infarction. The infarct expansion was assessed by the left ventricular cavity area and thickness of the infarcted wall. The results were as follows: 1) The number of deaths during the experimental procedure was six out of 15 rats in the control group, 20 out of 40 rats in treatment group 1(Tx 1), and 20 out of 32 rats in treatment group 2(Tx 2). There was no difference in death rate. 2) By the left ventricular tissue area method, the infarct size of the control group (five rats) was 19.2±6.2%, treatment group 1 (11 rats) 24.3±9.4%, and treatment group 2 (seven rats) 30.3±5.7%. By the left ventricular circumference method, the infarct size of the control group was 23.7+4.6%p, treatment group 124.5±9.7%, and treatment group 233.1±7.3% There was no difference between treatment group 1 and the control group. But the infarct size of treatment group 2 was larger than that of the contro group (p<0.01, p<0.05). 3) There was no difference in infarct thickness and infarct expansion between the treatment groups and the control group. It was concluded that the administration of verapamil in experimental myocardial infarction with reperfusion may increase the size of the infarct. So it was suggested to limit the use of calcium channel blockers in acute myocardial infarction.

급성심근경색에서 Troponin T 와 경색의 크기와의 상관관계

서창희(Chang Hee Suh),김한수(Han Soo Kim),강한걸(Han Geol Kang),신준한(Joon Han Shin),탁승제(Seung Jae Tahk),이승호(Seong Ho Lee),최병일(Byung Il William Choi) 대한내과학회 1997 대한내과학회지 Vol.52 No.1

N/A Objectives: The estimation of infarct size has been important in evaluation of prognosis of the patients who had acute myocardial infarction. The infarct size estimated by the thallium-201 SPECT has been known to correlate with the prognosis of patient. The enzymatic estimation by the total release of creatine kinase isoenzyme MB(CK-MB) has been widely used in estimating infarct size clinically, but inconvienent and not cardiospecific. Recently, serum troponin T, cardiospecific myofibrillar protein, has been used in the diagnosis of acute myocardial infarction, and used in the estimation of reperfusion following myocardial infarction. To assess the role of the late troponin T peak concentration on the estimation of infarct size, this prospective study was carried out. Methods: The patients with acute myocardial infarction who were admitted, within 48hours after the onset of chest pain, to Ajou University Hospital between April 1995 and August 1995 were evaluated. All patients were divided into anterior and inferior infarct and checked serum troponin T and CK-MB serially, and underwent stress Thallium-201 SPECT 1 week after infarction, In each group, we assessed the correlation of the late toponin T peak concentration, the total release of CK-MB, and the infarct size estimated by thallium-201 single photon emission computed tomography(SPECT). Results: 1) The eligible subjects consisted of 22 patients (17 men and 5 women), and age ranged from 29 to 77 years(mean 57.8±12.5 years). 2) The mean arrival time to the hospital after the onset of chest pain was 15.5±13.2 hours. The 19 patients had at least one risk factor for coronaryartery disease. 3) The late troponin T peak concentration and the total release of CK-MB in patients with anterior infarction were not different from those with inferior infarction. The infarct size estimated by the thallium-201 SPECT in patients with anterior infarction was larger than patients with inferior infarction The left ventricular ejection fraction in anterio infarction was lower than inferior infarction. 4) The late troponin T peak concentration ha: positive correlation with the infarct size estimated by the thallium-201 SPECT in the total patients, and both patients with anterior infarction and inferio infarction. 5) The total release of CK-MB correlated with the infarct size estimated by the thallium-20 SPECT in the total patients, and the patients of inferior infarction. Conclusion: The late troponin T peak concentration was more accurate than the total release o CK-MB in the estimation of infarct size. Therefore, when the patient arrived to the hospital less than 48hr after the onset of chest pain, the late troponin T peak concentration is useful in the decision and evaluation of therapeutic intervention and in the prediction of prognosis.

허혈성 전처치에 의한 심실기능과 심근괴사 크기의 변화

윤선화,김현,김호덕 중앙대학교 의과대학 의과학연구소 1998 中央醫大誌 Vol.23 No.1

짧은 기간 동안 허혈성 전처치를 반복하여 시행할 경우 후속되는 보다 긴 기간동안의 허혈에도 불구하고 심근괴사범위가 감소되는 등의 심근보호효과가 있는 것으로 알려져 있다. 본 연구에서는 저굴 토끼심장을 이용, 짧은 기간 동안 허혈-재관류를 1회 실시하여 허혈성 전처치를 유도한 후 좌심실의 기능변화와 지역에 따르는 괴사크기의 변화를 관찰하여 허혈-재관류 1회 실시로 허혈성 전처치의 심근보호 효과가 나타나는지를 알아보고자 하였다. 재관류 시작후 규칙적인 심박동이 유지되는데 걸린 시간은 대조군에서 5분이상이 소요된 반면 IP군에서는 4분 이내로 빨라졌다. 이와 더불어 IP군에서는 LVDP 및 관혈류량의 회복율 등이 대조군에 비하여 유의하게 증가하였다. 대조군에서는 LVEDP값이 31-38 mmHg로 상승폭이 매우 높은데 비하여 IP군에서는 22-28 mmHg로 상승폭이 상대적으로 낮았다. 심근괴사부위는 대부분에서 심첨으로부터 4번까지의 절편에서 뚜렷히 관찰되었고 그 크기 심첨에서 심저부로 이행함에 따라 두군 모두 심저부에 가까워질수록 감소하는 경향을 나타내었으나 대조군에 비하여 IP군에서는 특히 심첨에서 심저부로 향하여 4번째 절편까지에서 유의한 감소를 나타내었다. 이상으로 적출관류 토끼심장에서도 5분-10분 동안 허혈-재관류를 1회 실시하여 허혈성 전처치를 유도한 경우 후속되는 45-60분 동안의 허혈에 대하여 재관류시 좌심실기능 증가나 심근경색범위 한정 등의 심근보호 효과를 기대할 수 있을 것으로 생각된다. It has been demonstrated that brief periods of ischemia and reperfusion (ischemic preconditioning, IP) enhance recovery of post-ischemic contractile dysfunction and reduce incidences of reperfusion-induced arrhythmia or infarct size after a subsequent sustained ischemia. In the present study, the authors attempted to examine whether reduction in infarct size could be afforded by IP and how the infarct size changed in accordance to the geometry of the heart. 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-minute global ischemia followed by 120-minute reperfusion with IP (IP group) or without IP (control group, n=12). IP was induced by single episode of 5-minute global ischemia and 10-minute reperfusion (IP1, n=13). Left ventricular function including developed pressure (LVDP), dP/dt, heart rate, left ventricular end-diastolic pressure (LVEDP) and coronary flow (CF) was measured. Iinfarct size was determined by staining with TTC (tetrazolium salt) and planimetry. Data were analyzed by paired or unpaired t=tests and linear regression. Regular cardiac rhythm was restored within 4 minutes on reperfusion in the IP hearts, whereas it was done after 5 minutes in the control. The LVDO, dP/dt and CF were higher in the IP hearts than in the control, and especially the recovery of LVDP was maintained at 90% of the baseline value. In contrast, the increase of LVEDP was much higher in the control (31-38 mm Hg), while that in the IP hearts was 22-28 mm Hg. Infarct size was significantly reduced in the IP hearts compared to the control; infarct was evident within the first half of the cardiac tissue slices perpendicular to the long axis of the heart parallel from apex to base of the heart, however, infarct was not evident in the second half of the heart. These results indiate that in isolated Langendorff-perfused rabbit heart model, IP could improve post-ischemic contractile dysfunction and it has an infarct size-limiting effect.

흰쥐에서의 관상동맥 결찰/재관류도 유도된 심근경색에 대한 칼륨통로 개방제 KR-30450의 약리학적 효과

이재흥(Jae Heung Lee),권광일(Kwang Il Kwon),신화섭(Hwa Sup Shin) 대한약학회 1997 약학회지 Vol.41 No.1

The pharmacological effects of benzopyran potassium channel openers (lemakalim, KR-30450 and KR-30818) on the occlusion/reperfusion-induced myocardial infarction were investigated. In anesthetized rats, subjected to 45-min occlusion of the left anterior descending coronary artery (LAD) followed by 90-min reperfusion, the infarct size was measured by calculating the ratio of infarct zone to area at risk (IZ/AAR) with the Evans blue/TTC technique. Rats were intravenously given vehicle (1% DMSO), lemakalim, KR-30450, and KR-30818 alone or in combination with a selective KATP blacker glibenclamide, 30 min prior to coronary occlusion. Compared to vehicle, lemakalim (30 mcg/kg i.v.), the active enantiomer of cromakalim, had a tendancy to decrease infarct size. KR-30450(30 mcg/kg, i.v.). the newly synthetized potassium channel openers (PCOs), caused a reduction of infarct size (from 70+/-4%to 57+/-5%). but KR-30818 (30mcg/kg, i.v.), a metabolite of KR-30450. did not modify infarct size. It seem ed likely that glibenclamide (0.3mcg/kg, i.v.), given in combination, reduced the effects of these PCOs, especially KR-30450 (30mcg/kg, i.v.) on the infarct size. These results indicate that. in the coronary occluded rat model of ischemia, lemakalim and KR-30450 may exert cardioprotective activity through a reduction of infarct size, the effect being considered related to the opening of KATP channel.

허혈성 전처치의 심장보호 효과 : 허혈후 재관류시 관혈류와 심근기능 사이의 관계 relation between coronary flow and cardiac function during postischemic reperfusion

서중석,이우승,김현,김호덕,라봉진 중앙대학교 의과대학 의과학연구소 1998 中央醫大誌 Vol.23 No.4

It has been demonstrated that brief period of ischemia and reperfusion (ischemic preconditioning, IP) enhances recovery of post-ischemic contractile dysfunction and reduces incidences of reperfusion-induced arrhythmia or infarct size after a prolonged ischemia. Recent studies suggest that IP triggers activation of protein kinase C (PKC). In the present study, the author teated this hypothesis with PKC activator, phorbol ester (PMA, 0.01 nM) or inhibitor, calphostin C (200 nM) to measure the left ventricular function and infarct size; and assessed whether hemodynamics are related with each other or not. 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=7) or without IP (ischemic control group, n=7). IP was induced by single episode of 5 min global ischemia and 10 min reperfusion. In the PMA-treated group (n=13), the heart was subjected to perfusion with Tyrode solution containing PMA for 5 min after stabilization of the baseline, washing out (for 10 min with normal perfusion), and 45 min ischemia and 120 min reperfusion; in the calphostin C-treated preconditioned group (n=15), calphostin C was given for 15 min from 5 min before IP regimen. Left ventricular function including developed pressure (LVDP), dP/dt, heart rate, left ventricular end-diastolic pressure (LVEDP) and coronary flow (CF) was measured. Iinfarct size was determined by staining with tetrazolium salt and planimetry. Data were anaalyzed by one-way analysis of variance and Tukey's post-hoc test; and linear regression between hemodynamic values. In comparison with the ischemic control group, IP signifivantly increased the recovery of the left ventricular function including left ventricular developed pressure, contractility, and coronary flow. However, enhancement of the functional recovery disappeared by calphostin C or PMA treatment. IP and PMA also reduced infarct size (from 38 to 10-20%, p<0.05). However, calphostin C blocked infarct reduction effect of IP. These results suggest that in isolated Langendorff-perfused rabbit heart model, IP could improve post-ischemic contractile dysfunction, as well as it has an infarct size-liniting effect; these cardioprotective effect of IP may be related, at least in part, to trigger activation of PKC, however, there are any relationship between hemodynamics.

Repetitive Short Period of Ischmia(Ischemic Precondittioning) does not improve Ventricular Funtion but has an Infarct-Limiting Effect in Isolated Raggit Hearts

Kim, Hyun,Kim, Dae Joong,Lee, Sung Woo,Rah, Bong Jin,Kim, Ho Dirk 중앙대학교 의과대학 의과학연구소 1996 中央醫大誌 Vol.21 No.1

동물실험에서 짧은 기간동안의 허혈-재관류 반복(ischemic preconditioning, IP)으로 후속되는 보다 긴 기간 동안의 허혈에도 불구하고 재관류시 심근의 수축기능이 증가되며 심근괴사의 범위도 줄어드는 등의 심근 보호 효과가 있는 것으로 알려져 있으나 IP효과가 유지될 수 있는 IP후 후속되는 허혈기간이나 IP효과의 발생기전에 대하여는 논란이 많다. 본 연구에서는 저굴관류 토끼심장을 이용하여 IP효과와 허혈기간 사이의 관계를 알아보고자 하였다. 적추관류 흰토끼 심장을 이용하여 관류를 차단하는 방법으로 전체 허혈을 유도하였으며 전체허혈(5분), 재관류(5분)를 4회 반복하여 IP를 유도하고 60분에서 90분에 이르는 동안 전체허혈후 120분동안 재관류를 실시하였다(IP군, n=27). 대조군(n=22)에서는 IP없이 60분에서 90분에 이르는 동안 전체 허혈후 120분동안 재관류를 실시하였다. 허혈후 재관류기간동안 좌심실기능(좌심실내압, left ventricular developed pressure, LVDP ; 심박동수 : 관상혈류, coronary flow, CF), creatine kinase(CK) 유출과 세포의 칼슘농도를 측정하였고 심근괴사 범위를 결정하기 위하여 1% tetrazoliumsalt로 염색하여 형태계측하였다. 좌심실기능과 형태계측으로 얻은 측정치는 모두 통계학적으로 검정하였다. LVDP회복율, RPP(rate-pressure product)회복율, CF회복율 및 CK유출등은 모든 실험근 사이에서 유의한 차이를 볼 수 없었으나 60분 허혈군의 IP군에 비하여 다른 소실험군에서는 세포외 칼슘농도의 현저한 감소를 관찰할 수 있었다.(p<0.01 at 0 and 30 minute, p<0.05 at 10 minute on reperfusion). 뿐만 아니라 60분 허혈군의 IPrns에서는 심근괴사 범위가 16.98±1.4(mean±SEM)%로 다른 소실험군에 비하여 현저히 감소되어 있었으며 주로 외측벽에 국한되어 관찰되었다. 연구결과에서 적출관류 토끼심장에서 IPgn 60분 허혈-120분 재관류시 좌심실 수축기능을 증가시키지는 않으나 심근경색의 범위를 한정지어주는 보호효과가 있는 것으로 미루어 IP효과를 나타내는 최대한의 허혈기간은 60분 내외일 것으로 생각된다. Recent studies have demonstrated that ischemic preconditioning(IP) enhances cardiac function and reduces infarct size after a ischemia in isolated heart. The purpose of the present study was to assess whether cardioprotective effect of IP is present in a prolonged ischemia in isolated spontaneously beating rabbit heart. Left ventricular function including coronary flow, creatine kinase leakage, and infarct size were measured during reperfusion following sustained ischemia. Control(C, n=22) hearts received 60 to 90 min sustained ischemia followed by 120 min reperfusion. Preconditioned(IP, n=27) hearts received 4 cycles of 5 min global ischemia and 5 min reperfusion before sustained ischemia as in the C hearts. There were no significant differences in the left ventricular function including coronary flow and creatine kinase leakage between any of the study groups. However, infarct size was significantly different between the C and IP hearts of 60 min sustained ischemia (31.1±2.6% in the C versus 16.9±1.4% in the IP hearts, P<0.01). IP induced by repetitive 5 min ischemia did not enhance functional recovery in 60 min sustained ischemia in isolated rabbit heart model but is has an infarct size-limiting effect.

흰쥐의 영구 국소 뇌허혈에서 중등도 체온강하가 뇌경색 크기와 초기 국소 뇌포도당 대사율 변화에 미치는 영향

김봉수,최길수 대한신경외과학회 1997 Journal of Korean neurosurgical society Vol.26 No.6

급성 심근경색증 환자에서 Cardiac Troponin Ⅰ측정의 의의에 관한 연구

윤용선,강흥선,조정휘,김권삼,송정상,배종화 대한순환기학회 1998 Korean Circulation Journal Vol.28 No.10

실험연구 : Sufentanil 투여가 흰쥐적출심장에서 허혈시 심근기능 및 관상동맥혈류에 미치는 영향

서경원 ( Kyung Won Seo ),신명강 ( Myoung Gang Shin ),이윤숙 ( Yoon Sook Lee ),장문석 ( Moon Seok Chang ),김운영 ( Woon Young Kim ),김재환 ( Jae Hwan Kim ),박영철 ( Young Cheol Park ) 대한마취과학회 2006 Korean Journal of Anesthesiology Vol.51 No.2

Background: Some opioids have been shown to attenuate an ischemia-reperfusion injury in an isolated-heart model. The aim of this study was to evaluate the effect of sufentanil on the cardiac function in isolated-heart models when given before and after prolonged periods of low flow ischemia. Methods: Isolated rat hearts were stabilized for 30 minutes and subdivided into four groups (each n = 7). The control group was subjected to low flow ischemia (LFI 0.3 ml/min) of 5% dextrose water for 30 minutes, followed by perfusion with a modified Krebs solution at a constant pressure for 60 minutes. In the sufentanil groups, different sufentanil (12.5 mg/L, 25 mg/L, 50 mg/L) doses were administered with the modified Krebs solution after 30 minutes of stabilization until the end of the experiment with the exception of the LFI group. The left ventricular end systolic pressure (LVESP), dP/dt max, heart rate and coronary flow were measured. After reperfusion, the infarct size of all groups was measured. Results: The control and the sufentanil groups had a lower LVESP, dP/dt max, coronary effluent flow and arrhythmia duration after ischemia and reperfusion than those before ischemia. The infarct sizes in the sufentanil groups were smaller than those in the control group. However the infarct sizes of the sufentanil groups were similar. Conclusion: Sufentanil reduces the infarct size but does not improve the post-ischemic functional dysfunction. (Korean J Anesthesiol 2006; 51: 216~21)

데페록사민 전처치가 토끼 심근경색 크기의 감소에 미치는 효과

양관모,오동렬,박승현,박규남,이원재,김형국,황두영,최승필,채장성 대한응급의학회 1998 대한응급의학회지 Vol.9 No.4

Background: Reperfusion of ischemic myocardium has been postulated to result in a specific oxygen radical mediated tissue injury. Iron may liberate during ischemia and we hypothesized that administration of the iron chelator, deferoxamine during ischemia would result in improved recovery after postischemic reperfusion. Purpose: To test whether iron-catalyzed processes contribute to myocardial necrosis during ischemia and reperfusion, deferoxamine was administered to block iron catalyzed hydroxyl radical formation in rabbits. Methods: Eleven rabbits were divided into two groups : control group (n=5) and deferoxamine pretreatment group (n=6). The left circumflex coronay artery was ligated for 30 minutes and reperfused for 180 minutes. Area at risk (AR) was measured by non-stained area with methylene blue injection into left atrium after left circumflex coronary artery ligation. Infarct size was measured by weighing after triphenyltetrazolium chloride staining. Heart rate was measured using electrocardiographic recording and systemic blood pressure was monitored by pressure transducer connected to the catheter in the left ventricle. Results: 1. There was no significant difference of heart rate and blood pressure in deferoxamine pretreatment group compared with control group. 2. There was significant decrease of serum iron concentration after continuous infusion of deferoxamine compared with serum iron concentration before ligation of coronary artery(P<0.05). 3. There was no significant difference of area at risk between control and deferoxamine pretreatment group. 4. Area at necrosis to area at risk was significantly reduced in deferoxamine pretreatment group compared with control group(P<0.05). The results suggest that deferoxamine infusion prior to coronary artery occlusion has a significant benefit in reducing infarct size in this model.