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Objective To explore the biodistribution and quantitative value of 18F-Flurpiridaz in mini-swine,and compare with 13N-NH3 · H2O.Methods Ten Bama mini-swine were divided into normal group and myocardial infarction group (n=5 in each group).Normal group was not treated and myocardial infarction group was modeled by thoracotomy and coronary artery ligation.Both groups were preceded by 13N-NH3 · H2O imaging,followed by 18F-Flurpiridaz imaging (time interval ＞40 min).Injection dosage of 2 tracers was the same (185-370 MBq).18F-Flurpiridaz whole-body PET/CT imaging was also performed in normal group.Biological distribution of 18F-Flurpiridaz was observed,and the ratio of radioactive uptake of 18F-Flurpiridaz between myocardium and adjacent tissues or organs was calculated.Image quality score and rest myocardial blood flow (rMBF) of 2 imaging tracers in normal group were measured and compared.MPI image quality score,cardiac function parameters such as summed rest score (SRS),myocardial infarction area percentage,total perfusion defect (TPD),and left ventricular ejection fraction (LVEF) of 2 imaging tracers were compared in myocardial infarction group.Data was analyzed by paired t test.Results In normal group,18F-Flurpiridaz in the myocardium was clearly observed,with high radioactive uptake maintaining within 2 h postinjection.The radioactivity count ratios of left ventricular myocardium to cardiac pool,the lungs and liver were high (5.19-12.87,4.17-50.51,2.08-6.92).The quality of 18F-Flurpiridaz MPI images in both groups was excellent (10/10).The rMBF (ml · g-1 · min-1) in different regions of left ventricle measured by 18F-Flurpiridaz and 13N-NH3 · H2O imaging were not significantly different (left anterior descending:0.98±0.06 vs 0.92±0.13;left circumflex:0.98±0.05 vs 0.88±0.12;right coronary artery:0.95±0.07 vs 0.88±0.15;left ventricle:0.96±0.07 vs 0.90±0.13;t values:from-1.70 to-0.90,all P＞0.05).There was no significant difference in SRS,myocardial infarction area percentage,TPD,rMBF or LVEF between 18F-Flurpiridaz and 13N-NH3 · H2O (SRS:10.6±4.1 vs 9.2±4.6;myocardial infarction area percentage:(15.2±9.0)％ vs (12.6±6.6)％;TPD:(11.6±6.3)％ vs (9.6±3.9)％;LVEF:(68.6±11.1)％ vs (71.4±11.3)％;t values:-2.33-2.75,all P＞0.05).Conclusions Comparing with 13N-NH3 · H2O,18F-Flurpiridaz has the advantages of good MPI image quality,accurate measurement of cardiac function parameters and quantitative potential of myocardial blood flow,which make it as a promising positron myocardial perfusion imaging agent.
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Objective@#To explore the biodistribution and quantitative value of 18F-Flurpiridaz in mini-swine, and compare with 13N-NH3·H2O.@*Methods@#Ten Bama mini-swine were divided into normal group and myocardial infarction group (n=5 in each group). Normal group was not treated and myocardial infarction group was modeled by thoracotomy and coronary artery ligation. Both groups were preceded by 13N-NH3·H2O imaging, followed by 18F-Flurpiridaz imaging (time interval >40 min). Injection dosage of 2 tracers was the same (185-370 MBq). 18F-Flurpiridaz whole-body PET/CT imaging was also performed in normal group. Biological distribution of 18F-Flurpiridaz was observed, and the ratio of radioactive uptake of 18F-Flurpiridaz between myocardium and adjacent tissues or organs was calculated. Image quality score and rest myocardial blood flow (rMBF) of 2 imaging tracers in normal group were measured and compared. MPI image quality score, cardiac function parameters such as summed rest score (SRS), myocardial infarction area percentage, total perfusion defect (TPD), and left ventricular ejection fraction (LVEF) of 2 imaging tracers were compared in myocardial infarction group. Data was analyzed by paired t test.@*Results@#In normal group, 18F-Flurpiridaz in the myocardium was clearly observed, with high radioactive uptake maintaining within 2 h postinjection. The radioactivity count ratios of left ventricular myocardium to cardiac pool, the lungs and liver were high (5.19-12.87, 4.17-50.51, 2.08-6.92). The quality of 18F-Flurpiridaz MPI images in both groups was excellent (10/10). The rMBF (ml·g-1·min-1) in different regions of left ventricle measured by 18F-Flurpiridaz and 13N-NH3·H2O imaging were not significantly different (left anterior descending: 0.98±0.06 vs 0.92±0.13; left circumflex: 0.98±0.05 vs 0.88±0.12; right coronary artery: 0.95±0.07 vs 0.88±0.15; left ventricle: 0.96±0.07 vs 0.90±0.13; t values: from -1.70 to -0.90, all P>0.05). There was no significant difference in SRS, myocardial infarction area percentage, TPD, rMBF or LVEF between 18F-Flurpiridaz and 13N-NH3·H2O (SRS: 10.6±4.1 vs 9.2±4.6; myocardial infarction area percentage: (15.2±9.0)% vs (12.6±6.6)%; TPD: (11.6±6.3)% vs (9.6±3.9)%; LVEF: (68.6±11.1)% vs (71.4±11.3)%; t values: -2.33-2.75, all P>0.05).@*Conclusions@#Comparing with 13N-NH3·H2O, 18F-Flurpiridaz has the advantages of good MPI image quality, accurate measurement of cardiac function parameters and quantitative potential of myocardial blood flow, which make it as a promising positron myocardial perfusion imaging agent.
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PET myocardial perfusion imaging (MPI) is increasingly used in non-invasive detection and evaluation of coronary artery disease (CAD). However, the wide application of common PET MPI agents (15O-H2O, 13N-NH3·H2O, 82Rb) in clinic is limited by their inherent shortcomings. The development of 18F-Flurpiridaz has opened up a new field of positron blood flow imaging agents. Preliminary results of pre-clinical and clinical trials showed that 18F-Flurpiridaz has important properties (high myocardial uptake, high resolution of perfusion defect, slow myocardial clearance, stable target/non-target ratio, and the ability of quantitative myocardial flow analysis) as an ideal PET MPI agent, so it has a good clinical application prospect. In this paper, the present application and progress of 18F-Flurpiridaz PET MPI are reviewed.
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PET myocardial perfusion imaging ( MPI) is increasingly used in non-invasive detection and evaluation of coronary artery disease ( CAD) . However, the wide application of common PET MPI a-gents ( 15 O-H2 O, 13 N-NH3 ·H2 O, 82 Rb) in clinic is limited by their inherent shortcomings. The develop-ment of 18 F-Flurpiridaz has opened up a new field of positron blood flow imaging agents. Preliminary results of pre-clinical and clinical trials showed that 18 F-Flurpiridaz has important properties ( high myocardial up-take, high resolution of perfusion defect, slow myocardial clearance, stable target/non-target ratio, and the ability of quantitative myocardial flow analysis) as an ideal PET MPI agent, so it has a good clinical appli-cation prospect. In this paper, the present application and progress of 18 F-Flurpiridaz PET MPI are re-viewed.
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Objective To evaluate the relationship between calmodulin protein kinase Ⅱ (CaMK Ⅱ) and levosimendan against arrhythmias induced by myocardial ischemia-reperfusion (I/R) in rats in vitro.Methods Thirty male Wistar rats,weighing 250-300 g,were randomly divided into 3 groups (n =10 each) using a random number table:control group (group C),I/R group and levosimendan group (group L).Their hearts were rapidly excised and perfused in a langendorff apparatus with K-H solution saturated with 95％ O2-5％ CO2 at 36.5-37.5 ℃.At 20 min of equilibration,the hearts were perfused with K-H solution for 60 min in group C.The hearts were subjected to 30 min of ischemia followed by 30 min reperfusion with K-H solution in group I/R.The hearts were subjected to 30 min of ischemia followed by 30 min reperfusion with K-H solution containing 300 nmol/L levosimendan in group L.Left ventricle developed pressure (LVDP),left ventricle end-diastolic pressure (LVEDP),+ dP/dt-dP/dtmax and heart rate (HR) were recorded immediately before ischemia and at 15 and 30 min of reperfusion.Arrhythmia was recorded during reperfusion and scored.Specimens were obtained from the apex of heart at 30 min of reperfusion for determination of the intracellular calcium concentration ([Ca2 +] i).Myocardial specimens were obtained from the left ventricle at 30 min of reperfusion to detect CaMK Ⅱ activity.Results Compared with group C,arrhythmia score,[Ca2+]i and CaMK [Ⅱ activity were significantly increased,and LVDP,+ dP/dtmax,-dP/dtmax and HR were decreased,and LVEDP was increased at 15 and 30 min of reperfusion in group I/R.Compared with group I/R,the number of ventricular premature beat,arrhythmia score,[Ca2+] i and CaMK Ⅱ activity were significantly decreased,and LVDP,+ dP/dtmax,-dP/dtmax and HR were increased,and LVEDP was decreased at 15 and 30 min of reperfusion in group L.Conclusion Inhibition of CaMK Ⅱ activity is involved in the mechanism by which levosimendan decreases the development of arrhythmias induced by myocardial I/R in rats.
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Objective To investigate the effect of levosimendan on pulmonary artery pressure in patients with pulmonary hypertension undergoing mitral valve replacement.Methods Twenty-four ASA Ⅱ or Ⅲ and NY-HA class Ⅱ or Ⅲ patients,aged 35-60 yr,with mean pulmonary artery pressure (MPAP) ＞ 30 mm Hg,undergoing mitral valve replacement were randomly divided into 2 groups (n =12 each):control group (group C) and levosimendan group (group L).In group L,a loading dose of levosimendan 24 μg/kg was injected intravenously after aortic unclamping,followed by infusion of levosimendan at a rate of 0.2 μg· kg-1 · min-1 until 1 d after operation.Group C received the equal volume of normal saline.HR,MAP,MPAP,pulmonary capillary wedge pressure (PCWP),cardiac index (CI) were recorded at 5 min after induction (T0),at the end of CPB (T1) and at 1 h after operation (T2),and the pulmonary vascular resistance (PVR) and rate-pressure product (RPP) were calculated.The improvement in pulmonary hypertension was recorded.Results PCWP was significantly lower and CI higher at T1,2 in both groups,and HR was significantly higher at T1,2 and MPAP lower at T2 in group C,and MPAP and PVR were significantly lower at T1,2 in group L than at T0 (P ＜ 0.05).HR,MPAP and PVR were significantly lower and CI was significantly higher at T1,2,RPP was significantly lower at T2 and the improvement in pulmonary hypertension was higher in group L than in group C (P ＜ 0.05).Conclusion Levosimendan can improve pulmonary hypertension without increasing the myocardial oxygen consumption and with a significant increase in myocardial contractility in patients with pulmonary hypertension undergoing mitral valve replacement.
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Objective To investigate the effect of STH-2 cardioplegic solution containing levosimendan on ischemia-reperfusion (I/R) injury in isolated rat hearts. Methods Thirty-two male Wistar rats weighing 250-300 gwere anesthetized with intraperitoneal 3% pentobarbital 30 mg/kg. The hearts were rapidly excised and perfused with oxygenated (95% O2-5% CO2) K-H solution for 30 min in a Langendorff apparatus and then divided into 4groups (n = 8 each) according to the composition of cardioplegic solution: group Ⅰ control (group C) was perfused with STH-2 cardioplegic solution; group Ⅱ , Ⅲ and Ⅳ were peffused with STH-2 cardioplegic solution containing levosimendan 0.03 μmol/L (L1), 0.3 μmol/L (L2) and levosimendan 0.3 μmol/L + glibenclamide 10 μmol/L (L2+ G) respectively. The isolated hearts were first perfused with different cardioplegic solutions for 2 h and then with K-H solution for 30 min. The coronary effluent was collected before ischemia (baseline) and at 10, 20 and 30 min of reperfusion for measurement of creatine kinase (CK) and lactate dehydrogenase (LDH)activities. Myocardial specimens were obtained from apex at 30 min of reperfusion for determination of myocardial ATP and MDA contents and SOD activity. Results Perfusion with STH-2 cardioplegic solution significantly increased CK and LDH activities and MDA content, and significantly decreased SOD activity. Levosinendan 0.03or 0.3 μmol/L significantly attenuated the cardioplegia-induced increase in LDH,CK and SOD activities and MDA content. The protective effects of levosimendan on myocardium against I/R injury were reversed by glibenclamide to some extent. Conclusion Levosimendan can protect myocardium from I/R injury in a dose-dependent manner by opening KATP channel.
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The effects of C1-930, a known selective phosphodiesterase 111 inhibitor, on vascular resistance and rat aortic strip contraction were studied CI-930 025mg/kg injected into the perfused artery, reduced vascular resistance markedly in femoral artery and internal carotid artery in anaesthetized rats. The action lasted for about 15-20 min. CI-930 in vitro inhibited norepinephrine (NE) and TXA2/PGH, mimetic U-46619 induced rat aortic strip contraction significantly with PD, values of 6.71 and 5.5 respectively. The inhibitory effects of CI-930 on NE and U-46619 induced contraction were more potent than that of KG induced contraction. CI-930 0.01 - 10?mol/L exhibited a potential inhibitory effects on intracellular Ca2+ dependent contraction of rat aortic strip induced by NE, but had no effect on extracellular Ca2+ dependent contraction. The results suggest that CI-930 can possess a potent intracellular Ca2+ dependent vasodilating effects in vitro and in vivo.