These findings indicated that coronary microvascular spasm is one causative mechanism of ampulla cardiomyopathy.
SUMMARYWe examined the plasma levels of soluble Fas (sFas) or Fas ligand (sFas-L), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) in patients with idiopathic nonobstructive (HNCM) and dilated-phase (DHCM) hypertrophic cardiomyopathy.Patients with idiopathic hypertrophic cardiomyopathy (HCM) may deteriorate to DHCM and the pathogenesis is unknown.The levels of these plasma cytokines were measured by ELISA and echocardiography was performed in 38 HNCM and 11 DHCM patients, and 10 normal subjects. The followup period was three years.In HNCM, TNF-α (43.3 ± 45.2 versus 16.9 ± 4.3 pg/mL) and IL-6 (65.1 ± 86.4 versus 4.0 ± 2.1 pg/mL) were slightly higher compared to normal subjects and sFas (3.7 ± 1.2 versus 2.1 ± 0.7 ng/mL) increased significantly. sFas (3.9 ± 1.8), TNF-α (79.3 ± 72.4), and IL-6 (234.1 ± 135.2) in DHCM were significantly increased and only IL-6 was significantly different from HNCM. sFas-L (0.18 ± 0.08 versus 0.25 ± 0.05 ng/mL) in HNCM was significantly decreased, and the decrease was marked in DHCM (0.05 ± 0.02). In HNCM, TNF-α was negatively correlated with fractional shortening (r = -0.432, P = 0.0062) or positively with IL-6 (r = 0.665, P < 0.0001), while sFas-L was negatively correlated with IL-6 (r = -0.580, P < 0.0001). DHCM with high sFas had significantly higher cumulative incidences of worsening heart failure.The Fas/Fas-L system and proinflammatory cytokines may play an important role in the status of HCM and its progression to DHCM. (Int Heart J 2005; 46: 231-244)
-ray coronary angiography (CAG) is an indispensable examination technique for the diagnosis of coronary artery disease and for determination of therapeutic strategies. However, an anaphylactic reaction to the iodinated contrast media can be life-threatening. Gadolinium-based contrast media have been developed to improve the quality of magnetic resonance imaging (MRI) and are considered to be safer and less nephrotoxic than the iodinated agents. It has been recently reported that computed tomography (CT) and digital subtraction angiography (DSA) using gadolinium can provide images of largeand medium-sized vessels of acceptable quality in patients with allergy to iodinated media. 1-5 However, only a few studies of using gadolinium for CAG have been reported and only its safety in patients with renal insufficiency has been discussed. [6][7][8] We report successful CAG using gadodiamide hydrate (Gd DTPA-BMA; Omniscan ® Nycomed, Oslo. Norway) in 3 patients with allergy to iodinated contrast media. Written informed consent for the use of the contrast media was obtained from all patients. Case Reports Case 1A 70-year-old woman (52 kg) with a history of thyroidectomy for thyroid cancer and allergic reaction to iodinated contrast media was admitted to hospital after presenting with chest pain and dyspnea. Electrocardiography showed ST-segment elevation in leads V1-3 leads and T wave inversion in V2-4, and echocardiography showed hypokinesis in the apico-anteroseptal wall of the left ventricle. After sublingual administration of nitroglycerin, her symptoms Circulation Journal Vol. 69, April 2005 and the electrocardiographic findings improved. CAG was performed using 40 ml of undiluted Gd DTPA-BMA in a total of 7 injections because she had a previous, unspecified history of shock as a severe allergic reaction to treatment with an iodinated disinfectant. CAG revealed no significant stenoses in the major coronary arteries (Fig 1) and so we considered her anginal attack might be coronary arterial vasospasm in the left anterior descending artery. Case 2A 71-year-old man (68 kg) with gastric cancer and abdominal aortic aneurysm was admitted to hospital for gastric resection and artificial vessel replacement. He had a history of acute myocardial infarction at 63 years of age and an allergic reaction to an unspecified iodinated contrast media during abdominal CT performed when he was 60 years of age. 99m Tc-tetrofosmin myocardial scintigraphy on admission showed multivessel disease in his coronary arteries, so he underwent preoperative CAG using 40 ml of undiluted Gd DTPA-BMA in a total of 5 injections. Digital subtraction post-processing showed significant stenoses in the mid right coronary artery (segment 2: 75% stenosis), in the circumflex artery (segment 11: 75%, segment 13: 90%), and total occlusions in the distal right coronary artery (segment 4, postero-lateral branch) and the mid left anterior descending artery (segment 7) with contralateral collateral feedings (Fig 2). He underwent coronary artery bypass grafting be...
Administration of erythropoietin (EPO) during or immediately after myocardial ischemia can reduce subsequent myocardial apoptosis, a key phenomenon in myocardial ischemia-reperfusion injury. In this study, we assessed the effect of EPO on 99m Tcannexin V myocardial uptake and whether the accumulation of 99m Tc-annexin V can predict cardiac remodeling and functional deterioration. Methods: Eighteen rats with left coronary artery (LCA) occlusion were randomized to receive either an intravenous injection of EPO (EPO group) or saline (nontherapy [nT] group) immediately after release of the occlusion. After 20 min of LCA occlusion and 30 min of reperfusion, the rats were injected with 99m Tc-annexin V. One hour after 99m Tc-annexin V injection, the LCA was reoccluded and 201 Tl was injected intravenously, and the rats were sacrificed 1 min later. The heart was removed and sectioned, and dual-tracer autoradiography was performed to evaluate the distribution of the area at risk (defined on the thallium autoradiograph) and the area of apoptosis (defined on the annexin autoradiograph). Adjacent histologic specimens had deoxyuridine triphosphate nick-end labeling (TUNEL) staining to confirm the presence of apoptosis and were compared with autoradiography. Another 16 rats were randomized to EPO and nT groups and underwent echocardiography immediately after release of the LCA occlusion and at 2 and 4 wk after surgery. Results: The areas of 99m Tc-annexin V accumulation in the EPO group were smaller than those in the nT group, though the 201 Tl defect areas of these 2 groups were comparable (area ratio, 0.318 6 0.038 vs. 0.843 6 0.051, P , 0.001, for annexin and 24.8 6 2.1 vs. 25.9 6 2.6 mm 2 , P 5 NS, for thallium). 99m Tc-annexin V accumulation correlated with the density of TUNEL-positive cells (r 5 0.886, P , 0.001). In the nT group, left ventricular end-diastolic dimension (Dd) increased from baseline at 2 wk by 34.7% 6 3.8% and remained stable at 34.9% 6 5.0% at 4 wk after coronary occlusion. In the EPO group, Dd increased by 8.5% 6 2.1% (P , 0.01 vs. nT at 2 wk) and 13.2% 6 2.8% (P , 0.01 vs. nT at 4 wk). In the nT group, the left ventricular percentage of fractional shortening decreased by 42.2% 6 3.4% and 52.9% 6 3.4% at 2 and 4 wk, respectively, whereas in the EPO group it decreased 9.0% 6 1.9% at 2 wk (P , 0.01 vs. nT at 2 wk) and 11.1% 6 6.7% at 4 wk (P , 0.01 vs. nT at 4 wk). Conclusion: This study demonstrated that a single treatment with EPO immediately after release of coronary ligation suppressed cardiac remodeling and functional deterioration. 99m Tc-annexin V autoradiographs and TUNEL staining confirm that this change is due to a decrease in the extent of myocardial apoptosis in the ischemic/ reperfused region.
99mTc-HYNIC-annexin A5 can be considered as a benchmark in the field of apoptosis imaging. However, 99mTc-HYNIC-annexin A5 has characteristics of high uptake and long retention in non-target tissues such as kidney and liver. To minimize this problem, we developed a novel 99mTc-labeled annexin A5 using a bis(hydroxamamide) derivative [C3(BHam)2] as a bifunctional chelating agent, and evaluated its usefulness as an imaging agent for detecting apoptosis. The amino group of C3(BHam)2 was converted to a maleimide group, and was coupled to thiol groups of annexin A5 pretreated with 2-iminothiolane. 99mTc labeling was performed by a ligand exchange reaction with 99mTc-glucoheptonate. Biodistribution experiments for both 99mTc-C3(BHam)2-annexin A5 and 99mTc-HYNIC-annexin A5 were performed in normal mice. In addition, in tumor-bearing mice, the relationship between the therapeutic effects of chemotherapy (5-FU) and the tumor accumulation of 99mTc-C3(BHam)2-annexin A5 just after the first treatment of 5-FU was evaluated. 99mTc-C3(BHam)2-annexin A5 was prepared with a radiochemical purity of over 95%. In biodistribution experiments, 99mTc-C3(BHam)2-annexin A5 had a much lower kidney accumulation of radioactivity than 99mTc-HYNIC-annexin A5. In the organs for metabolism, such as liver and kidney, radioactivity after the injection of 99mTc-HYNIC-annexin A5 was residual for a long time. On the other hand, radioactivity after the injection of 99mTc-C3(BHam)2-annexin A5 gradually decreased. In therapeutic experiments, tumor growth in the mice treated with 5-FU was significantly inhibited. Accumulation of 99mTc-C3(BHam)2-annexin A5 in tumors significantly increased after 5-FU treatment. The accumulation of radioactivity in tumor correlated positively with the counts of TUNEL-positive cells. These findings suggest that 99mTc-C3(BHam)2-annexin A5 may contribute to the efficient detection of apoptotic tumor response after chemotherapy.
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