Taku Hirai

Evaluation of myocardial infarct size in rat heart by pinhole SPECT.

BackgroundHigh-resolution single photon emission computed tomography (SPECT) with a pinhole collimator is a new method for evaluating the regional properties of radiopharmaceuticals in small laboratory animals in vivo. Although several reports of normal images of rat taken by this new technique are available, there are as yet few reports on its use in disease models, such as myocardial infarction. In this study, we clearly visualized myocardial flow in the rat heart with myocardial infarction using this system, and evaluated the relationship between SPECT images and histologic analysis.Methods and ResultsFor visualization of myocardial flow in rat heart, 201Tl images were taken just before and 24 days after left coronary artery ligation. The images were taken using a 4-head SPECT scanner with pinhole collimators. The percent infarct size on 201Tl-SPECT imaging (%SI) and the defect score were then assessed and compared with the percent infarct size on histologic analysis (%HI). Both the %SI and defect score correlated well with %HI (r=0.97 and 0.74, respectively).ConclusionSerial SPECT imaging using pinhole collimators permits estimates of myocardial flow even in small laboratory animals noninvasively in vivo.

LOX-1 pathway affects the extent of myocardial ischemia-reperfusion injury

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) was originally identified as a receptor for oxidized low-density lipoprotein predominantly expressed in endothelial cells. LOX-1 expression can be induced in cardiomyocytes and that activation of LOX-1 is involved in apoptosis. To investigate possible roles of LOX-1 in myocardial ischemia-reperfusion injury, rats were subjected to coronary artery ligation for 1h followed by reperfusion for 2h. Immunohistochemistry revealed that expression of LOX-1 in cardiac myocytes was induced following ischemia-reperfusion but not ischemia alone. Administration of anti-LOX-1 monoclonal antibody resulted in a nearly 50% reduction in myocardial infarction size compared with that of normal IgG or saline (P<0.05). These findings suggest that activation of the LOX-1 pathway is involved in determining the extent of myocardial ischemia-reperfusion injury and that inhibition of the LOX-1 pathway may provide a novel strategy for treatment of acute myocardial infarction in humans.

Evaluation of coronary blood flow reserve by13N-NH3 positron emission computed tomography (PET) with dipyridamole in the treatment of hypertension with the ACE inhibitor (Cilazapril)

PurposeThe purpose of this study was to evaluate the effect of treatment with an angiotensin-converting enzyme (ACE) inhibitor (Cilazapril) for early hypertensive patients in terms of coronary blood flow reserve evaluated by13NH3-positron emission tomography (PET).MethodsBefore and after 12 weeks of ACE inhibitor treatment,13NH3-PET with dipyridamole provocation test was performed, and definite myocardial perfusion and coronary flow reserve (CFR) were calculated.ResultsCompared to our normal subjects previously reported (2.61±0.74), average coronary flow reserve was decreased (1.70±0.64 in hypertensive patients), and improved after treatment (1.77±0.52), but not significantly. Of 12 patients, five (42%) showed improved coronary flow reserve from 1.34 to 1.99 without a significant change in the resting flow. Only one patient (8%) showed deterioration after the ACE inhibitor treatment. The coronary vascular resistance (CVR) after ACE inhibitor treatment of the patients with CFR<2.0 decreased significantly compared with those with CFR≧2.0 (p<0.03).ConclusionsThese results indicate that hypertensive patients at the early stage show decreased coronary flow reserve despite having normal resting flow. Treatment with an ACE inhibitor (Cilazapril) for 12 weeks improved coronary flow reserve in 42% of our patients. The CVR of the patients with CFR<2.0 showed improvement compared to those with CFR≧2.0.This result indicates that an ACE inhibitor (e.g., Cilazapril) should be one of the choices for improving CFR if hypertensive patients in early stage show signs of ischemia or diastolic dysfunction, which may be one of the sequels of reserve restriction.

Basic kinetics of 15-(p-iodophenyl)-3-R, S-methylpentadecanoic acid (BMIPP) in canine myocardium

BMIPP is a radioiodinated fatty acid analogue used for myocardial single photon emission CT (SPECT) imaging based on high cardiac fatty acid metabolism. In normal dogs, 74% of the injected BMIPP was instantly extracted and was then retained in 65.3%. The washout of the retained radioactivity was low, and most of the washout was alpha- and beta-oxidation metabolites. ATP concentration plays an important role in the myocardial uptake and retention of BMIPP. The ATP-dependent BMIPP uptake at the TG pool was strongly regulated by etomoxir with modifying mitochondrial β-oxidation and subsequent ATP production. Thus, myocardial viability was reflected on the BMIPP uptake in acute ischemia. In spite of in-significant changes in early extraction and retention, BMIPP back diffusion (r=−0.92) and full-oxidation metabolite (r=0.78) were correlated with the severity of ischemia. Mismatched region of BMIPP with flow (Tl-201) showed decreased metabolic enzymes such as citrate synthase and 3-hydroxyacyl-CoA dehydrogenase. These data suggest that BMIPP would be feasible for detecting cellular energy state from lipid metabolism.

Myocardial metabolism of 123

1 Department of Cardiovascular Medicine, and Nuclear Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan 2 Department of Cardiology, Kitano Hospital, The Tazuke Kofukai Medical Research Institute, 2-4-20 Ohgimachi, Kita-ku, Osaka 530-8480, Japan 3 Molecular Imaging, Biomedical Imaging Research Center, Fukui Medical University, Fukui, Japan 4 Department of Cardiology, Nara Hospital, Kinki University School of Medicine, Nara, Japan