• 대한핵의학회지
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• 제27권2호
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• pp.203-209
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• 1993

Dipyridamole은 정맥주사시 매우 안전한 것으로 알려져 있으며 일반적으로그 약물효과는 혈압강하와 심계항진에 의한 증상이 대부분이다. 저자들은 dipyridamole 부하 심근 SPECT를 시행한 847명 환자에서 dipyridamole에 대한 반응양상과 부작용에 대해 조사하였다. 대상환자는 847명으로 이들 중 혈압과 맥박수의 측정기록이 있는 702명에서 심근의 관류결손부위에 따른 헐압과 맥박수의 곱과 곱의 비를 분석하여 dipyridamole에 대한 반응을 조사하였다. 1) Dipyridamole 투여후 나타난 부작용으로는 흉통이나 흉부불쾌감(20.3%)이 가장 많았고 두통이 14.8%, 숨이 차다고 한 예가 4.6%, 복통이 4.3%, 어지러움이 2.2%의 빈도를 보였다. 2) Dipyridamole 투여후 대부분의 환자에서 혈압감소를 보여 93.6%에서 혈압이 감소하였고, 0.9에서 혈압의 변동이 없었고, 5.5%에서는 오히려 혈압이 증가하였다. 3) Dipyridamole 부하전의 맥박수에 비해 10%이상의 증가를 보이지 않은 경우는 전체 대상환자의 8.3%였다. 당뇨환자의 16.9%, 비당뇨환자의 6.7%에서 맥박수의 증가를 보이지 않았다(p<0.005). 4)심근 SPECT상 관류결손이 없는 234명에서 연령과 RPPr의 관계는 연령이 증가함에 따라 RPPs/RPPr는 감소하는 경향을 보였다. 관류결손이 있는 환자 468 명에서도 연령과 RPPs, RPPs/RPPr이 같은 결과를 보이고 있다. 5) 휴식기 심근의 관류결손이 있는 환자군에서 심근의 관류결손의 크기와 RPPr과 RPPs/RPPr은 관련이 없었다. Dipyridamole에 의한 반응으로 비전형적인 반응을 보인 경우는 혈압증가가 5.5%, 맥박의 증가가 없는 경우가 8.3% 였다. 혈압과 맥박수의 곱 또는 곱의 비와 연령과의 관계는 휴식기 심장부하가 많은 고령의 환자에서 증가되어 있었으며 dipyridamole부하에 의한 심장부하량은 나이가 많은 환자에서 적어짐을 시사하였다. 관류결손이 있는 환자와 없는 환자에서 dipyridamole부하로 인한 심장부하량에는 유의한 차이가 없었다. Dipyridamole에 의한 부작용은 흉통, 두통, 복통 등의 순이었고 전예에서 호전되었으며 생명에 위험을 초래할 수 있는 정도의 심장마비나 심부정맥은 한 예에서도 없었다. 결론적으로 dipyridamole은 약물부하 심근 SPECT 검사에 안전하게 사용할 수 있는 약물로 사료된다.

• Journal of Pharmaceutical Investigation
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• 제36권1호
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• pp.45-51
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• 2006

A rapid, selective and sensitive reversed-phase HPLC method for the determination of dipyridamole in human serum was developed, validated, and applied to the pharmacokinetic study of dipyridamole. Dipyridamole and internal standard, loxapine, were extracted from human serum by liquid-liquid extraction with diethyl ether and analyzed on a Nova Pak $C_{I8}$ column with the mobile phase of 40 mM ammonium acetate:methanol:acetonitrile (35:35:30)(v/v/v, pH 7.8). Detection wavelength of 280 nm and flow rate of 1.0 mL/min were fixed for the study. The assay robustness for the changes of mobile phase pH, organic solvent content, and flow rate was confirmed by $3^3$ factorial design using a fixed dipyridamole concentration (50 ng/mL) with respect to its peak area and retention time. And also, the ruggedness of this method was investigated at three different laboratories using same quality control (QC) samples. This method showed linear response over the concentration range of 2-2000 ng/mL with correlation coefficients greater than 0.999. The lower limit of quantification using 0.5 mL of serum was 2 ng/mL, which was sensitive enough for pharmacokinetic studies of dipyridamole. The overall accuracy of the quality control samples ranged from 103.94 to 105.86% for dipyridamole with overall precision (% C.V.) being 4.60-11.49%. The relative mean recovery of dipyridamole for human serum was 97.64%. Stability studies showed that dipyridamole was stable during storage, or during the assay procedure in human serum. The peak area and retention time of dipyridamole were not significantly affected by the changes of mobile phase pH, organic solvent content, and flow rate under the conditions studied. This method showed good ruggedness (within 15% C.V.) and was successfully used for the analysis of dipyridamole in human serum samples for the pharmacokinetic studies of orally administered Dimor tablet (75 mg as dipyridamole) at three different laboratories, demonstrating the suitability of the method.

• 대한핵의학회지
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• 제25권1호
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• pp.27-36
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• 1991

Thirty-one patients with coronary artery disease and twenty-sir normal subjects underwent $^{99m}Tc-GBPS$ before and after coronary vasodilatation was induced by dipyridamle 0.54 mg/kg given IV over 4 min. LVEF, ${\Delta}EF$ and regional wall motion by phase analysis were measured during rest and dipyridamole infusion. The results were as follows: 1) Mean LVEF of normal subjects was significantly higher than that of MI group (p=0.001), but similar to that of angina group during rest. Among MI group, mean LVEF of anterior MI group was significantly lower than that of inferior MI group during rest (p=0.024). 2) The normal subjects had a significaat increase in mean LVEF during dipyridamole infusion $(+12{\pm}3.8)$, while the CAD group had no increase $(+2{\pm}5.0)$ (p<0.001). If an increase of LVEF during stress is less than 5%, it suggests an abnormality. The sensitivity and specificity of LVEF changes after dipyridamole infusion were 81%, 96%, respectively. 3) With phase analysis, LV mean phase angle of normal subjects and CAD patients was $143{\pm}20.5^{\circ},\;132{\pm}20.6^{\circ}$ respectively, durign rest (p=0.049). But an ncrease of LV mean phase angle during dipyridamole infusion in these two groups was not significantly different. Dipyridamole infusion did not affect standard deviation and FWHM of phase angle. 4) Regional wall motion was abnormal in 5 patients (16%) during dipyridamole infusion. 5) Side effects with dipyridamole infusion include; headache, angina pain, chest discomfirt, nausea, weakness sense. In conclusion, dipyridamole GBPS might be useful in detection and follow up of CAD.

• The Korean Journal of Physiology and Pharmacology
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• 제5권5호
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• pp.423-431
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• 2001

Some recent investigations revealed that vasodilatory action of adenosine is mainly not mediated by surface A2 receptor and suggested the existence of an intracellular action site. In the present study, we tried to differentiate intracellular from extracellular site of adenosine action in the regulation of coronary flow. In perfused rabbit hearts, concentration-response curve of coronary flow to exogenous adenosine was constructed in the presence or absence of dipyridamole, an inhibitor of transmembrane purine transport. Inhibition of cellular adenosine uptake by dipyridamole suppressed the increase of flow rate while enhancing the decrease in heart rate induced by exogenous adenosine. In another series of experiments, perfused rabbit hearts were subjected to energy deprivation in order to increase the production of endogenous adenosine. Energy deprivation along with dipyridamole administration resulted in higher coronary flow rate. Lower perfusate adenosine concentration was observed along with higher tissue adenosine content in this group. These results implied that coronary flow rate is determined not by interstitial adenosine concentration but by intracellular activity of adenosine. To confirm the effects of dypiridamole in vivo, direct measurement of interstitial adenosine concentration by mycrodialysis along with the assay of intracellular adenosine content was performed after intranenous dipyridamole administration. After dipyridamole infusion, intracellular adenosine content was markedly increased while interstitial adenosine concentration was not altered. In another series of experiments, the right shift of concentration-response curve of adenosine-induced vasodilation by 8-phenyltheophilline, a representative adenosine receptor antagonist, was mostly abolished by prior administration of prazosin, indicating that the influence of 8-PT on the adenosine action is not attributed to the inhibition of A2 receptor but related to the suppression of ${\alpha}-adrenoceptor$ activation. From these results, we concluded that adenosine acts intracellularly to regulate the coronary blood flow.

• Journal of Yeungnam Medical Science
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• 제11권1호
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• pp.146-152
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• 1994

저자들은 14명의 관상동맥질환이 의심되지 않는 건강한 젊은 남자를 대상으로 dipyridamole 부하 $^{99m}Tc$-MIBI 심근 SPECT를 시행하였다. 이를 이용하여 Cedars-Sinai방법으로 극성지도를 구하고 전체 심근을 9부분으로 나누어 각 부위의 상대적인 방사능 세기를 조사하고 분석하였다. 이와 함께 dipyridamole 부하 전후의 혈역동학적인 변화와 부작용을 알아보았다. 극성지도에서 부하기와 휴식기 모두 방사능 계수치가 가장 높은 부위는 Latero-anterior wall이었고, 가장 낮은 부위는 Infero-septal wall이었다. 부하기와 휴식기사이의 각 부위의 방사능세기는 서로간에 유의한 차이가 없었다. dipyridamole 투여후 심박수와 이완기 혈압 및 Double product는 유의한 변화를 보였다. dipyridamole에 의한 부작용은 14명 중 12명에서 나타나 비교적 높은 비율을 보였으나 중한 부작용은 관찰되지 않았다. 이상의 결과로 $^{99m}Tc$-MIBI 심근 SPECT에서 구한 극성지도에서 관상동맥질환을 판정할 때는 부위별로 혈류 저하를 판정하는 기준이 달라야만 할 것으로 생각된다.

• 대한핵의학회지
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• 제27권1호
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• pp.35-50
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• 1993

심근관류 스캔에서 약제부하 검사에 많이 이용되는 것으로는 adenosine, dipyridamole, dobutamine등이 있다. 이 약제들이 혈역학 및 thallium의 약동학에 미치는 효과를 검사하기 위하여 저자들은 15명의 건강인을 대상으로 이들 약제를 정맥주사한 후에와 그리고 운동부하를 시행한 후에 thallium-201 신근관류 스캔을 시행하여 thallium의 약동학에 미치는 영향에 대하여 서로 비교하였다. 부작용은 adenosine (87%), dipyridamole(80%), dobutamine (73%)을 정맥주사할 시에 흔히 나타났으나 경미하였다. 1예에서는 dobutamine을 주사할때의 부작용으로 인하여 최대용량을 투여하지는 못한바 있었다. 대상들은 dipyridamole (13%)이나 dobutamine (27%)보다 adenosine (60%)을 선호하였다 (P<0.05). Thallium의 절대 적인 심근섭취는 운동부하 검사보다 adenosine (1.3배), dipyridamole(1.2배), dobutamine(1.4배) 부하시에 더 많았고, 이들 약제 사이에는 유의한 차이는 없었다. Thallium의 심근제거율(%/hr)는 운동부하 검사보다 약제부하한 후에가 더 늦었다. 폐, 간, 비장, 및 내장지역에서 thallium의 섭취 및 제거는 운동부하 검사보다 약제부하시에 더 많았으나, 이들 약제 사이에는 유의한 차이가 없었다. Dobutamine 투여시의 thallium의 섭취 및 제거는 adenosine 또는 dipyridamole을 투여시의 결과와 상응하였다. 저자들은 adenosine, dipyridamole 및 dobutamine을 이용한 약제부하 thallium-201 심근관류 검사를 시행하는데 코든 대상들에서 어려움 없이 쉽게 시행할 수 있었다. Thallium의 심근내 섭취 및 제거는 각 약제부하에 따라서 다를 수가 있으므로 심근관류 스캔의 정량적인 분석을 시행할 때는 각각 약제에 대한 특별한 진단기준이 마련되어야 할 것으로 생각된다.

• 대한핵의학회지
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• 제27권1호
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• pp.51-58
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• 1993

We have anlayzed the polar maps of dipyridamole stress/rest $^{99m}Tc$-MIBI SPECT and compared the quantitated perfusion defects of dipyridamole stress polar map and the findings of coronary angiography in 56 pateints with coronary artery diseases. We performed the same day dipyridamole stress-rest myocardial SPECT, reconstructed the polar maps according to Cedars-Sinai method and quantitated perfusion detects of total myocardium and the territory of each artery, comparing the polar maps of patients with normal files. Stenosis more than 50 percent was considered significant and myocardial ischemic score was calculated as summed score of percents of main coronary arteries. Positive concordance of myocardial SPECT with coronary angiography were 82.6% with left anterior descending artery (LAD), 85.7% with left circumflex artery (LCx) and 78.6% with right coronary artery (RCA). Perfusion defect of SPECT polar map and the stenosis of coronary artery showed the contingency phi of 0.55 (p<0.0001) with total atreries, 0.38 (p = 0.016) with LAD, 0.50 (p<0.0001) with LCx and 0.40 (p = 0.007) with RCA. Dipyridamole stress percent defect of polar map was correlated with myocardial ischemic score with Spearman's rho of 0.47 (p = 0.001) in total arteries, 0.48 (p=0.001) in LAD, 0.56 (p < 0.001) in LCx and 0.38 (p=0.002) in RCA. These findings revealed that defect of the dipyridamole stress myocardial $^{99m}Tc$-MIBI SPECT and the percent extent of this defect were related with significant artery stenosis of individual arteries and the degree of stenosis. We thought that we could use the defects in the polar map of dipyridamole stress $^{99m}Tc$-MIBI SPECT for the quantification of myocardiasl perfusion decrease.

• 대한핵의학회지
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• 제27권1호
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• pp.59-64
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• 1993

To evaluate the usefulness and differences in diagnosing coronary artery disease (CAD) between men and women of intravenous dipyridamole $^{99m}Tc$-MIBI myocardial SPECT, we obtained $^{99m}Tc$-MIBI myocardial SPECT and compared with the findings of coronary angiographies. Ninety eight male and 37 female patients who underwent dipyridamole $^{99m}Tc$-MIBI myocardial imaging within one month of cardiac catheterization were studied. Scans were considered abnormal if perfusion defect was detected and the defect size was more than 12% for left anterior descending artery (LAD) and circumflex (LCX) and 8% for right coronary artery (RCA) territories. Lesions${\geqq}$50% luminal diameter narrowing were considered significant CAD. Overall sensitivity for detection of CAD was 94.3% in men and 96.4% in women; specificity was 70% in men and 52.6% in women (P=not significant, ns). Vessel-matched sensitivity was 75.3% in men and 72.7% in women (P=ns): specificity was 84.6% in men and 67.9% in women (P < 0.025). For individual coronary artery, the sensitivity in men and women was 87.7%, 81.8% for LAD; 78%, 83.3% for RCA and 52.2%, 46.7% for LCX (P=ns): the specificity was 80%, 40% for LAD (P<0.01), 82.5%, 68.4% for RCA, 88.9%, 86.4% for LCX (P=ns). The hemodynamic parameter after intravenous dipyridamole in men and women were significantly changed; the heart rate was increased and systolic, diastolic blood pressure was decreased. Adverse effects were reported in 58.8% of men and 72.7% in women (P=ns). The incidence of chest pain and headache were higher in women. There was no significant difference in the incidences of nausea, abdominal pain, dizziness, facial flushing, dyspnea. In conclusion, dipyridamole $^{99m}Tc$-MIBI myocardial SPECT is a safe, noninvasive test for evaluation of CAD. There was no gender difference to detect CAD, but more false-positive rate in women especially in the territory of LAD.

• 대한핵의학회지
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• 제25권2호
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• pp.177-185
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• 1991

Dipyridamole thallium imaging is one of the most widely accepted means of evaluating patients with suspected or known coronay artery disease. The results of thallium imaging help diagnose coronary artery disesse (CAD), determine the hemodynamic significance of coronary stenosis, evaluate viability of myocardium, assess the outcome of therapeutic interventions and stratify patients according to their risk for luther cardiac events. An increased lung thallium uptake and transient LV dilation has been reported as poor prognostic indicator and associated with extensive and severe coronary artery disease. We quantitated lung/heart uptake ratio (l/HUR) and transient left ventricular dilation ratio in 44 patients and 17 controls undertaking dipyridamole thallium-201 scintigraphy. The results are as follows: 1) The lung/heart uptake ratio was high in patients with CAD and which became higher according to increasing number of diseased vessel. The L/HUR of patients with low LVEF (<35%) was lower than those with normal LVEF. 2) Transient left ventricular dilation ratio of CAD patients had no close relation between numbers of diseased vessels and was not higher than normals. But transient left ventricular dilation ratio of patients with myocardial infartion was higher than normals. We concluded that lung/heart uptake ratio seems to be sensitive marker for severity of CAD and myocardial function, but transient left ventricular dilation ratio alone is not sufficient to be a marker for severe and extensive CAD.

• 대한핵의학회지
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• 제37권3호
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• pp.153-161
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• 2003

목적: 이 연구의 목적은 Tl-201 게이트 심근 SPECT시 나타나는 부하 후 일시적 좌심실 기능이상의 임상적 의미를 알아보고자 하는 것이다. 대상 및 방법: 연구대상은 디피리다몰 부하 게이트 심근 SPECT를 시행한 환자 중 관상동맥조영술을 두 달 이내에 시행한 환자로 이 중 심근경색이 있는 경우는 제외하였다. 게이트 SPECT는 부하기와 재분포기 모두 실시하였으며 부하시 좌심실 구혈률이 재 분포기에 비하여 11%이상 감소한 경우에 부하 후 심근 기절이 있다고 정의하였다. 총 93명의 대상환자를 관상동맥조영술 결과에 따라 정상(1군)과 관상동맥 질환(2군)의 두 군으로 나누어 부하 후 좌심실 기능이상의 빈도에 차이가 있는지 알아보았다. 결과: 정상 대조군에서 좌심실 구혈률은 4시간 재분포기에 비하여 부하기에 평균 3.1% 증가하였으나, 관상동맥질환군에서는 평균 4.1% 감소하였다(p<0.01). 이완기말 좌심실 용적은 두 군 모두 부하기에 증가를 보였으며, 두 군 간에 유의한 차이가 없었다. 수축기말 좌심실 용적은 정상 대조군에서는 부하기에 0.7% 감소하였으나, 관상동맥질환군에서는 7.2% 증가하였다(p<0.01). 부하 후 좌심실 기능 이상은 1군 62명 중 0명, 2군 44명 중 8명(18.2%)으로 2군에서 유의하게 많았다(p<0.01). 정상 대조군에서 부하 후 일시적 좌심실 기능이상은 한 예도 관찰되지 않았다. 44명의 관상동맥질환 환자 중 8명에서 일시적 좌심실 기능이상이 관찰되었는데 단일혈관 협착에서 1 예(9.1%), 2 혈관 협착에서 0(0%), 3혈관 협착에서 2 예(14.3%), 좌주간동맥협착에서 5 예(62.5%)였다. 관상동맥질환 환자군을 다시 단일과 두 혈관 협착군과 세 혈관협착과 좌주간동맥 협착군의 두 군으로 나누어 일시적 좌심실기능이상의 빈도를 비교하였을 때 4.5%와 31.8%로 유의한 차이를 보였다(p<0.05). 결론: 디피리다몰과 Tl-201을 이용한 게이트 심근 SPECT에서 심근경색을 제외한 관상동맥질환이 있는 경우 약 20%에서 부하 후 심근기절이 나타남을 알 수 있었으며, 하나 또는 두 혈관질환보다는 세 혈관 질환 또는 좌주간지 협착에서 더 많이 발생하는 경향이 있어 관상동맥질환의 중증도 계층화와 예후추정에 대한 부가적인 정보를 제공할 수 있을 것으로 보인다.