• The Korean Journal of Nuclear Medicine
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• v.27 no.2
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• pp.203-209
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• 1993

Dipyridamole is an agent that may be used to noninvasively evaluate coronary artery disease. The effect of dipyridamole infusion its generally related to its induced peripheral vasodilatory effect. In normal person, heart rate is generally increased slightly while blood pressure decrease, but the achieved double product and related myocardial oxygen consumption have no significant change. The purpose of this study is to examine the effect and side effect of dipyridamle, and to compare different response to dipyridamole among the patients. We evaluated 847 patients who underwent dipyridamole stress myocardial SPECT. 93.6% of them had induced hypotension, 0.9% showed no change of blood pressure, 5.5% had increased blood pressure. 8.3% had no change of pulse rate more than 10% of basal pulse rate. Among diabetes, 16.9% was not change of pulse rate, 6.7% in non-diabetes. There was no significant correlation between age and rate pressure product rest(RPPr), in patiens without perfusion defects on SPECT(y=7.1x+ 48.4 r=0.13 p>0.01). As increasing age, RPPs/RPPr was declined(y= -11.6x+68.9 r=0.17 p<0.01), similar results were obtained in patients with perfusion defect. The size of perfusion defect on myocardial SPECT have no correlation between RPPr and RPPs/RPPr. The side effects of dipyridamole included chest pain and chest tightness, headache, abdominal pain, dizzness, nausea, and dyspnea. As increasing age, dipyridamole-induced cardiac work at rest was increased, cardiac response to dipyridamole was decreased.

• Journal of Pharmaceutical Investigation
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• v.36 no.1
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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.

• The Korean Journal of Nuclear Medicine
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• v.25 no.1
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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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• v.5 no.5
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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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• v.11 no.1
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• pp.146-152
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• 1994

We performed the same day dipyridamole stress/rest myocardial SPECT in 14 healthy young men, reconstructed the polar maps according to Cedars-Sinai method and quantitated the radioactivity of myocardial wall. We divided the whole myocardium to 9 sectors. The latero-anterior wall contains the highest count. The infero-septal wall contains the lowest count. There isn't any significant differences of radioactivity in each segment between stress and rest polar map. The hemodynamic parameters after dipyridamole injection in the subjects were significantly changed except systolic blood pressure : the heart rate was increased and diastolic blood pressure was decreased. Adverse effects were reported in 85.7%. We suggest that these data can be used to dectect perfusion defect in the coromary artery disease.

• The Korean Journal of Nuclear Medicine
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• v.27 no.1
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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.

• The Korean Journal of Nuclear Medicine
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• v.27 no.1
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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.

• The Korean Journal of Nuclear Medicine
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• v.27 no.1
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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.

• The Korean Journal of Nuclear Medicine
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• v.25 no.2
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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.

• The Korean Journal of Nuclear Medicine
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• v.37 no.3
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• pp.153-161
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• 2003

Purpose: Recently the occurrence of dipyridamole stress-induced short term stunning was proven and it is reported that Bland Altman analysis by repeated acquisition Tl-201 gated myocardial SPECT (gSPECT) revealed the 95% limit of agreement for LVEF was 10.3 %. The purpose of this study was to investigate the clinical value of dipyridamole induced transient LV dysfunction on Tl-201 gSPECT. Materials and Methods: Total 93 patients were included and coronary angiography was peformed in all patients less than 2 month from gSPECT. The patients with myocardial infarction were excluded. All patients underwent both dipyridamole stress and 4-h redistribution Tl-201 gSPECT. Forty nine patients of total 93 showed normal coronary arteries (Group 1) and the remaining 44 patients had coronary artery disease (Group 2). We compared LV EF, EDV and ESV during post-stress and 4-h redistribution period calculated by gSPECT using quantitative gated SPECT software and the incidence of dipyridamole induced transient LV dysfunction between group 1 and 2. The criteria for transient LV dysfunction was defined more decrease ${\geq}11%$ of LVEF during post-stress than 4-h redistribution according to previous reported Bland Altman analysis. Results: During post-stress and 4-h redistribution average of 3.1% increment in LVEF, 6.6% increment in LVEDV and 0.7% decrement in LVESV were shown after stress in Group 1, whereas 4.1% decrement, 9.7% increment and 7.2% increment in Group 2 respectively. Dipyridamole induced transient LV dysfunction was only detected in group 2 (18.2%) and not in group 1. It was more frequently observed in triple vessel disease and left main disease (31.8%, N=22) than one and two vessel disease (4.5%, N=22). Conclusion: As with Tc-99m myocardial agent post-stress LV dysfunction was observed in dipyridamole Tl-201 gSPECT. It was only detected in CAD and more frequently occurred in multivessel disease. Thus this finding seems to provide additional information in the diagnosis of coronary artery disease and prediction of prognosis.