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Sample records for adenosine stress perfusion

  1. Development of Coronary Vasospasm during Adenosine-Stress Myocardial Perfusion CT Imaging.

    PubMed

    Nam, Jeong Gu; Choi, Seong Hoon; Kang, Byeong Seong; Bang, Min Seo; Kwon, Woon Jeong

    2015-01-01

    Adenosine is a short-acting coronary vasodilator, and it is widely used during pharmacological stress myocardial perfusion imaging. It has a well-established safety profile, and most of its side effects are known to be mild and transient. Until now, coronary vasospasm has been rarely reported as a side effect of adenosine during or after adenosine stress test. This study reports a case of coronary vasospasm which was documented on stress myocardial perfusion CT imaging during adenosine stress test.

  2. Prevalence of ECG changes during adenosine stress and its association with perfusion defect on myocardial perfusion scintigraphy.

    PubMed

    Taywade, Sameer K; Ramaiah, Vijayaraghavan L; Basavaraja, Harish; Venkatasubramaniam, Parameswaran R; Selvakumar, Job

    2017-04-01

    Myocardial perfusion scintigraphy (MPS) is a valuable, noninvasive imaging modality in the evaluation of patients with coronary artery disease. Adenosine stress may occasionally be associated with ECG changes. This study evaluated the strength of association between adenosine stress-related ECG changes and perfusion defects on Tc-MPS. 117 (mean age: 61.25±9.27 years; sex: men 87, women 30) patients with known/suspected coronary artery disease underwent adenosine stress MPS. ECG was monitored continuously during adenosine stress for ST-depression. On the basis of the summed difference score, reversible perfusion defects were categorized as follows: normal: less than 4, mild: 4-8, moderate: 9-13, and severe: more than 13. ST-depression was observed in 27/117 (23.1%) and reversible perfusion defects were observed in 18/27 (66.66%) patients. 2/27, 6/27, and 10/27 patients had mild, moderate, and severe ischemia, respectively. 9/27 patients had normal perfusion. ECG changes and perfusion defects showed a moderate strength of association (correlation coefficient r=0.35, P=0.006). The sensitivity, specificity, positive predictive value, and negative predictive value of ECG findings for prediction of ischemia were 35.29, 86.36, 67.67, and 63.33%, respectively. ECG changes during adenosine stress are not uncommon. It shows a moderate strength of association with reversible perfusion defects. ECG changes during adenosine merit critical evaluation of MPS findings.

  3. Adenosine stress thallium-201 myocardial perfusion imaging for detecting coronary artery disease at an early stage.

    PubMed

    Chen, Gui-Bing; Wu, Hua; He, Xiao-Jiang; Huang, Jin-Xiong; Yu, Dan; Xu, Wei-Yi; Yu, Hao

    2013-01-01

    The aims of this study were to evaluate the diagnostic value of adenosine thallium-201 myocardial perfusion imaging and to compare it with exercise stress thallium-201 myocardial perfusion imaging for detecting coronary artery disease (CAD) at an early stage. Forty-one patients suspected with CAD were randomly divided into two groups. In Group 1 (n=21) adenosine stress was undertaken; the exercise stress myocardial perfusion imaging was performed in Group 2 (n=20). Coronary angiography (CAG) was performed in each patient within 2 weeks before or after single photon emission computed tomography (SPECT). Adenosine stress group vs. exercise stress group, the sensitivity was 92.86% vs. 100.0%, specificity 57.14% vs. 60.0%, positive predictive value 81.25% vs. 71.43%, negative predictive value 80.0% vs. 100.0%, accuracy 80.95% vs. 80.0% respectively. Detection rates of vessels of coronary artery lesions were 66.67% in Group 1 and 72.22% in Group 2 (P> 0.05). The side effects were mild and transient. Our results demonstrated that adenosine stress myocardial perfusion imaging is a safe and reliable diagnostic method for an early stage of CAD. As a comparative sensitivity and accuracy with exercise stress thallium-201 myocardial perfusion imaging, adenosine stress testing may provide a feasible alternative pharmacological stress method in myocardial SPECT for detection of CAD.

  4. Adenosine Stress Induced Left Bundle Branch Block During Technetium-99m Tetrofosmin Myocardial Perfusion Imaging

    PubMed Central

    Jayanthi, Mohan Roop; Sasikumar, Arun; Gorla, Arun Kumar Reddy; Sood, Ashwani; Bhattacharya, Anish; Mittal, Bhagwant Rai

    2017-01-01

    The occurrence of left bundle branch block (LBBB) in electrocardiogram during exercise testing is a relatively rare finding. The incidence of LBBB during exercise testing ranges from 0.5% to 1.1%. The mechanism of exercise-induced LBBB (EI-LBBB) is poorly understood, but ischemia is a proposed etiology. Stress myocardial perfusion imaging (MPI) can be useful in patients with EI-LBBB to rule out coronary artery disease. Adenosine vasodilator stress is the preferred mode of stress in patients with LBBB for performing stress-MPI. Here we present an interesting case of adenosine-induced LBBB during stress-MPI in a 67-year-old female patient with normal coronary angiography. PMID:28217027

  5. Relation between quantitative coronary CTA and myocardial ischemia by adenosine stress myocardial CT perfusion.

    PubMed

    van Rosendael, Alexander R; Kroft, Lucia J; Broersen, Alexander; Dijkstra, Jouke; van den Hoogen, Inge J; van Zwet, Erik W; Bax, Jeroen J; de Graaf, Michiel A; Scholte, Arthur J

    2016-02-09

    Coronary-computed tomography angiography (CTA) has limited accuracy to predict myocardial ischemia. Besides luminal area stenosis, other coronary plaque morphology and composition parameters may help to assess ischemia. With the integration of coronary CTA and adenosine stress CT myocardial perfusion (CTP), reliable information regarding coronary anatomy and function can be derived in one procedure. This analysis aimed to investigate the association between coronary stenosis severity, plaque composition and morphology and the presence of ischemia measured with adenosine stress myocardial CTP. 84 patients (age, 62 ± 10 years; 48% men) who underwent sequential coronary CTA and adenosine stress myocardial CT perfusion were analyzed. Automated quantification was performed in all coronary lesions (quantitative CTA). Downstream myocardial ischemia was assessed by visual analysis of the rest and stress CTP images and defined as a summed difference score of ≥1. One or more coronary plaques were present in 146 coronary arteries of which 31 (21%) were ischemia-related. Of the lesions with a stenosis percentage <50%, 50%-70%, and >70%, respectively, 9% (6/67), 18% (9/51), and 57% (16/28) demonstrated downstream ischemia. Furthermore, mean plaque burden, plaque volume, lesion length, maximal plaque thickness, and dense calcium volume were significantly higher in ischemia-related lesions, but only stenosis severity (%) (OR 1.06; 95% CI 1.02-1.10; P = .006) and lesion length (mm) (OR 1.26; 95% CI 1.02-1.55; P = .029) were independent correlates. Increasing stenosis percentage by quantitative CTA is positively correlated to myocardial ischemia measured with adenosine stress myocardial CTP. However, stenosis percentage remains a moderate determinant. Lumen area stenosis and lesion length were independently associated with ischemia, adjusted for coronary plaque volume, mean plaque burden, maximal lesion thickness, and dense calcium volume.

  6. Effect of caffeine on myocardial perfusion imaging using single photon emission computed tomography during adenosine pharmacologic stress.

    PubMed

    Kovacs, Daniela; Pivonka, Robert; Khosla, Pam G; Khosla, Sandeep

    2008-01-01

    Approximately 6 million cardiac stress tests are performed annually in the United States, of which 2.4 million are pharmacologic stress tests using agents such as adenosine. Adenosine induces differential coronary hyperemia in normal coronary arteries versus coronary arteries with atherosclerosis, allowing single photon emission computed tomography (SPECT) imaging to identify reduced coronary flow in segments subtended by diseased coronary arteries. The potential attenuation of pharmacologic effects of adenosine in the presence of caffeine is why patients are routinely instructed to abstain from caffeine for 12 to 24 hours prior to administration of an adenosine stress test. Failure to abstain from caffeine results in cancellation or delaying of cardiac stress testing, resulting in procedural delays and its impact on patient throughput. Recent studies have evaluated such interaction and suggested a lack of clinically significant effect of caffeine on adenosine-induced hyperemia during myocardial SPECT imaging. This article reviews the clinical pharmacology of caffeine, adenosine, and dipyridamole and effect of caffeine on myocardial stress testing using adenosine and dipyridamole in clinical cardiovascular medicine. The limited published data are conflicting, but some recent publications suggest that myocardial perfusion SPECT imaging using adenosine may not be clinically significantly altered by routine consumption of caffeine, such as a cup of coffee. Although prospective randomized studies would be required to obtain a definitive answer to this question, it appears on the basis of some of the studies reviewed in this article that caffeine consumption prior to myocardial perfusion imaging may not necessitate cancellation or rescheduling of adenosine stress testing.

  7. Assessment of Coronary Flow Reserve by Adenosine Stress Myocardial Perfusion Imaging in Patients with Hypertension.

    PubMed

    Fu, Qiang; Zhang, Qian; Lu, Wen; Wang, Yuetao; Huang, Yijie; Wang, Yanjiong; Wu, Qiang; Lu, Cunzhi

    2015-11-01

    In this study, our aim was to assess the coronary flow reserve (CFR) by performing the adenosine stress (99m)Tc-MIBI single-photon computed tomographic (SPECT) myocardial perfusion imaging in patients with hypertension. 47 hypertensive patients with normal coronary angiography were divided into 2 groups, defined by the presence (LVH, n = 22) and absence (non-LVH, n = 25) of left ventricular hypertrophy with 17 normal cases as controls. All patients were administered the adenosine stress-rest (99m)Tc-MIBI scintigraphy. 0.14 mg/kg/min adenosine was administered by continuous infusion for 6 min. We found that adenosine-induced myocardial ischemia was present in 26 cases (55.3 %) with 87 segments (20.6 %) showing abnormal distribution in the hypertensive group versus a single case (5.9 %) (χ (2) = 31.12, P < 0.001) and segment (0.7 %) (χ (2) = 32.90, P < 0.001) in the control group by SPECT perfusion. In the LVH group, 17 cases (77.3 %) and 67 segments (33.8 %) of myocardial ischemia were present. In the non-LVH group, there were 9 cases (36.0 %) (χ (2) = 8.06, P < 0.001), 20 segments (8.9 %) (χ (2) = 40.13, P < 0.001). There was a significant decrease in coronary reserve in the hypertensive groups following adenosine infusion with a fourfold decrease in cases and a sixfold decrease in segments (P < 0.001). Our study suggests that assessing CFR by the (99m)Tc-MIBI adenosine stress by SPECT imaging is a relatively easy, safe, and non-invasive test in patients with hypertension. We noted a decrease in CFR in patients with hypertension. This decrease was especially remarkable for hypertensive patients with LVH. This study shows that administering the (99m)Tc-MIBI adenosine stress by SPECT imaging is a safe, simple, and non-invasive test for detecting CFR in patients with hypertension.

  8. Caffeine intake inverts the effect of adenosine on myocardial perfusion during stress as measured by T1 mapping.

    PubMed

    Kuijpers, Dirkjan; Prakken, Niek H; Vliegenthart, Rozemarijn; van Dijkman, Paul R M; van der Harst, Pim; Oudkerk, Matthijs

    2016-10-01

    Caffeine intake before adenosine stress myocardial perfusion imaging may cause false negative findings. We hypothesized that the antagonistic effect of caffeine can be measured by T1 relaxation times in rest and adenosine stress cardiac magnetic resonance imaging (CMR), as T1 mapping techniques are sensitive to changes in myocardial blood volume. We prospectively analyzed 105 consecutive patients with adenosine stress perfusion CMR on a 1.5-T MRI system. Rest and stress T1 mapping was performed using Modified Look-Locker Inversion recovery. T1 reactivity was defined as difference in T1rest and T1stress (∆T1). Fifteen patients drank coffee within 4 h of CMR (<4H caffeine group), and 10 patients had coffee the day before (>8H caffeine group). Comparison was made to patients without self-reported coffee intake: 50 with normal CMR (control group), 18 with myocardial ischemia, and 12 with myocardial infarction. The national review board approved the study; all patients gave written informed consent. The <4H caffeine group showed inverted ∆T1 of -7.8 % (T1rest 975 ± 42 ms, T1stress 898 ± 51 ms, p < 0.0005). The >8H caffeine group showed reduced T1 reactivity (1.8 %; T1rest 979 ms, T1stress 997 ms) compared to the controls (4.3 %; T1rest 977 ± 40 ms, T1stress 1018 ± 40 ms), p < 0.0005. Ischemic and infarcted myocardium showed minimal T1 reactivity (0.2 and 0.3 %, respectively). Caffeine intake inverts the adenosine effect during stress perfusion CMR as measured by T1 mapping. T1 reactivity can assess the adequacy of adenosine-induced stress in perfusion CMR.

  9. Incremental Value of Adenosine-induced Stress Myocardial Perfusion Imaging with Dual-Source CT at Cardiac CT Angiography1

    PubMed Central

    Rocha-Filho, Jose A.; Blankstein, Ron; Shturman, Leonid D.; Bezerra, Hiram G.; Okada, David R.; Rogers, Ian S.; Ghoshhajra, Brian; Hoffmann, Udo; Feuchtner, Gudrun; Mamuya, Wilfred S.; Brady, Thomas J.

    2010-01-01

    Purpose: First, to assess the feasibility of a protocol involving stress-induced perfusion evaluated at computed tomography (CT) combined with cardiac CT angiography in a single examination and second, to assess the incremental value of perfusion imaging over cardiac CT angiography in a dual-source technique for the detection of obstructive coronary artery disease (CAD) in a high-risk population. Materials and Methods: Institutional review board approval and informed patient consent were obtained before patient enrollment in the study. The study was HIPAA compliant. Thirty-five patients at high risk for CAD were prospectively enrolled for evaluation of the feasibility of CT perfusion imaging. All patients underwent retrospectively electrocardiographically gated (helical) adenosine stress CT perfusion imaging followed by prospectively electrocardiographically gated (axial) rest myocardial CT perfusion imaging. Analysis was performed in three steps: (a)Coronary arterial stenoses were scored for severity and reader confidence at cardiac CT angiography, (b)myocardial perfusion defects were identified and scored for severity and reversibility at CT perfusion imaging, and (c)coronary stenosis severity was reclassified according to perfusion findings at combined cardiac CT angiography and CT perfusion imaging. The sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) of cardiac CT angiography before and after CT perfusion analysis were calculated. Results: With use of a reference standard of greater than 50% stenosis at invasive angiography, all parameters of diagnostic accuracy increased after CT perfusion analysis: Sensitivity increased from 83% to 91%; specificity, from 71% to 91%; PPV, from 66% to 86%; and NPV, from 87% to 93%. The area under the receiver operating characteristic curve increased significantly, from 0.77 to 0.90 (P < .005). Conclusion: A combination protocol involving adenosine perfusion CT imaging and cardiac

  10. Subendocardial steal effect seen with real-time perfusion imaging at low emission power during adenosine stress: replenishment M-mode processing allows visualization of vertical steal.

    PubMed

    Tiemann, K; Ghanem, A; Schlosser, T; Ehlgen, A; Kuntz-Hehner, S; Haushofer, M; Bimmel, D; Borovac, M; Nanda, N C; Omran, H; Becher, H

    2001-11-01

    We present a patient in whom power pulse inversion imaging clearly demonstrated a subendocardial myocardial perfusion defect during contrast vasodilator stress using adenosine. The defect was best appreciated with M-mode postprocessing of power pulse inversion imaging data.

  11. Parametric quantification of myocardial ischaemia using real-time perfusion adenosine stress echocardiography images, with SPECT as reference method.

    PubMed

    Gudmundsson, P; Shahgaldi, K; Winter, R; Dencker, M; Kitlinski, M; Thorsson, O; Ljunggren, L; Willenheimer, R

    2010-01-01

    Real-time perfusion (RTP) adenosine stress echocardiography (ASE) can be used to visually evaluate myocardial ischaemia. The RTP power modulation technique, provides images for off-line parametric perfusion quantification using Qontrast software. From replenishment curves, this generates parametric images of peak signal intensity (A), myocardial blood flow velocity (beta) and myocardial blood flow (Axbeta) at rest and stress. This may be a tool for objective myocardial ischaemia evaluation. We assessed myocardial ischaemia by RTP-ASE Qontrast((R))-generated images, using 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) as reference. Sixty-seven patients admitted to SPECT underwent RTP-ASE (SONOS 5500) during Sonovue infusion, before and throughout adenosine stress, also used for SPECT. Quantitative off-line analyses of myocardial perfusion by RTP-ASE Qontrast-generated A, beta and Axbeta images, at different time points during rest and stress, were blindly compared to SPECT. We analysed 201 coronary territories [corresponding to the left anterior descendent (LAD), left circumflex (LCx) and right coronary (RCA) arteries] from 67 patients. SPECT showed ischaemia in 18 patients. Receiver operator characteristics and kappa values showed that A, beta and Axbeta image interpretation significantly identified ischaemia in all territories (area under the curve 0.66-0.80, P = 0.001-0.05). Combined A, beta and Axbeta image interpretation gave the best results and the closest agreement was seen in the LAD territory: 89% accuracy; kappa 0.63; P<0.001. Myocardial isachemia can be evaluated in the LAD territory using RTP-ASE Qontrast-generated images, especially by combined A, beta and Axbeta image interpretation. However, the technique needs improvements regarding the LCx and RCA territories.

  12. The influence of clinical and acquisition parameters on the interpretability of adenosine stress myocardial computed tomography perfusion.

    PubMed

    van Rosendael, Alexander R; de Graaf, Michiel A; Dimitriu-Leen, Aukelien C; van Zwet, Erik W; van den Hoogen, Inge J; Kharbanda, Rohit K; Bax, Jeroen J; Kroft, Lucia J; Scholte, Arthur J

    2017-02-01

    The interpretation of adenosine stress myocardial computed tomography perfusion (CTP) is often hampered by image artefacts caused by cardiac motion, beam hardening, and cone beam. The aim of the present analysis was to assess the influence of the heart-rate response during adenosine infusion, patient characteristics, and medication use on the interpretability of stress myocardial CTP examinations. Interpretability of stress myocardial CTP examinations was evaluated in 120 patients who underwent sequentially coronary CTA and adenosine stress myocardial CTP (320-row CT scanner, temporal resolution 175 ms) and scored as follows: excellent = absence of any artefact (n = 27, 22%); good = presence of artefacts that do not interfere with the study interpretability (n = 56, 47%); fair = artefacts that do interfere with interpretability (n = 35, 29%); poor = uninterpretable study due to artefacts (n = 2, 2%). 'Fair' and 'poor' were merged into 'reduced' for comparisons. Increasing heart rate during stress myocardial CTP acquisition was related to worse interpretability (excellent: 61.7 ± 13.4 bpm vs. good: 69.8 ± 13.5 bpm vs. reduced: 78.1 ± 17.0 bpm, P < 0.001). Thirteen (11%) of all examinations were considered non-diagnostic. In patients with a heart rate exceeding 85 bpm, 76% of the studies were 'reduced' interpretable. In multivariate analysis, no use of beta blocker (baseline or additional use prior to coronary CTA) (OR: 0.2, P = 0.012), increasing heart rate during coronary CTA (OR: 1.09, P = 0.032), younger age (OR: 0.92, P = 0.021), and the use of calcium antagonist (OR: 6.48, P = 0.017) were independently associated with a heart rate ≥85 bpm during stress myocardial CTP. Higher heart rate during the acquisition of stress myocardial CTP was related to worse interpretability. Furthermore, increasing heart rate during and no beta blocker use prior to the previously performed coronary CTA, younger age, and the use of calcium antagonist were independently

  13. Adenosine stress high-pitch 128-slice dual-source myocardial computed tomography perfusion for imaging of reversible myocardial ischemia: comparison with magnetic resonance imaging.

    PubMed

    Feuchtner, Gudrun; Goetti, Robert; Plass, André; Wieser, Monika; Scheffel, Hans; Wyss, Christophe; Stolzmann, Paul; Donati, Olivio; Schnabl, Johannes; Falk, Volkmar; Alkadhi, Hatem; Leschka, Sebastian; Cury, Ricardo C

    2011-09-01

    Coronary computed tomography angiography (CTA) enables accurate anatomic evaluation of coronary artery stenosis but lacks information about hemodynamic significance. The aim of this study was to evaluate 128-slice myocardial CT perfusion (CTP) imaging with adenosine stress using a high-pitch mode, in comparison with cardiac MRI (CMR). Thirty-nine patients with intermediate to high coronary risk profile underwent adenosine stress 128-slice dual source CTP (128×0.6 mm, 0.28 seconds). Among those, 30 patients (64 ± 10 years, 6% women) also underwent adenosine stress CMR (1.5T). The 2-step CTP protocol consisted of (1) adenosine stress-CTP using a high-pitch factor (3.4) ECG-synchronized spiral mode and (2) rest-CTP/coronary-CTA using either high-pitch (heart rate <63 bpm) or prospective ECG-triggering (heart rate >63 bpm). Results were compared with CMR and with invasive angiography in 25 patients. The performance of stress-CTP for detection of myocardial perfusion defects compared with CMR was sensitivity, 96%; specificity, 88%; positive predictive value (PPV), 93%; negative predictive value (NPV), 94% (per vessel); and sensitivity, 78%; specificity, 87%; PPV, 83%; NPV, 84% (per segment). The accuracy of stress-CTP for imaging of reversible ischemia compared with CMR was sensitivity, 95%; specificity, 96%; PPV, 95%; and NPV, 96% (per vessel). In 25 patients who underwent invasive angiography, the accuracy of CTA for detection of stenosis >70% was (per segment): sensitivity, 96%; specificity, 88%; PPV, 67%; and NPV, 98.9%. The accuracy improved from 84% to 95% after adding stress CTP to CTA. Radiation exposure of the entire stress/rest CT protocol was only 2.5 mSv. Adenosine-induced stress 128-slice dual-source high-pitch myocardial CTP allows for simultaneously assessment of reversible myocardial ischemia and coronary stenosis, with good diagnostic accuracy as compared with CMR and invasive angiography, at a very low radiation exposure.

  14. Functional changes in patients with internet addiction disclosed by adenosine stressed cerebral blood flow perfusion imaging (99m)Tc-ECD SPET.

    PubMed

    Liu, Guobing; Han, Lei; Hu, Yan; Xiao, Jie; Li, Yanli; Tan, Hui; Zhang, Yiqiu; Cheng, Dengfeng; Shi, Hongcheng

    2016-01-01

    To investigate the abnormal cerebral blood flow (CBF) perfusion in patients with internet addiction (IA) and its possible association with IA severity. Thirty-five adolescents who met the criteria for IA and 12 matched healthy volunteers were recruited for (99m)Tc-ethylcysteinate dimer based CBF perfusion imaging with single photon emission tomography (SPET) both at rest and in adenosine-stressed state. Regional CBF (rCBF) was measured and compared between IA subjects and the controls. Correlation analysis between those abnormal rCBF in adenosine-stressed state and the duration of IA was performed. At the resting state, the IA individuals showed significantly increased rCBF in the left mid-frontal gyrus and left angular gyrus, but significantly decreased in the left paracentral lobule, compared to the controls. In adenosine-stressed state, more cerebral regions with abnormal rCBF were identified. Specifically, increased rCBF was identified in the right paracentral lobule, right mid-frontal gyrus and left superior temporal gyrus, while decreased rCBF were demonstrated in right transverse temporal gyrus, left inferior frontal gyrus and left precuneus. Those rCBF in rCBF-increased regions in stress state were positively correlated with the duration of IA, while those in rCBF-decreased regions were negatively correlated with the duration of IA. We present specific functional changes in behaviour that may appear in IA patients related to the CBF findings in IA patients. Adenosine can be used as a pharmacological agent for stress CBF perfusion imaging in patients with IA, by which more cerebral regions of abnormal rCBF can be identified compared to the state at rest. These abnormal rCBF may indicate the neurological mechanism in IA patients.

  15. Negative predictive value of normal adenosine-stress cardiac MRI in the assessment of coronary artery disease and correlation with semiquantitative perfusion analysis.

    PubMed

    Pilz, Guenter; Eierle, Susanne; Heer, Tobias; Klos, Markus; Ali, Eman; Scheck, Roland; Wild, Michael; Bernhardt, Peter; Hoefling, Berthold

    2010-09-01

    To prospectively determine the negative predictive value of normal adenosine stress cardiac MR (CMR) in routine patients referred for evaluation of coronary artery disease (CAD), predominantly with intermediate to high pretest risk. Consecutive patients referred for coronary angiography were examined in a 1.5 Tesla whole-body scanner before catheterization. A total of 158 patients with normal CMR on qualitative assessment were included, and semiquantitative perfusion analysis was performed. Significant CAD was regarded as luminal narrowing of >or=70% in coronary angiography. In the 158 study patients, negative predictive value of normal adenosine-stress CMR for significant CAD was 96.2% (for stenosis >or=90%: 98.1%). True-negative and false-negative patients were comparable regarding clinical presentation, risk factors, and CMR findings. Semiquantitative perfusion analysis gave significantly prolonged arrival time index and peak time index in the false-negative group. Using cutoff values >1.8 for arrival time index or >1.2 for peak time index, the CMR negative predictive value increased to 98.7% (for stenosis >or=90%: to 100%). The very high negative predictive value for CAD supports CMR-based decision making for the indication to coronary angiography. Semiquantitative perfusion analysis seems promising to identify the small group of CAD patients not detectable by qualitative CMR assessment.

  16. Adenosine thallium 201 myocardial perfusion scintigraphy

    SciTech Connect

    Verani, M.S. )

    1991-07-01

    Pharmacologic coronary vasodilation as an adjunct to myocardial perfusion imaging has become increasingly important in the evaluation of patients with coronary artery disease, in view of the large number of patients who cannot perform an adequate exercise test or in whom contraindications render exercise inappropriate. Adenosine is a very potent coronary vasodilator and when combined with thallium 201 scintigraphy produces images of high quality, with the added advantages of a very short half-life (less than 10 seconds) and the ability to adjust the dose during the infusion, which may enhance safety and curtail the duration of side effects. The reported sensitivity and specificity of adenosine thallium 201 scintigraphy for the detection of coronary artery disease are high and at least comparable with imaging after exercise or dipyridamole administration. 23 refs.

  17. Adenosine triphosphate stress 99mTc-methoxyisobutylisonitrile gated myocardial perfusion imaging efficacy in diagnosing stent restenosis following coronary stent implantation

    PubMed Central

    Zhang, Pengfei; Chen, Song; Li, Yang; Du, Qiuhong; Wang, Lijuan; Sun, Yingxian; Li, Yaming

    2016-01-01

    Coronary stent restenosis rate following implantation is considerably high. The adenosine stress gated myocardial perfusion imaging (G-MPI) method has been widely used in the diagnosis, risk stratification and prognosis evaluation of coronary heart disease; however, the high cost of adenosine limits its clinical application. The aim of the present study was to investigate the efficacy of adenosine triphosphate (ATP) stress 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) G-MPI for diagnosis in-stent restenosis following coronary stent implantation. Data from 66 patients with typical angina pectoris symptoms who had undergone percutaneous coronary stent implantation >3 months prior to participation in the study were analyzed. All the patients underwent ATP stress 99mTc-MIBI G-MPI and coronary artery angiography as the criterion diagnostic standard within 1 month. The sensitivity, specificity, and accuracy of ATP stress 99mTc-MIBI G-MPI in the assessment of in-stent restenosis were calculated. In addition, Fisher's exact probability methods were used to compare differences between experimental groups. Among 66 patients with a total of 99 implanted coronary arterial branches, 39 patients (59%) with 45 coronary arteries (45%) presented in-stent restenosis. The diagnostic sensitivity, specificity, accuracy, positive predictive and negative predictive value of ATP stress 99mTc-MIBI G-MPI for assessing stent restenosis in all patients were 85, 89, 86, 92 and 80%, respectively. Similarly, these values in patients with myocardial infarction were 79, 88, 83, 88 and 78%, respectively, while in patients without myocardial infarction the values were 90, 91, 90, 95 and 83%, respectively. Therefore, the diagnostic efficacy of ATP stress 99mTc-MIBI G-MPI in patients without myocardial infarction was higher compared with those with myocardial infarction; however, no significant difference was observed between the two groups. Furthermore, the sensitivity, specificity and accuracy for

  18. Adenosine triphosphate stress (99m)Tc-methoxyisobutylisonitrile gated myocardial perfusion imaging efficacy in diagnosing stent restenosis following coronary stent implantation.

    PubMed

    Zhang, Pengfei; Chen, Song; Li, Yang; Du, Qiuhong; Wang, Lijuan; Sun, Yingxian; Li, Yaming

    2016-12-01

    Coronary stent restenosis rate following implantation is considerably high. The adenosine stress gated myocardial perfusion imaging (G-MPI) method has been widely used in the diagnosis, risk stratification and prognosis evaluation of coronary heart disease; however, the high cost of adenosine limits its clinical application. The aim of the present study was to investigate the efficacy of adenosine triphosphate (ATP) stress (99m)Tc-methoxyisobutylisonitrile ((99m)Tc-MIBI) G-MPI for diagnosis in-stent restenosis following coronary stent implantation. Data from 66 patients with typical angina pectoris symptoms who had undergone percutaneous coronary stent implantation >3 months prior to participation in the study were analyzed. All the patients underwent ATP stress (99m)Tc-MIBI G-MPI and coronary artery angiography as the criterion diagnostic standard within 1 month. The sensitivity, specificity, and accuracy of ATP stress (99m)Tc-MIBI G-MPI in the assessment of in-stent restenosis were calculated. In addition, Fisher's exact probability methods were used to compare differences between experimental groups. Among 66 patients with a total of 99 implanted coronary arterial branches, 39 patients (59%) with 45 coronary arteries (45%) presented in-stent restenosis. The diagnostic sensitivity, specificity, accuracy, positive predictive and negative predictive value of ATP stress (99m)Tc-MIBI G-MPI for assessing stent restenosis in all patients were 85, 89, 86, 92 and 80%, respectively. Similarly, these values in patients with myocardial infarction were 79, 88, 83, 88 and 78%, respectively, while in patients without myocardial infarction the values were 90, 91, 90, 95 and 83%, respectively. Therefore, the diagnostic efficacy of ATP stress (99m)Tc-MIBI G-MPI in patients without myocardial infarction was higher compared with those with myocardial infarction; however, no significant difference was observed between the two groups. Furthermore, the sensitivity, specificity and

  19. Detection of myocardial ischemia by automated, motion-corrected, color-encoded perfusion maps compared with visual analysis of adenosine stress cardiovascular magnetic resonance imaging at 3 T: a pilot study.

    PubMed

    Doesch, Christina; Papavassiliu, Theano; Michaely, Henrik J; Attenberger, Ulrike I; Glielmi, Christopher; Süselbeck, Tim; Fink, Christian; Borggrefe, Martin; Schoenberg, Stefan O

    2013-09-01

    The purpose of this study was to compare automated, motion-corrected, color-encoded (AMC) perfusion maps with qualitative visual analysis of adenosine stress cardiovascular magnetic resonance imaging for detection of flow-limiting stenoses. Myocardial perfusion measurements applying the standard adenosine stress imaging protocol and a saturation-recovery temporal generalized autocalibrating partially parallel acquisition (t-GRAPPA) turbo fast low angle shot (Turbo FLASH) magnetic resonance imaging sequence were performed in 25 patients using a 3.0-T MAGNETOM Skyra (Siemens Healthcare Sector, Erlangen, Germany). Perfusion studies were analyzed using AMC perfusion maps and qualitative visual analysis. Angiographically detected coronary artery (CA) stenoses greater than 75% or 50% or more with a myocardial perfusion reserve index less than 1.5 were considered as hemodynamically relevant. Diagnostic performance and time requirement for both methods were compared. Interobserver and intraobserver reliability were also assessed. A total of 29 CA stenoses were included in the analysis. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for detection of ischemia on a per-patient basis were comparable using the AMC perfusion maps compared to visual analysis. On a per-CA territory basis, the attribution of an ischemia to the respective vessel was facilitated using the AMC perfusion maps. Interobserver and intraobserver reliability were better for the AMC perfusion maps (concordance correlation coefficient, 0.94 and 0.93, respectively) compared to visual analysis (concordance correlation coefficient, 0.73 and 0.79, respectively). In addition, in comparison to visual analysis, the AMC perfusion maps were able to significantly reduce analysis time from 7.7 (3.1) to 3.2 (1.9) minutes (P < 0.0001). The AMC perfusion maps yielded a diagnostic performance on a per-patient and on a per-CA territory basis comparable with the visual analysis

  20. Effects of adenosine perfusion on the metabolism and contractile activity of Rana ridibunda heart.

    PubMed

    Lazou, A; Beis, I

    1987-01-01

    The effects of adenosine were examined on the isolated perfused heart of the frog Rana ridibunda. Adenosine produced negative chronotropic and inotropic effects on frog ventricle in a concentration-dependent manner. The effects of adenosine on cardiac metabolism were also investigated by measuring the tissue content of adenine nucleotides, lactate, pyruvate, adenosine and inorganic phosphate, during adenosine perfusion. Adenosine had no effect on the tissue content of metabolites. No net synthesis of adenine nucleotides was observed during perfusion with increasing concentrations of adenosine. Lactate output from the heart decreased significantly with adenosine perfusion. Correlation of adenosine effects on cardiac muscle with the effects of hypoxia are discussed.

  1. Detection of ischaemic myocardial lesions with coronary CT angiography and adenosine-stress dynamic perfusion imaging using a 128-slice dual-source CT: diagnostic performance in comparison with cardiac MRI

    PubMed Central

    Kim, S M; Choi, J-H; Chang, S-A

    2013-01-01

    Objective: We assessed the diagnostic performance of adenosine-stress dynamic CT perfusion (ASDCTP) imaging and coronary CT angiography (CCTA) for the detection of ischaemic myocardial lesions using 128-slice dual-source CT compared with that of 1.5 T cardiac MRI. Methods: This prospective study included 33 patients (61±8 years, 82% male) with suspected coronary artery diseases who underwent ASDCTP imaging and adenosine-stress cardiac MRI. Two investigators independently evaluated ASDCTP images in correlation with significant coronary stenosis on CCTA using two different thresholds of 50% and 70% diameter stenosis. Hypoattenuated myocardial lesions on ASDCTP associated with significant coronary stenoses on CCTA were regarded as true perfusion defects. All estimates of diagnostic performance were calculated and compared with those of cardiac MRI. Results: With use of a threshold of 50% diameter stenosis on CCTA, the diagnostic estimates per-myocardial segment were as follows: sensitivity, 81% [95% confidence interval (CI): 70–92%]; specificity, 94% (95% CI: 92–96%); and accuracy 93% (95% CI: 91–95%). With use of a threshold of 70%, the diagnostic estimates were as follows: sensitivity, 48% (95% CI: 34–62%); specificity, 99% (95% CI: 98–100%); and accuracy, 94% (95% CI: 92–96%). Conclusion: Dynamic CTP using 128-slice dual-source CT enables the assessment of the physiological significance of coronary artery lesions with high diagnostic accuracy in patients with clinically suspected coronary artery disease. Advances in knowledge: Combined CCTA and ASDCTP yielded high accuracy in the detection of perfusion defects regardless of the threshold of significant coronary stenosis. PMID:24096592

  2. Submaximal adenosine-induced coronary hyperaemia with 12 h caffeine abstinence: implications for clinical adenosine perfusion imaging tests.

    PubMed

    Carlsson, Marcus; Jögi, Jonas; Bloch, Karin M; Hedén, Bo; Ekelund, Ulf; Ståhlberg, Freddy; Arheden, Håkan

    2015-01-01

    Adenosine is widely used as a vasodilator agent in myocardial perfusion imaging. Caffeine inhibits the effect, but the time of caffeine abstinence needed is under discussion and varies from 12 to 24 h. Therefore, our aim was to examine whether the time of caffeine abstinence affects the hyperaemic response using quantification of coronary sinus flow (CS F) with cardiac magnetic resonance (CMR) during adenosine infusion. Healthy individuals (n = 16, eight females, age 41 ± 3 years) underwent two CMR examinations with 12 and 24 h of caffeine abstinence. CS F was quantified with phase-contrast velocity mapping (PC-)CMR during adenosine infusion (140 μg kg(-1)  min(-1) ) and rest and the CS F reserve between adenosine and rest was calculated. Myocardial perfusion (MP) was calculated as CS F × heart rate/left ventricular mass. Cardiac output (CO) was quantified using PC-CMR of the ascending aorta. The CS F reserve was lower after 12 h abstinence compared to 24 h (4·31 ± 0·57 versus 5·32 ± 0·76, P = 0·03). In six of 16 subjects (38%), CS F reserve was >30% higher with longer caffeine abstinence. MP during adenosine was lower after 12 h compared to 24 h caffeine abstinence (3·59 ± 0·37 versus 4·23 ± 0·28 ml min(-1) g(-1) ; P = 0·046). The increase in CO during adenosine between the two occasions did not differ (55 ± 7% and 55 ± 6%, P = 0·11). Interobserver variability for CS F/heartbeat was -0·05 ± 1·00 ml. Hyperaemia during adenosine is lower in some patients with 12 h of caffeine abstinence compared to 24 h. Longer caffeine abstinence, that is 24 h, is of value before pharmacological stress testing as the individual response is not known and the individual variation is large. © 2014 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  3. Comparison of rest and adenosine stress quantitative and semi-quantitative myocardial perfusion using magnetic resonance in patients with ischemic heart disease.

    PubMed

    Qayyum, Abbas A; Qayyum, Faiza; Larsson, Henrik B W; Kjaer, Andreas; Hasbak, Philip; Vejlstrup, Niels G; Kastrup, Jens

    The aim was to compare absolute quantified myocardial perfusion (MP) to semi-quantitative measurements of MP using MRI for detection of ischemia. Twenty-nine patients underwent rest and stress MP imaging obtained by 1.5T MRI and analyzed using own developed software and by commercial available software. Linear regression analysis demonstrated that absolute quantitative data correlated stronger to maxSI (rest: r=0.296, p=.193; stress: r=0.583, p=0.011; myocardial perfusion reserve (MPR): r=0.789, p<0.001; and Δ myocardial blood flow (Δ MBF: r=0.683, p=0.004) than to upslope (rest: r=0.420, p=0.058; stress: r=0.096, p=0.704; MPR: r=0.682, p=0.004; and Δ MBF: r=0.055, p=0.804). Absolute quantified MP was able to distinguish between ischemic and non-ischemic territories at rest (left anterior descending artery (LAD): 103.1±11.3mL/100g/min vs. 206.3±98.5mL/100g/min; p=0.001, right coronary artery (RCA): 124.1±45.2mL/100g/min vs. 241.3±81.7mL/100g/min; p<0.001, and left circumflex artery (LCX): 132.8±53.8mL/100g/min vs. 181.2±56.6mL/100g/min; p=0.060) and at stress (LAD: 148.1±47.2mL/100g/min vs. 296.6±111.6mL/100g/min; p=0.012, RCA: 173.4±63.7mL/100g/min vs. 290.2±100.6mL/100g/min; p=0.008, and LCX: 206.6±105.1mL/100g/min vs. 273.8±78.0mL/100g/min; p=0.186). The correlation between global maxSI and positron emission tomography data was non-significant at rest and borderline significant at stress (r=0.265, p=0.382 and r=0.601, p=0.050, respectively). Quantified MP may be useful in patients for detection of ischemia. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Characteristics of images of angiographically proven normal coronary arteries acquired by adenosine-stress thallium-201 myocardial perfusion SPECT/CT-IQ[Symbol: see text]SPECT with CT attenuation correction changed stepwise.

    PubMed

    Takahashi, Teruyuki; Tanaka, Haruki; Kozono, Nami; Tanakamaru, Yoshiki; Idei, Naomi; Ohashi, Norihiko; Ohtsubo, Hideki; Okada, Takenori; Yasunobu, Yuji; Kaseda, Shunichi

    2015-04-01

    Although several studies have shown the diagnostic and prognostic value of CT-based attenuation correction (AC) of single photon emission computed tomography (SPECT) images for diagnosing coronary artery disease (CAD), this issue remains a matter of debate. To clarify the characteristics of CT-AC SPECT images that might potentially improve diagnostic performance, we analyzed images acquired using adenosine-stress thallium-201 myocardial perfusion SPECT/CT equipped with IQ[Symbol: see text]SPECT (SPECT/CT-IQ[Symbol: see text]SPECT) from patients with angiographically proven normal coronary arteries after changing the CT attenuation correction (CT-AC) in a stepwise manner. We enrolled 72 patients (Male 36, Female 36) with normal coronary arteries according to findings of invasive coronary angiography or CT-angiography within three months after a SPECT/CT study. Projection images were reconstructed at CT-AC values of (-), 40, 60, 80 and 100 % using a CT number conversion program according to our definition and analyzed using polar maps according to sex. CT attenuation corrected segments were located from the mid- and apical-inferior spread through the mid- and apical-septal regions and finally to the basal-anterior and basal- and mid-lateral regions in males, and from the mid-inferior region through the mid-septal and mid-anterior, and mid-lateral regions in females as the CT-AC values increased. Segments with maximal mean counts shifted from the apical-anterior to mid-anterolateral region under both stress and rest conditions in males, whereas such segments shifted from the apical-septal to the mid-anteroseptal region under both stress and rest conditions in females. We clarified which part of the myocardium and to which degree CT-AC affects it in adenosine-stress thallium-201 myocardial perfusion SPECT/CT-IQ[Symbol: see text]SPECT images by changing the CT-AC value stepwise. We also identified sex-specific shifts of segments with maximal mean counts that changed as

  5. High-frequency Electrocardiogram Analysis in the Ability to Predict Reversible Perfusion Defects during Adenosine Myocardial Perfusion Imaging

    NASA Technical Reports Server (NTRS)

    Tragardh, Elin; Schlegel, Todd T.; Carlsson, Marcus; Pettersson, Jonas; Nilsson, Klas; Pahlm, Olle

    2007-01-01

    Background: A previous study has shown that analysis of high-frequency QRS components (HF-QRS) is highly sensitive and reasonably specific for detecting reversible perfusion defects on myocardial perfusion imaging (MPI) scans during adenosine. The purpose of the present study was to try to reproduce those findings. Methods: 12-lead high-resolution electrocardiogram recordings were obtained from 100 patients before (baseline) and during adenosine Tc-99m-tetrofosmin MPI tests. HF-QRS were analyzed regarding morphology and changes in root mean square (RMS) voltages from before the adenosine infusion to peak infusion. Results: The best area under the curve (AUC) was found in supine patients (AUC=0.736) in a combination of morphology and RMS changes. None of the measurements, however, were statistically better than tossing a coin (AUC=0.5). Conclusion: Analysis of HF-QRS was not significantly better than tossing a coin for determining reversible perfusion defects on MPI scans.

  6. Adenosine-stress dynamic myocardial perfusion imaging using 128-slice dual-source CT in patients with normal body mass indices: effect of tube voltage, tube current, and iodine concentration on image quality and radiation dose.

    PubMed

    Kim, Sung Mok; Cho, Young Kwon; Choe, Yeon Hyeon

    2014-12-01

    The aim of this study was to evaluate the image quality and radiation dose in adenosine-stress dynamic myocardial CT perfusion (CTP) imaging using different tube voltages, tube current settings, and contrast materials containing different iodine concentrations in subjects with normal body mass indices (BMI). We included 92 patients (BMI range, 18.5-24.8) who underwent dynamic CTP for the evaluation of coronary artery disease using a 128-slice dual-source computed tomography. The protocols employed the following dynamic scan parameters: protocol I with 100 kV, fixed tube current (FTC), and medium-concentration contrast material (MC, 350 mg iodine/mL); protocol II with 100 kV, automatic tube current modulation (ATCM), and MC; protocol III with 100 kV, ATCM, and high-concentration contrast material (HC, 400 mg iodine/mL); protocol IV with 80 kV, adopted FTC, and HC. Subjective image quality on a 1-3 point scale and objective image quality with respect to the contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) were assessed. Protocol IV showed higher CNR and SNR than the other protocols (P < 0.01), while the CNR and SNR values did not significantly differ among the other three protocols. There was no significant difference in subjective image quality among the protocols. The radiation dose in protocol IV was the lowest among the protocols (P < 0.01), while protocol IV resulted in a 54% overall reduction in mean effective radiation dose compared with protocol I. Dynamic myocardial CTP performed at 80 kV with adapted FTC provided high CNR and SNR while preserving subjective image quality and reducing radiation exposure.

  7. Comparison of the prognostic value of normal regadenoson with normal adenosine myocardial perfusion imaging with propensity score matching.

    PubMed

    Iqbal, Fahad M; Hage, Fadi G; Ahmed, Ali; Dean, Phillip J; Raslan, Saleem; Heo, Jaekyeong; Iskandrian, Ami E

    2012-10-01

    The aim of this study was to test the hypothesis that patients with normal regadenoson myocardial perfusion imaging (MPI) have a low rate of cardiac events, similar to patients with normal adenosine MPI. Regadenoson, a new selective adenosine A(2A) receptor agonist, is now a widely used stress agent for MPI. The low rate of cardiac events in patients with normal adenosine MPI is well-documented, but the prognostic implications of a normal regadenoson MPI have not been examined and compared with those with adenosine. Data on primary composite endpoint (cardiac death, myocardial infarction, and coronary revascularization) were collected for 2,000 patients (1,000 regadenoson, and 1,000 adenosine stress) with normal myocardial perfusion and left ventricular ejection fraction referred for vasodilator MPI. In addition, propensity scores were used to assemble a balanced cohort of 505 pairs of patients who were balanced on 36 baseline characteristics. The primary endpoint occurred in 21 (2.1%; 1.1%/year) patients in the regadenoson group and 33 (3.3%; 1.7%/year) patients in the adenosine group (hazard ratio [HR] for regadenoson vs. adenosine: 0.62; 95% confidence interval [CI]: 0.36 to 1.08; p = 0.090). In the propensity-matched pairs, the primary endpoint occurred in 7 (1.4%; 0.7%/year) patients in the regadenoson group and 13 (2.6%; 1.3%/year) patients in the adenosine group (matched HR: 0.58; 95% CI: 0.23 to 1.48; p = 0.257). Cardiac deaths were infrequent in the entire sample and in the propensity-matched groups; the cardiac death rate was 0.9%/year and 1.15%/year in the regadenoson and adenosine groups (HR: 0.77; 95% CI: 0.42 to 1.43; p = 0.404) in the pre-match sample and 0.5%/year and 0.7%/year in the matched groups, respectively (HR: 0.83; 95% CI: 0.25 to 2.73; p = 0.763). Major cardiac events are infrequent in patients with normal regadenoson MPI. These findings provide assurance that normal MPI using a simpler stress protocol with regadenoson provides prognostic

  8. Impact of pharmacological stress agent on patient motion during rubidium-82 myocardial perfusion PET/CT.

    PubMed

    Memmott, Matthew J; Tonge, Christine M; Saint, Kimberley J; Arumugam, Parthiban

    2017-01-04

    Patient motion has been demonstrated to have a significant impact on the quality and accuracy of rubidium-82 myocardial perfusion PET/CT. This study aimed to investigate the effect on patient motion of two pharmacological stressing agents, adenosine and regadenoson. Dynamic data were retrospectively analyzed in 90 patients undergoing adenosine (n = 30), incremental adenosine (n = 30), or regadenoson (n = 30) rubidium-82 myocardial perfusion PET/CT. Severity of motion was scored qualitatively using a four-point (0-3) scale and quantitatively using frame-to-frame pixel shifts. The type of motion, returning or non-returning, and the frame in which it occurred were also recorded. There were significant differences in both the qualitative and quantitative scores comparing regadenoson to adenosine (P = .025 and P < .001) and incremental adenosine (P = .014, P = .015), respectively. The difference in scores between adenosine and incremental adenosine was not significant. Where motion was present, significantly more adenosine patients were classed as non-returning (P = .018). The median frames for motion occurring were 12 for regadenoson and 14 for both adenosine cohorts. The choice of stressing protocol impacts significantly on patient motion. Patients stressed with regadenoson have significantly lower motion scores than those stressed with adenosine, using local protocols. This motion is more likely to be associated with a drift of the heart away from a baseline position, coinciding with the termination of infusion.

  9. Comparison of Hemodynamic Effects and Negative Predictive Value of Normal Adenosine Gated Myocardial Perfusion Scan With or Without Caffeine Abstinence.

    PubMed

    Uz Zaman, Maseeh; Fatima, Nosheen; Zaman, Areeba; Zaman, Unaiza; Tahseen, Rabia

    2016-09-01

    For vasodilator stress, myocardial perfusion imaging (MPI) with at least 12-h caffeine abstinence is recommended, as it attenuates cardiovascular hyperemic response of adenosine and dipyridamole. However, many published conflicting results have shown no significant effect upon perfusion abnormalities in MPI performed without caffeine abstinence. The aim of this study was to compare the hemodynamic changes and negative predictive value (NPV) of normal MPIs with adenosine stress performed with or without caffeine abstinence. This was a prospective study that accrued 50 patients from May 2013 till September 2013 and followed till November 2014. These patients had a normal adenosine-gated MPI (GMPI) with technetium-99m methoxy isobutyl isonitrile ((99m)Tc-MIBI) after 12-h caffeine abstinence (no-caffeine). Next day, all patients had a repeat adenosine stress within 60 min after ingestion of a cup of coffee (about 80 mg of caffeine) followed by no MPI in 30 patients due to concern about radiation dose (prior-caffeine adenosine-no MPI; group A). Twenty patients opted for a repeat MPI (prior-caffeine adenosine-MPI; group B). Adenosine-induced hemodynamic response and NPV of the normal MPI with no-caffeine and prior-caffeine protocols were compared. The mean age of the study cohort was 57 ± 9 years with a male-to-female ratio of 76:24% and mean body mass index (BMI) of 26.915 ± 4.121 kg/m(2). Prevalence of hypertension, diabetes, dyslipidemia, and positive family history were 76%, 20%, 22%, and 17%, respectively. Comparison of group A with group B revealed no significant difference in demographic parameters, hemodynamic or electrocardiography (ECG) parameters, or left ventricular (LV) function parameters during adenosine intervention with prior-caffeine and no-caffeine protocols. During the follow-up, no fatal myocardial infarction (MI) was reported but 6 nonfatal MIs were reported based upon the history of short hospitalization for chest pain but without biochemical or

  10. Prognostic value of normal regadenoson stress perfusion cardiovascular magnetic resonance

    PubMed Central

    2013-01-01

    Background Regadenoson is a vasodilator stress agent that selectively activates the A2A receptor. Compared to adenosine, regadenoson is easier to administer and results in fewer side effects. Although extensively studied in patients undergoing nuclear perfusion imaging (MPI), its use for perfusion cardiovascular magnetic resonance (CMR) is not well described. The aim of this study was to determine the prognostic value of a normal regadenoson perfusion CMR in patients with known or suspected coronary artery disease. Methods Patients with known or suspected coronary artery disease were prospectively enrolled to receive perfusion CMR (Philips 1.5 T) with regadenoson. Three short-axis slices of the left ventricle (LV) were obtained during first pass of contrast using a hybrid GRE-EPI pulse sequence (0.075 mmol/kg Gadolinium-DTPA-BMA at 4 ml/sec). Imaging was performed 1 minute after injection of regadenoson (0.4 mg) and repeated 15 minutes after reversal of hyperemia with aminophylline (125 mg). Perfusion defects were documented if they persisted for ≥2 frames after peak enhancement of the LV cavity. CMR was considered abnormal if there was a resting wall motion abnormality, decreased LVEF (<40%), presence of LGE, or the presence of a perfusion defect during hyperemia. All patients were followed for a minimum of 1 year for major adverse cardiovascular event (MACE) defined as coronary revascularization, non-fatal myocardial infarction, and cardiovascular death. Results 149 patients were included in the final analysis. Perfusion defects were noted in 43/149 (29%) patients; 59/149 (40%) had any abnormality on CMR. During the mean follow-up period of 24 ± 9 months, 17/149 (11.4%) patients experienced MACE. The separation in the survival distributions for those with perfusion defects and those without perfusion defects was highly significant (log-rank p = 0.0001). When the absence of perfusion defects was added to the absence of other resting CMR

  11. Stress-first Myocardial Perfusion Imaging.

    PubMed

    Hussain, Nasir; Parker, Matthew W; Henzlova, Milena J; Duvall, William Lane

    2016-02-01

    Stress-first approaches to myocardial perfusion imaging provide diagnostically and prognostically accurate perfusion data equivalent to a full rest-stress study, save time in the imaging laboratory, and reduce the radiation exposure to patients and laboratory staff. Converting a nuclear cardiology laboratory from a conventional rest-stress strategy to a stress-first approach involves challenges such as the need for attenuation correction, triage of patients to an appropriate protocol, real-time review of stress images, and consideration of differential reimbursement. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Cost-minimization analysis of intravenous adenosine and dipyridamole in thallous chloride TI 201 SPECT myocardial perfusion imaging.

    PubMed

    Hilleman, D E; Lucas, B D; Mohiuddin, S M; Holmberg, M J

    1997-09-01

    To conduct a cost-minimization analysis of intravenous adenosine and intravenous dipyridamole in thallous chloride TI 201 single-photon emission computed tomography (SPECT) myocardial perfusion imaging. A retrospective, open-label, cost-minimization analysis. University hospital, outpatient nuclear medicine department. Eighty-three patients undergoing dipyridamole TI 201 SPECT and 166 patients undergoing adenosine TI 201 SPECT. A cost-minimization analysis was conducted using a direct cost accounting approach estimating institutional costs. For the purpose of this study, sensitivity and specificity between adenosine SPECT and dipyridamole SPECT were assumed to be identical. Key costs evaluated included acquisition, administration, monitoring, treatment of adverse effects, follow-up care, and repeat tests. Adenosine increased heart rate and lowered blood pressure to a significantly greater extent than dipyridamole. The frequency of adverse reactions was not significantly different (p = 0.103) between adenosine (1.64 +/- 1.32 per patient) and dipyridamole (1.36 +/- 1.23 per patient). The frequency of prolonged and late-onset adverse effects was significantly greater for dipyridamole than for adenosine (p < 0.001). The frequency of adverse events requiring medical intervention was statistically greater for dipyridamole (24%) compared with adenosine (5%) (p < 0.00001). Total cost was significantly less for adenosine ($378.50 +/- $128.20 per patient) compared with dipyridamole ($485.60 +/- $230.40). Although adenosine had a significantly greater acquisition cost than dipyridamole (p < 0.0001), administration, monitoring, and adverse reaction costs were significantly less for adenosine than for dipyridamole. The cost of using dipyridamole is significantly greater than the cost of using adenosine despite adenosine's high acquisition cost. Adenosine is less expensive to use because of lower administration costs, monitoring costs, and adverse effect costs. Adenosine should

  13. [Regadenoson as a new stress agent in myocardial perfusion imaging. Initial experience in The Netherlands].

    PubMed

    Jager, P L; Buiting, M; Mouden, M; Oostdijk, A H J; Timmer, J; Knollema, S

    2014-01-01

    Regadenoson is a recently approved selective adenosine-2A receptor agonist to induce pharmacological stress in myocardial perfusion imaging (MPI) procedures using a single bolus injection. We included 123 patients referred for MPI because of suspected coronary arterial disease (CAD). Of these, 66 patients underwent a regadenoson stress test and 57 patients underwent an adenosine stress test preceding standard myocardial SPECT imaging. Technicians, physicians and patients were asked to report their experience using questionnaires. As compared to adenosine, regadenoson did not produce any atrio-ventricular block (0 vs. 10% with adenosine), but did produce minor tachycardia and minimal blood pressure changes while all other side effects were milder and shorter. There were fewer patients with severe complaints after taking regadenoson than adenosine (17% vs. 32%, respectively, p<0.01). The most frequent complaint reported was dyspnea, followed by flushing and chest pain. However, when they did occur, they usually disappeared rapidly. The overall symptom score, including severity and duration of side effects, was significantly lower after regadenoson than after adenosine (6.7±6.3 vs. 10.0±7.9, respectively; p<0.01.) SPECT imaging results were similar. The regadenoson procedure was faster and more practical. Regadenoson, the new selective adenosine-2A receptor agonist, is a stress agent for MPI with a patient- and department friendly profile. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  14. Unpredictable Chronic Stress Alters Adenosine Metabolism in Zebrafish Brain.

    PubMed

    Zimmermann, F F; Altenhofen, S; Kist, L W; Leite, C E; Bogo, M R; Cognato, G P; Bonan, C D

    2016-05-01

    Stress is considered a risk factor for several human disorders. Despite the broad knowledge of stress responses in mammals, data on the relationship between unpredictable chronic stress (UCS) and its effects on purinergic signaling are limited. ATP hydrolysis by ectonucleotidases is an important source of adenosine, and adenosine deaminase (ADA) contributes to the control of the nucleoside concentrations. Considering that some stress models could affect signaling systems, the objective of this study was to investigate whether UCS alters ectonucleotidase and ADA pathway in zebrafish brain. Additionally, we analyzed ATP metabolism as well as ada1, ada2.1, ada2.2, adaL, and adaasi gene expression in zebrafish brain. Our results have demonstrated that UCS did not alter ectonucleotidase and soluble ADA activities. However, ecto-ADA activity was significantly decreased (26.8%) in brain membranes of animals exposed to UCS when compared to the control group. Quantitative reverse transcription PCR (RT-PCR) analysis did not show significant changes on ADA gene expression after the UCS exposure. The brain ATP metabolism showed a marked increase in adenosine levels (ADO) in animals exposed to UCS. These data suggest an increase on extracellular adenosine levels in zebrafish brain. Since this nucleoside has neuromodulatory and anxiolytic effects, changes in adenosine levels could play a role in counteracting the stress, which could be related to a compensatory mechanism in order to restore the homeostasis.

  15. Importance of tissue perfusion in ST segment elevation myocardial infarction patients undergoing reperfusion strategies: role of adenosine.

    PubMed

    Forman, Mervyn B; Jackson, Edwin K

    2007-11-01

    High risk ST segment elevation myocardial infarction (STEMI) patients undergoing reperfusion therapy continue to exhibit significant morbidity and mortality due in part to myocardial reperfusion injury. Importantly, preclinical studies demonstrate that progressive microcirculatory failure (the "no-reflow" phenomenon) contributes significantly to myocardial reperfusion injury. Diagnostic techniques to measure tissue perfusion have validated this concept in humans, and it is now clear that abnormal tissue perfusion occurs frequently in STEMI patients undergoing reperfusion therapy. Moreover, because tissue perfusion correlates poorly with epicardial blood flow (TIMI flow grade), clinical studies show that tissue perfusion is an independent predictor of early and late mortality in STEMI patients and is associated with infarct size, ventricular function, CHF and ventricular arrhythmias. The mechanisms responsible for abnormal tissue perfusion are multifactorial and include both mechanical obstruction and vasoconstrictor humoral factors. Adenosine, an endogenous nucleoside, maintains microcirculatory flow following reperfusion by activating four well-characterized extracellular receptors. Because activation of adenosine receptors attenuates the mechanical and functional mechanisms leading to the "no reflow" phenomenon and activates other cardioprotective pathways as well, it is not surprising that both experimental and clinical studies show striking myocardial salvage with intravenous infusions of adenosine administered in the peri-reperfusion period. For example, a post hoc analysis of the AMISTAD II trial indicates a significant reduction in 1 and 6-month mortality in STEMI patients undergoing reperfusion therapy who are treated with adenosine within 3 hours of symptoms. In conclusion, adenosine's numerous cardioprotective effects, including attenuation of the "no-reflow" phenomenon, support its use in high risk STEMI undergoing reperfusion.

  16. Non-ischemic perfusion defects due to delayed arrival of contrast material on stress perfusion cardiac magnetic resonance imaging after coronary artery bypass graft surgery.

    PubMed

    Kim, Yeo Koon; Park, Eun-Ah; Park, Sang Joon; Cheon, Gi Jeong; Lee, Whal; Chung, Jin Wook; Park, Jae Hyung

    2014-01-01

    Herein we report about the adenosine stress perfusion MR imaging findings of a 50-year-old man who exhibited two different perfusion defects resulting from two different mechanisms after a coronary artery bypass surgery. An invasive coronary angiography confirmed that one perfusion defect at the mid-anterior wall resulted from an ischemia due to graft stenosis. However, no stenosis was detected on the graft responsible for the mid-inferior wall showing the other perfusion defect. It was assumed that the perfusion defect at the mid-inferior wall resulted from delayed perfusion owing to the long pathway of the bypass graft. The semiquantitative analysis of corrected signal-time curves supported our speculation, demonstrating that the rest-to-stress ratio index of the maximal slope of the myocardial territory in question was similar to those of normal myocardium, whereas that of myocardium with the stenotic graft showed a typical ischemic pattern. A delayed perfusion during long graft pathway in a post-bypass graft patient can mimick a true perfusion defect on myocardial stress MR imaging. Radiologists should be aware of this knowledge to avoid misinterpretation of graft and myocardial status in post bypass surgery patients.

  17. Meta-Analysis of Stress Myocardial Perfusion Imaging

    ClinicalTrials.gov

    2017-06-06

    Coronary Disease; Echocardiography; Fractional Flow Reserve, Myocardial; Hemodynamics; Humans; Magnetic Resonance Imaging; Myocardial Perfusion Imaging; Perfusion; Predictive Value of Tests; Single Photon Emission Computed Tomography; Positron Emission Tomography; Multidetector Computed Tomography; Echocardiography, Stress; Coronary Angiography

  18. Does stress perfusion imaging improve the diagnostic accuracy of late gadolinium enhanced cardiac magnetic resonance for establishing the etiology of heart failure?

    PubMed

    Gulsin, Gaurav S; Shetye, Abishek; Khoo, Jeffrey; Swarbrick, Daniel J; Levelt, Eylem; Lai, Florence Y; Squire, Iain B; Arnold, Jayanth R; McCann, Gerry P

    2017-04-08

    Late gadolinium enhanced cardiovascular magnetic resonance (LGE-CMR) has excellent specificity, sensitivity and diagnostic accuracy for differentiating between ischemic cardiomyopathy (ICM) and non-ischemic dilated cardiomyopathy (NICM). CMR first-pass myocardial perfusion imaging (perfusion-CMR) may also play role in distinguishing heart failure of ischemic and non-ischemic origins, although the utility of additional of stress perfusion imaging in such patients is unclear. The aim of this retrospective study was to assess whether the addition of adenosine stress perfusion imaging to LGE-CMR is of incremental value for differentiating ICM and NICM in patients with severe left ventricular systolic dysfunction (LVSD) of uncertain etiology. We retrospectively identified 100 consecutive adult patients (median age 69 years (IQR 59-73)) with severe LVSD (mean LV EF 26.6 ± 7.0%) referred for perfusion-CMR to establish the underlying etiology of heart failure. The cause of heart failure was first determined on examination of CMR cine and LGE images in isolation. Subsequent examination of complete adenosine stress perfusion-CMR studies (cine, LGE and perfusion images) was performed to identify whether this altered the initial diagnosis. On LGE-CMR, 38 patients were diagnosed with ICM, 46 with NICM and 16 with dual pathology. With perfusion-CMR, there were 39 ICM, 44 NICM and 17 dual pathology diagnoses. There was excellent agreement in diagnoses between LGE-CMR and perfusion-CMR (κ 0.968, p<0.001). The addition of adenosine stress perfusion images to LGE-CMR altered the diagnosis in only two of the 100 patients. The addition of adenosine stress perfusion-CMR to cine and LGE-CMR provides minimal incremental diagnostic yield for determining the etiology of heart failure in patients with severe LVSD.

  19. Myocardial stress perfusion magnetic resonance: initial experience in a pediatric and young adult population using regadenoson.

    PubMed

    Noel, Cory V; Krishnamurthy, Ramkumar; Moffett, Brady; Krishnamurthy, Rajesh

    2017-03-01

    Dipyridamole and adenosine are traditional pharmacological stressors for myocardial perfusion. Regadenoson, a selective adenosine A2A agonist, has a lower side effect profile with lower incidence of bronchospasm and bradycardia. There is a growing need for myocardial perfusion assessment within pediatrics. There is no report on the utility of regadenoson as a stress agent in children. To observe the safety and feasibility of regadenoson as a pharmacologic stressor for perfusion cardiac MR in a pilot cohort of pediatric patients weighing more than 40 kg who have congenital heart disease and pediatric acquired heart disease. We reviewed our initial experience with regadenoson stress cardiac MR in 31 pediatric patients 15.8 ± 1.7 years (range 12-22 years) with congenital heart disease and acquired heart disease. Mean patient weight was 60 ± 15 kg (range of 40-93 kg). All patients underwent cardiac MR because of concern for ischemia. The cohort included a heterogeneous group of patients at a pediatric institution with potential risk for ischemia. Subjects' heart rate and blood pressure were monitored and pharmacologic stress was induced by injection of 400 mcg of regadenoson. We evaluated their hemodynamic response and adverse effects using changes in vital signs and onset of symptoms. A pediatric cardiologist and radiologist qualitatively assessed myocardial perfusion and viability images. One child was unable to complete the stress perfusion portion of the examination, but did complete the remaining portion of the CMR. Resting heart rate was 72 ± 14 beats per minute (bpm) and rose to peak of 124 ± 17 bpm (95 ± 50% increase, P < 0.005) with regadenoson. Image quality was considered good or diagnostic in all cases. Three patients had irreversible perfusion defects. Four patients had reversible perfusion defects. Nine of the patients underwent cardiac catheterization with angiography and the findings showed excellent agreement

  20. Effect of exogenous adenosine and monensin on glycolytic flux in isolated perfused normoxic rat hearts: role of pyruvate kinase.

    PubMed

    Peltier, S; Burelle, Y; Novel-Chate, V; Demaison, L; Verdys, M; Saks, V; Keriel, C; Leverve, X M

    2005-09-01

    We studied the effect of exogenous adenosine in isolated perfused normoxic rat hearts on glycolytic flux through pyruvate kinase (PK). We compared its effect with that of myxothiazol, an inhibitor of mitochondrial ATP production. Moreover, we tested whether an increase of membrane ionic flux with monensin is linked to a stimulation of glycolytic flux through PK. After a 20-min stabilization period adenosine, myxothiazol or monensin were administrated to the perfusate continuously at various concentrations during 10 min. The contraction was monitored and the lactate production in coronary effluents evaluated. The amount of adenine nucleotides and phosphoenolpyruvate was measured in the frozen hearts. Myxothiazol induced a decrease of the left ventricular developed pressure (LVDP : -40%) together with a stimulation of glycolytic flux secondary to PK activation. In contrast, adenosine primarily reduced heart rate (HR: -30%) with only marginal effects on LVDP. This was associated with an inhibition of glycolysis at the level of PK. The Na+ ionophore monensin affected HR (+14%) and LVDP (+25%). This effect was associated with a stimulation of glycolysis secondary to the stimulation of PK. These results provide new information of action of adenosine in the heart and support the concept of a direct coupling between glycolysis and process regulating sarcolemmal ionic fluxes.

  1. Angiographic correlations of patients with small vessel disease diagnosed by adenosine-stress cardiac magnetic resonance imaging.

    PubMed

    Pilz, Guenter; Klos, Markus; Ali, Eman; Hoefling, Berthold; Scheck, Roland; Bernhardt, Peter

    2008-01-31

    Cardiac magnetic resonance imaging (CMR) with adenosine-stress myocardial perfusion is gaining importance for the detection and quantification of coronary artery disease (CAD). However, there is little knowledge about patients with CMR-detected ischemia, but having no relevant stenosis as seen on coronary angiography (CA). The aims of our study were to characterize these patients by CMR and CA and evaluate correlations and potential reasons for the ischemic findings. 73 patients with an indication for CA were first scanned on a 1.5T whole-body CMR-scanner including adenosine-stress first-pass perfusion. The images were analyzed by two independent investigators for myocardial perfusion which was classified as subendocardial ischemia (n = 22), no perfusion deficit (n = 27, control 1), or more than subendocardial ischemia (n = 24, control 2). All patients underwent CA, and a highly significant correlation between the classification of CMR perfusion deficit and the degree of coronary luminal narrowing was found. For quantification of coronary blood flow, corrected Thrombolysis in Myocardial Infarction (TIMI) frame count (TFC) was evaluated for the left anterior descending (LAD), circumflex (LCX) and right coronary artery (RCA). The main result was that corrected TFC in all coronaries was significantly increased in study patients compared to both control 1 and to control 2 patients. Study patients had hypertension or diabetes more often than control 1 patients. In conclusion, patients with CMR detected subendocardial ischemia have prolonged coronary blood flow. In connection with normal resting flow values in CAD, this supports the hypothesis of underlying coronary microvascular impairment. CMR stress perfusion differentiates non-invasively between this entity and relevant CAD.

  2. Comparison of the effects of adenine-ribose with adenosine for maintenance of ATP concentrations in 5-day hypothermically perfused dog kidneys.

    PubMed

    McAnulty, J F; Southard, J H; Belzer, F O

    1988-10-01

    The quality of preservation of kidneys is dependent upon a number of factors, one of which may be the concentration of adenine nucleotides in the tissue during long-term perfusion preservation. In this study we have investigated how adenine (5 mM) and ribose (5 mM) in combination affect the concentration of adenine nucleotides in dog kidney cortical tissue after 5 days of continuous hypothermic perfusion preservation. These results were compared to kidneys perfused with adenosine and without any added purine precursors of adenine nucleotide synthesis. Additionally, we investigated how these conditions affected renal tissue slice function after 5 days of preservation and how adenine plus ribose affected renal function after autotransplantation in the dog. Adenosine is nearly completely degraded during 5 days of perfusion but there was little loss of adenine (10%). The adenosine triphosphate concentration in kidney cortical tissue was higher in adenine/ribose-perfused kidneys (1.41 +/- 0.19 mumol/g) than in adenosine-perfused kidneys (0.71 +/- 0.1 mumol/g) after 5 days of preservation. Tissue slices prepared from kidneys preserved in the presence of adenine plus ribose were metabolically more functional (slice volume control and electrolyte pump activity) than slices from adenosine-perfused kidneys. Adenine plus ribose had no detrimental effects on kidneys preserved for 3 days as tested in the autotransplant model but did not yield successful 5-day preservation. Because of some potentially detrimental factors in using adenosine as an adenine nucleotide synthesis precursor, we have now switched to the combination of adenine and ribose for perfusion preservation of kidneys both in the laboratory and in the clinic.

  3. Myocardial uptake and clearance of T1-201 in healthy subjects: Comparison of adenosine-induced hyperemia and exercise stress

    SciTech Connect

    Siffring, P.A.; Gupta, N.C.; Mohiuddin, S.M.; Esterbrooks, D.J.; Hilleman, D.E.; Cheng, S.C.; Sketch, M.H. Sr.; Frick, M.P. )

    1989-12-01

    Pharmacologic stress testing with dipyridamole is useful in patients undergoing thallium-201 myocardial perfusion scintigraphy who cannot adequately exercise. Because dipyridamole increases coronary blood flow by reducing the metabolism of adenosine, the authors compared the uptake and clearance of T1-201 following exercise stress testing (EST) and resting intravenous infusion of adenosine (AI) in crossover fashion in 20 healthy men. No perfusion defects or areas of redistribution were noted in any of the scans. Mean absolute myocardial T1-201 uptake was 1.3 times greater with AI than with EST. Mean absolute extracardiac uptake was 2.0 times greater with AI. Mean T1-201 myocardial clearance was virtually the same in all AI and EST views. During AI, 70% of the subjects experienced subjective side effects, mean arterial blood pressure decreased by 15%, and heart rate increased by 48%. The effects of adenosine on T1-201 kinetics in the myocardium are similar to those of EST. Adenosine may be useful as a pharmacologic stress agent in patients undergoing T1-201 myocardial perfusion scintigraphy.

  4. Stress Computed Tomography Myocardial Perfusion Imaging: A New Topic in Cardiology.

    PubMed

    Seitun, Sara; Castiglione Morelli, Margherita; Budaj, Irilda; Boccalini, Sara; Galletto Pregliasco, Athena; Valbusa, Alberto; Cademartiri, Filippo; Ferro, Carlo

    2016-02-01

    Since its introduction about 15 years ago, coronary computed tomography angiography has become today the most accurate clinical instrument for noninvasive assessment of coronary atherosclerosis. Important technical developments have led to a continuous stream of new clinical applications together with a significant reduction in radiation dose exposure. Latest generation computed tomography scanners (≥ 64 slices) allow the possibility of performing static or dynamic perfusion imaging during stress by using coronary vasodilator agents (adenosine, dipyridamole, or regadenoson), combining both functional and anatomical information in the same examination. In this article, the emerging role and state-of-the-art of myocardial computed tomography perfusion imaging are reviewed and are illustrated by clinical cases from our experience with a second-generation dual-source 128-slice scanner (Somatom Definition Flash, Siemens; Erlangen, Germany). Technical aspects, data analysis, diagnostic accuracy, radiation dose and future prospects are reviewed.

  5. Appearance of adenosine triphosphate in the perfusate from working frog heart.

    PubMed

    Doyle, T B; Forrester, T

    1985-09-01

    Frog hearts (Rana pipiens) were perfused in situ with Ringer's solution and the perfusate tested on firefly extract for the presence of ATP. At a normal perfusion pressure of 8 cm. H2O the rate of release of ATP into the perfusate was 8.8 (+/- S.E.1.7) pmoles.min-1. When the workload was increased by raising the perfusion pressure to 12 cm. H2O the rate of release increased to 28.3 (+/- S.E.4.8) pmoles.min-1. The rate of release was found to be proportional to the amount of workload imposed upon the heart. It is postulated that the trigger for release is hypoxia and that the release of ATP from the cardiac cell will augment contractility of the myocardium through its action upon adjacent cells via the P2 purinergic receptor. cells via the P2 purinergic receptor.

  6. Ex Vivo Perfusion With Adenosine A2A Receptor Agonist Enhances Rehabilitation of Murine Donor Lungs After Circulatory Death.

    PubMed

    Stone, Matthew L; Sharma, Ashish K; Mas, Valeria R; Gehrau, Ricardo C; Mulloy, Daniel P; Zhao, Yunge; Lau, Christine L; Kron, Irving L; Huerter, Mary E; Laubach, Victor E

    2015-12-01

    Ex vivo lung perfusion (EVLP) enables assessment and rehabilitation of marginal donor lungs before transplantation. We previously demonstrated that adenosine A2A receptor (A2AR) agonism attenuates lung ischemia-reperfusion injury. The current study utilizes a novel murine EVLP model to test the hypothesis that A2AR agonist enhances EVLP-mediated rehabilitation of donation after circulatory death (DCD) lungs. Mice underwent euthanasia and 60 minutes warm ischemia, and lungs were flushed with Perfadex and underwent cold static preservation (CSP, 60 minutes). Three groups were studied: no EVLP (CSP), EVLP with Steen solution for 60 minutes (EVLP), and EVLP with Steen solution supplemented with ATL1223, a selective A2AR agonist (EVLP + ATL1223). Lung function, wet/dry weight, cytokines and neutrophil numbers were measured. Microarrays were performed using the Affymetrix GeneChip Mouse Genome 430A 2.0 Array. Ex vivo lung perfusion significantly improved lung function versus CSP, which was further, significantly improved by EVLP + ATL1223. Lung edema, cytokines, and neutrophil counts were reduced after EVLP and further, significantly reduced after EVLP + ATL1223. Gene array analysis revealed differential expression of 1594 genes after EVLP, which comprise canonical pathways involved in inflammation and innate immunity including IL-1, IL-8, IL-6, and IL-17 signaling. Several pathways were uniquely regulated by EVLP + ATL1223 including the downregulation of genes involved in IL-1 signaling, such as ADCY9, ECSIT, IRAK1, MAPK12, and TOLLIP. Ex vivo lung perfusion modulates proinflammatory genes and reduces pulmonary dysfunction, edema, and inflammation in DCD lungs, which are further reduced by A2AR agonism. This murine EVLP model provides a novel platform to study rehabilitative mechanisms of DCD lungs.

  7. Adenosine stress myocardial contrast echocardiography for the detection of coronary artery disease: a comparison with coronary angiography and cardiac magnetic resonance.

    PubMed

    Arnold, J Ranjit; Karamitsos, Theodoros D; Pegg, Tammy J; Francis, Jane M; Olszewski, Robert; Searle, Nick; Senior, Roxy; Neubauer, Stefan; Becher, Harald; Selvanayagam, Joseph B

    2010-09-01

    To evaluate the accuracy of adenosine myocardial contrast echocardiography (MCE) in diagnosing coronary artery disease (CAD). Adenosine stress echocardiography is not routinely used in the assessment of CAD. Since ultrasound microbubble contrast agents enable improved wall motion analysis and simultaneous assessment of myocardial perfusion, we sought to evaluate the diagnostic performance of combined wall motion/perfusion imaging with adenosine MCE in patients with suspected CAD. We evaluated the accuracy of adenosine MCE in identifying 1) the presence of anatomic disease, as defined by X-ray angiography, and 2) the functional significance of CAD, as determined by high field-strength (3-T), multiparametric cardiac magnetic resonance (CMR) imaging. Sixty-five patients with suspected CAD were studied before angiography with MCE and CMR, at stress (140 μg/kg/min intravenous adenosine) and at rest. For MCE, 2-, 3- and 4-chamber long-axis images were acquired during intravenous sulfur hexafluoride infusion. For CMR, short-axis first-pass perfusion and delayed enhancement images were acquired following intravenous gadolinium-diethylenetriaminepentaacetic acid bolus injections (0.05 mmol/kg). Quantitative coronary angiography served as a reference standard for anatomic disease (significant CAD defined as ≥ 50% reference diameter in vessels with diameter ≥ 2 mm). Compared with X-ray angiography, MCE provided diagnostic accuracy of 82%, sensitivity of 85%, and specificity of 76% for detecting significant coronary stenosis. Disease location was also identified with reasonable accuracy (diagnostic accuracy 81% for left anterior descending disease, 77% for left circumflex artery disease, and 84% for right coronary artery disease). With CMR as the reference standard for functional assessment, MCE provided diagnostic accuracy of 79%, sensitivity of 85%, and specificity of 74%. Interobserver agreement for MCE was 79% (95% confidence interval: 67% to 88%). Adenosine MCE

  8. Ex vivo lung perfusion with adenosine A2A receptor agonist allows prolonged cold preservation of lungs donated after cardiac death.

    PubMed

    Wagner, Cynthia E; Pope, Nicolas H; Charles, Eric J; Huerter, Mary E; Sharma, Ashish K; Salmon, Morgan D; Carter, Benjamin T; Stoler, Mark H; Lau, Christine L; Laubach, Victor E; Kron, Irving L

    2016-02-01

    Ex vivo lung perfusion has been successful in the assessment of marginal donor lungs, including donation after cardiac death (DCD) donor lungs. Ex vivo lung perfusion also represents a unique platform for targeted drug delivery. We sought to determine whether ischemia-reperfusion injury would be decreased after transplantation of DCD donor lungs subjected to prolonged cold preservation and treated with an adenosine A2A receptor agonist during ex vivo lung perfusion. Porcine DCD donor lungs were preserved at 4°C for 12 hours and underwent ex vivo lung perfusion for 4 hours. Left lungs were then transplanted and reperfused for 4 hours. Three groups (n = 4/group) were randomized according to treatment with the adenosine A2A receptor agonist ATL-1223 or the dimethyl sulfoxide vehicle: Infusion of dimethyl sulfoxide during ex vivo lung perfusion and reperfusion (DMSO), infusion of ATL-1223 during ex vivo lung perfusion and dimethyl sulfoxide during reperfusion (ATL-E), and infusion of ATL-1223 during ex vivo lung perfusion and reperfusion (ATL-E/R). Final Pao2/Fio2 ratios (arterial oxygen partial pressure/fraction of inspired oxygen) were determined from samples obtained from the left superior and inferior pulmonary veins. Final Pao2/Fio2 ratios in the ATL-E/R group (430.1 ± 26.4 mm Hg) were similar to final Pao2/Fio2 ratios in the ATL-E group (413.6 ± 18.8 mm Hg), but both treated groups had significantly higher final Pao2/Fio2 ratios compared with the dimethyl sulfoxide group (84.8 ± 17.7 mm Hg). Low oxygenation gradients during ex vivo lung perfusion did not preclude superior oxygenation capacity during reperfusion. After prolonged cold preservation, treatment of DCD donor lungs with an adenosine A2A receptor agonist during ex vivo lung perfusion enabled Pao2/Fio2 ratios greater than 400 mm Hg after transplantation in a preclinical porcine model. Pulmonary function during ex vivo lung perfusion was not predictive of outcomes after transplantation. Copyright

  9. Prognosis of normal stress-only gated-SPECT myocardial perfusion imaging: a single center study.

    PubMed

    Ferreira, Maria João Vidigal; Cunha, Maria João; Albuquerque, Anabela; Moreira, Ana Paula; Ramos, Domingos; Costa, Gracinda; Lima, João; Pego, Mariano

    2013-10-01

    It has been advocated that using the stress followed by rest protocol, if the stress images were normal there is no need of rest images, reducing radiation exposure and costs. Our purpose was to assess the prognosis of a group of patients with normal stress-only gated-SPECT myocardial perfusion imaging. This was retrospective study that includes 790 patients with normal myocardial stress only perfusion gated SPECT images. Images were considered as normal if a homogeneous myocardial distribution of the tracer was associated with a normal ejection fraction. The mean follow-up was of 42.8 ± 13.3 months. The considered events were death of all causes, myocardial infarction and myocardial revascularization. During this period there were 85 events (10.8 %), including 57 deaths of all causes (67.1 %), 9 myocardial infarctions (10.6 %), 19 revascularizations (2.4 %). In the first year of follow-up there were 32 events (4.0 %) and excluding non cardiac deaths there were 8 events (1.0 %). Using Cox survival analysis, diabetes (HR = 2.2; CI = 1.4-3.4; p ≤ 0.0005), the history of coronary artery disease (CAD) (HR = 2.1; CI = 1.3-3.2; p ≤ 0.001), age (HR = 1.0; CI = 1.0-1.0; p ≤ 0.05) and type of stress protocol were related with events (exercise test vs. adenosine) (Exercise test: HR = 0.5; CI = 0.3-0.8; p ≤ 0.01). In a multivariate analysis the independent predictors were diabetes, CAD and the type of stress protocol. Based on these results, normal stress-only images are associated with an excellent prognosis even in patients at higher risk, diabetics and patients with known CAD.

  10. Diagnostic Performance of Dual-Energy CT Stress Myocardial Perfusion Imaging: Direct Comparison With Cardiovascular MRI

    PubMed Central

    Ko, Sung Min; Song, Meong Gun; Chee, Hyun Kun; Hwang, Hweung Kon; Feuchtner, Gudrun Maria; Min, James K.

    2014-01-01

    OBJECTIVE The purpose of this study was to assess the diagnostic performance of stress perfusion dual-energy CT (DECT) and its incremental value when used with coronary CT angiography (CTA) for identifying hemodynamically significant coronary artery disease. SUBJECTS AND METHODS One hundred patients with suspected or known coronary artery disease without chronic myocardial infarction detected with coronary CTA underwent stress perfusion DECT, stress cardiovascular perfusion MRI, and invasive coronary angiography (ICA). Stress perfusion DECT and cardiovascular stress perfusion MR images were used for detecting perfusion defects. Coronary CTA and ICA were evaluated in the detection of ≥ 50% coronary stenosis. The diagnostic performance of coronary CTA for detecting hemodynamically significant stenosis was assessed before and after stress perfusion DECT on a pervessel basis with ICA and cardiovascular stress perfusion MRI as the reference standard. RESULTS The performance of stress perfusion DECT compared with cardiovascular stress perfusion MRI on a per-vessel basis in the detection of perfusion defects was sensitivity, 89%; specificity, 74%; positive predictive value, 73%; negative predictive value, 90%. Per segment, these values were sensitivity, 76%; specificity, 80%; positive predictive value, 63%; and negative predictive value, 88%. Compared with ICA and cardiovascular stress perfusion MRI per vessel territory the sensitivity, specificity, positive predictive value, and negative predictive value of coronary CTA were 95%, 61%, 61%, and 95%. The values for stress perfusion DECT were 92%, 72%, 68%, and 94%. The values for coronary CTA and stress perfusion DECT were 88%, 79%, 73%, and 91%. The ROC AUC increased from 0.78 to 0.84 (p = 0.02) with the use of coronary CTA and stress perfusion DECT compared with coronary CTA alone. CONCLUSION Stress perfusion DECT plays a complementary role in enhancing the accuracy of coronary CTA for identifying hemodynamically

  11. Meta-analysis of the diagnostic performance of stress perfusion cardiovascular magnetic resonance for detection of coronary artery disease.

    PubMed

    Hamon, Michèle; Fau, Georges; Née, Guillaume; Ehtisham, Javed; Morello, Rémy; Hamon, Martial

    2010-05-19

    Evaluation of the diagnostic accuracy of stress perfusion cardiovascular magnetic resonance for the diagnosis of significant obstructive coronary artery disease (CAD) through meta-analysis of the available data. Original articles in any language published before July 2009 were selected from available databases (MEDLINE, Cochrane Library and BioMedCentral) using the combined search terms of magnetic resonance, perfusion, and coronary angiography; with the exploded term coronary artery disease. Statistical analysis was only performed on studies that: (1) used a [greater than or equal to] 1.5 Tesla MR scanner; (2) employed invasive coronary angiography as the reference standard for diagnosing significant obstructive CAD, defined as a [greater than or equal to] 50% diameter stenosis; and (3) provided sufficient data to permit analysis. From the 263 citations identified, 55 relevant original articles were selected. Only 35 fulfilled all of the inclusion criteria, and of these 26 presented data on patient-based analysis. The overall patient-based analysis demonstrated a sensitivity of 89% (95% CI: 88-91%), and a specificity of 80% (95% CI: 78-83%). Adenosine stress perfusion CMR had better sensitivity than with dipyridamole (90% (88-92%) versus 86% (80-90%), P = 0.022), and a tendency to a better specificity (81% (78-84%) versus 77% (71-82%), P = 0.065). Stress perfusion CMR is highly sensitive for detection of CAD but its specificity remains moderate.

  12. Meta-analysis of the diagnostic performance of stress perfusion cardiovascular magnetic resonance for detection of coronary artery disease

    PubMed Central

    2010-01-01

    Aim Evaluation of the diagnostic accuracy of stress perfusion cardiovascular magnetic resonance for the diagnosis of significant obstructive coronary artery disease (CAD) through meta-analysis of the available data. Methodology Original articles in any language published before July 2009 were selected from available databases (MEDLINE, Cochrane Library and BioMedCentral) using the combined search terms of magnetic resonance, perfusion, and coronary angiography; with the exploded term coronary artery disease. Statistical analysis was only performed on studies that: (1) used a [greater than or equal to] 1.5 Tesla MR scanner; (2) employed invasive coronary angiography as the reference standard for diagnosing significant obstructive CAD, defined as a [greater than or equal to] 50% diameter stenosis; and (3) provided sufficient data to permit analysis. Results From the 263 citations identified, 55 relevant original articles were selected. Only 35 fulfilled all of the inclusion criteria, and of these 26 presented data on patient-based analysis. The overall patient-based analysis demonstrated a sensitivity of 89% (95% CI: 88-91%), and a specificity of 80% (95% CI: 78-83%). Adenosine stress perfusion CMR had better sensitivity than with dipyridamole (90% (88-92%) versus 86% (80-90%), P = 0.022), and a tendency to a better specificity (81% (78-84%) versus 77% (71-82%), P = 0.065). Conclusion Stress perfusion CMR is highly sensitive for detection of CAD but its specificity remains moderate. PMID:20482819

  13. Stress Perfusion Coronary Flow Reserve Versus Cardiac Magnetic Resonance for Known or Suspected CAD.

    PubMed

    Kato, Shingo; Saito, Naka; Nakachi, Tatsuya; Fukui, Kazuki; Iwasawa, Tae; Taguri, Masataka; Kosuge, Masami; Kimura, Kazuo

    2017-08-15

    Phase-contrast (PC) cine magnetic resonance imaging (MRI) of the coronary sinus is a noninvasive method to quantify coronary flow reserve (CFR). This study sought to compare the prognostic value of CFR by cardiac magnetic resonance (CMR) and stress perfusion CMR to predict major adverse cardiac events (MACE). Participants included 276 patients with known coronary artery disease (CAD) and 400 with suspected CAD. CFR was calculated as myocardial blood flow during adenosine triphosphate infusion divided by myocardial blood flow at rest using PC cine MRI of the coronary sinus. During a median follow-up of 2.3 years, 47 patients (7%) experienced MACE. Impaired CFR (<2.0) and >10% ischemia on stress perfusion CMR were significantly associated with MACE in patients with known CAD (hazard ratio [HR]: 5.17 and HR: 5.10, respectively) and suspected CAD (HR: 14.16 and HR: 6.50, respectively). The area under the curve for predicting MACE was 0.773 for CFR and 0.731 for stress perfusion CMR (p = 0.58) for patients with known CAD, and 0.885 for CFR and 0.776 for stress perfusion CMR (p = 0.059) in the group with suspected CAD. In patients with known CAD, sensitivity, specificity, and positive and negative predictive values to predict MACE were 64%, 91%, 38%, and 97%, respectively, for CFR, and 82%, 59%, 15%, and 97%, respectively, for stress perfusion CMR. In the suspected CAD group, these values were 65%, 99%, 80%, and 97%, respectively, for CFR, and 72%, 83%, 22%, and 98%, respectively, for stress perfusion CMR. The predictive values of CFR and stress perfusion CMR for MACE were comparable in patients with known CAD. In patients with suspected CAD, CFR showed higher HRs and areas under the curve than stress perfusion CMR, suggesting that CFR assessment by PC cine MRI might provide better risk stratification for patients with suspected CAD. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  14. Pre-procedural combined coronary angiography and stress myocardial perfusion imaging using 320-detector CT in unprotected left main and ostial left anterior descending artery intervention.

    PubMed

    Ko, Brian S; Crossett, Marcus; Seneviratne, Sujith K

    2015-07-01

    Pre-procedural anatomic and functional coronary assessment plays a crucial role in selection of patients suitable for unprotected left main percutaneous coronary intervention. Combined coronary computed tomography angiography and adenosine stress computed tomography myocardial perfusion imaging is a non-invasive technique which may provide this information. This is the first report describing its use to assist patient selection and procedural planning prior to elective left main and ostial left anterior descending artery coronary intervention.

  15. Comparison of the Safety of Adenosine and Regadenoson in Patients Undergoing Outpatient Cardiac Stress Testing.

    PubMed

    Brink, Heidi L; Dickerson, Jennifer A; Stephens, Julie A; Pickworth, Kerry K

    2015-12-01

    To compare the adverse effect profiles of adenosine and regadenoson in patients undergoing outpatient cardiac stress testing. Single-center retrospective cohort study. Two outpatient clinics, both of which are part of a single tertiary academic medical health system; one clinic exclusively used adenosine for cardiac stress testing, and the other clinic exclusively used regadenoson. A total of 489 patients who underwent an outpatient cardiac stress test between January 1, 2014, and December 31, 2014; of those patients, 254 received adenosine and 235 received regadenoson. Baseline characteristics were similar between groups, except for chronic kidney disease (p<0.001), congestive heart failure (p=0.041), and mean age (p=0.004). The primary outcome was the occurrence of adverse effects-arrhythmia, chest pain or tightness, dizziness, dyspnea, flushing, or headache, and use of the rescue agent aminophylline-in the adenosine and regadenoson groups. A significantly higher proportion of patients who were given regadenoson during cardiac stress testing experienced at least one adverse effect compared with patients who underwent an adenosine stress test (79.6% vs 31.5%, p<0.001). The patients given regadenoson experienced a significantly higher occurrence of arrhythmia (30.6% vs 16.1%, p<0.001), dyspnea (66.0% vs 17.7%, p<0.001), and headache (25.1% vs 3.1%, p<0.001), and they had a significantly higher rate of aminophylline rescue use (19.2% vs 0.8%, p<0.001). A secondary objective evaluated the financial impact of each agent, and adenosine exhibited a medication price that was more than $100/patient lower than regadenoson based on the average wholesale price. Among patients undergoing an outpatient pharmacologic stress test, the use of adenosine was associated with a lower occurrence of adverse effects and lower rate of a rescue agent use and may provide a potential medication cost savings opportunity compared with regadenoson. © 2015 Pharmacotherapy Publications, Inc.

  16. Noninvasive stress testing of myocardial perfusion defects: head-to-head comparison of thallium-201 SPECT to MRI perfusion.

    PubMed

    Vincenti, Gabriella; Nkoulou, René; Steiner, Charles; Imperiano, Hestia; Ambrosio, Giuseppe; Mach, François; Ratib, Osman; Vallee, Jean-Paul; Schindler, Thomas H

    2009-01-01

    To evaluate the diagnostic value of magnetic resonance imaging (MRI) of myocardial perfusion in the assessment of flow-limiting epicardial stenosis in a head-to-head comparison with abnormal thallium-201 ((201)TI) single photon emission tomography (SPECT) studies in patients with predominantly known coronary artery disease (CAD). Twenty-one patients (mean age 65 +/- 10 years) with reversible myocardial perfusion defects on (201)TI-SPECT images during dipyridamole-stimulated hyperemia were recruited for study purpose. Within 5 days of the (201)TI-SPECT study, myocardial perfusion was studied again with MRI during dipyridamole stimulation and at rest. Overall, (201)TI-SPECT identified 30 reversible regional perfusion defects. The sensitivity to detect hypoperfused segments was 70% (21/30) with the GRE-MRI perfusion analysis with (201)TI-SPECT as reference. When patients were subgrouped according to the extent of regional reversible perfusion defects on (201)TI-SPECT, mild- (SDS: 2-4), moderate- (SDS: 5-8), and severe- (SDS > 8) perfusion defects were also identified by GRE-MRI perfusion analysis in 75% (6/8), in 56% (9/16) and 100% (6/6), respectively. GRE-MRI first-pass stress perfusion imaging may not identify up to 30% of mild-to-moderate perfusion defects in a group of preselected patients with predominantly known CAD and abnormal (201)TI-SPECT studies.

  17. Ex vivo Perfusion with Adenosine A2A Receptor Agonist Enhances Rehabilitation of Murine Donor Lungs after Circulatory Death

    PubMed Central

    Stone, Mathew L.; Sharma, Ashish K.; Mas, Valeria. R.; Gehrau, Ricardo C.; Mulloy, Daniel P.; Zhao, Yunge; Lau, Christine L.; Kron, Irving L.; Laubach, Victor E.

    2015-01-01

    Background Ex vivo lung perfusion (EVLP) enables assessment and rehabilitation of marginal donor lungs prior to transplantation. We previously demonstrated that adenosine A2A receptor (A2AR) agonism attenuates lung ischemia-reperfusion injury. The current study utilizes a novel murine EVLP model to test the hypothesis that A2AR agonist enhances EVLP-mediated rehabilitation of donation after circulatory death (DCD) lungs. Methods Mice underwent euthanasia and 60 min warm ischemia, and lungs were flushed with Perfadex and underwent cold static preservation (CSP, 60 min). Three groups were studied: no EVLP (CSP), EVLP with Steen solution for 60 min (EVLP), and EVLP with Steen solution supplemented with ATL1223, a selective A2AR agonist (EVLP+ATL1223). Lung function, wet/dry weight, cytokines and neutrophil numbers were measured. Microarrays were performed using the Affymetrix GeneChip Mouse Genome 430A 2.0 Array. Results EVLP significantly improved lung function versus CSP, which was further, significantly improved by EVLP+ATL1223. Lung edema, cytokines and neutrophil counts were reduced after EVLP and further, significantly reduced after EVLP+ATL1223. Gene array analysis revealed differential expression of 1,594 genes after EVLP, which comprise canonical pathways involved in inflammation and innate immunity including IL-1, IL-8, IL-6 and IL-17 signaling. Several pathways were uniquely regulated by EVLP+ATL1223 including the downregulation of genes involved in IL-1 signaling such as ADCY9, ECSIT, IRAK1, MAPK12 and TOLLIP. Conclusion EVLP modulates pro-inflammatory genes and reduces pulmonary dysfunction, edema and inflammation in DCD lungs, which are further reduced by A2AR agonism. This murine EVLP model provides a novel platform to study rehabilitative mechanisms of DCD lungs. PMID:26262504

  18. Myocardial perfusion: near-automated evaluation from contrast-enhanced MR images obtained at rest and during vasodilator stress.

    PubMed

    Tarroni, Giacomo; Corsi, Cristiana; Antkowiak, Patrick F; Veronesi, Federico; Kramer, Christopher M; Epstein, Frederick H; Walter, James; Lamberti, Claudio; Lang, Roberto M; Mor-Avi, Victor; Patel, Amit R

    2012-11-01

    To develop and validate a technique for near-automated definition of myocardial regions of interest suitable for perfusion evaluation during vasodilator stress cardiac magnetic resonance (MR) imaging. The institutional review board approved the study protocol, and all patients provided informed consent. Image noise density distribution was used as a basis for endocardial and epicardial border detection combined with nonrigid registration. This method was tested in 42 patients undergoing contrast material-enhanced cardiac MR imaging (at 1.5 T) at rest and during vasodilator (adenosine or regadenoson) stress, including 15 subjects with normal myocardial perfusion and 27 patients referred for coronary angiography. Contrast enhancement-time curves were near-automatically generated and were used to calculate perfusion indexes. The results were compared with results of conventional manual analysis, using quantitative coronary angiography results as a reference for stenosis greater than 50%. Statistical analyses included the Student t test, linear regression, Bland-Altman analysis, and κ statistics. Analysis of one sequence required less than 1 minute and resulted in high-quality contrast enhancement curves both at rest and stress (mean signal-to-noise ratios, 17±7 [standard deviation] and 22±8, respectively), showing expected patterns of first-pass perfusion. Perfusion indexes accurately depicted stress-induced hyperemia (increased upslope, from 6.7 sec(-1)±2.3 to 15.6 sec(-1)±5.9; P<.0001). Measured segmental pixel intensities correlated highly with results of manual analysis (r=0.95). The derived perfusion indexes also correlated highly with (r up to 0.94) and showed the same diagnostic accuracy as manual analysis (area under the receiver operating characteristic curve, up to 0.72 vs 0.73). Despite the dynamic nature of contrast-enhanced image sequences and respiratory motion, fast near-automated detection of myocardial segments and accurate quantification of

  19. Increased norepinephrine release during sympathetic nerve stimulation and its inhibition by adenosine in the isolated perfused kidney of spontaneously hypertensive rats

    SciTech Connect

    Ekas, R.D. Jr.; Steenberg, M.L.; Lokhandwala, M.F.

    1983-01-01

    The present study was performed to measure norepinephrine release during sympathetic nerve stimulation and determine the inhibitory action of adenosine on stimulus-induced release of norepinephrine in the isolated perfused kidney of WKY and SHR. Norepinephrine release during periarterial nerve stimulation was measured as total /sup 3/H-overflow since greater than 75% of total /sup 3/H-overflow was /sup 3/H-norepinephrine in both the WKY and SHR. A significantly greater increase in /sup 3/H-norepinephrine overflow was observed during periarterial nerve stimulation in SHR in comparison with WKY. Adenosine (0.3, 1.0, 3.0 and 10.0 micrograms/ml) produced dose-dependent inhibition of /sup 3/H-norepinephrine overflow elicited by periarterial nerve stimulation. However, the effect of adenosine on transmitter release was more pronounced in the SHR in that the threshold dose required to cause inhibition of stimulus-induced release of /sup 3/H-norepinephrine was smaller in the SHR. These results demonstrate that while norepinephrine release during sympathetic nerve stimulation is greater in the SHR, this finding can not be explained on the basis of a decrease in the presynaptic inhibitory action of adenosine. Therefore, the mechanism responsible for the increased release of norepinephrine in the SHR remains to be determined.

  20. Resting cardiointegram: correlation with stress thallium perfusion studies

    SciTech Connect

    Gould, L.A.; Betzu, R.; Judge, D.; Lee, J.; Taddeo, M.; Yang, D.

    1988-04-01

    The cardiointegram is a noninvasive technique for the analysis of the electrical signals of the heart obtained by a transformation of the voltage versus time format by a series of integrations. The stress thallium perfusion study is a widely used test for the detection of coronary artery disease. In order to evaluate the correlation between the resting cardiointegram and the stress thallium 201 perfusion study, 20 patients with normal resting electrocardiograms underwent stress thallium tests and resting cardiointegrams. The cardiointegram was determined on two resting complexes of leads I, II, V4, V5, and V6 and called abnormal if five of ten complexes deviated outside a normalized template. There was concordance of the cardiointegram and the thallium study in 16 of 20 patients (80%). The sensitivity for the detection of coronary artery disease was 71%, and the specificity was 80%. The overall accuracy was 74%. Thus in patients with normal electrocardiograms, the cardiointegram is a useful noninvasive test for the detection of coronary artery disease.

  1. Feasibility of stress only rubidium-82 PET myocardial perfusion imaging.

    PubMed

    McMahon, Sean R; Kikut, Janusz; Pinckney, Richard G; Keating, Friederike K

    2013-12-01

    Stress only SPECT myocardial perfusion imaging (MPI) is a validated strategy to streamline cardiac diagnostic imaging. The potential use of Rb82 PET stress only MPI has not been investigated. Stress images from 200 Rb82 PET-MPI were reviewed by two blinded readers and categorized as not requiring additional rest images (normal) or requiring additional images (abnormal or equivocal). No additional images were deemed necessary for 95 (48%) and 99 (50%) by the two blinded readers. The stress only interpretation was compared to the previous read of the complete rest-stress study. The rate of detecting a normal result with stress only reading was 76%-79% with a negative predictive value of 94%-95%. Clinical predictors of a normal stress only PET-MPI included lower age, the absence of CAD, and female gender, but not body mass index. Blinded reads of 50 additional consecutive PET-MPI from patients with selected clinical predictors (age <65 years, no known CAD) were then performed. Of these, 40 (80%) were normal by previous rest-stress reading, and 34 (68%) were categorized as not requiring additional images after stress only reading. PET stress only imaging would have resulted in a mean reduction of radiation exposure of 2.4 mSv per study according to a published radiation estimate. Stress only Rb82 PET-MPI is a feasible strategy to reduce resource utilization and radiation exposure associated with MPI. This strategy would be most applicable to patients with a lower pretest likelihood.

  2. Stress-first single photon emission computed myocardial perfusion imaging

    PubMed Central

    Aquino, C I; Scarano, M; Squame, F; Casaburi, G; Nori, S L; Pace, L

    2016-01-01

    Background Myocardial perfusion imaging (MPI) with single photon emission tomography (SPET) is widely used in coronary artery disease evaluation. Recently major dosimetric concerns have arisen. The aim of this study was to evaluate if a pre-test scoring system could predict the results of stress SPET MPI, thus avoiding two radionuclide injections. Methods All consecutive patients (n=309) undergoing SPET MPI during the first 6 months of 2014 constituted the study group. The scoring system is based on these characteristics: age >65 years (1 point), diabetes (2 points), typical chest pain (2 points), congestive heart failure (3 points), abnormal ECG (4 points), male gender (4 points), and documented previous CAD (5 points). The patients were divided on the basis of the prediction score into 3 classes of risk for an abnormal stress-first protocol. Results An abnormal stress SPET MPI was present in 7/31 patients (23%) with a low risk score, in 24/90 (27%) with an intermediate score risk, and in 124/188 (66%) with an high score risk. ROC curve analysis showed good prediction of abnormal stress MPI. Conclusions Our results suggest an appropriate use of a pre-test clinical prediction formula of abnormal stress MPI in a routine clinical setting. PMID:27896227

  3. Non-invasive evaluation of internal thoracic artery anastomosed to the left anterior descending artery with 320-detector row computed tomography and adenosine thallium-201 myocardial perfusion scintigraphy.

    PubMed

    Takagi, Yasushi; Akita, Kiyotoshi; Kondo, Hiroshi; Ishida, Michiko; Kaneko, Kan; Sato, Masato; Ando, Motomi

    2012-01-01

    We evaluated the relationship between internal thoracic artery (ITA) stenosis anastomosed to the left anterior descending artery (LAD) and the degree of LAD stenosis using 320-detector row computed tomography (320-ADCT) and adenosine thallium-201 myocardial perfusion scintigraphy (Tl-201-MPS). We included 101 patients who underwent coronary artery bypass grafting (CABG) using ITA grafts; 320-ADCT and adenosine Tl-201-MPS were performed 2-3 months after CABG. Clinical parameters, degree of LAD stenosis, and regional myocardial ischemia of the LAD territory were compared between patients without ITA stenosis (Group A) and with ITA stenosis (Group B). Thirty patients (30%) had ≤75% LAD stenosis, and 9 patients (30%) showed significant ITA stenosis. Regional ischemia was noted in 23 patients (23%). There were no differences in clinical parameters between the 2 groups. Twenty-two patients (24%) in Group A and 8 patients (89%) in Group B had ≤75% LAD stenosis (P <0.002). No Group B patients had regional myocardial ischemia of the LAD territory. We concluded that ≤75% LAD stenosis significantly influences ITA stenosis, without associated regional myocardial ischemia of the LAD territory. Non-invasive 320-ADCT and adenosine Tl-201-MPS for ITA evaluation may be useful for long-term follow-up of patients after CABG.

  4. Use of adenosine echocardiography for diagnosis of coronary artery disease

    SciTech Connect

    Zoghbi, W.A. )

    1991-07-01

    Two-dimensional echocardiography combined with exercise is sensitive and specific in the detection of coronary artery disease (CAD) by demonstrating transient abnormalities in wall motion. Frequently, however, patients cannot achieve maximal exercise because of various factors. Pharmacologic stress testing with intravenous adenosine was evaluated as a means of detecting CAD in a noninvasive manner. Patients with suspected CAD underwent echocardiographic imaging and simultaneous thallium 201 single-photon emission computed tomography during the intravenous administration of 140 micrograms/kg/min of adenosine. An increase in heart rate, decrease in blood pressure, and increase in double product were observed during adenosine administration. Initial observations revealed that wall motion abnormalities were induced by adenosine in areas of perfusion defects. The adenosine infusion was well tolerated, and symptoms disappeared within 1 to 2 minutes after termination of the infusion. Therefore preliminary observations suggest that adenosine echocardiography appears to be useful in the assessment of CAD.

  5. Prognostic Utility of Calcium Scoring as an Adjunct to Stress Myocardial Perfusion Scintigraphy in End-Stage Renal Disease.

    PubMed

    Moody, William E; Lin, Erica L S; Stoodley, Matthew; McNulty, David; Thomson, Louise E; Berman, Daniel S; Edwards, Nicola C; Holloway, Benjamin; Ferro, Charles J; Townend, Jonathan N; Steeds, Richard P

    2016-05-01

    Coronary artery calcium score (CACS) is a strong predictor of adverse cardiovascular events in the general population. Recent data confirm the prognostic utility of single-photon emission computed tomographic (SPECT) imaging in end-stage renal disease, but whether performing CACS as part of hybrid imaging improves risk prediction in this population is unclear. Consecutive patients (n = 284) were identified after referral to a university hospital for cardiovascular risk stratification in assessment for renal transplantation. Participants underwent technetium-99m SPECT imaging after exercise or standard adenosine stress in those unable to achieve 85% maximal heart rate; multislice CACS was also performed (Siemens Symbia T16, Siemens, Erlangen, Germany). Subjects with known coronary artery disease (n = 88) and those who underwent early revascularization (n = 2) were excluded. The primary outcome was a composite of death or first myocardial infarction. An abnormal SPECT perfusion result was seen in 22% (43 of 194) of subjects, whereas 45% (87 of 194) had at least moderate CACS (>100 U). The frequency of abnormal perfusion (summed stress score ≥4) increased with increasing CACS severity (p = 0.049). There were a total of 15 events (8 deaths, and 7 myocardial infarctions) after a median duration of 18 months (maximum follow-up 3.4 years). Univariate analysis showed diabetes mellitus (Hazard ratio [HR] 3.30, 95% CI 1.14 to 9.54; p = 0.028), abnormal perfusion on SPECT (HR 5.32, 95% CI 1.84 to 15.35; p = 0.002), and moderate-to-severe CACS (HR 3.55, 95% CI 1.11 to 11.35; p = 0.032) were all associated with the primary outcome. In a multivariate model, abnormal perfusion on SPECT (HR 4.18, 95% CI 1.43 to 12.27; p = 0.009), but not moderate-to-severe CACS (HR 2.50, 95% CI 0.76 to 8.20; p = 0.130), independently predicted all-cause death or myocardial infarction. The prognostic value of CACS was not incremental to clinical and SPECT perfusion data (global chi-square change

  6. Role of adipokinetic hormone and adenosine in the anti-stress response in Drosophila melanogaster.

    PubMed

    Zemanová, Milada; Stašková, Tereza; Kodrík, Dalibor

    2016-01-01

    The role of adipokinetic hormone (AKH) and adenosine in the anti-stress response was studied in Drosophila melanogaster larvae and adults carrying a mutation in the Akh gene (Akh(1)), the adenosine receptor gene (AdoR(1)), or in both of these genes (Akh(1) AdoR(1) double mutant). Stress was induced by starvation or by the addition of an oxidative stressor paraquat (PQ) to food. Mortality tests revealed that the Akh(1) mutant was the most resistant to starvation, while the AdoR(1) mutant was the most sensitive. Conversely, the Akh(1) AdoR(1) double mutant was more sensitive to PQ toxicity than either of the single mutants. Administration of PQ significantly increased the Drome-AKH level in w(1118) and AdoR(1) larvae; however, this was not accompanied by a simultaneous increase in Akh gene expression. In contrast, PQ significantly increased the expression of the glutathione S-transferase D1 (GstD1) gene. The presence of both a functional adenosine receptor and AKH seem to be important for the proper control of GstD1 gene expression under oxidative stress, however, the latter appears to play more dominant role. On the other hand, differences in glutathione S-transferase (GST) activity among the strains, and between untreated and PQ-treated groups were minimal. In addition, the glutathione level was significantly lower in all untreated AKH- or AdoR-deficient mutant flies as compared with the untreated control w(1118) flies and further declined following treatment with PQ. All oxidative stress characteristics modified by mutations in Akh gene were restored or even improved by 'rescue' mutation in flies which ectopically express Akh. Thus, the results of the present study demonstrate the important roles of AKH and adenosine in the anti-stress response elicited by PQ in a D. melanogaster model, and provide the first evidence for the involvement of adenosine in the anti-oxidative stress response in insects. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. An ex vivo comparison of adenosine and lidocaine solution and University of Wisconsin solution for hypothermic machine perfusion of porcine kidneys: potential for development.

    PubMed

    Hamaoui, Karim; Aftab, Adeel; Gowers, Sally; Boutelle, Martyn; Cook, Terry; Rudd, Donna; Dobson, Geoffrey P; Papalois, Vassilios

    2017-02-01

    The optimal hypothermic machine perfusion (HMP) solution has not yet been developed. An adenosine and lidocaine (AL) solution has been shown to be protective in cardiac preservation. The aim of the present study was to examine a modified AL solution with low Ca(2+), 16 mM Mg(2+), and 4% albumin on kidney preservation compared with University Wisconsin solution (UW). Twenty donation of organs after cardiac death porcine kidneys underwent HMP for 10 h (AL, n = 10; UW, n = 10) and then 2 h of normothermic reperfusion. Perfusion dynamics, functional parameters, histology, and real-time microdialysis were used to assess kidney responses and viability. During HMP, modified AL-perfused kidneys maintained higher flow rates (21.5 versus 17.9 mL/min/100 g, P = 0.01), with perfusion flow index during the first 3 h 25% greater than with UW (AL = 0.50 ± 0.2, UW = 0.40 ± 0.17 mL/min/100 g/mmHg; P = 0.03), followed by an increase in UW kidneys which was not significantly different to AL over the remaining 7 h (0.54 versus 0.55 mL/min/100 g/mmHg, respectively). During warm reperfusion, there were no significant differences between the two HMP groups in creatinine clearance, oxygen, and glucose consumption between groups. Modified AL kidneys had significantly lower perfusate lactates (3.1 versus 4.1 mmol/L, P = 0.04) during reperfusion and lower cortical lactate levels (AL = 0.66 ± 0.31, UW = 0.89 ± 0.53 mM, P = 0.33). Histology showed similar degrees of reperfusion injury. We conclude that HMP with modified AL solution showed improved perfusion compared with UW and lower perfusate lactate levels during warm reperfusion. Further modification of the AL composition is warranted and may lead to more rapid kidney stabilization and improved graft viability assessment, potentially expanding donor pools. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Prognostic value of normal adenosine-stress cardiac magnetic resonance imaging.

    PubMed

    Pilz, Guenter; Jeske, Andrea; Klos, Markus; Ali, Eman; Hoefling, Berthold; Scheck, Roland; Bernhardt, Peter

    2008-05-15

    We investigated the prognostic value of normal adenosine stress cardiac magnetic resonance (CMR) in suspected coronary artery disease (CAD). Prospectively enrolled in the study were 218 patients with suspected CAD, no stress hypoperfusion, and no delayed enhancement in CMR, and consecutively deferred coronary angiography. The primary end point was a 12-month rate of major adverse cardiac events (MACE; cardiovascular mortality, myocardial infarction, revascularization, hospitalization due to cardiovascular event). CMR indication was symptomatic angina (Canadian Cardiovascular Society II in 42% and III in 7%) or evaluation of myocardial ischemia in patients with arrhythmia, syncope, and/or equivocal stress tests and cardiovascular risk factors (51%). As the main result, the 12-month MACE rate was 2/218 (1 stent implantation, 1 bypass surgery) and CMR negative predictive value 99.1%. There was no cardiac death or myocardial infarction. In conclusion, normal adenosine stress CMR predicts a very low MACE rate and an excellent 1-year prognosis in patients with suspected CAD. Our results provide clinical reassurance that patients at risk for CAD-associated MACE were not missed by CMR. Hence, CMR may serve as a reliable noninvasive gatekeeper to reduce the number of redundant coronary angiographies.

  9. Diagnostic advantage of stress computed tomography myocardial perfusion over single-photon emission computed tomography for the assessment of myocardial ischemia.

    PubMed

    Ueki, Yasushi; Izawa, Atsushi; Kashiwagi, Daisuke; Nishiyama, Shigeki; Aso, Shinichi; Suzuki, Chihiro; Sakurai, Shumpei; Oguchi, Kazuhiro; Yazaki, Yoshikazu; Ikeda, Uichi; Kuwahara, Koichiro

    2017-08-01

    This study compared adenosine stress computed tomography myocardial perfusion (CTP) with single-photon emission computed tomography (SPECT) in the diagnosis of functionally significant coronary artery stenosis using fractional flow reserve (FFR) as reference standard. We included a total of 93 coronary arteries from 31 patients in whom at least one vessel with ≥50% stenosis was detected with computed tomography coronary angiography. All patients underwent both SPECT and adenosine stress CTP, followed by invasive coronary angiography (ICA) and FFR. Diagnostic accuracy between CTP and SPECT was compared according to positive findings of either ≥99% stenosis on ICA or FFR ≤0.8. Among 78 vessels eligible for the quantitative analyses, significant coronary artery disease (CAD) was diagnosed in 22 vessels of 19 patients. Comparison of CTP vs. SPECT for sensitivity, specificity, positive predictive value (PPV), negative predictive value, and accuracy in detecting significant CAD were 59% vs. 18%, 96% vs. 93%, 87% vs. 50%, 86% vs. 74%, and 86% vs. 72%, respectively. CTP demonstrated a significant diagnostic advantage over SPECT in the identification of significant CAD, especially in terms of sensitivity and PPV. Adenosine stress CTP is useful for the noninvasive diagnosis of functionally significant CAD. Copyright © 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  10. Three-dimensional quantification of myocardial perfusion during regadenoson stress computed tomography.

    PubMed

    Mor-Avi, Victor; Kachenoura, Nadjia; Maffessanti, Francesco; Bhave, Nicole M; Port, Steven; Lodato, Joseph A; Chandra, Sonal; Freed, Benjamin H; Lang, Roberto M; Patel, Amit R

    2016-05-01

    There is no accepted methodology for CT-based vasodilator stress myocardial perfusion imaging and analysis. We developed a technique for quantitative 3D analysis of CT images, which provides several indices of myocardial perfusion. We sought to determine the ability of these indices during vasodilator stress to identify segments supplied by coronary arteries with obstructive disease and to test the accuracy of the detection of perfusion abnormalities against SPECT. We studied 93 patients referred for CT coronary angiography (CTCA) who underwent regadenoson stress. 3D analysis of stress CT images yielded segmental perfusion indices: mean X-ray attenuation, severity of defect and relative defect volume. Each index was averaged for myocardial segments, grouped by severity of stenosis: 0%, <50%, 50-70%, and >70%. Objective detection of perfusion abnormalities was optimized in 47 patients and then independently tested in the remaining 46 patients. CTCA depicted normal coronary arteries or non-obstructive disease in 62 patients and stenosis of >50% in 31. With increasing stenosis, segmental attenuation showed a 7% decrease, defect severity increased 11%, but relative defect volume was 7-fold higher in segments with obstructive disease (p<0.001). In the test group, detection of perfusion abnormalities associated with stenosis >50% showed sensitivity 0.78, specificity 0.54, accuracy 0.59. When compared to SPECT in a subset of 21 patients (14 with abnormal SPECT), stress CT perfusion analysis showed sensitivity 0.79, specificity 0.71, accuracy 0.76. 3D analysis of vasodilator stress CT images provides quantitative indices of myocardial perfusion, of which relative defect volume was most robust in identifying segments supplied by arteries with obstructive disease. This study may have implications on how CT stress perfusion imaging is performed and analyzed. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Effect of caffeine on SPECT myocardial perfusion imaging during regadenoson pharmacologic stress: rationale and design of a prospective, randomized, multicenter study.

    PubMed

    Tejani, Furqan H; Thompson, Randall C; Iskandrian, Ami E; McNutt, Bruce E; Franks, Billy

    2011-02-01

    Caffeine attenuates the coronary hyperemic response to adenosine by competitive A₂(A) receptor blockade. This study aims to determine whether oral caffeine administration compromises diagnostic accuracy in patients undergoing vasodilator stress myocardial perfusion imaging (MPI) with regadenoson, a selective adenosine A(2A) agonist. This multicenter, randomized, double-blind, placebo-controlled, parallel-group study includes patients with suspected coronary artery disease who regularly consume caffeine. Each participant undergoes three SPECT MPI studies: a rest study on day 1 (MPI-1); a regadenoson stress study on day 3 (MPI-2), and a regadenoson stress study on day 5 with double-blind administration of oral caffeine 200 or 400 mg or placebo capsules (MPI-3; n = 90 per arm). Only participants with ≥ 1 reversible defect on the second MPI study undergo the subsequent stress MPI test. The primary endpoint is the difference in the number of reversible defects on the two stress tests using a 17-segment model. Pharmacokinetic/pharmacodynamic analyses will evaluate the effect of caffeine on the regadenoson exposure-response relationship. Safety will also be assessed. The results of this study will show whether the consumption of caffeine equivalent to 2-4 cups of coffee prior to an MPI study with regadenoson affects the diagnostic validity of stress testing (ClinicalTrials.gov number, NCT00826280).

  12. Evidence that release of adenosine triphosphate from endothelial cells during increased shear stress is vesicular.

    PubMed

    Bodin, P; Burnstock, G

    2001-12-01

    In response to increased shear stress, vascular endothelial cells release adenosine triphosphate (ATP) by an unknown mechanism. We have investigated this mechanism using different approaches. First, we discovered that quinacrine, used to locate intracellular stores of ATP bound to peptides, displayed a granular fluorescence, typical of vesicular storage. Second, we found that two inhibitors of vesicular transport (monensin and N-ethylmaleimide) produced a highly significant reduction in the release of ATP from vascular endothelial cells in response to increased shear stress. Preliminary experiments using inhibitors of the cystic fibrosis transmembrane regulator, the sulfonylurea receptor, and the multidrug resistance protein showed no involvement of these ATP-binding cassette transporter proteins (previously characterized in endothelial cells) in the mechanism of release of ATP. We suggest, therefore, that the release of ATP from vascular endothelial cells, like that of nerve cells, is probably by vesicular exocytosis.

  13. Usefulness of adenosine triphosphate-atropine stress echocardiography for detecting coronary artery stenosis.

    PubMed

    Miyazono, Y; Kisanuki, A; Toyonaga, K; Matsushita, R; Otsuji, Y; Arima, S; Nakao, S; Tanaka, H

    1998-08-01

    There have been few studies on adenosine triphosphate (AT) stress echocardiography. The AT stress test may have fewer adverse effects than the adenosine stress test. The addition of atropine to AT echocardiography may enhance the sensitivity for detection of coronary artery disease (CAD). The purpose of this study was to determine the utility of AT-atropine echocardiography for detection of CAD. The group studied consisted of 112 patients with suspected CAD. Sixty-one patients did not have a history of prior myocardial infarction (group I) and 51 patients did (group II). AT was infused intravenously at 180 microg/kg/min for 14 minutes. Atropine (0.25 mg intravenously, repeated up to maximum total dose of 1 mg) was administered starting after 8 minutes of AT infusion. Ischemic response was defined as new or worsening wall motion abnormality occurring during the infusion. The sensitivity and specificity for detection of CAD were assessed using the representative echocardiograms during single AT infusion and AT-atropine infusion. Sixty-two patients had CAD. Fifty-eight patients (52%) developed minor side effects that resolved promptly. The rate-pressure product (10(3)/mm Hg beats/min) was significantly increased at 12 minutes of infusion (12.4+/-3.2) compared with that at baseline (9.1+/-2.3) and that at 6 minutes of infusion (9.4+/-2.1). The sensitivity for detection of CAD was 45% for AT echocardiography and 74% for AT-atropine echocardiography. The specificity was 94% for AT echocardiography and 90% for AT-atropine echocardiography. The sensitivity and specificity of AT-atropine echocardiography was 78% and 93%, respectively, in group I, and 70% and 86%, respectively, in group II. In conclusion, AT-atropine stress echocardiography seems to be well tolerated, safe, and useful for detection of CAD.

  14. Myocardial perfusion and oxygenation are impaired during stress in severe aortic stenosis and correlate with impaired energetics and subclinical left ventricular dysfunction

    PubMed Central

    2014-01-01

    Background Left ventricular (LV) hypertrophy in aortic stenosis (AS) is characterized by reduced myocardial perfusion reserve due to coronary microvascular dysfunction. However, whether this hypoperfusion leads to tissue deoxygenation is unknown. We aimed to assess myocardial oxygenation in severe AS without obstructive coronary artery disease, and to investigate its association with myocardial energetics and function. Methods Twenty-eight patients with isolated severe AS and 15 controls underwent cardiovascular magnetic resonance (CMR) for assessment of perfusion (myocardial perfusion reserve index-MPRI) and oxygenation (blood-oxygen level dependent-BOLD signal intensity-SI change) during adenosine stress. LV circumferential strain and phosphocreatine/adenosine triphosphate (PCr/ATP) ratios were assessed using tagging CMR and 31P MR spectroscopy, respectively. Results AS patients had reduced MPRI (1.1 ± 0.3 vs. controls 1.7 ± 0.3, p < 0.001) and BOLD SI change during stress (5.1 ± 8.9% vs. controls 18.2 ± 10.1%, p = 0.001), as well as reduced PCr/ATP (1.45 ± 0.21 vs. 2.00 ± 0.25, p < 0.001) and LV strain (−16.4 ± 2.7% vs. controls −21.3 ± 1.9%, p < 0.001). Both perfusion reserve and oxygenation showed positive correlations with energetics and LV strain. Furthermore, impaired energetics correlated with reduced strain. Eight months post aortic valve replacement (AVR) (n = 14), perfusion (MPRI 1.6 ± 0.5), oxygenation (BOLD SI change 15.6 ± 7.0%), energetics (PCr/ATP 1.86 ± 0.48) and circumferential strain (−19.4 ± 2.5%) improved significantly. Conclusions Severe AS is characterized by impaired perfusion reserve and oxygenation which are related to the degree of derangement in energetics and associated LV dysfunction. These changes are reversible on relief of pressure overload and hypertrophy regression. Strategies aimed at improving oxygen demand–supply balance to preserve myocardial

  15. Diagnostic Performance of Coronary CT Angiography, Stress Dual-Energy CT Perfusion, and Stress Perfusion Single-Photon Emission Computed Tomography for Coronary Artery Disease: Comparison with Combined Invasive Coronary Angiography and Stress Perfusion Cardiac MRI

    PubMed Central

    Chung, Hyun Woo; Hwang, Hweung Kon; So, Young; Yi, Jeong Geun; Lee, Eun Jeong

    2017-01-01

    Objective To investigate the diagnostic performance of coronary computed tomography angiography (CCTA), stress dual-energy computed tomography perfusion (DE-CTP), stress perfusion single-photon emission computed tomography (SPECT), and the combinations of CCTA with myocardial perfusion imaging (CCTA + DE-CTP and CCTA + SPECT) for identifying coronary artery stenosis that causes myocardial hypoperfusion. Combined invasive coronary angiography (ICA) and stress perfusion cardiac magnetic resonance (SP-CMR) imaging are used as the reference standard. Materials and Methods We retrospectively reviewed the records of 25 patients with suspected coronary artery disease, who underwent CCTA, DE-CTP, SPECT, SP-CMR, and ICA. The reference standard was defined as ≥ 50% stenosis by ICA, with a corresponding myocardial hypoperfusion on SP-CMR. Results For per-vascular territory analysis, the sensitivities of CCTA, DE-CTP, SPECT, CCTA + DE-CTP, and CCTA + SPECT were 96, 96, 68, 93, and 68%, respectively, and specificities were 72, 75, 89, 85, and 94%, respectively. The areas under the receiver operating characteristic curve (AUCs) were 0.84 ± 0.05, 0.85 ± 0.05, 0.79 ± 0.06, 0.89 ± 0.04, and 0.81 ± 0.06, respectively. For per-patient analysis, the sensitivities of CCTA, DE-CTP, SPECT, CCTA + DE-CTP, and CCTA + SPECT were 100, 100, 89, 100, and 83%, respectively; the specificities were 14, 43, 57, 43, and 57%, respectively; and the AUCs were 0.57 ± 0.13, 0.71 ± 0.11, 0.73 ± 0.11, 0.71 ± 0.11, and 0.70 ± 0.11, respectively. Conclusion The combination of CCTA and DE-CTP enhances specificity without a loss of sensitivity for detecting hemodynamically significant coronary artery stenosis, as defined by combined ICA and SP-CMR. PMID:28458600

  16. Diagnostic Performance of Coronary CT Angiography, Stress Dual-Energy CT Perfusion, and Stress Perfusion Single-Photon Emission Computed Tomography for Coronary Artery Disease: Comparison with Combined Invasive Coronary Angiography and Stress Perfusion Cardiac MRI.

    PubMed

    Chung, Hyun Woo; Ko, Sung Min; Hwang, Hweung Kon; So, Young; Yi, Jeong Geun; Lee, Eun Jeong

    2017-01-01

    To investigate the diagnostic performance of coronary computed tomography angiography (CCTA), stress dual-energy computed tomography perfusion (DE-CTP), stress perfusion single-photon emission computed tomography (SPECT), and the combinations of CCTA with myocardial perfusion imaging (CCTA + DE-CTP and CCTA + SPECT) for identifying coronary artery stenosis that causes myocardial hypoperfusion. Combined invasive coronary angiography (ICA) and stress perfusion cardiac magnetic resonance (SP-CMR) imaging are used as the reference standard. We retrospectively reviewed the records of 25 patients with suspected coronary artery disease, who underwent CCTA, DE-CTP, SPECT, SP-CMR, and ICA. The reference standard was defined as ≥ 50% stenosis by ICA, with a corresponding myocardial hypoperfusion on SP-CMR. For per-vascular territory analysis, the sensitivities of CCTA, DE-CTP, SPECT, CCTA + DE-CTP, and CCTA + SPECT were 96, 96, 68, 93, and 68%, respectively, and specificities were 72, 75, 89, 85, and 94%, respectively. The areas under the receiver operating characteristic curve (AUCs) were 0.84 ± 0.05, 0.85 ± 0.05, 0.79 ± 0.06, 0.89 ± 0.04, and 0.81 ± 0.06, respectively. For per-patient analysis, the sensitivities of CCTA, DE-CTP, SPECT, CCTA + DE-CTP, and CCTA + SPECT were 100, 100, 89, 100, and 83%, respectively; the specificities were 14, 43, 57, 43, and 57%, respectively; and the AUCs were 0.57 ± 0.13, 0.71 ± 0.11, 0.73 ± 0.11, 0.71 ± 0.11, and 0.70 ± 0.11, respectively. The combination of CCTA and DE-CTP enhances specificity without a loss of sensitivity for detecting hemodynamically significant coronary artery stenosis, as defined by combined ICA and SP-CMR.

  17. Does perfusion pattern influence stress-induced changes in left ventricular mechanical dyssynchrony on thallium-201-gated SPECT myocardial perfusion imaging?

    PubMed

    Singh, Harmandeep; Patel, Chetan D; Sharma, Punit; Naik, Nitish; Singh, Sandeep; Narang, Rajiv

    2015-02-01

    The relationship between perfusion pattern and stress-induced changes in left ventricular mechanical dyssynchrony (LVMD) on stress-rest thallium-201-gated SPECT myocardial perfusion imaging (Tl-201 SPECT MPI) is not clear. The aim of the study is to assess the relation of perfusion pattern with stress-induced changes in LVMD on Tl-201 MPI. Data of 194 patients who underwent exercise-rest Tl-201 MPI between January to December 2012 at our institute was retrospectively evaluated. Institute Ethical committee approval was obtained. Fifty patients who underwent Tl-201 MPI for suspected CAD and had normal LV perfusion and function on MPI were taken as normal group. Patients with perfusion abnormalities (n = 144) were divided into three groups: ischemia (n = 66), infarct (n = 32), and mixed group (n = 46; ischemia and infarct both). Summed stress score, summed rest score, summed difference score (SDS), and LV ejection fraction (EF) were evaluated. Two LVMD parameters, phase standard deviation (PSD) and phase histogram bandwidth (PHB), were assessed in post-stress and rest MPI images. ΔPSD (post-stress PSD - rest PSD) and ΔPHB (post-stress PHB - rest PHB) were calculated to measure stress-induced changes in LVMD. In all the groups, mean post-stress LVMD parameters were lower as compared to LVMD parameters at rest. Post-stress PSD was significantly lower than rest PSD in all groups. Similar trend was noted with PHB values also, but it was statistically significant in the normal and ischemia group only. Post-stress worsening of at least one of the LVMD parameters was noted in 28 patients and all these patients had perfusion abnormalities. But on subgroup analysis, no difference was found in proportion of patients showing post-stress worsening of LVMD between ischemia (13.6%), infarct (25%), and mixed (23.6%) groups. No significant correlation was found between ΔPSD/ΔPHB and ΔLVEF/SDS in any group. LV mechanical dyssynchrony parameters are smaller in post-exercise stress

  18. Induction of Inducible Nitric Oxide Synthase by Lipopolysaccharide and the Influences of Cell Volume Changes, Stress Hormones and Oxidative Stress on Nitric Oxide Efflux from the Perfused Liver of Air-Breathing Catfish, Heteropneustes fossilis

    PubMed Central

    Choudhury, Mahua G.; Saha, Nirmalendu

    2016-01-01

    The air-breathing singhi catfish (Heteropneustes fossilis) is frequently being challenged by bacterial contaminants, and different environmental insults like osmotic, hyper-ammonia, dehydration and oxidative stresses in its natural habitats throughout the year. The main objectives of the present investigation were to determine (a) the possible induction of inducible nitric oxide synthase (iNOS) gene with enhanced production of nitric oxide (NO) by intra-peritoneal injection of lipopolysaccharide (LPS) (a bacterial endotoxin), and (b) to determine the effects of hepatic cell volume changes due to anisotonicity or by infusion of certain metabolites, stress hormones and by induction of oxidative stress on production of NO from the iNOS-induced perfused liver of singhi catfish. Intra-peritoneal injection of LPS led to induction of iNOS gene and localized tissue specific expression of iNOS enzyme with more production and accumulation of NO in different tissues of singhi catfish. Further, changes of hydration status/cell volume, caused either by anisotonicity or by infusion of certain metabolites such as glutamine plus glycine and adenosine, affected the NO production from the perfused liver of iNOS-induced singhi catfish. In general, increase of hydration status/cell swelling due to hypotonicity caused decrease, and decrease of hydration status/cell shrinkage due to hypertonicity caused increase of NO efflux from the perfused liver, thus suggesting that changes in hydration status/cell volume of hepatic cells serve as a potent modulator for regulating the NO production. Significant increase of NO efflux from the perfused liver was also observed while infusing the liver with stress hormones like epinephrine and norepinephrine, accompanied with decrease of hydration status/cell volume of hepatic cells. Further, oxidative stress, caused due to infusion of t-butyl hydroperoxide and hydrogen peroxide separately, in the perfused liver of singhi catfish, resulted in

  19. Induction of Inducible Nitric Oxide Synthase by Lipopolysaccharide and the Influences of Cell Volume Changes, Stress Hormones and Oxidative Stress on Nitric Oxide Efflux from the Perfused Liver of Air-Breathing Catfish, Heteropneustes fossilis.

    PubMed

    Choudhury, Mahua G; Saha, Nirmalendu

    2016-01-01

    The air-breathing singhi catfish (Heteropneustes fossilis) is frequently being challenged by bacterial contaminants, and different environmental insults like osmotic, hyper-ammonia, dehydration and oxidative stresses in its natural habitats throughout the year. The main objectives of the present investigation were to determine (a) the possible induction of inducible nitric oxide synthase (iNOS) gene with enhanced production of nitric oxide (NO) by intra-peritoneal injection of lipopolysaccharide (LPS) (a bacterial endotoxin), and (b) to determine the effects of hepatic cell volume changes due to anisotonicity or by infusion of certain metabolites, stress hormones and by induction of oxidative stress on production of NO from the iNOS-induced perfused liver of singhi catfish. Intra-peritoneal injection of LPS led to induction of iNOS gene and localized tissue specific expression of iNOS enzyme with more production and accumulation of NO in different tissues of singhi catfish. Further, changes of hydration status/cell volume, caused either by anisotonicity or by infusion of certain metabolites such as glutamine plus glycine and adenosine, affected the NO production from the perfused liver of iNOS-induced singhi catfish. In general, increase of hydration status/cell swelling due to hypotonicity caused decrease, and decrease of hydration status/cell shrinkage due to hypertonicity caused increase of NO efflux from the perfused liver, thus suggesting that changes in hydration status/cell volume of hepatic cells serve as a potent modulator for regulating the NO production. Significant increase of NO efflux from the perfused liver was also observed while infusing the liver with stress hormones like epinephrine and norepinephrine, accompanied with decrease of hydration status/cell volume of hepatic cells. Further, oxidative stress, caused due to infusion of t-butyl hydroperoxide and hydrogen peroxide separately, in the perfused liver of singhi catfish, resulted in

  20. Geographic and demographic variabilities of quantitative parameters in stress myocardial computed tomography perfusion.

    PubMed

    Park, Jinoh; Kim, Hyun-Sook; Hwang, Hye Jeon; Yang, Dong Hyun; Koo, Hyun Jung; Kang, Joon-Won; Kim, Young-Hak

    2017-09-01

    To evaluate the geographic and demographic variabilities of the quantitative parameters of computed tomography perfusion (CTP) of the left ventricular (LV) myocardium in patients with normal coronary artery on computed tomography angiography (CTA). From a multicenter CTP registry of stress and static computed tomography, we retrospectively recruited 113 patients (mean age, 60 years; 57 men) without perfusion defect on visual assessment and minimal (< 20% of diameter stenosis) or no coronary artery disease on CTA. Using semiautomatic analysis software, quantitative parameters of the LV myocardium, including the myocardial attenuation in stress and rest phases, transmural perfusion ratio (TPR), and myocardial perfusion reserve index (MPRI), were evaluated in 16 myocardial segments. In the lateral wall of the LV myocardium, all quantitative parameters except for MPRI were significantly higher compared with those in the other walls. The MPRI showed consistent values in all myocardial walls (anterior to lateral wall: range, 25% to 27%; p = 0.401). At the basal level of the myocardium, all quantitative parameters were significantly lower than those at the mid- and apical levels. Compared with men, women had significantly higher values of myocardial attenuation and TPR. Age, body mass index, and Framingham risk score were significantly associated with the difference in myocardial attenuation. Geographic and demographic variabilities of quantitative parameters in stress myocardial CTP exist in healthy subjects without significant coronary artery disease. This information may be helpful when assessing myocardial perfusion defects in CTP.

  1. Lungs donated after circulatory death and prolonged warm ischemia are transplanted successfully after enhanced ex vivo lung perfusion using adenosine A2B receptor antagonism.

    PubMed

    Charles, Eric J; Mehaffey, J Hunter; Sharma, Ashish K; Zhao, Yunge; Stoler, Mark H; Isbell, James M; Lau, Christine L; Tribble, Curtis G; Laubach, Victor E; Kron, Irving L

    2017-04-12

    The current supply of acceptable donor lungs is not sufficient for the number of patients awaiting transplantation. We hypothesized that ex vivo lung perfusion (EVLP) with targeted drug therapy would allow successful rehabilitation and transplantation of donation after circulatory death lungs exposed to 2 hours of warm ischemia. Donor porcine lungs were procured after 2 hours of warm ischemia postcardiac arrest and subjected to 4 hours of cold preservation or EVLP. ATL802, an adenosine A2B receptor antagonist, was administered to select groups. Four groups (n = 4/group) were randomized: cold preservation (Cold), cold preservation with ATL802 during reperfusion (Cold + ATL802), EVLP (EVLP), and EVLP with ATL802 during ex vivo perfusion (EVLP + ATL802). Lungs subsequently were transplanted, reperfused, and assessed by measuring dynamic lung compliance and oxygenation capacity. EVLP + ATL802 significantly improved dynamic lung compliance compared with EVLP (25.0 ± 1.8 vs 17.0 ± 2.4 mL/cmH2O, P = .04), and compared with cold preservation (Cold: 12.2 ± 1.3, P = .004; Cold + ATL802: 10.6 ± 2.0 mL/cmH2O, P = .002). Oxygenation capacity was highest in EVLP (440.4 ± 37.0 vs Cold: 174.0 ± 61.3 mm Hg, P = .037). No differences in oxygenation or pulmonary edema were observed between EVLP and EVLP + ATL802. A significant decrease in interleukin-12 expression in tissue and bronchoalveolar lavage was identified between groups EVLP and EVLP + ATL802, along with less neutrophil infiltration. Severely injured donation after circulatory death lungs subjected to 2 hours of warm ischemia are transplanted successfully after enhanced EVLP with targeted drug therapy. Increased use of lungs after uncontrolled donor cardiac death and prolonged warm ischemia may be possible and may improve transplant wait list times and mortality. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  2. Real-time cine and myocardial perfusion with treadmill exercise stress cardiovascular magnetic resonance in patients referred for stress SPECT

    PubMed Central

    2010-01-01

    Background To date, stress cardiovascular magnetic resonance (CMR) has relied on pharmacologic agents, and therefore lacked the physiologic information available only with exercise stress. Methods 43 patients age 25 to 81 years underwent a treadmill stress test incorporating both Tc99m SPECT and CMR. After rest Tc99m SPECT imaging, patients underwent resting cine CMR. Patients then underwent in-room exercise stress using a partially modified treadmill. 12-lead ECG monitoring was performed throughout. At peak stress, Tc99m was injected and patients rapidly returned to their prior position in the magnet for post-exercise cine and perfusion imaging. The patient table was pulled out of the magnet for recovery monitoring. The patient was sent back into the magnet for recovery cine and resting perfusion followed by delayed post-gadolinium imaging. Post-CMR, patients went to the adjacent SPECT lab to complete stress nuclear imaging. Each modality's images were reviewed blinded to the other's results. Results Patients completed on average 9.3 ± 2.4 min of the Bruce protocol. Stress cine CMR was completed in 68 ± 14 sec following termination of exercise, and stress perfusion CMR was completed in 88 ± 8 sec. Agreement between SPECT and CMR was moderate (κ = 0.58). Accuracy in eight patients who underwent coronary angiography was 7/8 for CMR and 5/8 for SPECT (p = 0.625). Follow-up at 6 months indicated freedom from cardiovascular events in 29/29 CMR-negative and 33/34 SPECT-negative patients. Conclusions Exercise stress CMR including wall motion and perfusion is feasible in patients with suspected ischemic heart disease. Larger clinical trials are warranted based on the promising results of this pilot study to allow comparative effectiveness studies of this stress imaging system vs. other stress imaging modalities. PMID:20624294

  3. Free-Breathing Cardiac MR Stress Perfusion with Real-Time Slice Tracking

    PubMed Central

    Basha, Tamer A.; Roujol, Sébastien; Kissinger, Kraig V.; Goddu, Beth; Berg, Sophie; Manning, Warren J.; Nezafat, Reza

    2013-01-01

    Purpose To develop a free-breathing cardiac MR perfusion sequence with slice tracking for use after physical exercise. Methods We propose to use a leading navigator, placed immediately before each 2D slice acquisition, for tracking the respiratory motion and updating the slice location in real-time. The proposed sequence was used to acquire CMR perfusion datasets in 12 healthy adult subjects and 8 patients. Images were compared with the conventional perfusion (i.e. without slice tracking) results from the same subjects. The location and geometry of the myocardium were quantitatively analyzed, and the perfusion signal curves were calculated from both sequences to show the efficacy of the proposed sequence. Results The proposed sequence was significantly better compared to the conventional perfusion sequence in terms of qualitative image scores. Changes in the myocardial location and geometry decreased by ~50% in the slice tracking sequence. Furthermore, the proposed sequence had signal curves that are smoother and less noisy. Conclusion The proposed sequence significantly reduces the effect of the respiratory motion on the image acquisition in both rest and stress perfusion scans. PMID:24123153

  4. Free-breathing cardiac MR stress perfusion with real-time slice tracking.

    PubMed

    Basha, Tamer A; Roujol, Sébastien; Kissinger, Kraig V; Goddu, Beth; Berg, Sophie; Manning, Warren J; Nezafat, Reza

    2014-09-01

    To develop a free-breathing cardiac MR perfusion sequence with slice tracking for use after physical exercise. We propose to use a leading navigator, placed immediately before each 2D slice acquisition, for tracking the respiratory motion and updating the slice location in real-time. The proposed sequence was used to acquire CMR perfusion datasets in 12 healthy adult subjects and 8 patients. Images were compared with the conventional perfusion (i.e., without slice tracking) results from the same subjects. The location and geometry of the myocardium were quantitatively analyzed, and the perfusion signal curves were calculated from both sequences to show the efficacy of the proposed sequence. The proposed sequence was significantly better compared with the conventional perfusion sequence in terms of qualitative image scores. Changes in the myocardial location and geometry decreased by 50% in the slice tracking sequence. Furthermore, the proposed sequence had signal curves that are smoother and less noisy. The proposed sequence significantly reduces the effect of the respiratory motion on the image acquisition in both rest and stress perfusion scans. Copyright © 2013 Wiley Periodicals, Inc.

  5. Dipyridamole stress and rest transmural myocardial perfusion ratio evaluation by 64 detector-row computed tomography.

    PubMed

    Cury, Roberto C; Magalhães, Tiago A; Paladino, Antonio T; Shiozaki, Afonso A; Perini, Marcela; Senra, Tiago; Lemos, Pedro A; Cury, Ricardo C; Rochitte, Carlos E

    2011-01-01

    Myocardial stress CT perfusion (CTP) can detect myocardial ischemia. We evaluated the transmural perfusion ratio (TPR) of dipyridamole stress CTP to detect significant coronary stenosis (>70%) defined by quantitative invasive coronary angiography (ICA). Twenty-six patients (61.6 ± 8.0 years old; 14 males), without prior myocardial infarction, with positive single-photon emission computed tomography (SPECT; <2 months) and clinical indication for ICA, underwent a customized multidetector-row CT (MDCT) protocol with rest/stress myocardial perfusion evaluation and coronary CT angiography. TPR was defined as mean subendocardial divided by mean subepicardial attenuation and quantified on rest and stress MDCT images. Abnormal TPR was defined as 2 SDs below the mean rest TPR. All 26 patients completed the CT protocol with no adverse events. Rest TPR was measured in all patients with a mean of 1.06 ± 0.11, and abnormal TPR was considered <0.85. For 6 patients with normal coronary arteries by ICA, the mean TPR of territories with a previous positive perfusion defect in SPECT was 1.02 ± 0.18 (95% CI, 0.86-1.18; n = 6), and mean TPR of territories without perfusion defect in SPECT was 1.03 ± 0.09 (95% CI, -0.95 to 1.11; n = 12; P = 0.83). Mean stress TPR in territories with positive SPECT and significant coronary artery disease by quantitative ICA was 0.71 ± 0.13 (95% CI, -0.64 to 0.77) and in the remote myocardial was 1.01 ± 0.09 (95% CI, -0.96 to 1.06; P < 0001). In these territories, a significant Pearson's correlation was observed (r = -0.74, P < 0.001). TPR has a good correlation with SPECT and ICA to detect significant coronary stenosis. Copyright © 2011 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

  6. Assessment of adenosine deaminase (ADA) activity and oxidative stress in patients with chronic tonsillitis.

    PubMed

    Garca, Mehmet Fatih; Demir, Halit; Turan, Mahfuz; Bozan, Nazım; Kozan, Ahmet; Belli, Şeyda Bayel; Arslan, Ayşe; Cankaya, Hakan

    2014-06-01

    To emphasize the effectiveness of adenosine deaminase (ADA) enzyme, which has important roles in the differentiation of lymphoid cells, and oxidative stress in patients with chronic tonsillitis. Serum and tissue samples were obtained from 25 patients who underwent tonsillectomy due to recurrent episodes of acute tonsillitis. In the control group, which also had 25 subjects, only serum samples were taken as obtaining tissue samples would not have been ethically appropriate. ADA enzyme activity, catalase (CAT), carbonic anhydrase (CA), nitric oxide (NO) and malondialdehyde (MDA) were measured in the serum and tissue samples of patients and control group subjects. The serum values of both groups were compared. In addition, the tissue and serum values of patients were compared. Serum ADA activity and the oxidant enzymes MDA and NO values of the patient group were significantly higher than those of the control group (p < 0.001), the antioxidant enzymes CA and CAT values of the patient group were significantly lower than those of the control group (p < 0.001). In addition, while CA, CAT and NO enzyme levels were found to be significantly higher in the tonsil tissue of the patient group when compared to serum levels (p < 0.05), there was no difference between tissue and serum MDA and ADA activity (p > 0.05). Elevated ADA activity may be effective in the pathogenesis of chronic tonsillitis both by impairing tissue structure and contributing to SOR formation.

  7. Quantitative diagnosis of stress-induced myocardial ischemia using analysis of contrast echocardiographic parametric perfusion images.

    PubMed

    Toledo, Eran; Jacobs, Lawrence D; Lodato, Joseph A; DeCara, Jeanne M; Coon, Patrick; Mor-Avi, Victor; Lang, Roberto M

    2006-06-01

    Parametric imaging of myocardial perfusion provides useful visual information for the diagnosis of coronary artery disease (CAD). We developed a technique for automated detection of perfusion defects based on quantitative analysis of parametric perfusion images and validated it against coronary angiography. Contrast-enhanced, apical 2-, 3- and 4-chamber images were obtained at rest and with dipyridamole in 34 patients with suspected CAD. Images were analyzed to generate parametric perfusion images of the standard contrast-replenishment model parameters A, beta and A.beta. Each parametric image was divided into six segments, and mean parameter value (MPV) was calculated for each segment. Segmental MPV ratio between stress and rest was defined as a flow reserve index (FRI). Receiver operating characteristics (ROC) analysis was used in a Study group (N=17) to optimize FRI threshold and the minimal number of abnormal segments per vascular territory (LAD and non-LAD), required for automated detection of stress-induced perfusion defects. The optimized detection algorithm was then tested prospectively in the remaining 17 patients (Test group). LAD and non-LAD stenosis >70% was found in 19 and 17 patients, respectively. In the Study group, FRI threshold was: LAD=0.95 and non-LAD=0.68, minimal number of abnormal segments was four and two, correspondingly. Sensitivity, specificity and accuracy in the Test group were: 75%, 67% and 71% in the LAD, and 75%, 75% and 75% in the non-LAD territories. Automated quantitative analysis of contrast echocardiographic parametric perfusion images is feasible and may aid in the objective detection of CAD.

  8. Repeated administration of adenosine increases its cardiovascular effects in rats.

    PubMed

    Vidrio, H; García-Márquez, F; Magos, G A

    1987-01-20

    Hypotensive and negative chronotropic responses to adenosine in anesthetized rats increased after previous administration of the nucleoside. Bradycardia after adenosine in the isolated perfused rat heart was also potentiated after repeated administration at short intervals. This self-potentiation could be due to extracellular accumulation of adenosine and persistent stimulation of receptors caused by saturation or inhibition of cellular uptake of adenosine.

  9. Myocardial CT perfusion for the prediction of obstructive coronary artery disease, valuable or not?

    PubMed

    van Rosendael, Alexander R; de Graaf, Michiel A; Scholte, Arthur J

    2015-02-01

    Adenosine stress myocardial computed tomography perfusion (CTP) is a relatively new myocardial perfusion imaging technique. Together with coronary CT angiography (CTA) it provides anatomic and functional information of coronary artery disease (CAD). In previous studies, the combination of these techniques demonstrated to be valuable for identifying hemodynamically significant stenoses. George et al., performed a secondary analysis on the CORE320 study and compared the diagnostic performance of CTP to single positron emission computed tomography (SPECT) myocardial perfusion imaging (MPI) to diagnose obstructive CAD (defined as ≥50% luminal stenosis). In this editorial the results and limitations of the study are discussed, as well as opportunities that this new perfusion technique brings with it.

  10. Multicenter evaluation of stress-first myocardial perfusion image triage by nuclear technologists and automated quantification

    PubMed Central

    Chaudhry, Waseem; Hussain, Nasir; Ahlberg, Alan W.; Croft, Lori B.; Fernandez, Antonio B.; Parker, Mathew W.; Swales, Heather H.; Slomka, Piotr J.; Henzlova, Milena J.; Duvall, W. Lane

    2016-01-01

    Background A stress-first myocardial perfusion imaging (MPI) protocol saves time, is cost effective, and decreases radiation exposure. A limitation of this protocol is the requirement for physician review of the stress images to determine the need for rest images. This hurdle could be eliminated if an experienced technologist and/or automated computer quantification could make this determination. Methods Images from consecutive patients who were undergoing a stress-first MPI with attenuation correction at two tertiary care medical centers were prospectively reviewed independently by a technologist and cardiologist blinded to clinical and stress test data. Their decision on the need for rest imaging along with automated computer quantification of perfusion results was compared with the clinical reference standard of an assessment of perfusion images by a board-certified nuclear cardiologist that included clinical and stress test data. Results A total of 250 patients (mean age 61 years and 55% female) who underwent a stress-first MPI were studied. According to the clinical reference standard, 42 (16.8%) and 208 (83.2%) stress-first images were interpreted as “needing” and “not needing” rest images, respectively. The technologists correctly classified 229 (91.6%) stress-first images as either “needing” (n = 28) or “not needing” (n = 201) rest images. Their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 66.7%, 96.6%, 80.0%, and 93.5%, respectively. An automated stress TPD score ≥1.2 was associated with optimal sensitivity and specificity and correctly classified 179 (71.6%) stress-first images as either “needing” (n = 31) or “not needing” (n = 148) rest images. Its sensitivity, specificity, PPV, and NPV were 73.8%, 71.2%, 34.1%, and 93.1%, respectively. In a model whereby the computer or technologist could correct for the other's incorrect classification, 242 (96.8%) stress-first images were

  11. Multicenter evaluation of stress-first myocardial perfusion image triage by nuclear technologists and automated quantification.

    PubMed

    Chaudhry, Waseem; Hussain, Nasir; Ahlberg, Alan W; Croft, Lori B; Fernandez, Antonio B; Parker, Mathew W; Swales, Heather H; Slomka, Piotr J; Henzlova, Milena J; Duvall, W Lane

    2017-06-01

    A stress-first myocardial perfusion imaging (MPI) protocol saves time, is cost effective, and decreases radiation exposure. A limitation of this protocol is the requirement for physician review of the stress images to determine the need for rest images. This hurdle could be eliminated if an experienced technologist and/or automated computer quantification could make this determination. Images from consecutive patients who were undergoing a stress-first MPI with attenuation correction at two tertiary care medical centers were prospectively reviewed independently by a technologist and cardiologist blinded to clinical and stress test data. Their decision on the need for rest imaging along with automated computer quantification of perfusion results was compared with the clinical reference standard of an assessment of perfusion images by a board-certified nuclear cardiologist that included clinical and stress test data. A total of 250 patients (mean age 61 years and 55% female) who underwent a stress-first MPI were studied. According to the clinical reference standard, 42 (16.8%) and 208 (83.2%) stress-first images were interpreted as "needing" and "not needing" rest images, respectively. The technologists correctly classified 229 (91.6%) stress-first images as either "needing" (n = 28) or "not needing" (n = 201) rest images. Their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 66.7%, 96.6%, 80.0%, and 93.5%, respectively. An automated stress TPD score ≥1.2 was associated with optimal sensitivity and specificity and correctly classified 179 (71.6%) stress-first images as either "needing" (n = 31) or "not needing" (n = 148) rest images. Its sensitivity, specificity, PPV, and NPV were 73.8%, 71.2%, 34.1%, and 93.1%, respectively. In a model whereby the computer or technologist could correct for the other's incorrect classification, 242 (96.8%) stress-first images were correctly classified. The composite

  12. Perfusion functional MRI reveals cerebral blood flow pattern under psychological stress

    NASA Astrophysics Data System (ADS)

    Wang, Jiongjiong; Rao, Hengyi; Wetmore, Gabriel S.; Furlan, Patricia M.; Korczykowski, Marc; Dinges, David F.; Detre, John A.

    2005-12-01

    Despite the prevalence of stress in everyday life and its impact on happiness, health, and cognition, little is known about the neural substrate of the experience of everyday stress in humans. We use a quantitative and noninvasive neuroimaging technique, arterial spin-labeling perfusion MRI, to measure cerebral blood flow (CBF) changes associated with mild to moderate stress induced by a mental arithmetic task with performance monitoring. Elicitation of stress was verified by self-report of stress and emotional state and measures of heart rate and salivary-cortisol level. The change in CBF induced by the stress task was positively correlated with subjective stress rating in the ventral right prefrontal cortex (RPFC) and left insula/putamen area. The ventral RPFC along with right insula/putamen and anterior cingulate showed sustained activation after task completion in subjects reporting a high stress level during arithmetic tasks. Additionally, variations of baseline CBF in the ventral RPFC and right orbitofrontal cortex were found to correlate with changes in salivary-cortisol level and heart rate caused by undergoing stress tasks. We further demonstrated that the observed right prefrontal activation could not be attributed to increased cognitive demand accompanying stress tasks and extended beyond neural pathways associated with negative emotions. Our results provide neuroimaging evidence that psychological stress induces negative emotion and vigilance and that the ventral RPFC plays a key role in the central stress response. anterior cingulate cortex | arterial spin labeling | right prefrontal cortex

  13. Diagnostic accuracy of stress perfusion CMR in comparison with quantitative coronary angiography: fully quantitative, semiquantitative, and qualitative assessment.

    PubMed

    Mordini, Federico E; Haddad, Tariq; Hsu, Li-Yueh; Kellman, Peter; Lowrey, Tracy B; Aletras, Anthony H; Bandettini, W Patricia; Arai, Andrew E

    2014-01-01

    This study's primary objective was to determine the sensitivity, specificity, and accuracy of fully quantitative stress perfusion cardiac magnetic resonance (CMR) versus a reference standard of quantitative coronary angiography. We hypothesized that fully quantitative analysis of stress perfusion CMR would have high diagnostic accuracy for identifying significant coronary artery stenosis and exceed the accuracy of semiquantitative measures of perfusion and qualitative interpretation. Relatively few studies apply fully quantitative CMR perfusion measures to patients with coronary disease and comparisons to semiquantitative and qualitative methods are limited. Dual bolus dipyridamole stress perfusion CMR exams were performed in 67 patients with clinical indications for assessment of myocardial ischemia. Stress perfusion images alone were analyzed with a fully quantitative perfusion (QP) method and 3 semiquantitative methods including contrast enhancement ratio, upslope index, and upslope integral. Comprehensive exams (cine imaging, stress/rest perfusion, late gadolinium enhancement) were analyzed qualitatively with 2 methods including the Duke algorithm and standard clinical interpretation. A 70% or greater stenosis by quantitative coronary angiography was considered abnormal. The optimum diagnostic threshold for QP determined by receiver-operating characteristic curve occurred when endocardial flow decreased to <50% of mean epicardial flow, which yielded a sensitivity of 87% and specificity of 93%. The area under the curve for QP was 92%, which was superior to semiquantitative methods: contrast enhancement ratio: 78%; upslope index: 82%; and upslope integral: 75% (p = 0.011, p = 0.019, p = 0.004 vs. QP, respectively). Area under the curve for QP was also superior to qualitative methods: Duke algorithm: 70%; and clinical interpretation: 78% (p < 0.001 and p < 0.001 vs. QP, respectively). Fully quantitative stress perfusion CMR has high diagnostic accuracy for

  14. Adenosine and preeclampsia.

    PubMed

    Salsoso, Rocío; Farías, Marcelo; Gutiérrez, Jaime; Pardo, Fabián; Chiarello, Delia I; Toledo, Fernando; Leiva, Andrea; Mate, Alfonso; Vázquez, Carmen M; Sobrevia, Luis

    2017-06-01

    Adenosine is an endogenous nucleoside with pleiotropic effects in different physiological processes including circulation, renal blood flow, immune function, or glucose homeostasis. Changes in adenosine membrane transporters, adenosine receptors, and corresponding intracellular signalling network associate with development of pathologies of pregnancy, including preeclampsia. Preeclampsia is a cause of maternal and perinatal morbidity and mortality affecting 3-5% of pregnancies. Since the proposed mechanisms of preeclampsia development include adenosine-dependent biological effects, adenosine membrane transporters and receptors, and the associated signalling mechanisms might play a role in the pathophysiology of preeclampsia. Preeclampsia associates with increased adenosine concentration in the maternal blood and placental tissue, likely due to local hypoxia and ischemia (although not directly demonstrated), microthrombosis, increased catecholamine release, and platelet activation. In addition, abnormal expression and function of equilibrative nucleoside transporters is described in foetoplacental tissues from preeclampsia; however, the role of adenosine receptors in the aetiology of this disease is not well understood. Adenosine receptors activation may be related to abnormal trophoblast invasion, angiogenesis, and ischemia/reperfusion mechanisms in the placenta from preeclampsia. These mechanisms may explain only a low fraction of the associated abnormal transformation of spiral arteries in preeclampsia, triggering cellular stress and inflammatory mediators release from the placenta to the maternal circulation. Although increased adenosine concentration in preeclampsia may be a compensatory or adaptive mechanism favouring placental angiogenesis, a poor angiogenic state is found in preeclampsia. Thus, preeclampsia-associated complications might affect the cell response to adenosine due to altered expression and activity of adenosine receptors, membrane transporters

  15. Extracellular adenosine triphosphate and adenosine in cancer.

    PubMed

    Stagg, J; Smyth, M J

    2010-09-30

    Adenosine triphosphate (ATP) is actively released in the extracellular environment in response to tissue damage and cellular stress. Through the activation of P2X and P2Y receptors, extracellular ATP enhances tissue repair, promotes the recruitment of immune phagocytes and dendritic cells, and acts as a co-activator of NLR family, pyrin domain-containing 3 (NLRP3) inflammasomes. The conversion of extracellular ATP to adenosine, in contrast, essentially through the enzymatic activity of the ecto-nucleotidases CD39 and CD73, acts as a negative-feedback mechanism to prevent excessive immune responses. Here we review the effects of extracellular ATP and adenosine on tumorigenesis. First, we summarize the functions of extracellular ATP and adenosine in the context of tumor immunity. Second, we present an overview of the immunosuppressive and pro-angiogenic effects of extracellular adenosine. Third, we present experimental evidence that extracellular ATP and adenosine receptors are expressed by tumor cells and enhance tumor growth. Finally, we discuss recent studies, including our own work, which suggest that therapeutic approaches that promote ATP-mediated activation of inflammasomes, or inhibit the accumulation of tumor-derived extracellular adenosine, may constitute effective new means to induce anticancer activity.

  16. Feasibility and safety of adenosine cardiovascular magnetic resonance in patients with MR conditional pacemaker systems at 1.5 Tesla.

    PubMed

    Klein-Wiele, Oliver; Garmer, Marietta; Urbien, Rhyan; Busch, Martin; Kara, Kaffer; Mateiescu, Serban; Grönemeyer, Dietrich; Schulte-Hermes, Michael; Garbrecht, Marc; Hailer, Birgit

    2015-12-22

    Cardiovascular Magnetic Resonance (CMR) with adenosine stress is a valuable diagnostic tool in coronary artery disease (CAD). However, despite the development of MR conditional pacemakers CMR is not yet established in clinical routine for pacemaker patients with known or suspected CAD. A possible reason is that adenosine stress perfusion for ischemia detection in CMR has not been studied in patients with cardiac conduction disease requiring pacemaker therapy. Other than under resting conditions it is unclear whether MR safe pacing modes (paused pacing or asynchronous mode) can be applied safely because the effect of adenosine on heart rate is not precisely known in this entity of patients. We investigate for the first time feasibility and safety of adenosine stress CMR in pacemaker patients in clinical routine and evaluate a pacing protocol that considers heart rate changes under adenosine. We retrospectively analyzed CMR scans of 24 consecutive patients with MR conditional pacemakers (mean age 72.1 ± 11.0 years) who underwent CMR in clinical routine for the evaluation of known or suspected CAD. MR protocol included cine imaging, adenosine stress perfusion and late gadolinium enhancement. Pacemaker indications were sinus node dysfunction (n = 18) and second or third degree AV block (n = 6). Under a pacing protocol intended to avoid competitive pacing on the one hand and bradycardia due to AV block on the other no arrhythmia occurred. Pacemaker stimulation was paused to prevent competitive pacing in sinus node dysfunction with resting heart rate >45 bpm. Sympatho-excitatory effect of adenosine led to a significant acceleration of heart rate by 12.3 ± 8.3 bpm (p < 0.001), no bradycardia occurred. On the contrary in AV block heart rate remained constant; asynchronous pacing above resting heart rate did not interfere with intrinsic rhythm. Adenosine stress CMR appears to be feasible and safe in patients with MR conditional pacemakers. Heart rate response to adenosine

  17. Accelerated cardiac MR stress perfusion with radial sampling after physical exercise with an MR-compatible supine bicycle ergometer.

    PubMed

    Pflugi, Silvio; Roujol, Sébastien; Akçakaya, Mehmet; Kawaji, Keigo; Foppa, Murilo; Heydari, Bobby; Goddu, Beth; Kissinger, Kraig; Berg, Sophie; Manning, Warren J; Kozerke, Sebastian; Nezafat, Reza

    2015-08-01

    To evaluate the feasibility of accelerated cardiac MR (CMR) perfusion with radial sampling using nonlinear image reconstruction after exercise on an MR-compatible supine bike ergometer. Eight healthy subjects were scanned on two separate days using radial and Cartesian CMR perfusion sequences in rest and exercise stress perfusion. Four different methods (standard gridding, conjugate gradient SENSE [CG-SENSE], nonlinear inversion with joint estimation of coil-sensitivity profiles [NLINV] and compressed sensing with a total variation constraint [TV]) were compared for the reconstruction of radial data. Cartesian data were reconstructed using SENSE. All images were assessed by two blinded readers in terms of image quality and diagnostic value. CG-SENSE and NLINV were scored more favorably than TV (in both rest and stress perfusion cases, P < 0.05) and gridding (for rest perfusion cases, P < 0.05). TV images showed patchy artifacts, which negatively influenced image quality especially in the stress perfusion images acquired with a low number of radial spokes. Although CG-SENSE and NLINV received better scores than Cartesian sampling in both rest and exercise stress perfusion cases, these differences were not statistically significant (P > 0.05). We have demonstrated the feasibility of accelerated CMR perfusion using radial sampling after physical exercise using a supine bicycle ergometer in healthy subjects. For reconstruction of undersampled radial perfusion, CG-SENSE and NLINV resulted in better image quality than standard gridding or TV reconstruction. Further technical improvements and clinical assessment are needed before using this approach in patients with suspected coronary artery disease. © 2014 Wiley Periodicals, Inc.

  18. Clinical competence in myocardial perfusion scintigraphic stress testing: general training guidelines and assessment.

    PubMed

    Jones, Ian; Latus, Kate; Bartle, Luan; Gardner, Maureen; Parkin, Vicki

    2007-07-01

    The suggestion by the National Institute for Clinical Excellence (NICE) to more than triple the number of myocardial perfusion scintigraphy (MPS) procedures carried out by the NHS each year is a challenge both in terms of numbers of gamma cameras available to carry out the scans and qualified staff to supervise stress tests. In the past, exercise and pharmacological stress testing have been supervised only by doctors but, increasingly, this is taken on by suitably trained non-medical professionals such as nurses, radiographers and clinical technologists. The expansion of the numbers of non-medical professionals qualified to supervise stress testing will be key to meeting NICE's recommendations. This paper sets out how potential new stressors should be identified, what their training should cover and discusses the standards of competence they should meet. It provides guidelines for training non-medical stressors to perform a safe and efficient stress test during MPS and advice for maintaining competency.

  19. Thallium-201 perfusion imaging with atrial pacing or dipyridamole stress testing for evaluation of cardiac risk prior to nonvascular surgery

    SciTech Connect

    Stratmann, H.G.; Mark, A.L.; Williams, G.A. )

    1990-09-01

    Preoperative assessment of cardiac risk using thallium-201 scintigraphy and atrial pacing (n = 42) or dipyridamole stress testing (n = 35) was performed in 77 patients (mean age 65 +/- 7 years), who subsequently underwent elective nonvascular surgery. All patients were at low cardiac risk by clinical criteria; none could perform exercise stress testing due to physical limitations. ST depression consistent with ischemia occurred in 11 patients during atrial pacing and in 1 patient during dipyridamole stress testing (p less than 0.01). Nine patients had reversible perfusion defects with atrial pacing, and 10 patients with dipyridamole stress testing; fixed defects were present in 15 and 8 patients, respectively. Only one patient (fixed perfusion defect with atrial pacing, left main disease on coronary angiography) underwent preoperative coronary revascularization. Two patients subsequently had postoperative cardiac events. One patient (reversible perfusion defect with dipyridamole stress testing) experienced sudden death after a nonvascular procedure, while a second patient (normal thallium images with dipyridamole testing) had a nonfatal myocardial infarction. In patients having atrial pacing or dipyridamole stress testing, thallium-201 scans that are normal or show only a fixed perfusion defect confirm a low risk of cardiac complications following nonvascular surgery. The presence of a reversible perfusion defect does not preclude a postoperative course free of cardiac complications in patients at low cardiac risk by clinical criteria.

  20. Perfusion deficits and functional connectivity alterations in patients with post-traumatic stress disorder

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Li, Baojuan; Zhang, Xi; Zhang, Linchuan; Li, Liang; Lu, Hongbing

    2016-03-01

    To explore the alteration in cerebral blood flow (CBF) and functional connectivity between survivors with recent onset post-traumatic stress disorder (PTSD) and without PTSD, survived from the same coal mine flood disaster. In this study, a processing pipeline using arterial spin labeling (ASL) sequence was proposed. Considering low spatial resolution of ASL sequence, a linear regression method was firstly used to correct the partial volume (PV) effect for better CBF estimation. Then the alterations of CBF between two groups were analyzed using both uncorrected and PV-corrected CBF maps. Based on altered CBF regions detected from the CBF analysis as seed regions, the functional connectivity abnormities in PTSD patients was investigated. The CBF analysis using PV-corrected maps indicates CBF deficits in the bilateral frontal lobe, right superior frontal gyrus and right corpus callosum of PTSD patients, while only right corpus callosum was identified in uncorrected CBF analysis. Furthermore, the regional CBF of the right superior frontal gyrus exhibits significantly negative correlation with the symptom severity in PTSD patients. The resting-state functional connectivity indicates increased connectivity between left frontal lobe and right parietal lobe. These results indicate that PV-corrected CBF exhibits more subtle perfusion changes and may benefit further perfusion and connectivity analysis. The symptom-specific perfusion deficits and aberrant connectivity in above memory-related regions may be putative biomarkers for recent onset PTSD induced by a single prolonged trauma exposure and help predict the severity of PTSD.

  1. Measurement of hydraulic conductivity of single perfused Rana mesenteric microvessels between periods of controlled shear stress.

    PubMed

    Neal, C R; Bates, D O

    2002-09-15

    A new method for the determination of hydraulic conductivity in individually perfused microvessels in vivo is described. A vessel is cannulated at both ends with glass micropipettes and the fluid filtration rate across the vessel wall measured from the velocities of red cells when the pressure in the micropipettes is balanced. Hydraulic conductivity measured using this double-cannulation method (2.6 (+/- 0.9) x 10(-7) cm s(-1) cmH(2)O(-1)) was not significantly different from that measured using a previously described technique in the same vessel (2.4 (+/- 0.9) x 10(-7) cm s(-1) cmH(2)O(-1) using the Landis-Michel method). Shear stress on the vessel wall was controlled by changing the difference between the inflow and outflow pressures during periods of perfusion. The volume flow through the vessel, calculated from red cell velocity either in the vessel or in the pipette, was linearly proportional to this pressure difference. Higher flow rates could only be calculated from red cell velocities in the micropipette. There was no relationship between the imposed shear stress and intervening measurements of hydraulic conductivity (r = 0.029). This novel technique has advantages over the Landis-Michel method, which include the control of outflow resistance, the measurement of shear stress under conditions of controlled pressure, the elimination of compression damage to the vessel (since vessel occlusion is not necessary) and assessment of hydraulic conductivity over the same length of vessel throughout the experiment. The measurement of solute concentrations by indwelling micropipette electrodes and the collection of perfusate for analysis are other possibilities.

  2. Measurement of hydraulic conductivity of single perfused Rana mesenteric microvessels between periods of controlled shear stress

    PubMed Central

    Neal, CR; Bates, DO

    2002-01-01

    A new method for the determination of hydraulic conductivity in individually perfused microvessels in vivo is described. A vessel is cannulated at both ends with glass micropipettes and the fluid filtration rate across the vessel wall measured from the velocities of red cells when the pressure in the micropipettes is balanced. Hydraulic conductivity measured using this double-cannulation method (2.6 (± 0.9) × 10−7 cm s−1 cmH2O−1) was not significantly different from that measured using a previously described technique in the same vessel (2.4 (± 0.9) × 10−7 cm s−1 cmH2O−1 using the Landis-Michel method). Shear stress on the vessel wall was controlled by changing the difference between the inflow and outflow pressures during periods of perfusion. The volume flow through the vessel, calculated from red cell velocity either in the vessel or in the pipette, was linearly proportional to this pressure difference. Higher flow rates could only be calculated from red cell velocities in the micropipette. There was no relationship between the imposed shear stress and intervening measurements of hydraulic conductivity (r = 0.029). This novel technique has advantages over the Landis-Michel method, which include the control of outflow resistance, the measurement of shear stress under conditions of controlled pressure, the elimination of compression damage to the vessel (since vessel occlusion is not necessary) and assessment of hydraulic conductivity over the same length of vessel throughout the experiment. The measurement of solute concentrations by indwelling micropipette electrodes and the collection of perfusate for analysis are other possibilities. PMID:12231650

  3. Induction of biphasic changes in perfusion heterogeneity of rat liver after sequential stress in vivo.

    PubMed

    Kamoun, Walid S; Shin, Min C; Keller, Steve; Karaa, Amel; Huynh, Toan; Clemens, Mark G

    2005-10-01

    Trauma and subsequent sepsis lead to hepatic microcirculation disruption through various molecular mechanisms in which endothelin-1 (ET-1) plays a pivotal role. These stresses are thought to alter hepatic perfusion, heterogeneously leading to a mismatch of oxygen supply and demand. We hypothesize that mild remote stresses prime the liver to sequential sepsis through direct effects on the hepatic lobular flow distribution. We also propose to investigate the extent and the localization of the stress-induced microcirculation disruption. Sprague-Dawley rats were randomly divided into four experimental groups: sham, femur fracture (FFX), cecal ligation and puncture (CLP), and sequential stress (SS). Hepatic intravital microscopy was performed for in vivo assessment of the liver microcirculation flow distribution under baseline and after ET-1 infusion. Red blood cell motion distribution was used to quantify intralobular and interlobular heterogeneity of perfusion (HoP). Intralobular HoP, which reflects lobular regulation sites, was significantly increased in the FFX and CLP groups, but was not changed or decreased in the SS group compared with control. ET-1 infusion exerted opposite effects depending on the pathological condition, further increasing the difference between groups. SS induced decrease in intralobular HoP, contrasted with a significant increase in interlobular HoP, suggesting multiple disruption sites. Our data suggest that increased intralobular HoP may be indicative of a compensatory response to moderate stress; its decrease under sequential stress conditions corresponds with a total breakdown of hepatic lobular flow regulation. This may be another instance of the rich variability characteristic of normal physiology that "decomplexifies" under critical decompensated conditions.

  4. Neuroprotective effects of adenosine isolated from Cordyceps cicadae against oxidative and ER stress damages induced by glutamate in PC12 cells.

    PubMed

    Olatunji, Opeyemi J; Feng, Yan; Olatunji, Oyenike O; Tang, Jian; Ouyang, Zhen; Su, Zhaoliang; Wang, Dujun; Yu, Xiaofeng

    2016-06-01

    Glutamate has been proven to induce oxidative stress through the formation of reactive oxygen species (ROS) and increased calcium overload which results in neuronal injury, development of neurodegenerative diseases and death. Adenosine is one of the bioactive nucleosides found in Cordyceps cicadae and it has displayed several pharmacological activities including neuroprotection. In this study, the protective effects of adenosine from C. cicadae against glutamate-induce oxidative stress in PC12 cells were evaluated. The exposure of PC12 cells to glutamate (5mM) induced the formation of ROS, increased Ca(2+) influx, endoplasmic reticulum (ER) stress and up regulated the expression of pro-apoptotic factor Bax. However, pretreatment with adenosine markedly increased cell viability, decreased the elevated levels of ROS and Ca(2+) induced by glutamate. Furthermore adenosine increased the activities of GSH-Px and SOD, as well as retained mitochondria membrane potential (MMP), increased Bcl-2/Bax ratio, and reduced the expression of ERK, p38, and JNK. Overall, our results suggest that adenosine may be a promising potential therapeutic agent for the prevention and treatment of neurodegenerative disorders.

  5. The prognostic value of heart rate response during vasodilator stress myocardial perfusion imaging in patients with end-stage renal disease undergoing renal transplantation.

    PubMed

    AlJaroudi, Wael; Anokwute, Chiedozie; Fughhi, Ibtihaj; Campagnoli, Tania; Wassouf, Marwan; Vij, Aviral; Kharouta, Michael; Appis, Andrew; Ali, Amjad; Doukky, Rami

    2017-09-18

    In asymptomatic end-stage renal disease (ESRD) patients undergoing vasodilator stress myocardial perfusion imaging (MPI) prior to renal transplantation (RT), the impact of pre-transplant heart rate response (HRR) to vasodilator stress on post-RT outcomes is unknown. We analyzed a retrospective cohort of asymptomatic patients with ESRD who underwent a vasodilator stress SPECT-MPI and subsequently received RT. Blunted HRR was defined as HRR <28% for regadenoson stress and <20% for adenosine stress. The primary endpoint was major adverse cardiac events (MACE), defined as cardiac death or myocardial infarction. Clinical risk was assessed using the sum of risk factors set forth by the AHA/ACCF consensus statement on the assessment of RT candidates. Among 352 subjects, 140 had an abnormal pre-transplant HRR. During a mean follow-up of 3.2 ± 2.0 years, 85 (24%) MACEs were observed. Blunted HRR was associated with increased MACE risk (hazard ratio 1.72; 95% confidence interval 1.12-2.63, P = 0.013), and remained significant after adjustment for gender, sum of AHA/ACCF risk factors, summed stress score, baseline heart rate, and β-blocker use. HRR was predictive of MACE in patients with normal MPI and irrespective of clinical risk. Blunted HRR was associated with a significant increase in post-operative (30-day) MACE risk (17.9% vs 8.5%; P = 0.009). In asymptomatic ESRD patients being evaluated for RT, a blunted pre-transplant HRR was predictive of post-RT MACE. HRR may be a valuable tool in the risk assessment of RT candidates.

  6. A new myocardial perfusion scintigraphy stress protocol combining dipyridamole-dobutamine-atropine.

    PubMed

    Lima, Ronaldo Souza Leão; De Lorenzo, Andrea; Machado, Luiz S; Oliveira, Bernardo N; Pellini, Marcos P

    2012-03-01

    Pharmacological stress is often used, and the drugs most frequently utilized are dipyridamole (Dip) and dobutamine (Dob). We aimed to evaluate the safety and the results obtained with a new protocol associating Dip, Dob, and atropine, compared with the Dip protocol. Thirty-two patients underwent rest Tl/Dip stress Tc-sestamibi myocardial perfusion tomography on the same day. Dip was administered intravenously (0.56 mg/kg) for 4 min, and Tc-sestamibi was injected 3 min after the end of the Dip injection. On another day, patients received the same Dip dose, immediately followed by the infusion of Dob [20 μg/kg/min for the first 2 min and 40 μg/kg/min in the next 2 min, with atropine (1 mg) given in the interval between the two Dob doses]. Images were acquired with a two-detector camera. In a 17-segment model of the left ventricle, each segment was automatically scored 0-4 (normal to absent radiotracer activity), and perfusion scores were obtained as the sum of stress score and sum of rest segmental score (SSS and SRS, respectively) and the difference between them [summed difference score (SDS)]. All scans were interpreted by two experienced physicians as either definitely normal, probably normal, probably abnormal, or definitely abnormal. No serious complication was found independently of the protocol used. Heart rate and systolic and diastolic blood pressure were similar in both protocols at the basal level. Maximum heart rate (126 ± 21 vs. 82.7 ± 13.6, P<0.001) and the double product (18816 ± 4194 vs. 11449 ± 2438, P<0.001) showed a significant increase in the tests that used Dob and atropine compared with the Dip protocol. Stress studies with Dip-Dob had higher SSS compared with the Dip protocol (9.4 ± 10.1 vs. 7.7 ± 8.8, P<0.001). SDS was also higher in the Dip-Dob protocol than in the Dip protocol (6.1 ± 6.8 and 4.8 ± 5.8, respectively, P< 0.001). This work shows that a new protocol of pharmacological stress with a combination of Dip, Dob, and atropine

  7. Evolution and resolution of human brain perfusion responses to the stress of induced hypoglycemia.

    PubMed

    Teh, Ming Ming; Dunn, Joel T; Choudhary, Pratik; Samarasinghe, Yohan; Macdonald, Ian; O'Doherty, Michael; Marsden, Paul; Reed, Laurence J; Amiel, Stephanie A

    2010-11-01

    The relationship between the human brain response to acute stress and subjective, behavioural and physiological responses is poorly understood. We have examined the human cerebral response to the intense interoceptive stressor of hypoglycemia, controlling plasma glucose at either normal fasting concentrations (5 mmol/l, n=7) or at hypoglycemia (2.7 mmol/l, n=10) for 1 h in healthy volunteers. Hypoglycemia was associated with symptomatic responses, counterregulatory neuroendocrine responses and a sequential pattern of brain regional engagement, mapped as changes in relative cerebral perfusion using [(15)O]-H(2)O water positron emission tomography. The early cerebral response comprised activation bilaterally in anterior cingulate cortex (ACC) and thalamic pulvinar, with deactivation in posterior parahippocampal gyrus. Later responses (>20 min) engaged bilateral anterior insula, ventral striatum and pituitary. Following resolution of hypoglycemia, the majority of responses returned to baseline, save persistent engagement of the ACC and sustained elevation of growth hormone and cortisol. Catecholamine responses correlated with increased perfusion in pulvinar and medial thalamus, ACC and pituitary, while growth hormone and cortisol responses showed no correlation with thalamic activation but did show additional correlation with the hypothalamus and ventral striatum bilaterally. These data demonstrate complex dynamic responses to the stressor of hypoglycemia that would be expected to drive physiological and behavioural changes to remedy the state. Further, these data show that sustained stress and its aftermath engage distinct sets of brain regions, providing a neural substrate for adaptive or 'allostasic' responses to stressors.

  8. Caffeine acts through neuronal adenosine A2A receptors to prevent mood and memory dysfunction triggered by chronic stress.

    PubMed

    Kaster, Manuella P; Machado, Nuno J; Silva, Henrique B; Nunes, Ana; Ardais, Ana Paula; Santana, Magda; Baqi, Younis; Müller, Christa E; Rodrigues, Ana Lúcia S; Porciúncula, Lisiane O; Chen, Jiang Fan; Tomé, Ângelo R; Agostinho, Paula; Canas, Paula M; Cunha, Rodrigo A

    2015-06-23

    The consumption of caffeine (an adenosine receptor antagonist) correlates inversely with depression and memory deterioration, and adenosine A2A receptor (A2AR) antagonists emerge as candidate therapeutic targets because they control aberrant synaptic plasticity and afford neuroprotection. Therefore we tested the ability of A2AR to control the behavioral, electrophysiological, and neurochemical modifications caused by chronic unpredictable stress (CUS), which alters hippocampal circuits, dampens mood and memory performance, and enhances susceptibility to depression. CUS for 3 wk in adult mice induced anxiogenic and helpless-like behavior and decreased memory performance. These behavioral changes were accompanied by synaptic alterations, typified by a decrease in synaptic plasticity and a reduced density of synaptic proteins (synaptosomal-associated protein 25, syntaxin, and vesicular glutamate transporter type 1), together with an increased density of A2AR in glutamatergic terminals in the hippocampus. Except for anxiety, for which results were mixed, CUS-induced behavioral and synaptic alterations were prevented by (i) caffeine (1 g/L in the drinking water, starting 3 wk before and continued throughout CUS); (ii) the selective A2AR antagonist KW6002 (3 mg/kg, p.o.); (iii) global A2AR deletion; and (iv) selective A2AR deletion in forebrain neurons. Notably, A2AR blockade was not only prophylactic but also therapeutically efficacious, because a 3-wk treatment with the A2AR antagonist SCH58261 (0.1 mg/kg, i.p.) reversed the mood and synaptic dysfunction caused by CUS. These results herald a key role for synaptic A2AR in the control of chronic stress-induced modifications and suggest A2AR as candidate targets to alleviate the consequences of chronic stress on brain function.

  9. Caffeine acts through neuronal adenosine A2A receptors to prevent mood and memory dysfunction triggered by chronic stress

    PubMed Central

    Kaster, Manuella P.; Machado, Nuno J.; Silva, Henrique B.; Nunes, Ana; Ardais, Ana Paula; Santana, Magda; Baqi, Younis; Müller, Christa E.; Rodrigues, Ana Lúcia S.; Porciúncula, Lisiane O.; Chen, Jiang Fan; Tomé, Ângelo R.; Agostinho, Paula; Canas, Paula M.; Cunha, Rodrigo A.

    2015-01-01

    The consumption of caffeine (an adenosine receptor antagonist) correlates inversely with depression and memory deterioration, and adenosine A2A receptor (A2AR) antagonists emerge as candidate therapeutic targets because they control aberrant synaptic plasticity and afford neuroprotection. Therefore we tested the ability of A2AR to control the behavioral, electrophysiological, and neurochemical modifications caused by chronic unpredictable stress (CUS), which alters hippocampal circuits, dampens mood and memory performance, and enhances susceptibility to depression. CUS for 3 wk in adult mice induced anxiogenic and helpless-like behavior and decreased memory performance. These behavioral changes were accompanied by synaptic alterations, typified by a decrease in synaptic plasticity and a reduced density of synaptic proteins (synaptosomal-associated protein 25, syntaxin, and vesicular glutamate transporter type 1), together with an increased density of A2AR in glutamatergic terminals in the hippocampus. Except for anxiety, for which results were mixed, CUS-induced behavioral and synaptic alterations were prevented by (i) caffeine (1 g/L in the drinking water, starting 3 wk before and continued throughout CUS); (ii) the selective A2AR antagonist KW6002 (3 mg/kg, p.o.); (iii) global A2AR deletion; and (iv) selective A2AR deletion in forebrain neurons. Notably, A2AR blockade was not only prophylactic but also therapeutically efficacious, because a 3-wk treatment with the A2AR antagonist SCH58261 (0.1 mg/kg, i.p.) reversed the mood and synaptic dysfunction caused by CUS. These results herald a key role for synaptic A2AR in the control of chronic stress-induced modifications and suggest A2AR as candidate targets to alleviate the consequences of chronic stress on brain function. PMID:26056314

  10. Normal Myocardial Perfusion Gated SPECT and Positive Stress Test: Different Prognoses in Women and Men.

    PubMed

    Romero-Farina, Guillermo; Candell-Riera, Jaume; Ferreira-González, Ignacio; Aguadé-Bruix, Santiago; Pizzi, Nazarena; García-Dorado, David

    2015-06-01

    The aim of this study was to analyze different prognoses in women and men with normal myocardial perfusion gated SPECT, according to stress test results. Differences between women and men in terms of hard events (HE) (non-fatal acute myocardial infarction or cardiac death) and HE plus coronary revascularization (HE + CR) were analyzed in 2,414 consecutive patients (mean age 62.8 ± 13.5 years, 1,438 women) with a normal stress-rest gated SPECT, taking into account their stress test results. Four hundred and seven patients (16.9%) (15.9% women and 17.5% men) had a positive stress test (ST-segment depression ≥1 mm and/or angina). During a follow-up of 5.1 ± 3.4 years, there were more significant HE (6.5% vs 2.3%; P = .005) and HE + CR (11.6% vs 4.8%, P = .001) in men with a positive stress test than in men with a negative stress test. These differences were not observed in women. In multivariate regression models, HE and HE + CR were also more frequent in men with a positive stress test (HR:3.3 [95% CI 1.1% to 9.5%]; HR:4.2 [95% CI 1.8% to 9.9%]; respectively) vs women with a positive stress test. Although patients with normal gated SPECT studies have a favorable outcome, men with an abnormal stress test have a more adverse prognosis than women.

  11. Comparison between accelerated and conventional dobutamine stress protocols for myocardial perfusion scintigraphy.

    PubMed

    Issa, Aurora; De Lorenzo, Andrea; Oliveira, Bernardo; Pellini, Marcos; Lima, Ronaldo

    2012-10-01

    The conventional dobutamine (Dob) stress protocol for myocardial perfusion scintigraphy (MPS) is long, with frequent adverse effects, and generally requires atropine injection to reach target heart rate. Atropine is usually administered at the end of the protocol, when adverse effects are more frequent. Earlier atropine injection may be useful to shorten the stress protocol and reduce adverse effects. We sought to compare a Dob stress protocol with early atropine injection to a conventional Dob stress protocol in the same patients undergoing MPS. 30 patients underwent Dob-MPS with a conventional protocol (steps of 10, 20, 30 and 40 mcg/kg/min at 3 min intervals, adding atropine to the maximal Dob dose if necessary to achieve 85% of the age-corrected maximal predicted heart rate) and with an accelerated protocol with early atropine injection (at the end of the first stage). We compared stress duration, maximal heart rate (HR), percentage of maximal predicted HR, rate-pressure product, ST changes, MPS scores and the incidence of adverse effects between the 2 protocols. The accelerated protocol was shorter than the conventional protocol (7.1 ± 3.4 min vs. 11.8 ± 1.3 min; P < 0.0001), had the same efficacy to achieve hemodynamic parameters, without increasing adverse effects. The summed stress scores obtained by automatic analysis were similar in both protocols (6.3 ± 6.3 vs. 6.8 ± 6.3; P = NS) as well as the summed difference scores (2.5 ± 3.6 vs. 2.7 ± 3.4; P = NS). Early atropine injection during dobutamine stress protocol shortens stress duration. Our results suggest that patient safety and accuracy of MPS are unaltered, when compared to the conventional protocol, but further, larger studies are still necessary.

  12. Dipyridamole stress myocardial perfusion by computed tomography in patients with left bundle branch block

    PubMed Central

    Cabeda, Estêvan Vieira; Falcão, Andréa Maria Gomes; Soares Jr., José; Rochitte, Carlos Eduardo; Nomura, César Higa; Ávila, Luiz Francisco Rodrigues; Parga, José Rodrigues

    2015-01-01

    Background Functional tests have limited accuracy for identifying myocardial ischemia in patients with left bundle branch block (LBBB). Objective To assess the diagnostic accuracy of dipyridamole-stress myocardial computed tomography perfusion (CTP) by 320-detector CT in patients with LBBB using invasive quantitative coronary angiography (QCA) (stenosis ≥ 70%) as reference; to investigate the advantage of adding CTP to coronary computed tomography angiography (CTA) and compare the results with those of single photon emission computed tomography (SPECT) myocardial perfusion scintigraphy. Methods Thirty patients with LBBB who had undergone SPECT for the investigation of coronary artery disease were referred for stress tomography. Independent examiners performed per-patient and per-coronary territory assessments. All patients gave written informed consent to participate in the study that was approved by the institution’s ethics committee. Results The patients’ mean age was 62 ± 10 years. The mean dose of radiation for the tomography protocol was 9.3 ± 4.6 mSv. With regard to CTP, the per-patient values for sensitivity, specificity, positive and negative predictive values, and accuracy were 86%, 81%, 80%, 87%, and 83%, respectively (p = 0.001). The per-territory values were 63%, 86%, 65%, 84%, and 79%, respectively (p < 0.001). In both analyses, the addition of CTP to CTA achieved higher diagnostic accuracy for detecting myocardial ischemia than SPECT (p < 0.001). Conclusion The use of the stress tomography protocol is feasible and has good diagnostic accuracy for assessing myocardial ischemia in patients with LBBB. PMID:26421532

  13. Stress Myocardial Perfusion Imaging in the Emergency Department - New Techniques for Speed and Diagnostic Accuracy

    PubMed Central

    Harrison, Sheri D; Harrison, Mark A; Duvall, W Lane

    2012-01-01

    Emergency room evaluations of patients presenting with chest pain continue to rise, and these evaluations which often include cardiac imaging, are an increasing area of resource utilization in the current health system. Myocardial perfusion imaging from the emergency department remains a vital component of the diagnosis or exclusion of coronary artery disease as the etiology of chest pain. Recent advances in camera technology, and changes to the imaging protocols have allowed MPI to become a more efficient way of providing this diagnostic information. Compared with conventional SPECT, new high-efficiency CZT cameras provide a 3-5 fold increase in photon sensitivity, 1.65-fold improvement in energy resolution and a 1.7-2.5-fold increase in spatial resolution. With stress-only imaging, rest images are eliminated if stress images are normal, as they provide no additional prognostic or diagnostic value and cancelling the rest images would shorten the length of the test which is of particular importance to the ED population. The rapid but accurate triage of patients in an ED CPU is essential to their care, and stress-only imaging and new CZT cameras allow for shorter test time, lower radiation doses and lower costs while demonstrating good clinical outcomes. These changes to nuclear stress testing can allow for faster throughput of patients through the emergency department while providing a safe and efficient evaluation of chest pain. PMID:22708910

  14. [Cost-effectiveness of stress-only myocardial perfusion single photon emission computed tomography (SPECT) imaging].

    PubMed

    Vallejo, Enrique; Acevedo, César; Varela, Samuel; Alburez, José Carlos; Bialostozky, David

    2012-01-01

    Single photon emission computed tomography (SPECT) myocardial perfusion imaging is widely used for diagnosing coronary artery disease (CAD). However, SPECT costs, imaging time, and radiation exposure, limit SPECT indications. Determine whether a stress-only SPECT imaging would be enough to obtain a diagnosis of CAD improving nuclear laboratory efficiency. 122 patients with unknown CAD were evaluated with stress-only SPECT imaging. In order to evaluate diagnostic accuracy and the prognostic value of the stress-only protocol, patients with abnormal SPECT underwent invasive angiography and patients with normal SPECT were followed-up during 3 years. Diagnosis time, SPECT cost, and radiopharmaceutical dosage were significantly lower as compared with the conventional SPECT imaging protocol (30, 40 and 55%, respectively). Diagnostic accuracy and cardiac prognosis information were comparable to those obtained with the conventional imaging protocol (positive predictive value for CAD of 85% and negative predictive value for cardiac events of 97%). In patients with intermediate risk for CAD, stress-only SPECT imaging will significantly improve nuclear laboratory efficiency, and with similar accuracy than that the one obtained with the conventional protocol.

  15. Stress Perfusion Cardiovascular Magnetic Resonance Imaging Effectively Risk Stratifies Diabetic Patients With Suspected Myocardial Ischemia

    PubMed Central

    Heydari, Bobak; Juan, Yu-Hsiang; Liu, Hui; Abbasi, Siddique; Shah, Ravi; Blankstein, Ron; Steigner, Michael; Jerosch-Herold, Michael; Kwong, Raymond Y.

    2016-01-01

    Background Diabetics remain at high risk of cardiovascular disease and mortality despite advancements in medical therapy. Noninvasive cardiac risk profiling is often more difficult in diabetics owing to the prevalence of silent ischemia with unrecognized myocardial infarction (MI), reduced exercise capacity, non-diagnostic electrocardiographic changes, and balanced ischemia from diffuse epicardial coronary atherosclerosis and microvascular dysfunction. Methods and Results A consecutive cohort of 173 diabetic patients (mean age 61.7±11.9, 37% female) with suspected myocardial ischemia underwent stress perfusion CMR. Patients were evaluated for adverse cardiac events following CMR with mean follow-up time of 2.9 ± 2.5 years. Mean HbA1C for the population was 7.9±1.8%. Primary endpoint was a composite of cardiac death and nonfatal MI. Diabetics with no inducible ischemia (n=94) experienced an annualized event rate of 1.4% compared to 8.2% (P=0.0003) in those with inducible ischemia (n=79). Diabetics without late gadolinium enhancement or inducible ischemia had a very low annual cardiac event rate (0.5%/year). Presence of inducible ischemia was the strongest unadjusted predictor (HR 4.86, P<0.01) for cardiac death and nonfatal MI. This association remained robust in adjusted stepwise multivariable Cox regression analysis (HR 4.28, P=0.02). In addition, categorical net reclassification index (NRI) using 5-year risk cutoffs of 5% and 10% resulted in reclassification of 43.4% of the diabetic cohort with NRI of 0.38 (95% CI 0.20–0.56, P<0.0001). Conclusions Stress perfusion CMR provided independent prognostic utility and effectively reclassified risk in diabetic patients referred for ischemic assessment. Further evaluation is required to determine if a noninvasive imaging strategy with CMR can favorably impact downstream outcomes and improve cost-effectiveness of care in diabetics. PMID:27059504

  16. Role of Perfusion at Rest in the Diagnosis of Myocardial Infarction Using Vasodilator Stress Cardiovascular Magnetic Resonance.

    PubMed

    Patel, Mita B; Mor-Avi, Victor; Kawaji, Keigo; Nathan, Sandeep; Kramer, Christopher M; Lang, Roberto M; Patel, Amit R

    2016-04-01

    In clinical practice, perfusion at rest in vasodilator stress single-photon emission computed tomography is commonly used to confirm myocardial infarction (MI) and ischemia and to rule out artifacts. It is unclear whether perfusion at rest carries similar information in cardiovascular magnetic resonance (CMR). We sought to determine whether chronic MI is associated with abnormal perfusion at rest on CMR. We compared areas of infarct and remote myocardium in 31 patients who underwent vasodilator stress CMR (1.5 T), had MI confirmed by late gadolinium enhancement (LGE scar), and coronary angiography within 6 months. Stress perfusion imaging during gadolinium first pass was followed by reversal with aminophylline (75 to 125 mg), rest perfusion, and LGE imaging. Resting and peak-stress time-intensity curves were used to obtain maximal upslopes (normalized by blood pool upslopes), which were compared between infarcted and remote myocardial regions of interest. At rest, there was no significant difference between the slopes in the regions of interest supplied by arteries with and without stenosis >70% (0.31 ± 0.16 vs 0.26 ± 0.15 1/s), irrespective of LGE scar. However, at peak stress, we found significant differences (0.20 ± 0.11 vs 0.30 ± 0.22 1/s; p <0.05), reflecting the expected stress-induced ischemia. Similarly, at rest, there was no difference between infarcted and remote myocardium (0.27 ± 0.14 vs 0.30 ± 0.17 1/s), irrespective of stenosis, but significant differences were seen during stress (0.21 ± 0.16 vs 0.28 ± 0.18 1/s; p <0.001), reflecting inducible ischemia. In conclusion, abnormalities in myocardial perfusion at rest associated with chronic MI are not reliably detectable on CMR images. Accordingly, unlike single-photon emission computed tomography, normal CMR perfusion at rest should not be used to rule out chronic MI. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Value of attenuation correction in stress-only myocardial perfusion imaging using CZT-SPECT.

    PubMed

    van Dijk, J D; Mouden, M; Ottervanger, J P; van Dalen, J A; Knollema, S; Slump, C H; Jager, P L

    2017-04-01

    Attenuation correction (AC) improves the diagnostic outcome of stress-only myocardial perfusion imaging (MPI) using conventional SPECT. Our aim was to determine the value of AC using a cadmium zinc telluride-based (CZT)-SPECT camera. We retrospectively included 107 consecutive patients who underwent stress-optional rest MPI CZT-SPECT/CT. Next, we created three types of images for each patient; (1) only displaying reconstructed data without the CT-based AC (NC), (2) only displaying AC, and (3) with both NC and AC (NC + AC). Next, two experienced physicians visually interpreted these 321 randomized images as normal, equivocal, or abnormal. Image outcome was compared with all hard events over a mean follow-up time of 47.7 ± 9.8 months. The percentage of images interpreted as normal increased from 45% using the NC images to 72% using AC and to 67% using NC + AC images (P < .001). Hard event hazard ratios for images interpreted as normal were not different between using NC and AC (1.01, P = .99), or NC and NC + AC images (0.97, P = .97). AC lowers the need for additional rest imaging in stress-first MPI using CZT-SPECT, while long-term patient outcome remained identical. Use of AC reduces the need for additional rest imaging, decreasing the mean effective dose by up to 1.2 mSv.

  18. Qualitative and semi-quantitative evaluation of myocardium perfusion with 3 T stress cardiac MRI.

    PubMed

    Yun, Chun-Ho; Tsai, Jui-Peng; Tsai, Cheng-Ting; Mok, Greta S P; Sun, Jing-Yi; Hung, Chung-Lieh; Wu, Tung-Hsin; Huang, Wu-Ta; Yang, Fei-Shih; Lee, Jason Jeun-Shenn; Cury, Ricardo C; Fares, Anas; Nshisso, Lemba Dina; Bezerra, Hiram G

    2015-12-07

    3 T MRI has been adopted by some centers as the primary choice for assessment of myocardial perfusion over conventional 1.5 T MRI. However, there is no data published on the potential additional value of incorporating semi-quantitative data from 3 T MRI. This study sought to determine the performance of qualitative 3 T stress magnetic resonance myocardial perfusion imaging (3 T-MRMPI) and the potential incremental benefit of using a semi-quantitative perfusion technique in patients with suspected coronary artery disease (CAD). Fifty eight patients (41 men; mean age: 59 years) referred for elective diagnostic angiography underwent stress 3 T MRMPI with a 32-channel cardiac receiver coil. The MR protocol included gadolinium-enhanced stress first-pass perfusion (0.56 mg/kg, dipyridamole), rest perfusion, and delayed enhancement (DE). Visual analysis was performed in two steps. Ischemia was defined as a territory with perfusion defect at stress study but no DE or a territory with DE but additional peri-infarcted perfusion defect at stress study. Semi-quantitative analysis was calculated by using the upslope of the signal intensity-time curve during the first pass of contrast medium during dipyridamole stress and at rest. ROC analysis was used to determine the MPRI threshold that maximized sensitivity. Quantitative coronary angiography served as the reference standard with significant stenosis defined as >70 % diameter stenosis. Diagnostic performance was determined on a per-patient and per-vessel basis. Qualitative assessment had an overall sensitivity and specificity for detecting significant stenoses of 77 % and 80 %, respectively. By adding MPRI analysis, in cases with negative qualitative assessment, the overall sensitivity increased to 83 %. The impact of MPRI differed depending on the territory; with the sensitivity for detection of left circumflex (LCx) stenosis improving the most after semi-quantification analysis, (66 % versus 83 %). Pure

  19. Hyperemic stress myocardial perfusion cardiovascular magnetic resonance in mice at 3 Tesla: initial experience and validation against microspheres.

    PubMed

    Jogiya, Roy; Makowski, Markus; Phinikaridou, Alkystsis; Patel, Ashish S; Jansen, Christian; Zarinabad, Niloufar; Chiribiri, Amedeo; Botnar, Rene; Nagel, Eike; Kozerke, Sebastian; Plein, Sven

    2013-07-21

    Dynamic first pass contrast-enhanced myocardial perfusion is the standard CMR method for the estimation of myocardial blood flow (MBF) and MBF reserve in man, but it is challenging in rodents because of the high temporal and spatial resolution requirements. Hyperemic first pass myocardial perfusion CMR during vasodilator stress in mice has not been reported. Five C57BL/6 J mice were scanned on a clinical 3.0 Tesla Achieva system (Philips Healthcare, Netherlands). Vasodilator stress was induced via a tail vein catheter with an injection of dipyridamole. Dynamic contrast-enhanced perfusion imaging (Gadobutrol 0.1 mmol/kg) was based on a saturation recovery spoiled gradient echo method with 10-fold k-space and time domain undersampling (k-t PCA). One week later the mice underwent repeat anaesthesia and LV injections of fluorescent microspheres at rest and at stress. Microspheres were analysed using confocal microscopy and fluorescence-activated cell sorting. Mean MBF at rest measured by Fermi-function constrained deconvolution was 4.1 ± 0.5 ml/g/min and increased to 9.6 ± 2.5 ml/g/min during dipyridamole stress (P = 0.005). The myocardial perfusion reserve was 2.4 ± 0.54. The mean count ratio of stress to rest microspheres was 2.4 ± 0.51 using confocal microscopy and 2.6 ± 0.46 using fluorescence. There was good agreement between cardiovascular magnetic resonance CMR and microspheres with no significant difference (P = 0.84). First-pass myocardial stress perfusion CMR in a mouse model is feasible at 3 Tesla. Rest and stress MBF values were consistent with existing literature and perfusion reserve correlated closely to microsphere analysis. Data were acquired on a 3 Tesla scanner using an approach similar to clinical acquisition protocols, potentially facilitating translation of imaging findings between rodent and human studies.

  20. Hyperemic stress myocardial perfusion cardiovascular magnetic resonance in mice at 3 Tesla: initial experience and validation against microspheres

    PubMed Central

    2013-01-01

    Background Dynamic first pass contrast-enhanced myocardial perfusion is the standard CMR method for the estimation of myocardial blood flow (MBF) and MBF reserve in man, but it is challenging in rodents because of the high temporal and spatial resolution requirements. Hyperemic first pass myocardial perfusion CMR during vasodilator stress in mice has not been reported. Methods Five C57BL/6 J mice were scanned on a clinical 3.0 Tesla Achieva system (Philips Healthcare, Netherlands). Vasodilator stress was induced via a tail vein catheter with an injection of dipyridamole. Dynamic contrast-enhanced perfusion imaging (Gadobutrol 0.1 mmol/kg) was based on a saturation recovery spoiled gradient echo method with 10-fold k-space and time domain undersampling (k-t PCA). One week later the mice underwent repeat anaesthesia and LV injections of fluorescent microspheres at rest and at stress. Microspheres were analysed using confocal microscopy and fluorescence-activated cell sorting. Results Mean MBF at rest measured by Fermi-function constrained deconvolution was 4.1 ± 0.5 ml/g/min and increased to 9.6 ± 2.5 ml/g/min during dipyridamole stress (P = 0.005). The myocardial perfusion reserve was 2.4 ± 0.54. The mean count ratio of stress to rest microspheres was 2.4 ± 0.51 using confocal microscopy and 2.6 ± 0.46 using fluorescence. There was good agreement between cardiovascular magnetic resonance CMR and microspheres with no significant difference (P = 0.84). Conclusion First-pass myocardial stress perfusion CMR in a mouse model is feasible at 3 Tesla. Rest and stress MBF values were consistent with existing literature and perfusion reserve correlated closely to microsphere analysis. Data were acquired on a 3 Tesla scanner using an approach similar to clinical acquisition protocols, potentially facilitating translation of imaging findings between rodent and human studies. PMID:23870734

  1. Diagnostic accuracy of gated Tc-99m sestamibi stress myocardial perfusion SPECT with combined supine and prone acquisitions to detect coronary artery disease in obese and nonobese patients.

    PubMed

    Berman, Daniel S; Kang, Xingping; Nishina, Hidetaka; Slomka, Piotr J; Shaw, Leslee J; Hayes, Sean W; Cohen, Ishac; Friedman, John D; Gerlach, James; Germano, Guido

    2006-01-01

    The diagnostic value of gated myocardial perfusion single-photon emission computed tomography (MPS) with combined supine and prone acquisitions to detect coronary artery disease (CAD) in obese and nonobese patients has not been defined. We studied 1511 patients without prior myocardial infarction or coronary revascularization who either had coronary angiography within 3 months of MPS (n = 785) or had a low pretest likelihood of CAD (n = 726). All patients underwent rest thallium 201/gated exercise or adenosine stress technetium 99m sestamibi MPS in both the supine and prone positions. According to body mass index (BMI), patients were categorized as normal weight (BMI of 18.5-24.9 kg/m2), overweight (BMI of 25.0-29.9 kg/m2), or obese (BMI > or = 30.0 kg/m2). There were no significant differences in stress, fixed, or ischemic defects among patients in different weight categories. The sensitivity of MPS was 85%, 86%, and 89% for detecting patients with 50% or greater coronary stenosis and 89%, 91%, and 92% for detecting those with 70% or greater coronary stenosis in the normal-weight, overweight, and obese groups, respectively. Normalcy rates were nearly identical among the 3 weight groups (99%, 98%, and 99%, respectively). Multivariate logistic regression analysis further confirmed that BMI was a nonsignificant predictor for the detection of CAD. In a subset of 290 patients, automated quantitative MPS analysis confirmed that combined supine and prone MPS increased specificity (86%) in identifying CAD, without a significant reduction in sensitivity (83% for > or = 50% stenosis and 88% for > or = 70% stenosis). The findings of this study suggest that MPS performed with gating and combined supine and prone acquisitions without attenuation correction had a similar diagnostic accuracy for the detection of CAD in normal-weight, overweight, and obese patients.

  2. Phentolamine prevents the adverse effects of adenosine on glycolysis and mechanical function in isolated working rat hearts subjected to antecedent ischemia.

    PubMed

    Finegan, B A; Gandhi, M; Clanachan, A S

    2000-06-01

    Adenosine inhibits glycolysis from exogenous glucose, reduces proton production and enhances post-ischemic left ventricular minute work (LV work) following ischemia in isolated working rat hearts perfused with glucose and fatty acids. In hearts partially depleted of glycogen by antecedent ischemic stress (AIS)--two cycles of ischemia (10 min) and reperfusion (5 min)--adenosine stimulates rather than inhibits glycolysis, increases proton production and worsens recovery of post-ischemic LV work. We determined if the switch in adenosine effect on glycolysis and recovery of LV work following ischemia in hearts subject to AIS was due to the reduction in glycogen content per se or because of alpha-adrenoceptor stimulation. One series of hearts underwent a 35-min period of substrate-free Langendorff perfusion (substrate-free glycogen depletion; SFGD) and a second series of hearts was subjected to AIS. Both series of hearts had a similar glycogen content (approximately 70 micromol/g dry wt) prior to drug treatment. In SFGD hearts perfused aerobically, adenosine (500 microM) inhibited glycolysis from exogenous glucose and reduced proton production. In SFGD hearts reperfused after prolonged ischemia, adenosine exerted similar effects on glucose metabolism and enhanced recovery of post-ischemic LV work (87.2 +/- 2.2% of preischemic values) relative to untreated hearts (25.9 +/- 13.3% of preischemic values). In AIS hearts perfused aerobically or subject to ischemia and reperfusion, phentolamine (1 microM) given in combination with adenosine, prevented adenosine-induced stimulation of glycolysis from exogenous glucose and reduced calculated proton production from glucose. Recoveries of post-ischemic LV work in AIS hearts for untreated, adenosine, phentolamine and adenosine/phentolamine groups were 34.4 +/- 11.4%, 8.6 +/- 3.9%, 16.3 +/- 13.5% and 73.2 +/- 13.1% respectively, of preischemic values. Glycogen depletion in the absence of ischemia does not switch the effect of

  3. Stress Perfusion Cardiac Magnetic Resonance Imaging Effectively Risk Stratifies Diabetic Patients With Suspected Myocardial Ischemia.

    PubMed

    Heydari, Bobak; Juan, Yu-Hsiang; Liu, Hui; Abbasi, Siddique; Shah, Ravi; Blankstein, Ron; Steigner, Michael; Jerosch-Herold, Michael; Kwong, Raymond Y

    2016-04-01

    Diabetics remain at high risk of cardiovascular disease and mortality despite advancements in medical therapy. Noninvasive cardiac risk profiling is often more difficult in diabetics owing to the prevalence of silent ischemia with unrecognized myocardial infarction, reduced exercise capacity, nondiagnostic electrocardiographic changes, and balanced ischemia from diffuse epicardial coronary atherosclerosis and microvascular dysfunction. A consecutive cohort of 173 patients with diabetes mellitus (mean age, 61.7±11.9 years; 37% women) with suspected myocardial ischemia underwent stress perfusion cardiac magnetic resonance imaging. Patients were evaluated for adverse cardiac events after cardiac magnetic resonance imaging with mean follow-up time of 2.9±2.5 years. Mean hemoglobin A1c for the population was 7.9±1.8%. Primary end point was a composite of cardiac death and nonfatal myocardial infarction. Diabetics with no inducible ischemia (n=94) experienced an annualized event rate of 1.4% compared with 8.2% (P=0.0003) in those with inducible ischemia (n=79). Diabetics without late gadolinium enhancement or inducible ischemia had a low annual cardiac event rate (0.5% per year). The presence of inducible ischemia was the strongest unadjusted predictor (hazard ratio, 4.86; P<0.01) for cardiac death and nonfatal myocardial infarction. This association remained robust in adjusted stepwise multivariable Cox regression analysis (hazard ratio, 4.28; P=0.02). In addition, categorical net reclassification index using 5-year risk cutoffs of 5% and 10% resulted in reclassification of 43.4% of the diabetic cohort with net reclassification index of 0.38 (95% confidence interval, 0.20-0.56; P<0.0001). Stress perfusion cardiac magnetic resonance imaging provided independent prognostic utility and effectively reclassified risk in patients with diabetes mellitus referred for ischemic assessment. Further evaluation is required to determine whether a noninvasive imaging strategy with

  4. Glutamate and Hypoxia as a Stress Model for the Isolated Perfused Vertebrate Retina

    PubMed Central

    Januschowski, Kai; Müller, Sebastian; Krupp, Carlo; Spitzer, Martin S.; Hurst, José; Schultheiss, Maximilian; Bartz-Schmidt, Karl-Ulrich; Szurman, Peter; Schnichels, Sven

    2015-01-01

    Neuroprotection has been a strong field of investigation in ophthalmological research in the past decades and affects diseases such as glaucoma, retinal vascular occlusion, retinal detachment, and diabetic retinopathy. It was the object of this study to introduce a standardized stress model for future preclinical therapeutic testing. Bovine retinas were prepared and perfused with an oxygen saturated standard solution, and the ERG was recorded. After recording stable b-waves, hypoxia (pure N2) or glutamate stress (250 µm glutamate) was exerted for 45 min. To investigate the effects on photoreceptor function alone, 1 mM aspartate was added to obtain a-waves. ERG-recovery was monitored for 75 min. For hypoxia, a decrease in a-wave amplitude of 87.0% was noted (p <0.01) after an exposition time of 45 min (decrease of 36.5% after the end of the washout p = 0.03). Additionally, an initial decrease in b-wave amplitudes of 87.23% was recorded, that reached statistical significance (p <0.01, decrease of 25.5% at the end of the washout, p = 0.03). For 250 µm glutamate, an initial 7.8% reduction of a-wave amplitudes (p >0.05) followed by a reduction of 1.9% (p >0.05). A reduction of 83.7% of b-wave amplitudes (p <0.01) was noted; after a washout of 75 min the reduction was 2.3% (p = 0.62). In this study, a standardized stress model is presented that may be useful to identify possible neuroprotective effects in the future. PMID:25868118

  5. Confluence of Depression and Acute Psychological Stress Among Patients With Stable Coronary Heart Disease: Effects on Myocardial Perfusion

    PubMed Central

    Burg, Matthew M.; Meadows, Judith; Shimbo, Daichi; Davidson, Karina W.; Schwartz, Joseph E.; Soufer, Robert

    2014-01-01

    Background Depression is prevalent in coronary heart disease (CHD) patients and increases risk for acute coronary syndrome (ACS) recurrence and mortality despite optimal medical care. The pathways underlying this risk remain elusive. Psychological stress (PS) can provoke impairment in myocardial perfusion and trigger ACS. A confluence of acute PS with depression might reveal coronary vascular mechanisms of risk. We tested whether depression increased risk for impaired myocardial perfusion during acute PS among patients with stable CHD. Methods and Results Patients (N=146) completed the Beck Depression Inventory‐I (BDI‐I), a measure of depression linked to recurrent ACS and post‐ACS mortality, and underwent single‐photon emission computed tomography myocardial perfusion imaging at rest and during acute PS. The likelihood of new/worsening impairment in myocardial perfusion from baseline to PS as a function of depression severity was tested. On the BDI‐I, 41 patients scored in the normal range, 48 in the high normal range, and 57 in the depressed range previously linked to CHD prognosis. A BDI‐I score in the depressed range was associated with a significantly greater likelihood of new/worsening impairment in myocardial perfusion from baseline to PS (odds ratio =2.89, 95% CI: 1.26 to 6.63, P=0.012). This remained significant in models controlling ACS recurrence/mortality risk factors and medications. There was no effect for selective serotonin reuptake inhibitor medications. Conclusions Depressed patients with CHD are particularly susceptible to impairment in myocardial perfusion during PS. The confluence of PS with depression may contribute to a better understanding of the depression‐associated risk for ACS recurrence and mortality. PMID:25359402

  6. Characterization of the H+ Translocating Adenosine Triphosphatase and Pyrophosphatase of Vacuolar Membranes Isolated by Means of a Perfusion Technique from Chara corallina1

    PubMed Central

    Takeshige, Kazuhiko; Tazawa, Masashi; Hager, Achim

    1988-01-01

    Sealed tonoplast vesicles were isolated from single cells of Chara corallina with the aid of an intracellular perfusion technique in combination with a 3/10% Percoll two step gradient centrifugation. The isolated tonoplast fraction was free from plasmalemma and chloroplasts, and showed no activities of cytochrome c oxidase, and latent IDPase, but had about 10% of the NADH-cytochrome c reductase activity. The vesicles had both ATPase and PPase activities, which could be stimulated in the presence of 10 micromolar gramicidin by 170 and 130%, respectively, demonstrating the existence of sealed vesicles. Furthermore, ATP- and PPi-dependent H+ pumping through the membrane into the vesicles was shown. Both ATPase and PPase had pH optima around pH 8.5. At the physiological pH, 7.3, they still had more than 80% of their maximal activities. Ammonium molybdate, azide, and vanadate had no or little effect on the activities of both enzymes or their associated H+ pumping activities. N,N′-dicyclohexylcarbodiimide inhibited the ATPase strongly (I50 = 20 micromolar) but the PPase only weakly. The ATPase was also more sensitive to N-ethylmaleimide than the PPase. 4,4′-Stilbenedisulfonic acid affected both enzyme activities and their associated H+ pumping activities. This is in contrast to the H+-PPase of higher plants which is 4,4′-stilbenedisulfonic acid insensitive. PMID:16666049

  7. A brain stress test: Cerebral perfusion during memory encoding in mild cognitive impairment

    PubMed Central

    Xie, Long; Dolui, Sudipto; Das, Sandhitsu R.; Stockbower, Grace E.; Daffner, Molly; Rao, Hengyi; Yushkevich, Paul A.; Detre, John A.; Wolk, David A.

    2016-01-01

    Arterial spin labeled perfusion magnetic resonance imaging (ASL MRI) provides non-invasive quantification of cerebral blood flow, which can be used as a biomarker of brain function due to the tight coupling between cerebral blood flow (CBF) and brain metabolism. A growing body of literature suggests that regional CBF is altered in neurodegenerative diseases. Here we examined ASL MRI CBF in subjects with amnestic mild cognitive impairment (n = 65) and cognitively normal healthy controls (n = 62), both at rest and during performance of a memory-encoding task. As compared to rest, task-enhanced ASL MRI improved group discrimination, which supports the notion that physiologic measures during a cognitive challenge, or “stress test”, may increase the ability to detect subtle functional changes in early disease stages. Further, logistic regression analysis demonstrated that ASL MRI and concomitantly acquired structural MRI provide complementary information of disease status. The current findings support the potential utility of task-enhanced ASL MRI as a biomarker in early Alzheimer's disease. PMID:27222794

  8. Determinants of the response of left ventricular ejection fraction to vasodilator stress in electrocardiographically gated (82)rubidium myocardial perfusion PET.

    PubMed

    Brown, Tracy L Y; Merrill, Jennifer; Volokh, Lana; Bengel, Frank M

    2008-02-01

    Myocardial perfusion imaging with (82)Rb PET allows for ECG-gated studies to be obtained early after radiotracer injection, capturing ventricular function close to peak pharmacologic action of dipyridamole. This is different from gated SPECT and may potentially provide additional diagnostic information. We sought to identify potential correlates of the PET-derived ejection fraction response to vasodilator stress. One hundred ten consecutive patients undergoing (82)Rb PET myocardial perfusion imaging during evaluation for coronary artery disease were included. Using a GE Discovery STRx PET-CT scanner, ECG-gated images (eight bins) were obtained at rest and 4 min after dipyridamole infusion, 90 s after infusion of 1,480-2,220 MBq of (82)Rb. Summed rest, stress, and difference scores (SRS, SSS, and SDS) were determined using a five-point scoring system and 20-segment model. Ejection fraction was calculated using automated QGS software. Significant reversibility (SDS > or = 4) was found in 23 patients (21%). Mean LVEF in all patients was 47 +/- 13% at rest and 53 +/- 13% during dipyridamole. LVEF increased in 89 patients, and decreased in 17 patients during vasodilation. The change in LVEF was inversely correlated with SDS (r = -0.26; p = 0.007). Additionally, it was inversely correlated with resting LVEF (r = -0.20; p = 0.03) and SSS (r = -0.25; p = 0.009). No significant correlations were observed with SRS, heart rate, blood pressure, age, hypertension, hypercholesterolemia, or pretest likelihood of disease. At multivariate regression analysis, SDS was an independent predictor of the change in LVEF. Gated (82)Rb PET during pharmacologic stress allows for assessment of the functional response to vasodilation. The magnitude of LVEF increase is determined by stress perfusion/reversible perfusion defects. Functional response to hyperemia may thus be incorporated in future evaluations of diagnostic and prognostic algorithms based on (82)Rb PET.

  9. Impact of hypertension on the accuracy of exercise stress myocardial perfusion imaging for the diagnosis of coronary artery disease

    PubMed Central

    Elhendy, A; van Domburg, R T; Sozzi, F; Poldermans, D; Bax, J; Roelandt, J

    2001-01-01

    AIM—To compare the accuracy of exercise stress myocardial perfusion single photon emission computed tomography (SPECT) imaging for the diagnosis of coronary artery disease in patients with and without hypertension.
METHODS—A symptom limited bicycle exercise stress test in conjunction with 99m technetium sestamibi or tetrofosmin SPECT imaging was performed in 332 patients (mean (SD) age, 57 (10) years; 257 men, 75 women) without previous myocardial infarction who underwent coronary angiography. Of these, 137 (41%) had hypertension. Rest SPECT images were acquired 24 hours after the stress test. An abnormal scan was defined as one with reversible or fixed perfusion defects.
RESULTS—In hypertensive patients, myocardial perfusion abnormalities were detected in 79 of 102 patients with significant coronary artery disease and in nine of 35 patients without. In normotensive patients, myocardial perfusion abnormalities were detected in 104 of 138 patients with significant coronary artery disease and in 16 of 57 patients without. There were no differences between normotensive and hypertensive patients in sensitivity (77% (95% confidence interval (CI) 69% to 86%) v 75% (95% CI 68% to 83%)), specificity (74% (95% CI 60% to 89%) v 72% (95% CI 60% to 84%)), and accuracy (77% (95% CI 70% to 84%) v 74% (95% CI 68% to 80%)) of exercise SPECT for diagnosing coronary artery disease. The accuracy of SPECT was greater than electrocardiography, both in hypertensive patients (p = 0.005) and in normotensive patients (p = 0.0001). For the detection of coronary artery disease in individual vessels, sensitivity was 58% (95% CI 51% to 65%) v 57% (95% CI 51% to 64%), specificity was 86% (95% CI 82% to 90%) v 85% (95% CI 81% to 89%), and accuracy was 74% (95% CI 70% to 78%) v 74% (95% CI 70% to 78%) in patients with and without hypertension (NS).
CONCLUSIONS—In the usual clinical setting, the value of exercise myocardial perfusion scintigraphy for diagnosing

  10. Adenosine and sleep

    SciTech Connect

    Yanik, G.M. Jr.

    1987-01-01

    Behavioral and biochemical approaches have been used to determine the relative contribution of endogenous adenosine and adenosine receptors to the sleep-wake cycle in the rat. Adenosine concentrations in specific areas of the rat brain were not affected by 24 hours of total sleep deprivation, or by 24 or 48 hours of REM sleep deprivation. In order to assess the effect of REM sleep deprivation on adenosine A/sub 1/ receptors, /sup 3/H-L-PIA binding was measured. The Bmax values for /sup 3/H-L-PIA binding to membrane preparations of the cortices and corpus striata from 48 hour REM sleep-deprived animals were increased 14.8% and 23%, respectively. These increases were not maintained following the cessation of sleep deprivation and recovered within 2 hours. The results of a 96 hour REM deprivation experiment were similar to those of the 48 hour REM sleep deprivation experiment. However, these increases were not evident in similar structures taken from stress control animals, and conclusively demonstrated that the changes in /sup 3/H-L-PIA binding resulted from REM sleep deprivation and not from stress.

  11. Small average differences in attenuation corrected images between men and women in myocardial perfusion scintigraphy: a novel normal stress database.

    PubMed

    Trägårdh, Elin; Sjöstrand, Karl; Jakobsson, David; Edenbrandt, Lars

    2011-10-03

    The American Society of Nuclear Cardiology and the Society of Nuclear Medicine state that incorporation of attenuation-corrected (AC) images in myocardial perfusion scintigraphy (MPS) will improve image quality, interpretive certainty, and diagnostic accuracy. However, commonly used software packages for MPS usually include normal stress databases for non-attenuation corrected (NC) images but not for attenuation-corrected (AC) images. The aim of the study was to develop and compare different normal stress databases for MPS in relation to NC vs. AC images, male vs. female gender, and presence vs. absence of obesity. The principal hypothesis was that differences in mean count values between men and women would be smaller with AC than NC images, thereby allowing for construction and use of gender-independent AC stress database. Normal stress perfusion databases were developed with data from 126 male and 205 female patients with normal MPS. The following comparisons were performed for all patients and separately for normal weight vs. obese patients: men vs. women for AC; men vs. women for NC; AC vs. NC for men; and AC vs. NC for women. When comparing AC for men vs. women, only minor differences in mean count values were observed, and there were no differences for normal weight vs. obese patients. For all other analyses major differences were found, particularly for the inferior wall. The results support the hypothesis that it is possible to use not only gender independent but also weight independent AC stress databases.

  12. Transmural myocardial perfusion gradients in relation to coronary artery stenoses severity assessed by cardiac multidetector computed tomography.

    PubMed

    Linde, Jesper James; Kühl, Jørgen Tobias; Hove, Jens Dahlgaard; Sørgaard, Mathias; Kelbæk, Henning; Nielsen, Walter Bjørn; Kofoed, Klaus Fuglsang

    2015-01-01

    To assess the relationship between epicardial coronary artery stenosis severity and the corresponding regional transmural perfusion at rest and during adenosine stress, using multidetector computed tomography (MDCT). We evaluated the relationship between the severity of coronary artery diameter stenosis assessed by MDCT angiography and semi-quantitative myocardial MDCT perfusion in 200 symptomatic patients. The perfusion index (PI = mean myocardial attenuation density/mean left ventricular lumen attenuation density) at rest and during adenosine stress, the myocardial perfusion reserve (MPR = stress - PI/rest - PI), and the transmural perfusion ratio (TPR = subendocardium/subepicardium) were calculated. A coronary artery stenosis ≥50 % was present in 49 patients (25 %). Rest-PI and rest-TPR values were similar in patients with and without a coronary artery stenosis ≥50 %, whereas stress-PI, stress-TPR and MPR were significantly reduced in patients with a stenosis ≥50 % (p < 0.001, p < 0.0001 and p = 0.02, respectively). Subendocardial PI was significantly higher than subepicardial PI at rest and during stress for patients without a significant stenosis, whereas this difference was blurred during stress in patients with ≥50 % stenosis. In a broad spectrum of stenosis severity groups, TPR at rest remained unchanged until the group of patients with total occlusions, whereas TPR during stress decreased progressively when a threshold of 50 % was superseded. In this study we establish the relationship between semi-quantitative perfusion measurements by MDCT and severity of coronary artery stenoses and find the transmural myocardial perfusion ratio to be a potential strong functional index of the hemodynamic significance of coronary artery atherosclerotic lesions.

  13. Tachycardic vs. pharmacologic stress myocardial perfusion imaging: differential implications in multi-vessel ischemia

    PubMed Central

    Nguyen, Thanh H; Horowitz, John D; Unger, Steven A

    2012-01-01

    Background In patients unable to exercise, potential methods of induction of reversible myocardial ischemia include physiological heart rate acceleration via pacing or dobutamine infusion and asymmetric coronary vasodilatation using dipyridamole. Although their bases for induction of ischemia are widely disparate, no direct comparison of these techniques has previously been reported. Methods We performed a randomised, paired comparison of dipyridamole and pacing myocardial perfusion imaging (MPI) in 28 patients in whom exercise stress imaging was precluded, comparing the detection, localisation and quantitation of ischemia. Results Reversible myocardial ischemia was detected in 21 patients, concordantly in 13 (p = 0.042). There was a high degree of concordance (p < 0.0001) regarding locations of sites of ischemia. While there was a good correlation (r = 0.74, p < 0.0001) between size of total ischemic zones with dipyridamole and pacing, the magnitude of ischemia tended to be greater with dipyridamole (mean percentage of left ventricular myocardium ± SD, 9.4 ± 11.0% vs. 7.0 ± 9.0%, p = 0.091). Furthermore, this difference resulted from accentuation of the primary ischemic zone with dipyridamole in patients with multi-vessel ischemia (mean ± SD, 28.1 ± 21.1% vs. 18.7 ± 16.1%, p = 0.046). Conclusions Despite major differences in mechanism(s) of induction of ischemia, dipyridamole and pacing produce similar results regarding detection, localisation and severity of ischemia. However, dipyridamole accentuates ischemia in primary (vs. secondary) ischemic zones, consistent with known induction of coronary “steal". This should be taken into account in interpretation of scan results. PMID:22254212

  14. Transcapillary adenosine transport and interstitial adenosine concentration in guinea pig hearts

    PubMed Central

    WANGLER, ROGER D.; GORMAN, MARK W.; WANG, C. Y.; DEWITT, DONALD F.; CHAN, I. S.; BASSINGTHWAIGHTE, JAMES B.; SPARKS, HARVEY V.

    2010-01-01

    We used the multiple-indicator-dilution technique to observe the capillary transport of adenosine in isolated Krebs-Henseleit-perfused guinea pig hearts. Tracer concentrations of radiolabeled albumin, sucrose, and adenosine were injected into the coronary inflow; outflow samples were collected for 10-25 s and analyzed by high-performance liquid chromatography (HPLC) and by γ- and β-counting. The albumin data define the intravascular transport characteristics; the sucrose data define permeation through interendothelial clefts and dilution in interstitial fluid (ISF). Parameters calculated from adenosine data include permeability-surface area products for endothelial cell uptake at the luminal and abluminal membranes and intraendothelial metabolism. We found that in situ endothelial cells avidly take up and metabolize adenosine. Tracer adenosine in the capillary lumen is twice as likely to enter an endothelial cell as it is to permeate the clefts. There was no adenosine in the arterial perfusate. Under control conditions, the steady-state venous adenosine concentration was 3.6 ± 0.8 nM, which from the flow and the parameters estimated from the tracer data gave a calculated ISF concentration of 6.8 ± 1.5 nM. During dipyridamole infusion (10 μM) at constant pressure, the cell permeabilities went essentially to zero, whereas the venous adenosine concentration increased to 44.0 ± 12.6 nM, giving an estimated ISF concentration of 191 ± 53 nM. With constant flow perfusion, venous concentration during dipyridamole infusion was 30.9 ± 6.3 nM, and estimated ISF concentration was 88 ± 20 mM. We conclude that in this preparation, at rest, the ISF adenosine concentration is about twice the venous concentration and the ISF adenosine concentration increases with dipyridamole administration. PMID:2750952

  15. Myocardial CT perfusion for the prediction of obstructive coronary artery disease, valuable or not?

    PubMed Central

    van Rosendael, Alexander R.; de Graaf, Michiel A.

    2015-01-01

    Adenosine stress myocardial computed tomography perfusion (CTP) is a relatively new myocardial perfusion imaging technique. Together with coronary CT angiography (CTA) it provides anatomic and functional information of coronary artery disease (CAD). In previous studies, the combination of these techniques demonstrated to be valuable for identifying hemodynamically significant stenoses. George et al., performed a secondary analysis on the CORE320 study and compared the diagnostic performance of CTP to single positron emission computed tomography (SPECT) myocardial perfusion imaging (MPI) to diagnose obstructive CAD (defined as ≥50% luminal stenosis). In this editorial the results and limitations of the study are discussed, as well as opportunities that this new perfusion technique brings with it. PMID:25774350

  16. High frequency QRS ECG predicts ischemic defects during myocardial perfusion imaging

    NASA Technical Reports Server (NTRS)

    Rahman, Atiar

    2006-01-01

    Background: Changes in high frequency QRS components of the electrocardiogram (HF QRS ECG) (150-250 Hz) are more sensitive than changes in conventional ST segments for detecting myocardial ischemia. We investigated the accuracy of 12-lead HF QRS ECG in detecting ischemia during adenosine tetrofosmin myocardial perfusion imaging (MPI). Methods and Results: 12-lead HF QRS ECG recordings were obtained from 45 patients before and during adenosine technetium-99 tetrofosmin MPI tests. Before the adenosine infusions, recordings of HF QRS were analyzed according to a morphological score that incorporated the number, type and location of reduced amplitude zones (RAZs) present in the 12 leads. During the adenosine infusions, recordings of HF QRS were analyzed according to the maximum percentage changes (in both the positive and negative directions) that occurred in root mean square (RMS) voltage amplitudes within the 12 leads. The best set of prospective HF QRS criteria had a sensitivity of 94% and a specificity of 83% for correctly identifying the MPI result. The sensitivity of simultaneous ST segment changes (18%) was significantly lower than that of any individual HF QRS criterion (P<0.001). Conclusions: Analysis of 12-lead HF QRS ECG is highly sensitive and specific for detecting ischemic perfusion defects during adenosine MPI stress tests and significantly more sensitive than analysis of conventional ST segments.

  17. High frequency QRS ECG predicts ischemic defects during myocardial perfusion imaging

    NASA Technical Reports Server (NTRS)

    Rahman, Atiar

    2006-01-01

    Background: Changes in high frequency QRS components of the electrocardiogram (HF QRS ECG) (150-250 Hz) are more sensitive than changes in conventional ST segments for detecting myocardial ischemia. We investigated the accuracy of 12-lead HF QRS ECG in detecting ischemia during adenosine tetrofosmin myocardial perfusion imaging (MPI). Methods and Results: 12-lead HF QRS ECG recordings were obtained from 45 patients before and during adenosine technetium-99 tetrofosmin MPI tests. Before the adenosine infusions, recordings of HF QRS were analyzed according to a morphological score that incorporated the number, type and location of reduced amplitude zones (RAZs) present in the 12 leads. During the adenosine infusions, recordings of HF QRS were analyzed according to the maximum percentage changes (in both the positive and negative directions) that occurred in root mean square (RMS) voltage amplitudes within the 12 leads. The best set of prospective HF QRS criteria had a sensitivity of 94% and a specificity of 83% for correctly identifying the MPI result. The sensitivity of simultaneous ST segment changes (18%) was significantly lower than that of any individual HF QRS criterion (P<0.001). Conclusions: Analysis of 12-lead HF QRS ECG is highly sensitive and specific for detecting ischemic perfusion defects during adenosine MPI stress tests and significantly more sensitive than analysis of conventional ST segments.

  18. High frequency QRS ECG predicts ischemic defects during myocardial perfusion imaging

    NASA Technical Reports Server (NTRS)

    2004-01-01

    Changes in high frequency QRS components of the electrocardiogram (HF QRS ECG) (150-250 Hz) are more sensitive than changes in conventional ST segments for detecting myocardial ischemia. We investigated the accuracy of 12-lead HF QRS ECG in detecting ischemia during adenosine tetrofosmin myocardial perfusion imaging (MPI). 12-lead HF QRS ECG recordings were obtained from 45 patients before and during adenosine technetium-99 tetrofosmin MPI tests. Before the adenosine infusions, recordings of HF QRS were analyzed according to a morphological score that incorporated the number, type and location of reduced amplitude zones (RAZs) present in the 12 leads. During the adenosine infusions, recordings of HF QRS were analyzed according to the maximum percentage changes (in both the positive and negative directions) that occurred in root mean square (RMS) voltage amplitudes within the 12 leads. The best set of prospective HF QRS criteria had a sensitivity of 94% and a specificity of 83% for correctly identifying the MPI result. The sensitivity of simultaneous ST segment changes (18%) was significantly lower than that of any individual HF QRS criterion (P less than 0.00l). Analysis of 12-lead HF QRS ECG is highly sensitive and specific for detecting ischemic perfusion defects during adenosine MPI stress tests and significantly more sensitive than analysis of conventional ST segments.

  19. Lumped-parameter tissue temperature-blood perfusion model of a cold-stressed fingertip.

    PubMed

    Shitzer, A; Stroschein, L A; Gonzalez, R R; Pandolf, K B

    1996-05-01

    A lumped-parameter model of a fingertip is presented. The semispherical model includes the effects of heat storage, heat exchange with the environment, and heat transport by blood perfusion. The thermal insulation on the surface of the fingertip is represented by the overall heat transfer coefficient that is calculated by common engineering formulas. The model is solved analytically for the simple case of constant blood perfusion rate. The general case of variable blood perfusion rates is solved by an Euler finite difference technique. At this stage, the model does not include active control mechanisms of blood perfusion. Thus the effects of cold-induced vasodilatation have to be superimposed and are modeled by symmetrical triangular waveforms because these were found to best depict the behavior of fingers exposed to cold environments. Results of this model were compared with experimental data obtained in two separate studies. One included 60-min infrared thermograms of the dorsal surface of bare hands of sedentary subjects horizontally suspended on a fish net in a 0 degree C environment. Another study, on gloved finger temperatures, involved 0 and -6.7 degrees C environments. Fingertip (nail bed) temperatures of both these studies were compared with model predictions. Blood perfusion rates were assumed and adjusted within physiologically reasonable limits. Comparison of measured and computed temperature records showed very good conformity in both cases studied.

  20. Effects of adenosine and a selective A2A adenosine receptor agonist on hemodynamic and thallium-201 and technetium-99m-sestaMIBI biodistribution and kinetics.

    PubMed

    Mekkaoui, Choukri; Jadbabaie, Farid; Dione, Donald P; Meoli, David F; Purushothaman, Kailasnath; Belardinelli, Luiz; Sinusas, Albert J

    2009-10-01

    The purpose of this study was to compare a selective A(2A) adenosine receptor agonist (regadenoson) with adenosine in clinically relevant canine models with regard to effects on hemodynamics and thallium-201 ((201)Tl) and technetium-99m ((99m)Tc)-sestaMIBI biodistribution and kinetics. The clinical application of vasodilator stress for perfusion imaging requires consideration of the effects of these vasodilating agents on systemic hemodynamics, coronary flow, and radiotracer uptake and clearance kinetics. Sequential imaging and arterial blood sampling was performed on control, anesthetized closed-chest canines (n = 7) to evaluate radiotracer biodistribution and kinetics after either a bolus administration of regadenoson (2.5 microg/kg) or 4.5-min infusion of adenosine (280 microg/kg). The effects of regadenoson on coronary flow and myocardial radiotracer uptake were then evaluated in an open-chest canine model of a critical stenosis (n = 7). Results from ex vivo single-photon emission computed tomography were compared with tissue well-counting. The use of regadenoson compared favorably with adenosine in regard to the duration and magnitude of the hemodynamic effects and the effect on (201)Tl and (99m)Tc-sestaMIBI biodistribution and kinetics. The arterial blood clearance half-time was significantly faster for (99m)Tc-sestaMIBI (regadenoson: 1.4 +/- 0.03 min; adenosine: 1.5 +/- 0.08 min) than for (201)Tl (regadenoson: 2.5 +/- 0.16 min, p < 0.01; adenosine: 2.7 +/- 0.04 min, p < 0.01) for both vasodilator stressors. The relative microsphere flow deficit (0.34 +/- 0.02%) during regadenoson stress was significantly greater than the relative perfusion defect with (99m)Tc-sestaMIBI (0.69 +/- 0.03%, p < 0.001) or (201)Tl (0.53 +/- 0.02%, p < 0.001), although (201)Tl tracked the flow deficit within the ischemic region better than (99m)Tc-sestaMIBI. The perfusion defect score was larger with (201)Tl (22 +/- 2.8% left ventricular) than with (99m)Tc-sestaMIBI (17 +/- 1

  1. The prevalence of a false-positive myocardial perfusion stress SPET test in a skinny patient, induced by projection truncation.

    PubMed

    Tsougos, Ioannis; Alexiou, Sotiria; Theodorou, Kiki; Valotassiou, Varvara; Georgoulias, Panagiotis

    2015-01-01

    During the last decade, technical developments in myocardial perfusion single photon emission tomography (SPET) imaging systems have significantly improved the accuracy of diagnosing coronary artery disease. Nevertheless, the patient's position and/or the acquisition protocol can affect the studies' quality, possibly leading to misdiagnoses. In HJNM and in other journals the importance of proper positioning of the heart of the patient to be examined by myocardial perfusion SPET stress/rest testing, has been emphasized. According to our knowledge, only three cases of truncation artifact during SPET myocardial perfusion imaging acquired with original SPET cameras, related to improper positioning in very thin patients, have been reported. In all cases, patients were examined according to a single day stress/rest technetium-99m-sestamibi protocol, using a dual 90 degree detector system, equipped with high resolution, parallel-hole collimators. However, several published manuscripts have underlined the significance of appropriate patients' positioning in myocardial perfusion scintigraphy using dedicated, cadmium-zinc-telluride (CZT) or small field-of-view cardiac SPET systems. A typical case is that of a 47 years old man (height 187cm, weight 67kg), heavy smoker, with atypical chest pain. He exercised very well according to the Bruce protocol, achieving 95% of maximal age-predicted heart-rate and a technetium-99m-tetrofosmin ((99m)Tc-TF) myocardial perfusion imaging with 370MBq of (99m)Tc-TF followed with a dual head camera (Infinia GE, USA), equipped with low-energy, high-resolution, parallel-hole collimators at 90° (L-mode configuration). Projection images were obtained from 45° RAO to 45° LPO position, in step and shoot mode (60 projections, 30sec per projection; matrix 64×64 and zoom 1.3). Auto body contour was not used. Unprocessed raw data, showed neither patient motion nor significant extracardiac activity that could result in false positive defects on

  2. Relation between perfusion defects on stress technetium-99m sestamibi SPECT scintigraphy and the location of a subsequent acute myocardial infarction.

    PubMed

    Miller, G L; Herman, S D; Heller, G V; Kalla, S; Levin, W A; Stillwell, K M; Travin, M I

    1996-07-01

    Although the presence of perfusion defects on stress myocardial perfusion imaging has been shown to correlate with future cardiac events, including acute myocardial infarction (AMI), it is unknown whether the location of the AMI can be predicted. Therefore, for 25 patients who had an AMI following a stress technetium-99m sestamibi single-photon emission computed tomographic (SPECT) imaging study and whose infarct location could be determined, the territory of infarction was correlated with the location of previous myocardial perfusion defects. A SPECT perfusion defect had been present in 24 patients (96%). The AMI occurred in territories that showed a reversible defect in 14 patients (56%), whereas 3 infarctions (12%) were in territories that revealed a fixed defect, and 8 infarctions (32%) were in territories that had not shown a defect on prior SPECT imaging. Whereas the incidence of infarction in territories with a reversible defect was highest at 14 of 26 (54%), the incidence of infarction in territories with a fixed defect was 3 of 7 (43%), and in territories with no defect was 8 of 42 (19%) (p = 0.011). Neither the time interval between SPECT imaging and infarction, nor the perfusion defect severity, was related to the correlation between perfusion defect and infarct location. Thus, although AMI occurs most often at the site of previous perfusion defects, reversible or fixed, a substantial percentage occur in territories without a perfusion defect. These findings suggest that abnormalities on SPECT perfusion imaging, although they serve as markers of significant coronary disease and increase the likelihood of infarction, do not always predict the exact location of infarction.

  3. Prediction of cardiac events in patients with transient left ventricle dilation on stress myocardial perfusion SPECT images.

    PubMed

    Fukuda, Hiroshi; Moroi, Masao

    2005-10-01

    The purpose of this study was to investigate cardiac events in patients with transient left ventricle (LV) dilation on stress myocardial perfusion single-photon emission computed tomography images (MPI). Consecutive patients (n=53, 31 males, mean age 71 years) with transient LV dilation on thallium-201 stress MPI (treadmill: 21, pharmacologic: 32) were followed for 17 months. Follow-up time was censored at the occurrence of cardiac death, congestive heart failure, acute coronary syndrome, or revascularization. Images were scored and then the summed stress score (SSS), summed rest score, and summed difference score were calculated. Cardiac death occurred in 3 patients, hospitalization occurred in 8 patients, and revascularization occurred in 20 patients. The combined cardiac event rate was 59% (76% for exercise stress vs 47% for pharmacologic stress, p=0.034). Cox regression analysis demonstrated that a combination of higher SSS and slow washout rate was the best predictor of cardiac events (hazard ratio =3.3, p=0.029). A high cardiac event rate is associated with transient LV dilation on thallium-201 stress MPI. The event rate is particularly high for exercise stress MPI. Furthermore, a combination of the SSS and thallium-201 slow washout is the best predictor of cardiac events in patients with transient LV dilation.

  4. Wheel running alters patterns of uncontrollable stress-induced cfos mRNA expression in rat dorsal striatum direct and indirect pathways: a possible role for plasticity in adenosine receptors

    PubMed Central

    Clark, Peter J.; Ghasem, Parsa R.; Mika, Agnieszka; Day, Heidi E.; Herrera, Jonathan J.; Greenwood, Benjamin N.; Fleshner, Monika

    2014-01-01

    Emerging evidence indicates that adenosine is a major regulator of striatum activity, in part, through the antagonistic modulation of dopaminergic function. Exercise can influence adenosine and dopamine activity, which may subsequently promote plasticity in striatum adenosine and dopamine systems. Such changes could alter activity of medium spiny neurons and impact striatum function. The purpose of this study was two-fold. The first was to characterize the effect of long-term wheel running on adenosine 1 (A1R), adenosine 2A (A2AR), dopamine 1 (D1R), and dopamine 2 (D2R) receptor mRNA expression in adult rat dorsal and ventral striatum structures using in situ hybridization. The second was to determine if changes to adenosine and dopamine receptor mRNA from running are associated with altered cfos mRNA induction in dynorphin- (direct pathway) and enkephalin- (indirect pathway) expressing neurons of the dorsal striatum following stress exposure. We report that chronic running, as well as acute uncontrollable stress, reduced A1R and A2AR mRNA levels in the dorsal and ventral striatum. Running also modestly elevated D2R mRNA levels in striatum regions. Finally, stress-induced cfos was potentiated in dynorphin and attenuated in enkephalin expressing neurons of running rats. These data suggest striatum adenosine and dopamine systems are targets for neuroplasticity from exercise, which may contribute to changes in direct and indirect pathway activity. These findings may have implications for striatum mediated motor and cognitive processes, as well as exercise facilitated stress-resistance. PMID:25017571

  5. Continuum of Vasodilator Stress From Rest to Contrast Medium to Adenosine Hyperemia for Fractional Flow Reserve Assessment.

    PubMed

    Johnson, Nils P; Jeremias, Allen; Zimmermann, Frederik M; Adjedj, Julien; Witt, Nils; Hennigan, Barry; Koo, Bon-Kwon; Maehara, Akiko; Matsumura, Mitsuaki; Barbato, Emanuele; Esposito, Giovanni; Trimarco, Bruno; Rioufol, Gilles; Park, Seung-Jung; Yang, Hyoung-Mo; Baptista, Sérgio B; Chrysant, George S; Leone, Antonio M; Berry, Colin; De Bruyne, Bernard; Gould, K Lance; Kirkeeide, Richard L; Oldroyd, Keith G; Pijls, Nico H J; Fearon, William F

    2016-04-25

    This study compared the diagnostic performance with adenosine-derived fractional flow reserve (FFR) ≤0.8 of contrast-based FFR (cFFR), resting distal pressure (Pd)/aortic pressure (Pa), and the instantaneous wave-free ratio (iFR). FFR objectively identifies lesions that benefit from medical therapy versus revascularization. However, FFR requires maximal vasodilation, usually achieved with adenosine. Radiographic contrast injection causes submaximal coronary hyperemia. Therefore, intracoronary contrast could provide an easy and inexpensive tool for predicting FFR. We recruited patients undergoing routine FFR assessment and made paired, repeated measurements of all physiology metrics (Pd/Pa, iFR, cFFR, and FFR). Contrast medium and dose were per local practice, as was the dose of intracoronary adenosine. Operators were encouraged to perform both intracoronary and intravenous adenosine assessments and a final drift check to assess wire calibration. A central core lab analyzed blinded pressure tracings in a standardized fashion. A total of 763 subjects were enrolled from 12 international centers. Contrast volume was 8 ± 2 ml per measurement, and 8 different contrast media were used. Repeated measurements of each metric showed a bias <0.005, but a lower SD (less variability) for cFFR than resting indexes. Although Pd/Pa and iFR demonstrated equivalent performance against FFR ≤0.8 (78.5% vs. 79.9% accuracy; p = 0.78; area under the receiver-operating characteristic curve: 0.875 vs. 0.881; p = 0.35), cFFR improved both metrics (85.8% accuracy and 0.930 area; p < 0.001 for each) with an optimal binary threshold of 0.83. A hybrid decision-making strategy using cFFR required adenosine less often than when based on either Pd/Pa or iFR. cFFR provides diagnostic performance superior to that of Pd/Pa or iFR for predicting FFR. For clinical scenarios or health care systems in which adenosine is contraindicated or prohibitively expensive, cFFR offers a universal technique to

  6. Myocardial perfusion cardiac magnetic resonance for the diagnosis of coronary artery disease: do we need rest images?

    PubMed

    Krittayaphong, Rungroj; Boonyasirinant, Thananya; Saiviroonporn, Pairash; Nakyen, Supaporn; Thanapiboonpol, Prajak; Yindeengam, Ahthit; Udompunturak, Suthipol

    2009-04-01

    Adenosine stress cardiovascular magnetic resonance (CMR) has been reported to be useful for the diagnosis of coronary artery disease (CAD). Most studies use rest and stress perfusion images. The objectives of this study were to determine (Barkhausen et al. in J Magn Reson Imaging 19(6):750-757, 1) the accuracy of visual assessment and myocardial perfusion reserve index (MPRI) in the diagnosis of CAD and (Rieber et al. in Fur Heart J 27(12):1465-1471, 2) the accuracy of analysis based on rest-stress and stress images. We enrolled patients with suspected CAD and referred them for coronary angiography (CAG). All the patients underwent adenosine stress CMR before CAG. Rest and stress perfusion images were analyzed by calculation of MPRI and visual assessment separately. Visual assessment was performed separately by using rest and stress images and by using only stress images. CAG was considered the gold standard. Sensitivity, specificity, and accuracy of both methods were calculated and compared. A total of 66 patients (mean age, 61.3 +/- 11.7 years) were studied. Thirty-eight patients (57.6%) were diagnosed with CAD. The sensitivity and specificity for the diagnosis of CAD (> or =50% stenosis) were 89.5 and 78.6% for MPRI, 76.3 and 75% for stress-rest visual method, and 86.8 and 75% for stress visual method, respectively. CMR perfusion had a relatively lower accuracy in patients with left ventricular systolic dysfunction, high left ventricular mass, or presence of late gadolinium enhancement than in patients without those CMR findings. Visual assessment of stress image of CMR perfusion is accurate and comparable to MPRI for the detection of CAD.

  7. Physiological basis for angina and ST-segment change PET-verified thresholds of quantitative stress myocardial perfusion and coronary flow reserve.

    PubMed

    Johnson, Nils P; Gould, K Lance

    2011-09-01

    This study aimed to determine the quantitative low-flow threshold for stress-induced perfusion defects with severe angina and/or significant ST-segment depression during dipyridamole hyperemia. Vasodilator stress reveals differences in regional perfusion without ischemia in most patients. However, in patients with a perfusion defect, angina, and/or significant ST-segment depression during dipyridamole stress, quantitative absolute myocardial perfusion and coronary flow reserve (CFR) at the exact moment of definite ischemia have not been established. Defining these low-flow thresholds of angina or ST-segment changes may offer insight into physiological disease severity in patients with atherosclerosis. Patients underwent rest-dipyridamole stress positron emission tomography (PET) with absolute flow quantification in ml/min/g. Definite ischemia was defined as a new or worse perfusion defect during dipyridamole stress with significant ST-segment depression and/or severe angina requiring pharmacological treatment. Indeterminate clinical features required only 1 of these 3 abnormalities. The comparison group included patients without prior myocardial infarction, or angina or electrocardiographic changes after dipyridamole. In 1,674 sequential PET studies, we identified 194 (12%) with definite ischemia, 840 (50%) studies with no ischemia, and 301 (18%) that were clinically indeterminate. A vasodilator stress perfusion cutoff of 0.91 ml/min/g optimally separated definite from no ischemia with an area under the receiver-operator characteristic curve (AUC) of 0.98 and a CFR cutoff of 1.74 with an AUC = 0.91, reflecting excellent discrimination at the exact moment of definite ischemia. Thresholds of low myocardial vasodilator stress perfusion in ml/min/g and CFR sharply separate patients with angina or ST-segment change from those without these manifestations of ischemia during dipyridamole stress with excellent discrimination. Stress flow below 0.91 ml/min/g in dipyridamole

  8. Metformin and sulodexide restore cardiac microvascular perfusion capacity in diet-induced obese rats.

    PubMed

    van Haare, Judith; Kooi, M Eline; van Teeffelen, Jurgen W G E; Vink, Hans; Slenter, Jos; Cobelens, Hanneke; Strijkers, Gustav J; Koehn, Dennis; Post, Mark J; van Bilsen, Marc

    2017-04-11

    Disturbances in coronary microcirculatory function, such as the endothelial glycocalyx, are early hallmarks in the development of obesity and insulin resistance. Accordingly, in the present study myocardial microcirculatory perfusion during rest and stress was assessed following metformin or sulodexide therapy in a rat model of diet-induced obesity. Additionally, the effect of degradation of the glycocalyx on myocardial perfusion was assessed in chow-fed rats. Rats were fed a high fat diet (HFD) for 8 weeks and were divided into a group without therapy, and groups that received the anti-diabetic drug metformin or the glycocalyx-stabilizing drug sulodexide in their drinking water during the last 4 weeks of the feeding period. Myocardial microvascular perfusion was determined using first-pass perfusion MRI before and after adenosine infusion. The effect of HFD on microcirculatory properties was also assessed by sidestream darkfield (SDF) imaging of the gastrocnemius muscle. In an acute experimental setting, hyaluronidase was administered to chow-fed control rats to determine the effect of enzymatical degradation of the glycocalyx on myocardial perfusion. HFD-rats developed central obesity and insulin sensitivity was reduced as evidenced by the marked reduction in insulin-induced phosphorylation of Akt in both cardiac and gastrocnemius muscle. We confirmed our earlier findings that the robust increase in myocardial perfusion in chow-fed rats after an adenosine challenge (+56%, p = 0.002) is blunted in HFD rats (+8%, p = 0.68). In contrast, 4-weeks treatment with metformin or sulodexide partly restored the increase in myocardial perfusion during adenosine infusion in HFD rats (+81%, p = 0.002 and +37%, p = 0.02, respectively). Treating chow-fed rats acutely with hyaluronidase, to enzymatically degrade the glyocalyx, completely blunted the increase in myocardial perfusion during stress. In early stages of HFD-induced insulin resistance myocardial perfusion

  9. [Assessment of myocardial perfusion by cardiovascular magnetic resonance: comparison with coronary angiography].

    PubMed

    Pons Lladó, Guillem; Carreras, Francesc; Leta, Rubén; Pujadas, Sandra; García Picart, Joan

    2004-05-01

    The assessment of regional myocardial perfusion by cardiovascular magnetic resonance imaging makes it possible to detect significant coronary artery lesions. The purpose of this study was to determine the usefulness of this technique in non-selected patients with ischemic heart disease. The study group included 32 patients (26 men; mean age: 65 years old). Gadolinium (0.05 mmol/kg) for first-pass imaging was administered through a peripheral vein, both at rest and after adenosine infusion (140 mg/kg for 6 min). The presence of a regional perfusion defect was assessed visually, and these images were compared against coronary angiographic images. Angiography showed 49 significant (> 70%) obstructive lesions in a coronary artery. Magnetic resonance showed a perfusion defect at rest (fixed) in 35 myocardial segments, and only after adenosine infusion (reversible) in 16 additional regions, for a total of 51 segments with perfusion defect. Sensitivity for the detection of an angiographically significant coronary lesion was 78%, with a specificity of 75%. These figures decreased to 54% and 65%, respectively, when only fixed defects were considered. There were no visible defects in 26% of the myocardial territories with proven previous necrosis, although effective reperfusion and patent culprit arteries were frequently seen in these cases. The detection of a regional myocardial perfusion defect by visual analysis with first-pass gadolinium and cardiovascular magnetic resonance imaging shows good diagnostic accuracy for the presence of significant coronary artery obstruction, provided that both rest and pharmacological stress studies are performed.

  10. Comparison of Myocardial Perfusion Estimates From Dynamic Contrast-Enhanced Magnetic Resonance Imaging With Four Quantitative Analysis Methods

    PubMed Central

    Pack, Nathan A.; DiBella, Edward V. R.

    2012-01-01

    Dynamic contrast-enhanced MRI has been used to quantify myocardial perfusion in recent years. Published results have varied widely, possibly depending on the method used to analyze the dynamic perfusion data. Here, four quantitative analysis methods (two-compartment modeling, Fermi function modeling, model-independent analysis, and Patlak plot analysis) were implemented and compared for quantifying myocardial perfusion. Dynamic contrast-enhanced MRI data were acquired in 20 human subjects at rest with low-dose (0.019 ± 0.005 mmol/kg) bolus injections of gadolinium. Fourteen of these subjects were also imaged at adenosine stress (0.021 ± 0.005 mmol/kg). Aggregate rest perfusion estimates were not significantly different between all four analysis methods. At stress, perfusion estimates were not significantly different between two-compartment modeling, model-independent analysis, and Patlak plot analysis. Stress estimates from the Fermi model were significantly higher (~20%) than the other three methods. Myocardial perfusion reserve values were not significantly different between all four methods. Model-independent analysis resulted in the lowest model curve-fit errors. When more than just the first pass of data was analyzed, perfusion estimates from two-compartment modeling and model-independent analysis did not change significantly, unlike results from Fermi function modeling. PMID:20577976

  11. [Variables that influence the indication of a second myocardial perfusion gated-SPECT after a normal stress-rest gated SPECT].

    PubMed

    Romero-Farina, G; Candell-Riera, J; Aguadé-Bruix, S; Cuberas-Borrós, G; Pizzi, M N; Santos, A; de León, G; García-Dorado, D

    2014-01-01

    The objective of this study was to investigate predictor variables at the moment of normal stress-rest myocardial perfusion gated SPECT for indication of a second gated SPECT. A prospective, single center cohort study was conducted. We evaluated 2326 consecutive patients (age 63.6 ± 13 years, 57.3% females) without perfusion defects and with normal left ventricular ejection fraction on a myocardial perfusion gated SPECT. Clinical and stress test variables were studied to predict indication of a second gated SPECT and presence of reversible perfusion defects in the second gated SPECT. During a mean follow-up of 3.6 ± 2 years a second gated SPECT was performed in 286 patients (12.3%). Independent predictor variables of a second gated SPECT were presence of three or more cardiovascular risk factors (χ(2): 5.510; HR: 1.4; p=0.019), previous acute myocardial infarction (χ(2): 3.867; HR: 1.4; p=0.049), previous coronary revascularization (χ(2): 41.081; HR: 2.5; p<0.001), and a positive stress test (χ(2): 8.713; HR: 1.5; p=0.003). Observation of perfusion defects in the 280 patients in whom a second stress-rest gated SPECT was performed was more likely in male patients (χ(2): 4.322; HR: 1.9; p=0.038) who had a first pure pharmacological gated-SPECT (χ(2): 7.182; HR: 2.6; p=0.007). In patients with a first normal myocardial perfusion gated SPECT, various clinical factors and variables derived from the stress test affect the indication of a second gated SPECT and the presence of ischemia in the latter. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

  12. Cardiac perfusion imaging using hyperpolarized (13)C urea using flow sensitizing gradients.

    PubMed

    Lau, Angus Z; Miller, Jack J; Robson, Matthew D; Tyler, Damian J

    2016-04-01

    To demonstrate the feasibility of imaging the first passage of a bolus of hyperpolarized (13)C urea through the rodent heart using flow-sensitizing gradients to reduce signal from the blood pool. A flow-sensitizing bipolar gradient was optimized to reduce the bright signal within the cardiac chambers, enabling improved contrast of the agent within the tissue capillary bed. The gradient was incorporated into a dynamic golden angle spiral (13)C imaging sequence. Healthy rats were scanned during rest (n = 3) and under adenosine stress-induced hyperemia (n = 3). A two-fold increase in myocardial perfusion relative to rest was detected during adenosine stress-induced hyperemia, consistent with a myocardial perfusion reserve of two in rodents. The new pulse sequence was used to obtain dynamic images of the first passage of hyperpolarized (13)C urea in the rodent heart, without contamination from bright signal within the neighboring cardiac lumen. This probe of myocardial perfusion is expected to enable new hyperpolarized (13)C studies in which the cardiac metabolism/perfusion mismatch can be identified. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance. © 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

  13. Analysis of myocardial perfusion from vasodilator stress computed tomography: does improvement in image quality by iterative reconstruction lead to improved diagnostic accuracy?

    PubMed

    Bhave, Nicole M; Mor-Avi, Victor; Kachenoura, Nadjia; Freed, Benjamin H; Vannier, Michael; Dill, Karin; Lang, Roberto M; Patel, Amit R

    2014-01-01

    Iterative reconstruction (IR) in cardiac CT has been shown to improve confidence of interpretation of noninvasive coronary CT angiography (CTA). We hypothesized that IR would also improve the quality of vasodilator stress coronary CT images acquired with low tube voltage to assess myocardial perfusion and the accuracy of the detection of perfusion abnormalities by using quantitative 3-dimensional (3D) analysis. We studied 39 consecutive patients referred for coronary CTA (256-slice scanner; Philips), who underwent additional imaging (100 kV, prospective gating) with regadenoson (0.4 mg; Astellas). Stress images were reconstructed with different algorithms: filtered back projection (FBP) and IR (iDose; Philips). Image quality was quantified by signal-to-noise and contrast-to-noise ratios in the blood pool and the myocardium. Then, FBP and separately IR images were analyzed with custom 3D analysis software to quantitatively detect perfusion defects. Accuracy of detection was compared with perfusion abnormalities predicted by coronary stenosis >50% on coronary CTA. Five patients with image artifacts were excluded. In the remaining 34 patients, both signal-to-noise and contrast-to-noise ratios increased with IR, indicating improvement in image quality compared with FBP. For 3D perfusion analysis, 10 patients with normal coronary arteries were used as a reference to correct for x-ray attenuation variations in normal myocardium. In the remaining 24 patients, reduced noise levels in the IR images compared with FBP resulted in tighter attenuation distribution and improved detection of perfusion abnormalities. IR significantly improves image quality on regadenoson stress CT images acquired with low tube voltage, leading to improved 3D quantitative evaluation of myocardial perfusion. Copyright © 2014 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

  14. The significance of post-stress decrease in left ventricular ejection fraction in patients undergoing regadenoson stress gated SPECT myocardial perfusion imaging.

    PubMed

    Gomez, Javier; Golzar, Yasmeen; Fughhi, Ibtihaj; Olusanya, Adebayo; Doukky, Rami

    2017-02-08

    The significance of post-stress decrease in left ventricular ejection fraction (LVEF) with regadenoson stress gated SPECT (GSPECT) myocardial perfusion imaging (MPI) has not been studied. Consecutive patients who underwent rest/regadenoson stress GSPECT-MPI followed by coronary angiography within 6 months were analyzed. Change in LVEF by GSPECT-MPI was calculated as stress LVEF minus rest LVEF; a significant decrease was tested at 5% and 10% thresholds. In a diagnostic cohort of 793 subjects, LVEF change was not predictive of severe/extensive coronary artery disease (area under the curve, 0.50; 95% confidence interval, 0.44-0.57; P = 0.946). There was no significant difference in the rates of severe/extensive coronary artery disease in patients with or without a decrease in LVEF, irrespective of MPI findings. In an outcome cohort of the 929 subjects followed for 30 ± 16 months, post-regadenoson stress decrease in LVEF was not associated with increased risk of the composite endpoint of cardiac death or myocardial infarction or in the risk of coronary revascularization. In patients selected to undergo coronary angiography following regadenoson stress GSPECT-MPI, a decrease in LVEF after regadenoson stress is not predictive of severe/extensive CAD or adverse clinical outcomes, irrespective of MPI findings.

  15. Adenosine A2 receptor activation ameliorates mitochondrial oxidative stress upon reperfusion through the posttranslational modification of NDUFV2 subunit of complex I in the heart.

    PubMed

    Xu, Jingman; Bian, Xiyun; Liu, Yuan; Hong, Lan; Teng, Tianming; Sun, Yuemin; Xu, Zhelong

    2017-05-01

    While it is well known that adenosine receptor activation protects the heart from ischemia/reperfusion injury, the precise mitochondrial mechanism responsible for the action remains unknown. This study probed the mitochondrial events associated with the cardioprotective effect of 5'-(N-ethylcarboxamido) adenosine (NECA), an adenosine A2 receptor agonist. Isolated rat hearts were subjected to 30min ischemia followed by 10min of reperfusion, whereas H9c2 cells experienced 20min ischemia and 10min reperfusion. NECA prevented mitochondrial structural damage, decreases in respiratory control ratio (RCR), and collapse of mitochondrial membrane potential (ΔΨm). Both the adenosine A2A receptor antagonist SCH58261 and A2B receptor antagonist MRS1706 inhibited the action of NECA. NECA reduced mitochondrial proteins carbonylation, H2O2, and superoxide generation at reperfusion, but did not change superoxide dismutase (SOD) activity. In support, the protective effects of NECA and Peg-SOD on ΔΨm upon reperfusion were additive, implying that NECA's protection is attributable to the reduced superoxide generation but not to the enhancement of the superoxide-scavenging capacity. NECA increased the mitochondrial Src tyrosine kinase activity and suppressed complex I activity at reperfusion in a Src-dependent manner. NECA also reduced mitochondrial superoxide through Src tyrosine kinase. Studies with liquid chromatography-mass spectrometer (LC-MS) identified Tyr118 of the NDUFV2 subunit of complex 1 as a likely site of the tyrosine phosphorylation. Furthermore, the complex I activity of cells transfected with the Y118F mutant was increased, suggesting that this site might be a negative regulator of complex I activity. In support, NECA failed to suppress complex I activity at reperfusion in cells transfected with the Y118F mutant of NDUFV2. In conclusion, NECA prevents mitochondrial oxidative stress by decreasing mitochondrial superoxide generation through inhibition of complex I

  16. Hypertensive response with exercise does not increase the prevalence of abnormal Tc-99m SPECT stress perfusion images.

    PubMed

    Kane, Garvan C; Askew, John W; Chareonthaitawee, Panithaya; Miller, Todd D; Gibbons, Raymond J

    2008-05-01

    Systemic hypertension and an exaggerated blood pressure (BP) response with exercise have been associated with 'false-positive' findings on stress electrocardiography and echocardiography; however, limited data is available for stress myocardial perfusion imaging (MPI). The purpose of this study was to investigate whether an exaggerated elevation in BP with exercise is associated with an increased prevalence of abnormal MPI. BP responses to exercise were assessed in a cohort of 7,205 patients who underwent stress testing with technetium 99m-SPECT MPI (7/1999-6/2005) for the evaluation of chest pain or dyspnea. A hypertensive response, defined as a peak systolic BP > or = 220 mmHg, occurred in 355 (4.9%) and was not associated with higher rates of ischemic ECG changes (16.1 versus 16.6%; P = .7), differences in Duke treadmill scores (4.7 +/- 4 versus 5.1 +/- 5; P = .3) or an increased prevalence of abnormal perfusion images (30.1% versus 32.9%; P = .3) to those without a hypertensive exercise response. Patients with a hypertensive response and either intermediate or high-risk MPI (on the basis of summed-difference-scores) referred for coronary angiography, had a high prevalence of coronary artery disease which was similar to those without a hypertensive response (88% versus 83%; P = .5). In an analysis of a community-based patient subset, a hypertensive response was not associated with a difference in either all-cause mortality or subsequent myocardial infarction, coronary revascularization or cardiac death (8% versus 9%; P = .7). A hypertensive BP response to exercise is not associated with increased rates of ischemic ECG changes, higher-risk Duke treadmill scores, greater degrees of abnormal MPI or worse clinical outcome.

  17. Effects of electric stress on glucose metabolism, glucose-stimulated cyclic adenosine 3',5'-monophosphate accumulation and 45 Ca++ efflux in isolated pancreatic islets from rats fed with a high fat diet.

    PubMed

    Yamaguchi, K; Goko, H; Matsuoka, A

    1979-10-01

    The effects of the electric stress on glucose oxidation, cyclic adenosine 3', 5'-monophosphate (AMP) accumulation and 45Ca++ efflux in response to glucose were studied in pancreatic islets isolated from rats fed on a control (C) or a high fat diet (F) for 12 weeks. The half of rats on each diet were subjected to electrical shocks in the random time schedule for 1 hr per day for the last 3 weeks of the feeding period (group C-S and F-S). The remaining rats were not given any shocks (group C-NS and F-NS). The rats in F-S group had the high levels of plasma epinephrine, dopamine and blood glucose. The basal content of cyclic AMP after 20 min of incubation with 2.8 mM glucose was decreased in islets from F-S group without affecting insulin release. After 20 min of incubation with 25 mM glucose, the cyclic AMP content in islets from F-S group, which was identical with that in F-NS group, was only 50% of that in C-S group. Insulin release in response to high glucose was significantly inhibited in islets from F-S group. In spite of a remarkable increase of cyclic AMP content in islets from C-S group, insulin release did not differ from that in C-NS group. Glucose (16.7 mM)-stimulated 45Ca++ efflux from the perfused islets was greatly inhibited by the high fat diet rather than by stress. The rate of glucose oxidation with 16.7 mM glucose was decreased in islets from F-S group. It is suggested that the decreased insulin release in response to glucose provoked by the combined effects of the feeding of a high fat diet and electric stress may be mediated by changes of the adenylate cyclase-cyclic AMP system on the plasma membrane of the B-cell or be related to changes in glucose metabolism in islets.

  18. Integrated microdevice for long-term automated perfusion culture without shear stress and real-time electrochemical monitoring of cells.

    PubMed

    Li, Lin-Mei; Wang, Wei; Zhang, Shu-Hui; Chen, Shi-Jing; Guo, Shi-Shang; Français, Olivier; Cheng, Jie-Ke; Huang, Wei-Hua

    2011-12-15

    Electrochemical techniques based on ultramicroelectrodes (UMEs) play a significant role in real-time monitoring of chemical messengers' release from single cells. Conversely, precise monitoring of cells in vitro strongly depends on the adequate construction of cellular physiological microenvironment. In this paper, we developed a multilayer microdevice which integrated high aspect ratio poly(dimethylsiloxane) (PDMS) microfluidic device for long-term automated perfusion culture of cells without shear stress and an independently addressable microelectrodes array (IAMEA) for electrochemical monitoring of the cultured cells in real time. Novel design using high aspect ratio between circular "moat" and ring-shaped micropillar array surrounding cell culture chamber combined with automated "circular-centre" and "bottom-up" perfusion model successfully provided continuous fresh medium and a stable and uniform microenvironment for cells. Two weeks automated culture of human umbilical endothelial cell line (ECV304) and neuronal differentiation of rat pheochromocytoma (PC12) cells have been realized using this device. Furthermore, the quantal release of dopamine from individual PC12 cells during their culture or propagation process was amperometrically monitored in real time. The multifunctional microdevice developed in this paper integrated cellular microenvironment construction and real-time monitoring of cells during their physiological process, and would possibly provide a versatile platform for cell-based biomedical analysis.

  19. Myocardial Creatine Levels Do Not Influence Response to Acute Oxidative Stress in Isolated Perfused Heart

    PubMed Central

    Aksentijević, Dunja; Zervou, Sevasti; Faller, Kiterie M. E.; McAndrew, Debra J.; Schneider, Jurgen E.; Neubauer, Stefan; Lygate, Craig A.

    2014-01-01

    Background Multiple studies suggest creatine mediates anti-oxidant activity in addition to its established role in cellular energy metabolism. The functional significance for the heart has yet to be established, but antioxidant activity could contribute to the cardioprotective effect of creatine in ischaemia/reperfusion injury. Objectives To determine whether intracellular creatine levels influence responses to acute reactive oxygen species (ROS) exposure in the intact beating heart. We hypothesised that mice with elevated creatine due to over-expression of the creatine transporter (CrT-OE) would be relatively protected, while mice with creatine-deficiency (GAMT KO) would fare worse. Methods and Results CrT-OE mice were pre-selected for creatine levels 20–100% above wild-type using in vivo 1H–MRS. Hearts were perfused in isovolumic Langendorff mode and cardiac function monitored throughout. After 20 min equilibration, hearts were perfused with either H2O2 0.5 µM (30 min), or the anti-neoplastic drug doxorubicin 15 µM (100 min). Protein carbonylation, creatine kinase isoenzyme activities and phospho-PKCδ expression were quantified in perfused hearts as markers of oxidative damage and apoptotic signalling. Wild-type hearts responded to ROS challenge with a profound decline in contractile function that was ameliorated by co-administration of catalase or dexrazoxane as positive controls. In contrast, the functional deterioration in CrT-OE and GAMT KO hearts was indistinguishable from wild-type controls, as was the extent of oxidative damage and apoptosis. Exogenous creatine supplementation also failed to protect hearts from doxorubicin-induced dysfunction. Conclusions Intracellular creatine levels do not influence the response to acute ROS challenge in the intact beating heart, arguing against creatine exerting (patho-)physiologically relevant anti-oxidant activity. PMID:25272153

  20. Markers of left ventricular dysfunction induced by exercise, dipyridamole or combined stress on ECG-gated myocardial perfusion scans.

    PubMed

    Hurwitz, G A; O'Donoghue, J P; MacDonald, A C; Laurin, N R; Powe, J E

    1993-04-01

    An index of left ventricular contraction can be extracted from the cavitary time-activity curve of electrocardiographic (ECG)-gated myocardial perfusion scans. To assess the induction of stress-induced myocardial depression, we compared contraction indexes derived from immediate poststress and delayed 201Tl images with indexes of ventricular dilation and lung uptake in the prediction of severe coronary artery disease (defined as two or more 90% stenoses). Stress procedures were performed in 93 patients with symptom-limited supine bicycle exercise alone, and in 227 with intravenous dipyridamole, combined where possible with exercise. The immediate and delayed contraction indexes reflected left ventricular dysfunction on ventriculography (P < 0.0001), but additionally the immediate index was reduced (P < 0.0001) in severe coronary disease. Stress-induced hypokinesis was seen frequently after each of the test modes. The relationship with angiographic findings was better defined for indexes of contraction than for lung uptake or ventricular dilation (P < 0.01). The prediction of severe coronary disease was optimized by combining the poststress contraction index and lung uptake. These data support the use of ECG-gated myocardial scans in evaluating the functional consequences of stress/imaging procedures.

  1. Prospective evaluation of a new protocol for the provisional use of perfusion imaging with exercise stress testing.

    PubMed

    Duvall, W Lane; Savino, John A; Levine, Elliot J; Hermann, Luke K; Croft, Lori B; Henzlova, Milena J

    2015-02-01

    Previous literature suggests that myocardial perfusion imaging (MPI) adds little to the prognosis of patients who exercise >10 metabolic equivalents (METs) during stress testing. With this in mind, we prospectively tested a provisional injection protocol in emergency department (ED) patients presenting for the evaluation of chest pain in which a patient would not receive an injection of radioisotope if adequate exercise was achieved without symptoms and a negative ECG response. All patients who presented to the ED over a 5-year period who were referred for stress testing as part of their ED evaluation were included. Patients considered for a provisional protocol were: exercise stress, age <65 years, no known coronary artery disease, and an interpretable rest ECG. Criteria for not injecting included a maximal predicted heart rate ≥85%, ≥10 METs of exercise, no anginal symptoms during stress, and no ECG changes. Groups were compared based on stress test results, all-cause and cardiac mortality, follow-up cardiac testing, subsequent revascularization, and cost. A total of 965 patients were eligible with 192 undergoing exercise-only and 773 having perfusion imaging. After 41.6 ± 19.6 months of follow-up, all-cause mortality was similar in the exercise-only versus the exercise plus imaging group (2.6% vs. 2.1%, p = 0.59). There were no cardiac deaths in the exercise-only group. At 1 year there was no difference in the number of repeat functional stress tests (1.6% vs. 2.1%, p = 0.43), fewer angiograms (0% vs. 4.0%, p = 0.002), and a significantly lower cost ($65 ± $332 vs $506 ± $1,991, p = 0.002; values are in US dollars) in the exercise-only group. The radiation exposure in the exercise plus imaging group was 8.4 ± 2.1 mSv. A provisional injection protocol has a very low mortality, few follow-up diagnostic tests, and lower cost compared to standard imaging protocols. If adopted it would decrease radiation exposure, save time and

  2. Prognostic Value of Combined CT Angiography and Myocardial Perfusion Imaging versus Invasive Coronary Angiography and Nuclear Stress Perfusion Imaging in the Prediction of Major Adverse Cardiovascular Events: The CORE320 Multicenter Study.

    PubMed

    Chen, Marcus Y; Rochitte, Carlos E; Arbab-Zadeh, Armin; Dewey, Marc; George, Richard T; Miller, Julie M; Niinuma, Hiroyuki; Yoshioka, Kunihiro; Kitagawa, Kakuya; Sakuma, Hajime; Laham, Roger; Vavere, Andrea L; Cerci, Rodrigo J; Mehra, Vishal C; Nomura, Cesar; Kofoed, Klaus F; Jinzaki, Masahiro; Kuribayashi, Sachio; Scholte, Arthur J; Laule, Michael; Tan, Swee Yaw; Hoe, John; Paul, Narinder; Rybicki, Frank J; Brinker, Jeffrey A; Arai, Andrew E; Matheson, Matthew B; Cox, Christopher; Clouse, Melvin E; Di Carli, Marcelo F; Lima, João A C

    2017-07-01

    Purpose To compare the prognostic importance (time to major adverse cardiovascular event [MACE]) of combined computed tomography (CT) angiography and CT myocardial stress perfusion imaging with that of combined invasive coronary angiography (ICA) and stress single photon emission CT myocardial perfusion imaging. Materials and Methods This study was approved by all institutional review boards, and written informed consent was obtained. Between November 2009 and July 2011, 381 participants clinically referred for ICA and aged 45-85 years were enrolled in the Combined Noninvasive Coronary Angiography and Myocardial Perfusion Imaging Using 320-Detector Row Computed Tomography (CORE320) prospective multicenter diagnostic study. All images were analyzed in blinded independent core laboratories, and a panel of physicians adjudicated all adverse events. MACE was defined as revascularization (>30 days after index ICA), myocardial infarction, or cardiac death; hospitalization for chest pain or congestive heart failure; or arrhythmia. Late MACE was defined similarly, except for patients who underwent revascularization within the first 182 days after ICA, who were excluded. Comparisons of 2-year survival (time to MACE) used standard Kaplan-Meier curves and restricted mean survival times bootstrapped with 2000 replicates. Results An MACE (49 revascularizations, five myocardial infarctions, one cardiac death, nine hospitalizations for chest pain or congestive heart failure, and one arrhythmia) occurred in 51 of 379 patients (13.5%). The 2-year MACE-free rates for combined CT angiography and CT perfusion findings were 94% negative for coronary artery disease (CAD) versus 82% positive for CAD and were similar to combined ICA and single photon emission CT findings (93% negative for CAD vs 77% positive for CAD, P < .001 for both). Event-free rates for CT angiography and CT perfusion versus ICA and single photon emission CT for either positive or negative results were not

  3. Novel insights into the pathophysiology of different forms of stress testing.

    PubMed

    Hochgruber, Thomas; Reichlin, Tobias; Wasila, Mariusz; Vogler, Eliane; Twerenbold, Raphael; Sou, Seoung Mann; Roost, Kathrin; Lee, Gino; Fischer, Andreas; Freidank, Heike; Osswald, Stefan; Zellweger, Michael J; Mueller, Christian

    2014-04-01

    The impact of different forms of cardiac stress testing (exercise versus pharmacological stress testing) on cardiac wall stress and myocardial ischemia is incompletely understood. In a prospective study, 331 consecutive patients with suspected myocardial ischemia referred for nuclear perfusion imaging were enrolled: 266 underwent exercise (bicycle) stress testing and 65 adenosine stress testing. Levels of B-type natriuretic peptide (BNP) measured before and 1 min after stress testing, ischemic ECG changes, and typical angina symptoms were used to compare the 2 testing modalities. Cardiac wall stress as quantified by changes in BNP levels significantly increased in the exercise stress group, but not in the adenosine group (increase in BNP levels 22 pg/ml (IQR 6-46) versus -3 pg/ml (IQR -3 to 28); p<0.001). In the bicycle exercise stress group, patients with reversible defects on nuclear perfusion imaging more often had angina symptoms (25% vs. 9%, p=0.0001) and ischemic ECG changes (33% vs. 12%, p=0.0001) during the stress test, and a greater increase in BNP levels (28 (IQR 11-58) versus 16 (IQR 3-34) pg/ml, p=0.001) compared to those without reversible defects. Those differences between patients with and without reversible defects were not observed with the adenosine protocol (p-values all >0.05). Exercise stress testing but not adenosine stress results in an increase of cardiac wall stress, angina symptoms and ECG changes. The absence of these surrogates of myocardial ischemia suggests that adenosine stress does not induce acute myocardial ischemia, but rather displays relative perfusion differences. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  4. Diagnostic accuracy of supine and prone thallium-201 stress myocardial perfusion single-photon emission computed tomography to detect coronary artery disease in inferior wall of left ventricle.

    PubMed

    Katayama, Takuji; Ogata, Nobuhiko; Tsuruya, Yoshio

    2008-05-01

    Prone thallium-201 ((201)Tl) myocardial perfusion single-photon emission computed tomography (SPECT) reduces false-positive rates when evaluating inferior wall abnormalities by minimizing diaphragmatic attenuation. The present study investigates the diagnostic validity of prone (201)Tl stress myocardial perfusion SPECT for detecting coronary artery disease in the inferior wall of the left ventricle in Japanese patients. Of the 104 consecutive patients who underwent (201)Tl stress myocardial perfusion SPECT to diagnose coronary artery disease, we evaluated 46 who underwent image acquisition in both the supine and prone positions, and coronary angiography within 3 months thereafter. Images were acquired in the routine supine position immediately following (201)Tl (111 MBq) injection and 4 h following early acquisition. Images were acquired in the prone position only during the early phase following supine acquisition. We evaluated the SPECT images of the inferior half segments of the left ventricle using a five-point defect scoring system. According to the coronary angiographic findings, we investigated the diagnostic accuracy of stress-rest supine, stress supine, stress prone, and combined supine-prone images. Reduced uptake in the stress supine image of the combined images was considered as attenuation when uptake was normal in the prone image. The sensitivity of the stress-rest supine, stress supine, stress prone, and stress-combined supine-prone images was 77%, 86%, 55%, and 55%, and the specificity was 71%, 54%, 79%, and 83%, respectively. Diagnostic accuracy was the highest in stress-rest supine images. Prone images tended to improve the specificity of detecting coronary artery disease in the inferior wall, but not diagnostic accuracy compared with stress-rest supine images because of decreased sensitivity.

  5. Reversible ischemia in severe stress Tc-99m-Sestamibi perfusion defects: Assessment with gated tomographic polar map Fourier amplitude and amplitude/perfusion ratio images and correlation with resting images

    SciTech Connect

    Williams, K.A.; Taillon, L.A.

    1994-05-01

    Reversible ischemia in myocardial segments with severe hypoperfusion ({le}50% of normal activity) on stress Tc-99m-Sestamibi (MIBI) images was assessed with ECG-gated tomographic (GSPECT) indices of myocardial thickening, as reflected by an increase in regional count density during systole. GSPECT bullseye plots were generated for each of 8 frames acquired after stress MIBI injection in 39 patients with coronary artery disease and at least one severe perfusion defect on summed SPECT images. Using first harmonic Fourier amplitude (AMP) and AMP to perfusion ratio (APR) images, regional myocardial systolic thickening was assessed using a 5-segment model, scored 0 to 3, for absent, minimal, mildly reduced or normal thickening. These data were regionally compared with defect reversibility assessed using a separate-day or a preceding same-day resting MIBI injection images, in which these segments were scored from 0 to 3 for absent, minimal, partial or complete defect reversibility. Of 91 severe stress defects, 16 showed absent, 18 minimal, 43 partial, and 14 complete reversibility on resting images. Both AMP and APR scores were in statistically significant agreement (p=.0218 and .0006) with resting image reversibility grades, with 79% (p=.0324) and 86% (p=.0001) agreement on the presence of reversibility on resting imaging, respectively. AMP correctly identified 89% of the reversibility defects on rest images, while the APR identified 99% (p=.0248 vs. AMP). On analysis of segment scores, the AMP slightly underestimated the degree of rest image reversibility (p=.0235), while APR images indicated more reversibility thin did resting images (p=.0092). In conclusion, GSPECT MIBI bullseye Fourier AMP images correlate well with the pattern of reversibility on resting MIBI in severe stress perfusion defects. When indexed for the degree of hypoperfusion, the Fourier images depict a greater degree of defect reversibility than resting MIBI images.

  6. Comparison of exercise electrocardiography and stress perfusion CMR for the detection of coronary artery disease in women

    PubMed Central

    2012-01-01

    Background Exercise electrocardiography (ECG) is frequently used in the work-up of patients with suspected coronary artery disease (CAD), however the accuracy is reduced in women. Cardiovascular magnetic resonance (CMR) stress testing can accurately diagnose CAD in women. To date, a direct comparison of CMR to ECG has not been performed. Methods and results We prospectively enrolled 88 consecutive women with chest pain or other symptoms suggestive of CAD. Patients underwent a comprehensive clinical evaluation, exercise ECG, a CMR stress test including perfusion and infarct imaging, and x-ray coronary angiography (CA) within 24 hours. CAD was defined as stenosis ≥70% on quantitative analysis of CA. Exercise ECG, CMR and CA was completed in 68 females (age 66.4 ± 8.8 years, number of CAD risk factors 3.5 ± 1.4). The prevalence of CAD on CA was 29%. The Duke treadmill score (DTS) in the entire group was −3.0 ± 5.4 and was similar in those with and without CAD (−4.5 ± 5.8 and −2.4 ± 5.1; P = 0.12). Sensitivity, specificity and accuracy for CAD diagnosis was higher for CMR compared with exercise ECG (sensitivities 85% and 50%, P = 0.02, specificities 94% and 73%, P = 0.01, and accuracies 91% and 66%, P = 0.0007, respectively). Even after applying the DTS the accuracy of CMR was higher compared to exercise ECG (area under ROC curve 0.94 ± 0.03 vs 0.56 ± 0.07; P = 0.0001). Conclusions In women with intermediate-to-high risk for CAD who are able to exercise and have interpretable resting ECG, CMR stress perfusion imaging has higher accuracy for the detection of relevant obstruction of the epicardial coronaries when directly compared to exercise ECG. PMID:22697372

  7. In African American Type 2 Diabetic Patients, Is Vitamin D Deficiency Associated with Lower Blood Levels of Hydrogen Sulfide and Cyclic Adenosine Monophosphate, and Elevated Oxidative Stress?

    PubMed Central

    Manna, Prasenjit; Micinski, David; Lieblong, Benjamin J.; Kahlon, Gunjan; Morehead, Lester; Hoeldtke, Robert; Bass, Pat Farrington; Levine, Steven N.

    2013-01-01

    Abstract African Americans (AA) have a higher incidence of cardiovascular disease and vitamin D (VD) deficiency compared with Caucasians. Hydrogen sulfide (H2S) is an important signaling molecule. This study examined the hypothesis that blood levels of H2S are lower in AA type 2 diabetic patients (T2D). Fasting blood was obtained from T2D and healthy controls. Results showed a significant decrease in plasma levels of cyclic adenosine monophosphate (cAMP) and H2S in AA T2D but not in Caucasian T2D when compared with those of respective age- and race-matched healthy controls. Plasma VD levels were significantly lower in AA T2D compared with Caucasian T2D. Cell culture studies demonstrate that 1,25(OH)2-VD supplementation significantly increased expression of cystathionine-γ-lyase (CSE), H2S formation, and cAMP secretion, but decreased reactive oxygen species in high glucose-treated U937 monocytes. This suggests that VD supplementation upregulates CSE and H2S formation and decreases oxidative stress, and that VD deficiency may contribute to the malfunctioning of H2S signaling and thus a higher incidence of vascular inflammation in AA. These results lead to the hypothesis that VD supplementation can replenish blood concentrations of H2S and cAMP and lower oxidative stress and cardiovascular disease in AA T2D. Antioxid. Redox Signal. 18, 1154–1158. PMID:22852873

  8. In African American type 2 diabetic patients, is vitamin D deficiency associated with lower blood levels of hydrogen sulfide and cyclic adenosine monophosphate, and elevated oxidative stress?

    PubMed

    Jain, Sushil K; Manna, Prasenjit; Micinski, David; Lieblong, Benjamin J; Kahlon, Gunjan; Morehead, Lester; Hoeldtke, Robert; Bass, Pat Farrington; Levine, Steven N

    2013-04-01

    African Americans (AA) have a higher incidence of cardiovascular disease and vitamin D (VD) deficiency compared with Caucasians. Hydrogen sulfide (H(2)S) is an important signaling molecule. This study examined the hypothesis that blood levels of H(2)S are lower in AA type 2 diabetic patients (T2D). Fasting blood was obtained from T2D and healthy controls. Results showed a significant decrease in plasma levels of cyclic adenosine monophosphate (cAMP) and H(2)S in AA T2D but not in Caucasian T2D when compared with those of respective age- and race-matched healthy controls. Plasma VD levels were significantly lower in AA T2D compared with Caucasian T2D. Cell culture studies demonstrate that 1,25(OH)(2)-VD supplementation significantly increased expression of cystathionine-γ-lyase (CSE), H(2)S formation, and cAMP secretion, but decreased reactive oxygen species in high glucose-treated U937 monocytes. This suggests that VD supplementation upregulates CSE and H(2)S formation and decreases oxidative stress, and that VD deficiency may contribute to the malfunctioning of H(2)S signaling and thus a higher incidence of vascular inflammation in AA. These results lead to the hypothesis that VD supplementation can replenish blood concentrations of H(2)S and cAMP and lower oxidative stress and cardiovascular disease in AA T2D.

  9. Adenosine and Ischemic Preconditioning

    PubMed Central

    Liang, Bruce T.; Swierkosz, Tomasz A.; Herrmann, Howard C.; Kimmel, Stephen; Jacobson, Kenneth A.

    2012-01-01

    Adenosine is released in large amounts during myocardial ischemia and is capable of exerting potent cardioprotective effects in the heart. Although these observations on adenosine have been known for a long time, how adenosine acts to achieve its anti-ischemic effect remains incompletely understood. However, recent advances on the chemistry and pharmacology of adenosine receptor ligands have provided important and novel information on the function of adenosine receptor subtypes in the cardiovascular system. The development of model systems for the cardiac actions of adenosine has yielded important insights into its mechanism of action and have begun to elucidate the sequence of signalling events from receptor activation to the actual exertion of its cardioprotective effect. The present review will focus on the adenosine receptors that mediate the potent anti-ischemic effect of adenosine, new ligands at the receptors, potential molecular signalling mechanisms downstream of the receptor, mediators for cardioprotection, and possible clinical applications in cardiovascular disorders. PMID:10607860

  10. Estimating myocardial perfusion from dynamic contrast-enhanced CMR with a model-independent deconvolution method

    PubMed Central

    Pack, Nathan A; DiBella, Edward VR; Rust, Thomas C; Kadrmas, Dan J; McGann, Christopher J; Butterfield, Regan; Christian, Paul E; Hoffman, John M

    2008-01-01

    Background Model-independent analysis with B-spline regularization has been used to quantify myocardial blood flow (perfusion) in dynamic contrast-enhanced cardiovascular magnetic resonance (CMR) studies. However, the model-independent approach has not been extensively evaluated to determine how the contrast-to-noise ratio between blood and tissue enhancement affects estimates of myocardial perfusion and the degree to which the regularization is dependent on the noise in the measured enhancement data. We investigated these questions with a model-independent analysis method that uses iterative minimization and a temporal smoothness regularizer. Perfusion estimates using this method were compared to results from dynamic 13N-ammonia PET. Results An iterative model-independent analysis method was developed and tested to estimate regional and pixelwise myocardial perfusion in five normal subjects imaged with a saturation recovery turboFLASH sequence at 3 T CMR. Estimates of myocardial perfusion using model-independent analysis are dependent on the choice of the regularization weight parameter, which increases nonlinearly to handle large decreases in the contrast-to-noise ratio of the measured tissue enhancement data. Quantitative perfusion estimates in five subjects imaged with 3 T CMR were 1.1 ± 0.8 ml/min/g at rest and 3.1 ± 1.7 ml/min/g at adenosine stress. The perfusion estimates correlated with dynamic 13N-ammonia PET (y = 0.90x + 0.24, r = 0.85) and were similar to results from other validated CMR studies. Conclusion This work shows that a model-independent analysis method that uses iterative minimization and temporal regularization can be used to quantify myocardial perfusion with dynamic contrast-enhanced perfusion CMR. Results from this method are robust to choices in the regularization weight parameter over relatively large ranges in the contrast-to-noise ratio of the tissue enhancement data. PMID:19014509

  11. Respiratory arrest during dipyridamole stress testing.

    PubMed Central

    Hillis, G. S.; al-Mohammad, A.; Jennings, K. P.

    1997-01-01

    There is an increasing usage of radionuclide scanning to assess myocardial perfusion, with dipyridamole, the most commonly used stress agent. Although this is an effective, and usually very safe, means by which to assess myocardial blood supply, there have been several incidents of acute bronchospasm in asthmatic patients. There have, however, been no previous reports of respiratory arrest occurring in patients with emphysema. This case illustrates the dangers of administering intravenous dipyridamole, or even adenosine, to patients with chronic lung disease. PMID:9196707

  12. Prognostic role of stress/rest myocardial perfusion scintigraphy in patients with cardiac syndrome x.

    PubMed

    Fragasso, Gabriele; Lauretta, Ludovica; Busnardo, Elena; Cera, Michela; Godino, Cosmo; Colombo, Antonio; Calori, Giliola; Todeschini, Paola; Spinapolice, Elena; Cappelletti, Alberto; Gianolli, Luigi; Margonato, Alberto

    2014-05-15

    The prognostic utility of myocardial perfusion scintigraphy (MPS) in patients with angiographically normal coronary arteries has not been evaluated yet. Our aim was to determine the prognostic role of positive MPS in patients with angina, positive exercise test and smooth coronary arteries (syndrome X). A total of 156 patients with angina, positive exercise test, positive MPS and normal coronary arteries and 172 patients with angina and positive exercise test who had negative MPS were selected for study. The primary endpoint was combined all-cause mortality and hospitalizations for cardiac causes. The secondary endpoint was hospitalization for cardiac causes. Kaplan-Meier analysis showed a greater (p=0.001) incidence of the primary endpoint in patients with positive MPS, compared to those with negative MPS. Additionally, Kaplan-Meier analysis for cardiovascular hospitalization showed a significant difference (p=0.003) between the two groups. Cox regression analysis, adjusted for age, sex, BMI and antianginal therapy confirmed a significant risk increase for patients with positive MPS, with a hazard ratio (HR)=3.20 (CI 95%: 1.14-9.02; p=0.028). Cox analysis for cardiovascular hospitalization also showed a significant risk increase for patients with positive MPS (HR=3.19; CI 95%: 1.13-9.00; p=0.03). Finally, Cox analysis showed that patients with positive MPS tend to have a higher risk to remain symptomatic in the follow-up period (HR=1.614; CI 95%: 0.999-2.607; p=0.51). This study shows that inducible myocardial hypoperfusion at MPS in patients with syndrome X could discriminate patients with a more severe prognosis, especially in terms of further hospitalization and symptomatic burden. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  13. Environmental heat stress enhances mental fatigue during sustained attention task performing: evidence from an ASL perfusion study.

    PubMed

    Qian, Shaowen; Li, Min; Li, Guoying; Liu, Kai; Li, Bo; Jiang, Qingjun; Li, Li; Yang, Zhen; Sun, Gang

    2015-03-01

    This study was to investigate the potential enhancing effect of heat stress on mental fatigue progression during sustained attention task using arterial spin labeling (ASL) imaging. Twenty participants underwent two thermal exposures in an environmental chamber: normothermic (NT) condition (25°C, 1h) and hyperthermic (HT) condition (50°C, 1h). After thermal exposure, they performed a twenty-minute psychomotor vigilance test (PVT) in the scanner. Behavioral analysis revealed progressively increasing subjective fatigue ratings and reaction time as PVT progressed. Moreover, heat stress caused worse performance. Perfusion imaging analyses showed significant resting-state cerebral blood flow (CBF) alterations after heat exposure. Specifically, increased CBF mainly gathered in thalamic-brainstem area while decreased CBF predominantly located in fronto-parietal areas, anterior cingulate cortex, posterior cingulate cortex, and medial frontal cortex. More importantly, diverse CBF distributions and trend of changes between both conditions were observed as the fatigue level progressed during subsequent PVT task. Specifically, higher CBF and enhanced rising trend were presented in superior parietal lobe, precuneus, posterior cingulate cortex and anterior cingulate cortex, while lower CBF or inhibited rising trend was found in dorsolateral frontal cortex, medial frontal cortex, inferior parietal lobe and thalamic-brainstem areas. Furthermore, the decrease of post-heat resting-state CBF in fronto-parietal cortex was correlated with subsequent slower reaction time, suggesting prior disturbed resting-state CBF might be indicator of performance potential and fatigue level in following task. These findings may provide proof for such a view: heat stress has a potential fatigue-enhancing effect when individual is performing highly cognition-demanding attention task.

  14. Prediction of 14-year cardiovascular outcomes by dobutamine stress (99m)Tc-tetrofosmin myocardial perfusion SPECT in elderly patients unable to perform exercise testing.

    PubMed

    Roest, Stefan; Boiten, Hendrik J; van Domburg, Ron T; Valkema, Roelf; Schinkel, Arend F L

    2016-07-05

    Dobutamine stress myocardial perfusion imaging (MPI) is a useful alternative for the evaluation of coronary artery disease (CAD) in elderly patients who are unable to perform an exercise stress test. However, data on the long-term prognostic value of stress MPI in elderly patients are lacking. Therefore, this study evaluated the long-term prognostic value of dobutamine stress MPI in elderly patients unable to perform an exercise test. The study population consisted of 247 elderly patients (mean age 71 ± 5 years) who underwent dobutamine stress single-photon emission computed tomography (SPECT) MPI. An abnormal SPECT study was defined as the presence of fixed and/or reversible perfusion defects. A summed stress score (SSS) was obtained to estimate the extent and severity of perfusion defects. End points during follow-up were all-cause mortality, cardiac mortality, and nonfatal myocardial infarction (MI). During a median follow-up of 14 years (range 12-16), 168 (68%) patients died (all-cause mortality), of which 56 (23%) were due to cardiac causes. Nonfatal MI occurred in 19 (8%) patients. Kaplan-Meier survival curves showed that MPI provided optimal risk stratification in patients with normal and abnormal MPI. Multivariable analysis identified an abnormal MPI as a strong significant predictor of all-cause mortality and cardiac events. A multivariable analysis also revealed that a reversible defect and SSS were strong long-term predictors of cardiac mortality and hard cardiac events. Dobutamine stress (99m)Tc-tetrofosmin SPECT provides incremental prognostic information for the prediction of long-term cardiovascular outcomes in elderly patients, unable to perform exercise testing. Dobutamine stress MPI is useful in risk classifying elderly patients.

  15. Usefulness for Predicting Cardiac Events After Orthotopic Liver Transplantation of Myocardial Perfusion Imaging and Dobutamine Stress Echocardiography Preoperatively.

    PubMed

    Snipelisky, David; Ray, Jordan; Vallabhajosyula, Saraschandra; Matcha, Gautam; Squier, Samuel; Lewis, Jacob; Holliday, Rex; Aggarwal, Niti; Askew, J Wells; Shapiro, Brian; Anavekar, Nandan

    2017-04-01

    Patients undergoing orthotopic liver transplantation have high rates of cardiac morbidity and mortality. Although guidelines recommend noninvasive stress testing as part of the preoperative evaluation, little data have evaluated clinical outcomes following orthotopic liver transplantation. A retrospective study at 2 high-volume liver transplantation centers was performed. All patients undergoing noninvasive stress testing (myocardial perfusion imaging [MPI] or dobutamine stress echocardiography [DSE]) over a 5-year period were included. Descriptive analyses, including clinical outcomes and perioperative and postoperative ischemic events, were performed. Comparisons were made between subsets of patients within each stress modality based on abnormal versus normal results. A total of 506 patients were included, of which 343 underwent DSE and 163 MPI. Few patients had abnormal results, with 19 (5.5%) in the DSE group and 13 (8%) in the MPI group. Perioperative and postoperative cardiac complications were low (n = 20, 5.8% and n = 3, 0.9% in DSE group and n = 15, 9.2% and n = 3, 1.8% in MPI group). Comparisons between abnormal versus normal findings showed a trend toward periprocedural cardiac complications in the abnormal DSE group (n = 3, 15.8% vs n = 17, 5.25%; p = 0.09) with no difference in 6-month postprocedural complications (n = 0 vs n = 3, 0.9%; p = 1.0). In the MPI group, a trend toward periprocedural ischemic complications (n = 3, 23.1% vs n = 12, 8%; p = 0.1) was noted with no difference in 6-month postprocedural complications (n = 0 vs n = 3, 2%; p = 1.0). In conclusion, our study found a significantly lower than reported cardiac event rate. In addition, it demonstrated that ischemic cardiac events are uncommon in patients with normal stress testing. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Mobile lipid production after confluence and pH stress in perfused C6 cells.

    PubMed

    Barba, I; Mann, P; Cabañas, M E; Arús, C; Gasparovic, C

    2001-02-01

    NMR-visible mobile lipid (ML) has been observed in aggressive tumors and also in in vitro tumor cell models subjected to growth-inhibiting conditions, such as confluence or low-pH stress. The aim of the present study was to determine if ML production after confluence or low pH stress in a cultured cell model of brain tumor is due to growth arrest alone. ML was observed in situ by one- and two-dimensional (1)H NMR in viable but growth-arrested C6 glioma cells superfused for a period of 48 h after harvesting. The rate of ML production in cells harvested at subconfluence was compared to the rate in cells confluent for one cell cycle and to the rate in subconfluent-harvested cells superfused at low pH (pH 6.1). Confluent-harvested cells produced ML at a markedly greater rate than that of cells harvested at subconfluence, suggesting the involvement of prior cell-cell contact rather than simple growth arrest. A high rate was also observed in subconfluent-harvested cells subjected to low pH, indicating that ML in pH-stressed cells also does not arise from growth arrest alone. Furthermore, two-dimensional data on the degree of unsaturation of the ML fatty acyl chains and one-dimensional (31)P and two-dimensional (1)H NMR data on the GPC content of the cells suggest distinct metabolic pathways for the production of ML following confluence and low-pH stress.

  17. Effect of improving spatial or temporal resolution on image quality and quantitative perfusion assessment with k-t SENSE acceleration in first-pass CMR myocardial perfusion imaging.

    PubMed

    Maredia, Neil; Radjenovic, Aleksandra; Kozerke, Sebastian; Larghat, Abdulghani; Greenwood, John P; Plein, Sven

    2010-12-01

    k-t Sensitivity-encoded (k-t SENSE) acceleration has been used to improve spatial resolution, temporal resolution, and slice coverage in first-pass cardiac magnetic resonance myocardial perfusion imaging. This study compares the effect of investing the speed-up afforded by k-t SENSE acceleration in spatial or temporal resolution. Ten healthy volunteers underwent adenosine stress myocardial perfusion imaging using four saturation-recovery gradient echo perfusion sequences: a reference sequence accelerated by sensitivity encoding (SENSE), and three k-t SENSE-accelerated sequences with higher spatial resolution ("k-t High"), shorter acquisition window ("k-t Fast"), or a shared increase in both parameters ("k-t Hybrid") relative to the reference. Dark-rim artifacts and image quality were analyzed. Semiquantitative myocardial perfusion reserve index (MPRI) and Fermi-derived quantitative MPR were also calculated. The k-t Hybrid sequence produced highest image quality scores at rest (P = 0.015). Rim artifact thickness and extent were lowest using k-t High and k-t Hybrid sequences (P < 0.001). There were no significant differences in MPRI and MPR values derived by each sequence. Maximizing spatial resolution by k-t SENSE acceleration produces the greatest reduction in dark rim artifact. There is good agreement between k-t SENSE and standard acquisition methods for semiquantitative and fully quantitative myocardial perfusion analysis.

  18. Attenuation of exercise vasodilatation by adenosine deaminase in anaesthetized dogs.

    PubMed Central

    Goonewardene, I P; Karim, F

    1991-01-01

    1. In dogs anaesthetized with sodium pentobarbitone and artificially ventilated, the gracilis muscles were vascularly isolated and perfused at a constant flow of 28.4 +/- 4.6 ml min-1 (100 g muscle tissue)-1 (99.8 +/- 4.5% of maximum free flow, means +/- standard error of the mean (S.E.M.), n = 9). 2. Three to five minutes of electrical stimulation of the cut peripheral end of the obturator nerve (4 Hz, 6 V, 0.2 ms) resulted in muscle contraction (0.61 +/- 0.14 kg (100 g)-1 during solvent infusion and 0.56 +/- 0.10 kg (100 g)-1 during intra-arterial adenosine deaminase infusion (50 U min-1) and an immediate decrease in arterial perfusion pressure from 184.5 +/- 8.1 mmHg to 148.2 +/- 5.7 mmHg (18.7 +/- 3.4% decrease) during solvent infusion, and from 193.5 +/- 7.16 to 142.0 +/- 10.2 mmHg (25.4 +/- 6.1% decrease) during adenosine deaminase infusion 10 s after the commencement of muscle stimulation. After about 5 min of muscle contractions, the arterial perfusion pressure decreased to 120.8 +/- 7.8 mmHg (32.9 +/- 5.8% decrease) during solvent infusion, and to 152.8 +/- 11.2 mmHg (20.9 +/- 5.3% decrease) during adenosine deaminase infusion (i.e. 37.9 +/- 6.2% attenuation of the fall in arterial perfusion pressure). The time taken for 90% recovery of the arterial perfusion pressure was 72.1 +/- 10.9 s during solvent infusion, and 51.5 +/- 9.3 s during adenosine deaminase infusion (P less than 0.05). 3. Adenosine (2 x 10(-3) mol l-1) infusion in the resting muscle during solvent infusion (final concentration in arterial blood 1.3 x 10(-4) +/- 6.0 x 10(-5) mol l-1) resulted in a 34.8 +/- 7.2% fall in arterial perfusion pressure but a fall of only 7.2 +/- 1.8% during adenosine deaminase infusion (50 U min-1; P less than 0.05; n = 5) indicating that adenosine deaminase infused at 50 U min-1 was more than adequate to metabolize endogenous adenosine produced during muscle contractions. 4. These data suggest that adenosine contributes about 40% to the sustained

  19. Vasodilator stress perfusion CMR imaging is feasible and prognostic in obese patients.

    PubMed

    Shah, Ravi V; Heydari, Bobak; Coelho-Filho, Otavio; Abbasi, Siddique A; Feng, Jiazhuo H; Neilan, Tomas G; Francis, Sanjeev; Blankstein, Ron; Steigner, Michael; Jerosch-Herold, Michael; Kwong, Raymond Y

    2014-05-01

    This study sought to determine feasibility and prognostic performance of stress cardiac magnetic resonance (CMR) in obese patients (body mass index [BMI] ≥30 kg/m(2)). Current stress imaging methods remain limited in obese patients. Given the impact of the obesity epidemic on cardiovascular disease, alternative methods to effectively risk stratify obese patients are needed. Consecutive patients with a BMI ≥30 kg/m(2) referred for vasodilating stress CMR were followed for major adverse cardiovascular events (MACE), defined as cardiac death or nonfatal myocardial infarction. Univariable and multivariable Cox regressions for MACE were performed to determine the prognostic association of inducible ischemia or late gadolinium enhancement (LGE) by CMR beyond traditional clinical risk indexes. Of 285 obese patients, 272 (95%) completed the CMR protocol, and among these, 255 (94%) achieved diagnostic imaging quality. Mean BMI was 35.4 ± 4.8 kg/m(2), with a maximum weight of 200 kg. Reasons for failure to complete CMR included claustrophobia (n = 4), intolerance to stress agent (n = 4), poor gating (n = 4), and declining participation (n = 1). Sedation was required in 19 patients (7%; 2 patients with intravenous sedation). Sixteen patients required scanning by a 70-cm-bore system (6%). Patients without inducible ischemia or LGE experienced a substantially lower annual rate of MACE (0.3% vs. 6.3% for those with ischemia and 6.7% for those with ischemia and LGE). Median follow-up of the cohort was 2.1 years. In a multivariable stepwise Cox regression including clinical characteristics and CMR indexes, inducible ischemia (hazard ratio 7.5; 95% confidence interval: 2.0 to 28.0; p = 0.002) remained independently associated with MACE. When patients with early coronary revascularization (within 90 days of CMR) were censored on the day of revascularization, both presence of inducible ischemia and ischemia extent per segment maintained a strong association with MACE

  20. A three-dimensional computational fluid dynamics model of shear stress distribution during neotissue growth in a perfusion bioreactor.

    PubMed

    Guyot, Y; Luyten, F P; Schrooten, J; Papantoniou, I; Geris, L

    2015-12-01

    Bone tissue engineering strategies use flow through perfusion bioreactors to apply mechanical stimuli to cells seeded on porous scaffolds. Cells grow on the scaffold surface but also by bridging the scaffold pores leading a fully filled scaffold following the scaffold's geometric characteristics. Current computational fluid dynamic approaches for tissue engineering bioreactor systems have been mostly carried out for empty scaffolds. The effect of 3D cell growth and extracellular matrix formation (termed in this study as neotissue growth), on its surrounding fluid flow field is a challenge yet to be tackled. In this work a combined approach was followed linking curvature driven cell growth to fluid dynamics modeling. The level-set method (LSM) was employed to capture neotissue growth driven by curvature, while the Stokes and Darcy equations, combined in the Brinkman equation, provided information regarding the distribution of the shear stress profile at the neotissue/medium interface and within the neotissue itself during growth. The neotissue was assumed to be micro-porous allowing flow through its structure while at the same time allowing the simulation of complete scaffold filling without numerical convergence issues. The results show a significant difference in the amplitude of shear stress for cells located within the micro-porous neo-tissue or at the neotissue/medium interface, demonstrating the importance of taking along the neotissue in the calculation of the mechanical stimulation of cells during culture.The presented computational framework is used on different scaffold pore geometries demonstrating its potential to be used a design as tool for scaffold architecture taking into account the growing neotissue. Biotechnol. Bioeng. 2015;112: 2591-2600. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  1. Regadenoson in Myocardial Perfusion Study - First Institutional Experiences in Bosnia and Herzegovina

    PubMed Central

    Beslic, Nermina; Milardovic, Renata; Sadija, Amera; Ceric, Sejla; Raic, Zeljka

    2016-01-01

    Introduction: Myocardial perfusion imaging (MPI) is widely used in the evaluation of known and suspected coronary artery disease (CAD). Imaging of heart in stress and rest enables the comparison of myocardial uptake of radiotracer in proportion to the needs and coronary flow, which is used for detection of perfusion defects. Exercise stress and pharmacologic agents are used for the stressing purpose. Novel pharmacologic stressor regadenoson is A2A selective adenosine agonist, which selectively binds to the adenosine receptors in coronary arteries causing coronary dilatation. Materials and methods: We analyzed 50 myocardial perfusion studies performed with regadenoson as a pharmacologic agent that was injected before Tc99m-sestamibi in stress imaging. Stress and rest sets of images were evaluated for relative uptake of Tc99m-sestamibi in order to detect and characterize perfusion defects. After the injection of regadenoson, hemodynamic parameters and potential side-effects were closely monitored. Side-effects were stratified per severity as mild, moderate and severe. Studies were read by nuclear medicine physicians using quantitative perfusion SPECT software. Additional diagnostic information such as wall motion and wall thickening were provided by gating. Results: Thirty-three patients (66%) experienced one or more side-effects upon the administration of regadenoson, most commonly warmth and chest discomfort. In all patients but one (98%), the symptoms were mild, of short duration and self-limiting. Out of all side-effects registered, 44 (96%) were mild, and 2 (4%) were moderate. Two moderate side-effects developed in one patient with a prior history of asthma, and included shortness of breath and cough. Heart rate changed by 16 +- 31 bpm. Highest increase in blood pressure was 30 mm Hg for systolic, and 10 mm Hg for diastolic. One case of significant decrease in blood pressure was noted from the hypertensive basal values, 50 mm for systolic, and 30 mm Hg for

  2. Structural requirements for parathyroid hormone action in mature bone. Effects on release of cyclic adenosine monophosphate and bone gamma-carboxyglutamic acid-containing protein from perfused rat hindquarters.

    PubMed Central

    Calvo, M S; Fryer, M J; Laakso, K J; Nissenson, R A; Price, P A; Murray, T M; Heath, H

    1985-01-01

    To determine the structural requirements for parathyroid hormone (PTH) activity in mature bone, we perfused the surgically isolated hindquarters of adult male rats with either native bovine PTH-(1-84) [bPTH-(1-84)] or the synthetic amino-terminal fragment, bovine PTH-(1-34) [bPTH-(1-34)]. Changes in the release of cyclic AMP (cAMP) and bone Gla protein (BGP) were monitored as evidence of bone-specific response to PTH; tissue specificity of the cAMP response was confirmed through in vitro examination on nonskeletal tissue response to PTH. Biologically active, monoiodinated 125I-bPTH-(1-84) was administered to determine if mature murine bone cleaves native hormone. We found that perfused rat bone continuously releases BGP, and that both bPTH-(1-84) and bPTH-(1-34) acutely suppress this release. In addition, both hormones stimulate cAMP release from perfused rat hindquarters. When examined on a molar basis, the magnitude of the cAMP response was dose-dependent and similar for both hormones, with doses yielding half-maximal cAMP responses. The response for bPTH-(1-34) was 0.5 nmol and for bPTH-(1-84) was 0.7 nmol. Moreover, biologically active 125I-bPTH-(1-84) was not metabolized in our hindquarter perfusion system. These findings indicate that PTH-(1-84) does not require extraskeletal or skeletal cleavage to an amino-terminal fragment in order to stimulate cAMP generation in, or suppress BGP release from, mature rat bone. PMID:3001148

  3. Cardiovascular risk stratification in diabetic patients following stress single-photon emission-computed tomography myocardial perfusion imaging: the impact of achieved exercise level.

    PubMed

    Padala, Santosh K; Ghatak, Abhijit; Padala, Sandeep; Katten, Deborah M; Polk, Donna M; Heller, Gary V

    2014-12-01

    Previous studies have demonstrated that diabetic patients undergoing exercise stress single-photon emission-computed tomography (SPECT) myocardial perfusion imaging (MPI) have significantly lower cardiac events when compared to the diabetic patients undergoing pharmacologic stress SPECT MPI across all perfusion categories. However, there are limited data on the level of exercise achieved during exercise SPECT MPI among diabetic patients and its impact on cardiovascular outcomes. We retrospectively analyzed 14,849 consecutive patients (3,654 diabetics and 11,195 non-diabetics) undergoing exercise stress, combined exercise and pharmacologic stress, and pharmacologic stress SPECT MPI from 1996 to 2005 at a single tertiary care center. Diabetic and non-diabetic patients were categorized into 3 groups based on the metabolic equivalents (METs) achieved: ≥5 METs, <5 METs, and pharmacologic stress groups. All studies were interpreted using the 17-segment ASNC model. The presence, extent, severity of perfusion defects were calculated using the summed stress score (SSS), and patients were classified into normal (SSS < 4), mildly abnormal (SSS 4-8), and moderate-severely abnormal (SSS > 8) categories. Annualized event rates (AER) for the composite end point of non-fatal myocardial infarction and cardiac death were calculated over a mean follow-up period of 2.4 ± 1.4 years with a maximum of 6 years. In moderate-severe perfusion abnormality (SSS > 8) category, diabetic patients who were able to achieve ≥5 METs had significantly lower AER compared to diabetic patients who were unable to achieve ≥5 METs (3% vs 5.5%, P = .04), and non-diabetic patients unable to achieve ≥5 METs (3% vs 4.8%, P < .001). Diabetic patients who achieved a high workload of ≥10 METs had a very low AER of 0.9%. Diabetic patients, who attempted exercise but were unable to achieve ≥5 METs, still had significantly lower AER than diabetics undergoing pharmacologic stress MPI across all perfusion

  4. Cardiac screening with electrocardiography, stress echocardiography, or myocardial perfusion imaging: advice for high-value care from the American College of Physicians.

    PubMed

    Chou, Roger

    2015-03-17

    Cardiac screening in adults with resting or stress electrocardiography, stress echocardiography, or myocardial perfusion imaging can reveal findings associated with increased risk for coronary heart disease events, but inappropriate cardiac testing of low-risk adults has been identified as an important area of overuse by several professional societies. Narrative review based on published systematic reviews; guidelines; and articles on the yield, benefits, and harms of cardiac screening in low-risk adults. Cardiac screening has not been shown to improve patient outcomes. It is also associated with potential harms due to false-positive results because they can lead to subsequent, potentially unnecessary tests and procedures. Cardiac screening is likely to be particularly inefficient in adults at low risk for coronary heart disease given the low prevalence and predictive values of testing in this population and the low likelihood that positive findings will affect treatment decisions. In this patient population, clinicians should focus on strategies for mitigating cardiovascular risk by treating modifiable risk factors (such as smoking, diabetes, hypertension, hyperlipidemia, and overweight) and encouraging healthy levels of exercise. Clinicians should not screen for cardiac disease in asymptomatic, low-risk adults with resting or stress electrocardiography, stress echocardiography, or stress myocardial perfusion imaging.

  5. Dietary effects of adenosine monophosphate to enhance growth, digestibility, innate immune responses and stress resistance of juvenile red sea bream, Pagrus major.

    PubMed

    Hossain, Md Sakhawat; Koshio, Shunsuke; Ishikawa, Manabu; Yokoyama, Saichiro; Sony, Nadia Mahjabin

    2016-09-01

    Our study explored the dietary effects of adenosine monophosphate (AMP) to enhance growth, digestibility, innate immune responses and stress resistance of juvenile red sea bream. A semi-purified basal diet supplemented with 0% (Control), 0.1% (AMP-0.1), 0.2% (AMP-0.2), 0.4% (AMP-0.4) and 0.8% (AMP-0.8) purified AMP to formulate five experimental diets. Each diet was randomly allocated to triplicate groups of fish (mean initial weight 3.4 g) for 56 days. The results indicated that dietary AMP supplements tended to improve growth performances. One of the best ones was found in diet group AMP-0.2, followed by diet groups AMP-0.1, AMP-0.4 and AMP-0.8. The Apparent digestibility coefficients (dry matter, protein and lipid) also improved by AMP supplementation and the significantly highest dry matter digestibility was observed in diet group AMP-0.2. Fish fed diet groups AMP-0.2 and AMP-0.4 had significantly higher peroxidase and bactericidal activities than fish fed the control diet. Nitro-blue-tetrazolium (NBT) activity was found to be significantly (P < 0.05) greater in fish fed diet groups AMP-0.4 and AMP-0.8. Total serum protein, lysozyme activity and agglutination antibody titer were also increased (P > 0.05) by dietary supplementation. In contrast, catalase activity decreased with AMP supplementation. Moreover, the fish fed AMP supplemented diets had better improvement (P < 0.05) in body lipid contents, condition factor, hematocrit content and glutamyl oxaloacetic transaminase (GOT) level than the control group. Supplementation also improved both freshwater and oxidative stress resistances. Interestingly, the fish fed diet groups AMP-0.2 and AMP-0.4 showed the least oxidative stress condition. Finally it is concluded that, dietary AMP supplementation enhanced the growth, digestibility, immune response and stress resistance of red sea bream. The regression analysis revealed that a dietary AMP supplementation between 0.2 and 0.4% supported weight gain and

  6. Altered resting-state functional connectivity in post-traumatic stress disorder: a perfusion MRI study

    NASA Astrophysics Data System (ADS)

    Li, Baojuan; Liu, Jian; Liu, Yang; Lu, Hong-Bing; Yin, Hong

    2013-03-01

    The majority of studies on posttraumatic stress disorder (PTSD) so far have focused on delineating patterns of activations during cognitive processes. Recently, more and more researches have started to investigate functional connectivity in PTSD subjects using BOLD-fMRI. Functional connectivity analysis has been demonstrated as a powerful approach to identify biomarkers of different brain diseases. This study aimed to detect resting-state functional connectivity abnormities in patients with PTSD using arterial spin labeling (ASL) fMRI. As a completely non-invasive technique, ASL allows quantitative estimates of cerebral blood flow (CBF). Compared with BOLD-fMRI, ASL fMRI has many advantages, including less low-frequency signal drifts, superior functional localization, etc. In the current study, ASL images were collected from 10 survivors in mining disaster with recent onset PTSD and 10 survivors without PTSD. Decreased regional CBF in the right middle temporal gyrus, lingual gyrus, and postcentral gyrus was detected in the PTSD patients. Seed-based resting-state functional connectivity analysis was performed using an area in the right middle temporal gyrus as region of interest. Compared with the non-PTSD group, the PTSD subjects demonstrated increased functional connectivity between the right middle temporal gyrus and the right superior temporal gyrus, the left middle temporal gyrus. Meanwhile, decreased functional connectivity between the right middle temporal gyrus and the right postcentral gyrus, the right superior parietal lobule was also found in the PTSD patients. This is the first study which investigated resting-state functional connectivity in PTSD using ASL images. The results may provide new insight into the neural substrates of PTSD.

  7. The effect of pressure or flow stress on right ventricular protein synthesis in the face of constant and restricted coronary perfusion.

    PubMed Central

    Schreiber, S S; Rothschild, M A; Evans, C; Reff, F; Oratz, M

    1975-01-01

    Cardiac stress produced by hypertension or excess volume loading results in different types of hypertrophy. Elevated left ventricular pressure rapidly results in increased myocardial protein synthesis in vivo and in vitro, but such rapid alterations are not consistently seen in volume loading. The difference in response is difficult to clarify since it is not possible to effect alterations in left ventricular pressure or perfusion without profoundly affecting coronary perfusion. The present study describes cardiac protein synthesis in the right ventricle of the young guinea pig heart in vitro by utilizing a perfusion model in which the right ventricle could be stressed by elevations of pressure or volume loading in the presence of constant and restricted coronary perfusion. With coronary flow maintained at 4 ml/min per heart equivalent to 25 ml/min/g dry wt, an increase in right ventricular pressure from normal levels of 3 mm Hg to 11 mm Hg resulted in a 60 percent increase of myocardial incorporation of (14C)lysine into protein. However, with further increases of right ventricular pressure to 22 mm Hg, protein synthesis dropped back to normal levels. The falloff in protein synthesis was not due to decreased contractility, alterations in intracellular lysine pool specific activity, or alterations in distribution of coronary flow. a 60 percent increase in coronary perfusion was again associated with a similar response of protein synthesis to progressive elevations of pressure despite a rise in the ATP levels and a fall in lactate production. Thus, a deficiency of O2 did not entirely explain the decline of protein synthesis with maximal pressures. At all levels of coronary perfusion, volume loading for 3 h did not result in increased protein incorporation of (14C)lysine. The studies support a relationship between ventricular pressure and protein synthesis unrelated to coronary flow per se. A pressure receptor triggering protein synthesis within the ventricular wall

  8. Assessment of the ability of myocardial contrast echocardiography with harmonic power Doppler imaging to identify perfusion abnormalities in patients with Kawasaki disease at rest and during dipyridamole stress.

    PubMed

    Ishii, M; Himeno, W; Sawa, M; Iemura, M; Furui, J; Muta, H; Sugahara, Y; Egami, K; Akagi, T; Ishibashi, M; Kato, H

    2002-01-01

    The aim of our study was to assess the ability of myocardial contrast echocardiography (MCE) with harmonic power Doppler imaging (HPDI) to identify perfusion abnormalities in patients with Kawasaki disease at rest and during pharmacological stress imaging with dipyridamole. Results were compared with those of 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) imaging as the clinical reference standard. MCE with HPDI was performed on 20 patients with a history of Kawasaki disease. Images were obtained at baseline and during dipyridamole infusion (0.56 mg x kg(-1)) in the apical two- and four-chamber views. Myocardial opacification suitable for the analysis was obtained in all patients. Nine patients with stenotic lesions had a reversible defect after dipyridamole infusion detected by both MCE with HPDI and SPECT, and 3 patients with a history of myocardial infarction had a partially or completely irreversible defect detected by both methods. Three patients with coronary aneurysm without stenotic lesion, 4 patients with regressed coronary aneurysm, and 2 patients with normal coronary artery in acute phase also had normal perfusion at rest and after pharmacological stress by both methods. A 96% concordance (kappa = 0.87) was obtained when comparing the respective segmental perfusion scores using the two methods at baseline, and an 86% concordance (kappa = 0.81) was obtained at postdipyridamole infusion. After combining baseline and postdipyridamole images, each segment was labeled as having normal perfusion, irreversible defects, or reversible defects. Using these classifications, concordance for the two methods was 92% (kappa = 0.87). MCE with HPDI is a safe and feasible method by which to detect asymptomatic ischemia due to severe stenotic lesion, and it may be an important addition to the modalities used to identify patients at risk for myocardial infarction as a complication of Kawasaki disease.

  9. Effects of a N(6)-disubstituted adenosine derivative on myocardial metabolism and ischemic stress following coronary occlusion.

    PubMed

    Kahles, H; Junggeburth, J; Lick, T; Schäfer, W; Kochsiek, K

    1987-10-01

    The effect of N(6)-phenyl-N(6)-allyladenosine (PAA, BM 11.189) on myocardial ischemic stress was evaluated in six open-chest mongrel dogs during repeated coronary occlusions of 3 min. Whereas there was not significant change in hemodynamic parameters before and during coronary occlusions after treatment, PAA reduced significantly epicardial ST-segment elevations (-34%) during ischemia and myocardial release of lactate (-43%), phosphate (-44%), and potassium (-48%) in the early reperfusion period. PAA lowered significantly arterial non esterified fatty acids and converted oxidative myocardial metabolism from lipid to predominantly carbohydrate utilization, reflected by a shift of cardiac respiratory quotient from 0.81 to 1.01. The beneficial effects of PAA on myocardial ischemic injury could be explained by an improved economy of oxidative myocardial energy supply in the jeopardized border zone of the ischemic myocardium.

  10. Regadenoson-stress myocardial CT perfusion and single-photon emission CT: rationale, design, and acquisition methods of a prospective, multicenter, multivendor comparison.

    PubMed

    Cury, Ricardo C; Kitt, Therese M; Feaheny, Kathleen; Akin, Jamie; George, Richard T

    2014-01-01

    Pharmacologic stress myocardial CT perfusion (CTP) has been reported to be a viable imaging modality for detection of myocardial ischemia compared with single-photon emission CT (SPECT) in several single-center studies. However, regadenoson-stress CTP has not previously been compared with SPECT in a multicenter, multivendor study. The rationale and design of a phase 2, randomized, cross-over study of regadenoson-stress myocardial perfusion imaging by CTP compared with SPECT are described herein. The study will be conducted at approximately 25 sites by using 6 different CT scanner models, including 64-, 128-, 256-, and 320-slice systems. Subjects with known/suspected coronary artery disease will be randomly assigned to 1 of 2 imaging procedure sequences; rest and regadenoson-stress SPECT on day 1, then regadenoson-stress CTP and rest CTP/coronary CT angiography (same acquisition) on day 2; or regadenoson-stress CTP and rest CTP/CT angiography on day 1, then rest and regadenoson-stress SPECT on day 2. The prespecified primary analysis examines the agreement rate between CTP and SPECT for detecting or excluding ischemia (≥2 or 0-1 reversible defects, respectively), as assessed by 3 independent blinded readers for each modality. Non-inferiority will be indicated if the lower boundary of the 95% CI for the agreement rate is within 0.15 of 0.78 (the observed agreement rate in the regadenoson pivotal trials). The protocol described herein will support the first evaluation of regadenoson-stress CTP by using multiple scanner types compared with SPECT.

  11. The Effect of Heart Rate on Exposure Window and Best Phase for Stress Perfusion Computed Tomography: Lessons From the CORE320 Study.

    PubMed

    Steveson, Chloe; Schuijf, Joanne D; Vavere, Andrea L; Mather, Richard T; Caton, Teresa; Mehra, Vishal; Betoko, Aisha; Cox, Christopher; Lima, Joao Ac; George, Richard T

    The aim of this study is to evaluate the effect of heart rate on exposure window, best phase, and image quality for stress computed tomography perfusion (CTP) in the CORE320 study. The CTP data sets were analyzed to determine the best phase for perfusion analysis. A predefined exposure window covering 75% to 95% of the R-R cycle was used. Of the 368 patients included in the analysis, 93% received oral β blockade before the rest scan. The median heart rate during the stress acquisition was 69 bpm (interquartile range [IQR], 60-77). The median best phase was 81% (IQR, 76-90), and length of exposure window was 22% (IQR, 19-24). The best phase was significantly later in the cardiac cycle with higher heart rates (P < 0.001), and higher heart rates resulted in a small, but higher number of poor quality scans (6%, P < 0.001). The median effective dose of the stress scan was 5.3 mSv (IQR, 3.8-6.1). Stress myocardial CTP imaging can be performed using prospective electrocardiography triggering, an exposure window of 75% to 95%, and β-blockade resulting in good or excellent image quality in the majority (80%) of patients while maintaining a low effective radiation dose.

  12. Clinical characteristics of silent myocardial ischemia diagnosed with adenosine stress 99mTc-tetrofosmin myocardial scintigraphy in Japanese patients with acute cerebral infarction.

    PubMed

    Nomura, Tetsuya; Kusaba, Tetsuro; Kodama, Naotoshi; Terada, Kensuke; Urakabe, Yota; Nishikawa, Susumu; Keira, Natsuya; Matsubara, Hiroaki; Tatsumi, Tetsuya

    2013-01-01

    It is well known that silent myocardial ischemia (SMI) often complicates patients with cerebral infarction and that stroke patients often die of ischemic heart disease. Therefore, it is considered important to treat myocardial ischemia in stroke patients. This study investigated SMI complicating Japanese patients with fresh stroke, using (99m)Tc-tetrofosmin myocardial scintigraphy with pharmacologic stress testing to elucidate their clinical manifestations. This study included 41 patients (26 men, mean age 76.0 ± 10.7 years) with acute cerebral infarction and no history of coronary artery disease. All patients underwent (99m)Tc-tetrofosmin myocardial scintigraphy with intravenous administration of adenosine to diagnose SMI. Of the 41 patients, myocardial ischemia was confirmed in 17 patients (41.5%). Atherosclerotic etiology was the major cause of stroke in the ischemia(+) group and embolic origin was the major cause in the ischemia(-) group. Patients with myocardial ischemia had a higher incidence of diabetes mellitus (52.9 vs 20.8%; P = 0.0323) and more than two conventional cardiovascular risk factors (64.7 vs 25.0%; P = 0.0110) compared with the nonischemic patients. Infarction subtype of atherosclerotic origin was an independent positive predictor of asymptomatic myocardial ischemia in patients with stroke. These findings indicate that the prevalence of asymptomatic myocardial ischemia is relatively high, especially in patients with stroke of atherosclerotic origin. Therefore, it is beneficial for us to narrow the target population who are at the highest risk when screening for SMI in Japanese patients with acute cerebral infarction.

  13. Stress-only myocardial perfusion scintigraphy: a prospective study on the accuracy and observer agreement with quantitative coronary angiography as the gold standard.

    PubMed

    Ejlersen, June A; May, Ole; Mortensen, Jesper; Nielsen, Gitte L; Lauridsen, Jeppe F; Allan, Johansen

    2017-09-06

    Patients with normal stress perfusion have an excellent prognosis. Prospective studies on the diagnostic accuracy of stress-only scans with contemporary, independent examinations as gold standards are lacking. A total of 109 patients with typical angina and no previous coronary artery disease underwent a 2-day stress (exercise)/rest, gated, and attenuation-corrected (AC), 99m-technetium-sestamibi perfusion study, followed by invasive coronary angiography. The stress datasets were evaluated twice by four physicians with two different training levels (expert and novice): familiar and unfamiliar with AC. The two experts also made a consensus reading of the integrated stress-rest datasets. The consensus reading and quantitative data from the invasive coronary angiography were applied as reference methods. The sensitivity/specificity were 0.92-1.00/0.73-0.90 (reference: expert consensus reading), 0.93-0.96/0.63-0.82 (reference: ≥1 stenosis>70%), and 0.75-0.88/0.70-0.88 (reference: ≥1 stenosis>50%). The four readers showed a high and fairly equal sensitivity independent of their familiarity with AC. The expert familiar with AC had the highest specificity independent of the reference method. The intraobserver and interobserver agreements on the stress-only readings were good (readers without AC experience) to excellent (readers with AC experience). AC stress-only images yielded a high sensitivity independent of the training level and experience with AC of the nuclear physician, whereas the specificity correlated positively with both. Interobserver and intraobserver agreements tended to be the best for physicians with AC experience.

  14. Effect of spinal cord stimulation on myocardial perfusion reserve in patients with refractory angina pectoris.

    PubMed

    Saraste, Antti; Ukkonen, Heikki; Varis, Antti; Vasankari, Tuija; Tunturi, Satu; Taittonen, Markku; Rautakorpi, Pirkka; Luotolahti, Matti; Airaksinen, K E Juhani; Knuuti, Juhani

    2015-04-01

    Epidural spinal cord stimulation (SCS) provides symptom relief in refractory angina pectoris, but its mechanism of action remains incompletely understood. We studied effects of short-term SCS therapy on myocardial ischaemia tolerance, myocardial perfusion reserve (MPR), and endothelium-mediated vasodilatation induced by cold pressor test (CPT) in patients with refractory angina pectoris. We prospectively recruited 18 patients with refractory angina pectoris and studied them after implantation of SCS device at baseline before starting the therapy and after 3 weeks of continuous SCS therapy. Myocardial ischaemia was evaluated by dobutamine stress echocardiography. Global and regional myocardial blood flow (MBF) were measured using positron emission tomography and (15)O-water at rest, during adenosine stress, and in response to CPT. Systemic haemodynamics were comparable before and after 3 weeks of SCS at rest, during adenosine stress and during CPT. Appearance of angina pectoris induced by dobutamine stress was delayed after SCS therapy. Global MPR increased (P = 0.02) from 1.7 ± 0.6 at baseline to 2.0 ± 0.6 after 3-week SCS therapy. This was associated with a significant reduction in global MBF at rest and increase in MBF induced by adenosine in the ischaemic regions. Global MBF response to CPT was improved after SCS (0.27 ± 0.20 vs. 0.40 ± 0.15, P = 0.03). Short-term SCS therapy improved myocardial ischaemia tolerance, absolute MPR, and endothelium-mediated vasomotor function in refractory angina pectoris, indicating that this therapy can alleviate myocardial perfusion abnormalities in advanced CAD. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  15. Oxidative Stress Parameters and Erythrocyte Membrane Adenosine Triphosphatase Activities in Streptozotocin-induced Diabetic Rats Administered Aqueous Preparation of Kalanchoe Pinnata Leaves

    PubMed Central

    Menon, Nikhil; Sparks, Jean; Omoruyi, Felix O.

    2016-01-01

    Background: Diabetes mellitus is a chronic metabolic disease that according to the World Health Organization affects more than 382 million people. The rise in diabetes mellitus coupled with the lack of an effective treatment has led many to investigate medicinal plants to identify a viable alternative. Objective: To evaluate red blood cell (RBC) membrane adenosine triphosphatase (ATPase) activities and antioxidant levels in streptozotocin-induced diabetic rats administered aqueous preparation of Kalanchoe pinnata leaves. Materials and Methods: Diabetes mellitus was induced in rats by a single administration of streptozotocin (60 mg/kg). Diabetic rats were then treated with aqueous K. pinnata preparation (three mature leaves ~ 9.96 g/70 kg body weight or about 0.14 g/kg body weight/day) for 30 days. Serum glucose, RBC membrane ATPase activities, and antioxidant levels were determined. Results: We noted weight loss and reduced food consumption in the treated diabetic group. Serum glucose levels were reduced in the treated diabetic group compared to the other groups. Superoxide dismutase activity and glutathione levels were not significantly elevated in the treated group compared to the diabetic group. However, serum catalase activity was significantly (P < 0.05) increased in the treated diabetic group compared to the other groups. Serum thiobarbituric acid reactive substances were not significantly altered among the groups. There was a significant (P < 0.05) increase in Mg2+ ATPase activity and a nonsignificant increase in Na+/K+ ATPase activity in the RBC membrane of the treated diabetic group compared to the diabetic group. Conclusion: The consumption of aqueous preparation of K. pinnata may accrue benefits in the management of diabetes by lowering oxidative stress often associated with the disease and improving the availability of cellular magnesium through an increase in the magnesium ATPase pump in the RBC membrane for increased cellular metabolism of glucose

  16. Oxidative Stress Parameters and Erythrocyte Membrane Adenosine Triphosphatase Activities in Streptozotocin-induced Diabetic Rats Administered Aqueous Preparation of Kalanchoe Pinnata Leaves.

    PubMed

    Menon, Nikhil; Sparks, Jean; Omoruyi, Felix O

    2016-01-01

    Diabetes mellitus is a chronic metabolic disease that according to the World Health Organization affects more than 382 million people. The rise in diabetes mellitus coupled with the lack of an effective treatment has led many to investigate medicinal plants to identify a viable alternative. To evaluate red blood cell (RBC) membrane adenosine triphosphatase (ATPase) activities and antioxidant levels in streptozotocin-induced diabetic rats administered aqueous preparation of Kalanchoe pinnata leaves. Diabetes mellitus was induced in rats by a single administration of streptozotocin (60 mg/kg). Diabetic rats were then treated with aqueous K. pinnata preparation (three mature leaves ~ 9.96 g/70 kg body weight or about 0.14 g/kg body weight/day) for 30 days. Serum glucose, RBC membrane ATPase activities, and antioxidant levels were determined. We noted weight loss and reduced food consumption in the treated diabetic group. Serum glucose levels were reduced in the treated diabetic group compared to the other groups. Superoxide dismutase activity and glutathione levels were not significantly elevated in the treated group compared to the diabetic group. However, serum catalase activity was significantly (P < 0.05) increased in the treated diabetic group compared to the other groups. Serum thiobarbituric acid reactive substances were not significantly altered among the groups. There was a significant (P < 0.05) increase in Mg(2+) ATPase activity and a nonsignificant increase in Na(+)/K(+) ATPase activity in the RBC membrane of the treated diabetic group compared to the diabetic group. The consumption of aqueous preparation of K. pinnata may accrue benefits in the management of diabetes by lowering oxidative stress often associated with the disease and improving the availability of cellular magnesium through an increase in the magnesium ATPase pump in the RBC membrane for increased cellular metabolism of glucose through the glycolytic pathway. We noted weight loss and

  17. Role of perfusion medium, oxygen and rheology for endoplasmic reticulum stress-induced cell death after hypothermic machine preservation of the liver.

    PubMed

    Manekeller, Steffen; Schuppius, Andrea; Stegemann, Judith; Hirner, Andreas; Minor, Thomas

    2008-02-01

    Recently, the endoplasmic reticulum (ER) has been disclosed as subcellular target reactive to ischaemia/reperfusion and possibly influenced by hypothermic machine preservation. Here, the respective role of perfusate, perfusion itself, and the effect of continuous oxygenation to trigger ER-stress in the graft should be investigated. Livers were retrieved 30 min after cardiac arrest of male Wistar rats and preserved by cold storage (CS) in histidine-tryptophan-ketoglutarate (HTK) for 18 h at 4 degrees C. Other organs were subjected to aerobic conditions either by oxygenated machine perfusion with HTK (MP-HTK) or Belzer solution (MP-Belzer) at 4 degrees C or by venous insufflation of gaseous oxygen during cold storage (VSOP). Viability of livers was evaluated upon reperfusion in vitro according to previously validated techniques for 120 min at 37 degrees C. Oxygenation during preservation (MP-HTK, MP-Belzer or VSOP) concordantly improved functional recovery (bile flow, ammonia clearance), reduced parenchymal enzyme leakage and histological signs of necrosis and significantly attenuated mitochondrial induction of apoptosis (cleavage of caspase 9) compared to CS. However, MP with either medium produced about 500% elevated protein expression of CHOP/GADD153, suggesting pro-apoptotic ER-stress responses, paralleled by a significant elevation of caspase-12 enzyme activity compared to CS or VSOP. Although MP also promoted a slight (20%) induction of the cytoprotective ER-protein Bax inhibitor protein (BI-1), prevailing of proapoptotic reactions was seen by increased cleavage of caspase-3 and poly (ADP-Ribase)-polymerase (PARP) in both MP-groups. Endoplasmic stress activation is conjectured a specific side effect of long-term machine preservation irrespective of the medium, actually promoting cellular apoptosis via activation of caspase-12. The simple insufflation of gaseous O2 may be considered a feasible alternative, apparently indifferent to the endoplasmic reticulum.

  18. Comparative efficiency of exercise stress testing with and without stress-only myocardial perfusion imaging in patients with low-risk chest pain.

    PubMed

    Amirian, Jossef; Javdan, Omid; Misher, Jason; Diamond, Joseph; Raio, Christopher; Rudolph, Gary; Druz, Regina S

    2017-01-12

    To compare major adverse cardiac event (MACE), downstream resource utilization, and direct cost of care for low-risk chest pain patients observed in the clinical decision unit (CDU) with exercise treadmill testing (ETT) and with stress-only myocardial perfusion imaging (sMPI). CDUs are poised to increase efficiency and resource utilization. However, the optimal testing strategy that would assure favorable outcomes while decreasing cost is not defined. 1016 subjects from 2 locations were propensity score-matched (PSM) by age, gender, pre-test likelihood, Duke treadmill score, and test results. Outcomes were length of stay >24 hours, MACE (acute coronary syndrome, revascularization, cardiac death), downstream resource use (admission for chest pain, repeat testing, angiography), and mean direct cost per patient. PSM yielded 680 patients (340 matches). 98% of all tests were normal. 96.6% of patients were discharged from the CDU within 24 hours but twice as many exceeded 24 hours in the sMPI group. There were no cardiac deaths. MACE rate was 1.47% at 72 hours and 1% at 1 year. Downstream resource use was 4.82% at 72 hours, and 7.69% at 1 year. The sMPI group was event-free longer than the ETT group reflecting less repeat testing. The mean direct cost was 30% higher for sMPI ($3168.70) vs. ETT ($2226.96). Low-risk chest pain patients in the observation unit had low MACE rate, not different for ETT vs. sMPI. The majority of ETT and sMPI tests were normal. The sMPI reduced additional testing, but resulted in greater expense and longer stay.

  19. Dose reduction in dynamic CT stress myocardial perfusion imaging: comparison of 80-kV/370-mAs and 100-kV/300-mAs protocols.

    PubMed

    Fujita, Makiko; Kitagawa, Kakuya; Ito, Tatsuro; Shiraishi, Yasuyuki; Kurobe, Yusuke; Nagata, Motonori; Ishida, Masaki; Sakuma, Hajime

    2014-03-01

    To determine the effect of reduced 80-kV tube voltage with increased 370-mAs tube current on radiation dose, image quality and estimated myocardial blood flow (MBF) of dynamic CT stress myocardial perfusion imaging (CTP) in patients with a normal body mass index (BMI) compared with a 100-kV and 300-mAs protocol. Thirty patients with a normal BMI (<25 kg/m(2)) with known or suspected coronary artery disease underwent adenosine-stress dual-source dynamic CTP. Patients were randomised to 80-kV/370-mAs (n = 15) or 100-kV/300-mAs (n = 15) imaging. Maximal enhancement and noise of the left ventricular (LV) cavity, contrast-to-noise ratio (CNR) and MBF of the two groups were compared. Imaging with 80-kV/370-mAs instead of 100-kV/300-mAs was associated with 40% lower radiation dose (mean dose-length product, 359 ± 66 vs 628 ± 112 mGy[Symbol: see text]cm; P < 0.001 ) with no significant difference in CNR (34.5 ± 13.4 vs 33.5 ± 10.4; P = 0.81) or MBF in non-ischaemic myocardium (0.95 ± 0.20 vs 0.99 ± 0.25 ml/min/g; P = 0.66). Studies obtained using 80-kV/370-mAs were associated with 30.9% higher maximal enhancement (804 ± 204 vs 614 ± 115 HU; P < 0.005), and 31.2% greater noise (22.7 ± 3.5 vs 17.4 ± 2.6; P < 0.001). Dynamic CTP using 80-kV/370-mA instead of 100-kV/300-mAs allowed 40% dose reduction without compromising image quality or MBF. Tube voltage of 80-kV should be considered for individuals with a normal BMI. • CT stress perfusion imaging (CTP) is increasingly used to assess myocardial function. • Dynamic CTP is feasible at 80-kV in patients with normal BMI. • An 80-kV/370-mAs protocol allows 40% dose reduction compared with 100-kV/300-mAs. • Contrast-to-noise ratio and myocardial blood flow of the two protocols were comparable.

  20. A relative quantitative assessment of myocardial perfusion by first-pass technique: animal study

    NASA Astrophysics Data System (ADS)

    Chen, Jun; Zhang, Zhang; Yu, Xuefang; Zhou, Kenneth J.

    2015-03-01

    The purpose of this study is to quantitatively assess the myocardial perfusion by first-pass technique in swine model. Numerous techniques based on the analysis of Computed Tomography (CT) Hounsfield Unit (HU) density have emerged. Although these methods proposed to be able to assess haemodynamically significant coronary artery stenosis, their limitations are noticed. There are still needs to develop some new techniques. Experiments were performed upon five (5) closed-chest swine. Balloon catheters were placed into the coronary artery to simulate different degrees of luminal stenosis. Myocardial Blood Flow (MBF) was measured using color microsphere technique. Fractional Flow Reserve (FFR) was measured using pressure wire. CT examinations were performed twice during First-pass phase under adenosine-stress condition. CT HU Density (HUDCT) and CT HU Density Ratio (HUDRCT) were calculated using the acquired CT images. Our study presents that HUDRCT shows a good (y=0.07245+0.09963x, r2=0.898) correlation with MBF and FFR. In receiver operating characteristic (ROC) curve analyses, HUDRCT provides excellent diagnostic performance for the detection of significant ischemia during adenosine-stress as defined by FFR indicated by the value of Area Under the Curve (AUC) of 0.927. HUDRCT has the potential to be developed as a useful indicator of quantitative assessment of myocardial perfusion.

  1. Nitric oxide generation by endothelial cells exposed to shear stress in glass tubes perfused with red blood cell suspensions: role of aggregation.

    PubMed

    Yalcin, Ozlem; Ulker, Pinar; Yavuzer, Ugur; Meiselman, Herbert J; Baskurt, Oguz K

    2008-05-01

    Endothelial function is modulated by wall shear stress acting on the vessel wall, which is determined by fluid velocity and the local viscosity near the vessel wall. Red blood cell (RBC) aggregation may affect the local viscosity by favoring axial migration. The aim of this study was to investigate the role of RBC aggregation, with or without altered plasma viscosity, in the mechanically induced nitric oxide (NO)-related mechanisms of endothelial cells. Human umbilical vein endothelial cells (HUVEC) were cultured on the inner surface of cylindrical glass capillaries that were perfused with RBC suspensions having normal and increased aggregation at a nominal shear stress of 15 dyn/cm(2). RBC aggregation was enhanced by two different approaches: 1) poloxamer-coated RBC suspended in normal, autologous plasma, resulting in enhanced aggregation but unchanged plasma viscosity and 2) normal RBC suspended in autologous plasma containing 0.5% dextran (mol mass 500 kDa), with a similar level of RBC aggregation but higher plasma viscosity. Compared with normal cells in unmodified plasma, perfusion with suspensions of poloxamer-coated RBC in normal plasma resulted in decreased levels of NO metabolites and serine 1177 phosphorylation of endothelial nitric oxide synthase (eNOS). Perfusion with normal RBC in plasma containing dextran resulted in a NO level that remained elevated, whereas only a modest decrease of phosphorylated eNOS level was observed. The results of this study suggest that increases of RBC aggregation tendency affect endothelial cell functions by altering local blood composition, especially if the alterations of RBC aggregation are due to modified cellular properties and not to plasma composition changes.

  2. The relationship between ischemia-induced left ventricular dysfunction, coronary flow reserve, and coronary steal on regadenoson stress-gated 82Rb PET myocardial perfusion imaging

    PubMed Central

    Van Tosh, Andrew; Votaw, John R.; Reichek, Nathaniel; Palestro, Christopher J.; Nichols, Kenneth J.

    2014-01-01

    Background Gated rubidium-82 (82Rb) positron emission tomography (PET) imaging studies are acquired both at rest and during pharmacologic stress. Stress-induced ischemic left ventricular dysfunction (LVD) can produce a significant decrease in left ventricular ejection fraction (LVEF) from rest to stress. We determined the prevalence on PET of stress LVD with reduced ejection fraction (EF) and its association with absolute global and regional coronary flow reserve (CFR), and with relative perfusion defect summed difference score (SDS). Methods and Results We studied 205 patients with known or suspected coronary disease (120 M, 75 F, age 69 ± 13 years) who had clinically indicated rest/regadenoson stress 82Rb PET/CT studies. Data were acquired in dynamic gated list mode. Global and 17-segment regional CFR values were computed from first-pass flow data using a 2-compartment model and factor analysis applied to auto-generated time-activity curves. Rest and stress LVEF and SDS were quantified from gated equilibrium myocardial perfusion tomograms using Emory Cardiac Toolbox software. LVD was defined as a change in LVEF of ≤−5% from rest to stress. A subgroup of 109 patients also had coronary angiography. Stress LVD developed in 32 patients (16%), with mean EF change of −10 ± 5%, vs +6 ± 7% for patients without LVD (P < .0001). EF was similar at rest in patients with and without stress LVD (57 ± 18% vs 56 ± 16%, P = .63), but lower during stress for patients with LVD (47 ± 20% vs 61 ± 16%, P = .0001). CFR was significantly lower in patients with LVD (1.61 ± 0.67 vs 2.21 ± 1.03, Wilcoxon P = .002), and correlated significantly with change in EF (r = 0.35, P < .0001), but not with SDS (r = −0.13, P = .07). The single variable most strongly associated with high risk of CAD (i.e., left main stenosis ≥50%, LAD % stenosis ≥70%, and/or 3-vessel disease) was stress EF (χ2 = 17.3, P < .0001). There was a higher prevalence of patients with territorial CFR

  3. The predictive value of chronic kidney disease for assessing cardiovascular events under consideration of pretest probability for coronary artery disease in patients who underwent stress myocardial perfusion imaging.

    PubMed

    Furuhashi, Tatsuhiko; Moroi, Masao; Joki, Nobuhiko; Hase, Hiroki; Masai, Hirofumi; Kunimasa, Taeko; Fukuda, Hiroshi; Sugi, Kaoru

    2013-02-01

    Pretest probability of coronary artery disease (CAD) facilitates diagnosis and risk stratification of CAD. Stress myocardial perfusion imaging (MPI) and chronic kidney disease (CKD) are established major predictors of cardiovascular events. However, the role of CKD to assess pretest probability of CAD has been unclear. This study evaluates the role of CKD to assess the predictive value of cardiovascular events under consideration of pretest probability in patients who underwent stress MPI. Patients with no history of CAD underwent stress MPI (n = 310; male = 166; age = 70; CKD = 111; low/intermediate/high pretest probability = 17/194/99) and were followed for 24 months. Cardiovascular events included cardiac death and nonfatal acute coronary syndrome. Cardiovascular events occurred in 15 of the 310 patients (4.8 %), but not in those with low pretest probability which included 2 CKD patients. In patients with intermediate to high pretest probability (n = 293), multivariate Cox regression analysis identified only CKD [hazard ratio (HR) = 4.88; P = 0.022) and summed stress score of stress MPI (HR = 1.50; P < 0.001) as independent and significant predictors of cardiovascular events. Cardiovascular events were not observed in patients with low pretest probability. In patients with intermediate to high pretest probability, CKD and stress MPI are independent predictors of cardiovascular events considering the pretest probability of CAD in patients with no history of CAD. In assessing pretest probability of CAD, CKD might be an important factor for assessing future cardiovascular prognosis.

  4. Simultaneous assessment of left ventricular wall motion and myocardial perfusion with technetium-99m-methoxy isobutyl isonitrile at stress and rest in patients with angina: Comparison with thallium-201 SPECT

    SciTech Connect

    Villanueva-Meyer, J.; Mena, I.; Narahara, K.A. )

    1990-04-01

    The newly developed technetium-99m ({sup 99m}Tc) isonitriles can be used for the simultaneous evaluation of ventricular function and myocardial perfusion. We compared technetium-99m hexakis-2-methoxy isobutyl isonitrile (({sup 99m}Tc) MIBI) derived first-pass left ventricular wall motion at stress and rest with simultaneous myocardial perfusion defined by ({sup 99m}Tc)MIBI SPECT. These results were then compared with {sup 201}TI SPECT. We examined 28 patients with coronary artery disease; 25 had a previous myocardial infarction. We found concordance between segmental wall motion and myocardial perfusion imaging in defining normal, ischemic, and infarcted myocardium in 68% and 69% of segments using ({sup 99m}Tc)MIBI and {sup 201}TI respectively. The best agreement between wall motion and myocardial perfusion was seen in the inferior wall, while most of the discrepancies were found at the apex. Agreement between ({sup 99m}Tc)MIBI and {sup 201}TI SPECT myocardial perfusion was seen in 93% of segments. Technetium-99m-MIBI appears to be an ideal radiopharmaceutical for the simultaneous evaluation of ventricular function and myocardial perfusion during stress and at rest.

  5. Does risk for major adverse cardiac events in patients undergoing vasodilator stress with adjunctive exercise differ from patients undergoing either standard exercise or vasodilator stress with myocardial perfusion imaging?

    PubMed

    Nair, Sanjeev U; Ahlberg, Alan W; Katten, Deborah M; Heller, Gary V

    2015-02-01

    In patients with functional limitations, the use of adjunctive exercise with vasodilator stress has advantages over vasodilator stress alone in single photon emission computed tomography myocardial perfusion imaging (MPI) for technical reasons and with regards to more effective cardiac risk stratification. Whether patients who undergo vasodilator with adjunctive exercise stress MPI possess clinical characteristics and cardiac risk that differs from those who undergo standard exercise or vasodilator stress MPI is unknown. Prospectively collected data on 19,367 consecutive patients referred for stress MPI to a tertiary care center (9,331 [48%] underwent exercise-only, 3,793 [20%] underwent vasodilator plus exercise, and 6,243 [32%] underwent vasodilator-only) were analyzed. Perfusion data were scored using the ASNC 17-segment with a summed stress score (SSS) < 4 = normal, 4-8 = mildly abnormal, and > 8 = moderate to severely abnormal. Patients were followed a mean of 1.96 ± 0.95 years. Demographics, clinical characteristics, and the occurrence of major adverse cardiac events (cardiac death or nonfatal myocardial infarction) were compared between the three stress modality groups. Comparison of demographics and clinical characteristics revealed significant differences in gender, age, cardiac risk factors, and stress MPI between the three stress modality groups (P < .001). In follow-up, cardiac event-free survival of patients in the vasodilator plus exercise stress group was significantly higher than those in the vasodilator-only group but lower than those in the exercise-only group (P < .001). Annualized cardiac event rates of patients in the vasodilator plus exercise stress group were significantly lower than those in the vasodilator-only group for all three categories of the SSS (P < .001). After multivariable adjustment, with exercise-only as reference category, vasodilator plus exercise and vasodilator-only stress emerged as independent predictors (more likely

  6. Adenosine induces G2/M cell-cycle arrest by inhibiting cell mitosis progression.

    PubMed

    Jia, Kun-Zhi; Tang, Bo; Yu, Lu; Cheng, Wei; Zhang, Rong; Zhang, Jian-Fa; Hua, Zi-Chun

    2009-12-16

    Cellular adenosine accumulates under stress conditions. Few papers on adenosine are concerned with its function in the cell cycle. The cell cycle is the essential mechanism by which all living things reproduce and the target machinery when cells encounter stresses, so it is necessary to examine the relationship between adenosine and the cell cycle. In the present study, adenosine was found to induce G-2/M cell-cycle arrest. Furthermore, adenosine was found to modulate the expression of some important proteins in the cell cycle, such as cyclin B and p21, and to inhibit the transition of metaphase to anaphase in mitosis.

  7. Adenosine triphosphate in milk.

    PubMed

    Zulak, I M; Patton, S; Hammerstedt, R H

    1976-08-01

    Freshly secreted goat's milk contains a number of viable metabolic pathways including those for the synthesis of triglycerides and phospholipids. Toward understanding this matter, amounts of the fundamentally important energy substrate, adenosine triphosphate, in goat's milk were evaluated. Milk left in the goat udder overnight had less adenosine triphosphate (12.4 muM) than fresh secreted milk (37.6 muM). In similar experiments the skim milk derived from whole accumulating in the udder overnight was lower in adenosine triphosphate (14.2 muM) than skim milk from freshly secreted milk (26.0 muM). To determine changes in quantities of adenosine triphosphate after milking, milks were divided into two parts, one containing only milk and the other milk plus 2,4-dinitrophenol and sodium arsenate, inhibitors of oxidative and substrate level phosphorylation. Adenosine triphosphate in milk decreased during 4-h in vitro incubations, and the rate of decline was markedly greater in the presence of the inhibitors. Thus, freshly secreted goat's milk contains significant amounts of adenosine triphosphate, and more can be synthesized therein after removal from the udder. In limited samples human and bovine milks contained much lower concentrations of the compound than those in goat's milk.

  8. The role of curcumin as an inhibitor of oxidative stress caused by ischaemia re-perfusion injury in tetralogy of Fallot patients undergoing corrective surgery.

    PubMed

    Sukardi, Rubiana; Sastroasmoro, Sudigdo; Siregar, Nurjati C; Djer, Mulyadi M; Suyatna, Fransciscus D; Sadikin, Mohammad; Ibrahim, Nurhadi; Rahayuningsih, Sri E; Witarto, Arief B

    2016-03-01

    Cardiopulmonary bypass during tetralogy of Fallot corrective surgery is associated with oxidative stress, and contributes to peri-operative problems. Curcumin has been known as a potent scavenger of reactive oxygen species, which enhances the activity of antioxidants and suppresses phosphorylation of transcription factors involved in inflamation and apoptosis. To evaluate the effects of curcumin as an antioxidant by evaluating the concentrations of malondialdehyde and glutathione, activity of nuclear factor-kappa B, c-Jun N-terminal kinase, caspase-3, and post-operative clinical outcomes. Tetralogy of Fallot patients for corrective surgery were randomised to receive curcumin (45 mg/day) or placebo orally for 14 days before surgery. Malondialdehyde and glutathione concentrations were evaluated during the pre-ischaemia, ischaemia, re-perfusion phases, and 6 hours after aortic clamping-off. Nuclear factor-kappa B, c-Jun N-terminal kinase, and caspase-3, taken from the infundibulum, were assessed during the pre-ischaemia, ischaemia, and re-perfusion phases. Haemodynamic parameters were monitored until day 5 after surgery. In all the observation phases, malondialdehyde and glutathione concentrations were similar between groups. There was no significant difference in nuclear factor-kappa B activity between the groups for three observations; however, in the curcumin group, c-Jun N-terminal kinase significantly decreased from the pre-ischaemia to the re-perfusion phases, and caspase-3 expression was lower in the ischaemia phase. Patients in the curcumin group had lower temperature and better ventricular functions, but no significant differences were found in mechanical ventilation day or length of hospital stay in the two groups. Cardioprotective effects of curcumin may include inhibition of the c-Jun N-terminal kinase pathway and caspase-3 in cardiomyocytes, particularly in the ischaemia phase.

  9. Characterization and correction of beam-hardening artifacts during dynamic volume CT assessment of myocardial perfusion.

    PubMed

    Kitagawa, Kakuya; George, Richard T; Arbab-Zadeh, Armin; Lima, João A C; Lardo, Albert C

    2010-07-01

    To fully characterize beam-hardening effects caused by iodinated contrast medium in the left ventricular (LV) cavity and aorta in the assessment of myocardial perfusion at computed tomography (CT) and to validate a beam-hardening artifact correction algorithm that considers fluid-filled vessels and chambers important sources of beam hardening. The Johns Hopkins University animal care and use committee approved all procedures. An anatomically correct LV and myocardial phantom to characterize beam-hardening artifacts was designed. Following validation in the phantom, the beam-hardening correction (BHC) algorithm was applied to 256-detector row dynamic volume CT images in a canine ischemia model (n = 5) during adenosine stress, and the effect of beam hardening was determined by comparing regional dynamic volume CT perfusion metrics (myocardial upslope normalized by maximum LV blood pool attenuation) with microsphere-derived myocardial blood flow (MBF). A paired Student t test was used to compare continuous variables from the same subject but under different conditions, while linear regression analysis was performed to estimate the slope and statistical significance of the relationship between CT-derived perfusion metrics and microsphere-derived MBF. Beam-hardening artifacts were successfully reproduced in phantom studies and were eliminated with the BHC algorithm. The correlation coefficient of CT-derived perfusion metrics and microsphere-derived MBF improved from 0.60 to 0.74 (P > .05) following correction in the animal model. Beam-hardening artifacts confound dynamic volume CT assessment of myocardial perfusion. Application of the BHC algorithm is helpful for improving accuracy of myocardial perfusion at dynamic volume CT.

  10. Validation and evaluation of model-based crosstalk compensation method in simultaneous /sup 99m/Tc stress and /sup 201/Tl rest myocardial perfusion SPECT

    NASA Astrophysics Data System (ADS)

    Song, X.; Frey, E. C.; Wang, W. T.; Du, Y.; Tsui, B. M. W.

    2004-02-01

    Simultaneous acquisition of /sup 99m/Tc stress and /sup 201/Tl rest myocardial perfusion SPECT has several potential advantages, but the image quality is degraded by crosstalk between the Tc and Tl data. We have previously developed a crosstalk model that includes estimates of the downscatter and Pb X-ray for use in crosstalk compensation. In this work, we validated the model by comparing the crosstalk from /sup 99m/Tc to the Tl window calculated using a combination of the SimSET-MCNP Monte Carlo simulation codes. We also evaluated the model-based crosstalk compensation method using both simulated data from the 3-D MCAT phantom and experimental data from a physical phantom with a myocardial defect. In these studies, the Tl distributions were reconstructed from crosstalk contaminated data without crosstalk compensation, with compensation using the model-based crosstalk estimate, and with compensation using the known true crosstalk, and were compared with the Tl distribution reconstructed from uncontaminated Tl data. Results show that the model gave good estimates of both the downscatter photons and Pb X-rays in the simultaneous dual-isotopes myocardial perfusion SPECT. The model-based compensation method provided image quality that was significantly improved as compared to no compensation and was very close to that from the separate acquisition.

  11. Adenosine receptor neurobiology: overview.

    PubMed

    Chen, Jiang-Fan; Lee, Chien-fei; Chern, Yijuang

    2014-01-01

    Adenosine is a naturally occurring nucleoside that is distributed ubiquitously throughout the body as a metabolic intermediary. In the brain, adenosine functions as an important upstream neuromodulator of a broad spectrum of neurotransmitters, receptors, and signaling pathways. By acting through four G-protein-coupled receptors, adenosine contributes critically to homeostasis and neuromodulatory control of a variety of normal and abnormal brain functions, ranging from synaptic plasticity, to cognition, to sleep, to motor activity to neuroinflammation, and cell death. This review begun with an overview of the gene and genome structure and the expression pattern of adenosine receptors (ARs). We feature several new developments over the past decade in our understanding of AR functions in the brain, with special focus on the identification and characterization of canonical and noncanonical signaling pathways of ARs. We provide an update on functional insights from complementary genetic-knockout and pharmacological studies on the AR control of various brain functions. We also highlight several novel and recent developments of AR neurobiology, including (i) recent breakthrough in high resolution of three-dimension structure of adenosine A2A receptors (A2ARs) in several functional status, (ii) receptor-receptor heterodimerization, (iii) AR function in glial cells, and (iv) the druggability of AR. We concluded the review with the contention that these new developments extend and strengthen the support for A1 and A2ARs in brain as therapeutic targets for neurologic and psychiatric diseases. © 2014 Elsevier Inc. All rights reserved.

  12. A prospective comparison of rubidium-82 PET and thallium-201 SPECT myocardial perfusion imaging utilizing a single dipyridamole stress in the diagnosis of coronary artery disease

    SciTech Connect

    Go, R.T.; Marwick, T.H.; MacIntyre, W.J.; Saha, G.B.; Neumann, D.R.; Underwood, D.A.; Simpfendorfer, C.C. )

    1990-12-01

    The purpose of the present study is to prospectively compare myocardial perfusion imaging with rubidium-82 ({sup 82}Rb) by positron emission tomography (PET) with thallium-201 ({sup 201}Tl) imaging by single-photon emission tomography (SPECT) by recording both studies with a single dipyridamole handgrip stress, and reading both sets of images with the same display technique. In a series of 202 patients with previous coronary arteriography, the sensitivity, specificity, and accuracy of {sup 82}Rb PET were 93%, 78%, and 90% and for {sup 201}Tl SPECT 76%, 80%, and 77%, respectively. When 70 patients with previous therapeutic interventions were excluded, the remaining 132 patients showed a sensitivity, specificity, and accuracy of 95%, 82% and 92% for {sup 82}Rb PET and 79%, 76%, and 78% for {sup 201}Tl SPECT. The improved contrast resolution of PET resulted in markedly superior images and a more confident identification of defects.

  13. Myocardial Perfusion SPECT 2015 in Germany

    PubMed Central

    Burchert, Wolfgang; Schäfer, Wolfgang; Hacker, Marcus

    2016-01-01

    Summary Aim The working group Cardiovascular Nuclear Medicine of the German Society of Nuclear Medicine presents the results of the 7th survey of myocardial perfusion SPECT (MPS) of the reporting year 2015. Method 268 questionnaires (173 practices [PR], 67 hospitals [HO], 28 university hospitals [UH]) were evaluated. Results of the last survey from 2012 are set in squared brackets. Results MPS of 121 939 [105 941] patients were reported. 98 % [95 %] of all MPS were performed with Tc-99m radiopharmaceuticals and 2 % [5 %] with Tl-201. 78 % [79 %] of all patients were studied in PR, 14 % [15 %] in HO, and 8 % [6 %] in UH. A pharmacological stress test was performed in 43 % [39 %] (22 % [24 %] adenosine, 20 % [9 %] regadenoson, 1% [6 %] dipyridamole or dobutamine). Attenuation correction was applied in 25 % [2009: 10 %] of MPS. Gated SPECT was performed in 78 % [70 %] of all rest MPS, in 80 % [73 %] of all stress and in 76 % [67 %] of all stress and rest MPS. 53 % [33 %] of all nuclear medicine departments performed MPS scoring by default, whereas 24 % [41 %] did not apply any quantification. 31 % [26 %] of all departments noticed an increase in their counted MPS and 29 % [29 %] no changes. Data from 89 departments which participated in all surveys showed an increase in MPS count of 11.1 % (PR: 12.2 %, HO: 4.8 %, UH: 18.4 %). 70 % [60 %] of the MPS were requested by ambulatory care cardiologists. Conclusion The 2015 MPS survey reveals a high-grade adherence of routine MPS practice to current guidelines. The positive trend in MPS performance and number of MPS already observed in 2012 continues. Educational training remains necessary in the field of SPECT scoring. PMID:27909712

  14. Caffeine and adenosine.

    PubMed

    Ribeiro, Joaquim A; Sebastião, Ana M

    2010-01-01

    Caffeine causes most of its biological effects via antagonizing all types of adenosine receptors (ARs): A1, A2A, A3, and A2B and, as does adenosine, exerts effects on neurons and glial cells of all brain areas. In consequence, caffeine, when acting as an AR antagonist, is doing the opposite of activation of adenosine receptors due to removal of endogenous adenosinergic tonus. Besides AR antagonism, xanthines, including caffeine, have other biological actions: they inhibit phosphodiesterases (PDEs) (e.g., PDE1, PDE4, PDE5), promote calcium release from intracellular stores, and interfere with GABA-A receptors. Caffeine, through antagonism of ARs, affects brain functions such as sleep, cognition, learning, and memory, and modifies brain dysfunctions and diseases: Alzheimer's disease, Parkinson's disease, Huntington's disease, Epilepsy, Pain/Migraine, Depression, Schizophrenia. In conclusion, targeting approaches that involve ARs will enhance the possibilities to correct brain dysfunctions, via the universally consumed substance that is caffeine.

  15. Three-class ROC analysis: a sequential decision model developed for the diagnostic task rest-stress myocardial perfusion SPECT imaging

    NASA Astrophysics Data System (ADS)

    He, Xin; Frey, Eric C.

    2008-03-01

    Previously we have developed a decision model for three-class ROC analysis where classification is made three simultaneously, i.e., with a single decision. In this paper, an alternative sequential decision model was developed for the specific three-class diagnostic procedure of rest-stress myocardial perfusion SPECT (MPS) imaging. This sequential decision model was developed based on the fact that sometimes this diagnostic task is performed using a two-step process. First, the stress ( 99m Tc) image is read to determine whether a patient is normal or abnormal based on the presence of a defect in the stress image. If a defect is found, the rest ( 201Tl) image is then read to determine whether this is a reversible defect or a fixed defect based on the presence of defect on the rest image. In fact, in some MPS protocols where sequential stress/rest imaging is performed, the rest imaging is not performed if there is no defect in the stress image. Therefore, the three-class task is decomposed to a sequence of two two-class tasks. For this task we determined, by maximizing the expected utility of both steps of the decision process, that log likelihood ratios were the optimal decision variables and provide the optimal ROC surface under the assumption that incorrect decisions have equal utilities under the same hypothesis. The properties of the sequential decision model were then studied. We found that the sequential decision model shares most of the features of a 2-class ROC curve. While this model was developed in the context of rest-stress MPS, it may have applications to other two-step diagnostic tasks.

  16. Prognostic value of dobutamine stress myocardial perfusion echocardiography in patients with known or suspected coronary artery disease and normal left ventricular function

    PubMed Central

    Mattoso, Angele A. A.; Tsutsui, Jeane M.; Kowatsch, Ingrid; Cruz, Vitória Y. L.; Sbano, João C. N.; Ribeiro, Henrique B.; Kalil Filho, Roberto; Porter, Thomas R.; Mathias, Wilson

    2017-01-01

    Objective We sought to determine the prognostic value of qualitative and quantitative analysis obtained by real-time myocardial perfusion echocardiography (RTMPE) in patients with known or suspected coronary artery disease (CAD). Background Quantification of myocardial blood flow reserve (MBFR) in patients with CAD using RTMPE has been demonstrated to further improve accuracy over the analysis of wall motion (WM) and qualitative analysis of myocardial perfusion (QMP). Methods From March 2003 to December 2008, we prospectively studied 168 patients with normal left ventricular function (LVF) who underwent dobutamine stress RTMPE. The replenishment velocity reserve (β) and MBFR were derived from RTMPE. Acute coronary events were: cardiac death, myocardial infarction and unstable angina with need for urgent coronary revascularization. Results During a median follow-up of 34 months (5 days to 6.9 years), 17 acute coronary events occurred. Abnormal β reserve in ≥2 coronary territories was the only independent predictor of events hazard ratio (HR) = 21, 95% CI = 4.5–99; p<0.001). Both, abnormal β reserve and MBFR added significant incremental value in predicting events over qualitative analysis of WM and MP (χ2 = 6.6 and χ2 = 24.6, respectively; p = 0.001 and χ2 = 6.6 and χ2 = 15.5, respectively; p = 0.012, respectively). When coronary angiographic data was added to the multivariate analysis model, β reserve remained the only predictor of events with HR of 21.0 (95% CI = 4.5–99); p<0.001. Conclusion Quantitative dobutamine stress RTMPE provides incremental prognostic information over clinical variables, qualitative analysis of WM and MP, and coronary angiography in predicting acute coronary events. PMID:28234978

  17. Extracellular cAMP-adenosine pathways in the mouse kidney

    PubMed Central

    Ren, Jin; Cheng, Dongmei; Mi, Zaichuan

    2011-01-01

    The renal extracellular 2′,3′-cAMP-adenosine and 3′,5′-cAMP-adenosine pathways (extracellular cAMPs→AMPs→adenosine) may contribute to renal adenosine production. Because mouse kidneys provide opportunities to investigate renal adenosine production in genetically modified kidneys, it is important to determine whether mouse kidneys express these cAMP-adenosine pathways. We administered (renal artery) 2′,3′-cAMP and 3′,5′-cAMP to isolated, perfused mouse kidneys and measured renal venous secretion rates of 2′,3′-cAMP, 3′,5′-cAMP, 2′-AMP, 3′-AMP, 5′-AMP, adenosine, and inosine. Arterial infusions of 2′,3′-cAMP increased (P < 0.0001) the mean venous secretion of 2′-AMP (390-fold), 3′-AMP (497-fold), adenosine (18-fold), and inosine (adenosine metabolite; 7-fold), but they did not alter 5′-AMP secretion. Infusions of 3′,5′-cAMP did not affect venous secretion of 2′-AMP or 3′-AMP, but they increased (P < 0.0001) secretion of 5′-AMP (5-fold), adenosine (17-fold), and inosine (6-fold). Energy depletion (metabolic inhibitors) increased the secretion of 2′,3′-cAMP (8-fold, P = 0.0081), 2′-AMP (4-fold, P = 0.0028), 3′-AMP (4-fold, P = 0.0270), 5′-AMP (3-fold, P = 0.0662), adenosine (2-fold, P = 0.0317), and inosine (7-fold, P = 0.0071), but it did not increase 3′,5′-cAMP secretion. The 2′,3′-cAMP-adenosine pathway was quantitatively similar in CD73 −/− vs. +/+ kidneys. However, 3′,5′-cAMP induced a 6.7-fold greater increase in 5′-AMP, an attenuated increase (61% reduction) in inosine and a similar increase in adenosine in CD73 −/− vs. CD73 +/+ kidneys. In mouse kidneys, 1) 2′,3′-cAMP and 3′,5′-cAMP are metabolized to their corresponding AMPs, which are subsequently metabolized to adenosine; 2) energy depletion activates the 2′,3′-cAMP-adenosine, but not the 3′,5′-cAMP-adenosine, pathway; and 3) although CD73 is involved in the 3′,5′-AMP-adenosine pathway, alternative

  18. Effect of a patient-specific minimum activity in stress myocardial perfusion imaging using CZT-SPECT: Prognostic value, radiation dose, and scan outcome.

    PubMed

    van Dijk, J D; Borren, N M; Mouden, M; van Dalen, J A; Ottervanger, J P; Jager, P L

    2017-08-18

    SPECT Myocardial perfusion imaging (MPI) is associated with a relatively high radiation burden and decreasing image quality in heavy patients. Patient-specific low-activity protocols (PLAPs) are suggested but follow-up data is lacking. Our aim was to compare the use of a standard fixed-activity protocol (FAP) with a PLAP in cadmium zinc telluride (CZT)-SPECT MPI. We retrospectively included 1255 consecutive patients who underwent CZT-SPECT stress-optional rest MPI. 668 Patients were scanned using FAP (370 MBq) and 587 patients using PLAP (2.25 MBq·kg(-1)). Percentage of scans interpreted as normal, radiation dose, and 1-year follow-up including hard event rates (all-cause death or non-fatal myocardial infarction) were collected and compared. The percentage of scans interpreted as normal was 67% in FAP and 70% in PLAP groups (P = .29). The annualized hard event rates in these patients were 1.0% in the FAP and 0.9% in the PLAP group (P = .86). However, the mean radiation dose decreased by 23% for stress-only and by 15% to 2.6 mSv for stress-optional rest MPI after introduction of the PLAP (p<0.001). Introduction of a patient-specific low-activity protocol does not affect the percentage of scans interpreted as normal or prognosis but significantly lowers the radiation dose for CZT-SPECT MPI.

  19. Endogenous adenosine is an autacoid feedback inhibitor of chloride transport in the shark rectal gland.

    PubMed Central

    Kelley, G G; Aassar, O S; Forrest, J N

    1991-01-01

    The present studies define the physiologic role of endogenous adenosine in the perfused shark rectal gland, a model epithelia for hormone-stimulated chloride transport. Chloride ion secretion, and venous adenosine and inosine concentrations increased in parallel in response to hormone stimulation. From a basal rate of 157 +/- 26 mu eq/h per g, chloride secretion increased to 836 +/- 96 and 2170 +/- 358 with 1 and 10 microM forskolin, venous adenosine increased from 5.0 +/- 1 to 126 +/- 29 and 896 +/- 181 nM, and inosine increased from 30 +/- 9 to 349 +/- 77 and 1719 +/- 454 nM (all P less than 0.01). Nitrobenzylthioinosine (NBTI), a nucleoside transport inhibitor, completely blocked the release of adenosine and inosine. Inhibition of chloride transport with bumetanide, an inhibitor of the Na+/K+/2Cl- cotransporter, or ouabain, an inhibitor of Na+/K+ ATPase activity, reduced venous adenosine and inosine to basal values. When the interaction of endogenous adenosine with extracellular receptors was prevented by adenosine deaminase, NBTI, or 8-phenyltheophylline, the chloride transport response to secretagogues increased by 1.7-2.3-fold. These studies demonstrate that endogenous adenosine is released in response to hormone-stimulated cellular work and acts at A1 adenosine receptors as a feedback inhibitor of chloride transport. Images PMID:1752953

  20. Comparison of myocardial transmural perfusion gradient by magnetic resonance imaging to fractional flow reserve in patients with suspected coronary artery disease.

    PubMed

    Pan, Jingwei; Huang, Siyi; Lu, Zhigang; Li, Jingbo; Wan, Qing; Zhang, Jiayin; Gao, Chengjie; Yang, Xin; Wei, Meng

    2015-05-15

    The goal of this study was to evaluate the diagnostic accuracy of transmural perfusion gradient (TPG) and transmural perfusion gradient reserve (TPGR) with 3.0 T cardiac magnetic resonance (CMR) against invasively determined fractional flow reserve (FFR) to detect coronary artery stenosis. Quantitative analysis of myocardial perfusion with CMR to diagnosis coronary artery disease (CAD) has been widely accepted. However, traditional transmural myocardial perfusion analysis with CMR neglects that endocardium is more vulnerable to ischemia than epicardium. TPG and TPGR can take the inhomogenous perfusion impairment into account and be more sensitive and specific for diagnosis of CAD. In this study, 71 patients (57 men, age 60.1 ± 6.4 years) with known or suspected CAD referred for invasive angiography study underwent rest and adenosine-induced stress CMR perfusion imaging scan. FFR was attempted to be measured in all major epicardial coronary arteries. FFR ≤0.75 was regarded to indicate a hemodynamic significant coronary lesion. A TPG ≤0.85 predicted significant CAD with sensitivity and specificity of 74.55% and 83.65%, respectively. Sensitivity and specificity of TPGR ≤0.81 were 90.91% and 89.94%, respectively. Area under the receiver-operating curve to detect FFR ≤0.75 was 0.86 for TPG and 0.95 for TPGR. TPGR yielded significantly better sensitivity and specificity for diagnosis of CAD than traditional myocardial blood flow, myocardial perfusion reserve, and TPG (p < 0.0001). In conclusion, TPG and TPGR analyses with MRI are capable of detecting hemodynamic stenosis of coronary artery and superior to traditional myocardial perfusion analysis. Furthermore, TPGR appears to be superior to TPG in the diagnosis of coronary artery stenosis. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Temporal and mechanistic dissociation of ATP and adenosine release during ischaemia in the mammalian hippocampus1

    PubMed Central

    Frenguelli, Bruno G; Wigmore, Geoffrey; Llaudet, Enrique; Dale, Nicholas

    2007-01-01

    Abstract Adenosine is well known to be released during cerebral metabolic stress and is believed to be neuroprotective. ATP release under similar circumstances has been much less studied. We have now used biosensors to measure and compare in real time the release of ATP and adenosine during in vitro ischaemia in hippocampal slices. ATP release only occurred following the anoxic depolarisation, whereas adenosine release was apparent almost immediately after the onset of ischaemia. ATP release required extracellular Ca2+. By contrast adenosine release was enhanced by removal of extracellular Ca2+, whilst TTX had no effect on either ATP release or adenosine release. Blockade of ionotropic glutamate receptors substantially enhanced ATP release, but had only a modest effect on adenosine release. Carbenoxolone, an inhibitor of gap junction hemichannels, also greatly enhanced ischaemic ATP release, but had little effect on adenosine release. The ecto-ATPase inhibitor ARL 67156, whilst modestly enhancing the ATP signal detected during ischaemia, had no effect on adenosine release. Adenosine release during ischaemia was reduced by pre-treament with homosysteine thiolactone suggesting an intracellular origin. Adenosine transport inhibitors did not inhibit adenosine release, but instead they caused a twofold increase of release. Our data suggest that ATP and adenosine release during ischaemia are for the most part independent processes with distinct underlying mechanisms. These two purines will consequently confer temporally distinct influences on neuronal and glial function in the ischaemic brain. PMID:17459147

  2. Possible therapeutic benefits of adenosine-potentiating drugs in reducing age-related degenerative disease in dogs and cats.

    PubMed

    Scaramuzzi, R J; Baker, D J

    2003-10-01

    Adenosine is a ubiquitous, biologically important molecule that is a precursor of other biologically active molecules. It also is a component of some co-factors and has distinct physiological actions in its own right. Levels are maintained by synthesis from dietary precursors and re-cycling. The daily turnover of adenosine is very high. Adenosine can act either as a hormone by binding to adenosine receptors, four adenosine receptor subtypes have been identified, and as an intracellular modulator, after transport into the cell by membrane transporter proteins. One of the principal intracellular actions of adenosine is inhibition of the enzyme phosphodiesterase. Extracellular adenosine also has specific neuromodulatory actions on dopamine and glutamate. Selective and nonselective agonists and antagonists of adenosine are available. The tasks of developing, evaluating and exploiting the therapeutic potential of these compounds is still in its infancy. Adenosine has actions in the central nervous system (CNS), heart and vascular system, skeletal muscle and the immune system and the presence of receptors suggests potential actions in the gonads and other organs. Adenosine agonists improve tissue perfusion through actions on vascular smooth muscle and erythrocyte fluidity and they can be used to improve the quality of life in aged dogs. This article reviews the therapeutic potential of adenosine-potentiating drugs in the treatment of age-related conditions in companion animals, some of which may be exacerbated by castration or spaying at an early age.

  3. Assessment of coronary ischaemia by myocardial perfusion dipyridamole stress technetium-99 m tetrofosmin, single-photon emission computed tomography, and coronary angiography in children with Kawasaki disease: pre- and post-coronary bypass grafting.

    PubMed

    Mostafa, Mostafa S; Sayed, Ashraf O; Al Said, Yasser M

    2015-06-01

    Coronary artery lesions in Kawasaki disease invasively assessed by coronary angiography. Evaluation of myocardial perfusion by single-photon emission computed tomography may identify the haemodynamic significance of coronary lesions. To evaluate diagnostic accuracy of dipyridamole stress technetium-99 m tetrofosmin, single-photon emission computed tomography as a possible alternative to invasive coronary angiography for detection and follow-up of myocardial ischaemia in patients with Kawasaki disease, and pre- and post-coronary bypass grafting. Coronary angiography and single-photon emission computed tomography were performed on 21 patients who were classified into three groups - group I (stenosis), group II (giant aneurysms), and group III (small aneurysms). Of the 21 patients, 16 (groups I and II) patients with myocardial perfusion defects, who underwent coronary bypass grafting, were followed up with single-photon emission computed tomography. In group I, all patients had significant coronary stenosis and 100% of them had perfusion defects in the anterior and septal walls. In group II, all patients had giant aneurysms and 83% of them had inferior and inferolateral perfusion defects. In group III, all patients had small aneurysms and 100% of them had normal perfusion. Pre-coronary bypass grafting myocardial ischaemic defects disappeared in all patients after surgery. Sensitivity, specificity, and accuracy of single-photon emission computed tomography were 94, 100, and 95%, respectively. Technetium-99 m tetrofosmin single-photon emission computed tomography can be applied as an accurate non-invasive diagnostic technique for detecting myocardial perfusion defects with coronary artery lesions, and to show improved or even normalised perfusion of the myocardium in patients after surgical revascularisation.

  4. Integrated cardiac magnetic resonance imaging with coronary magnetic resonance angiography, stress-perfusion, and delayed-enhancement imaging for the detection of occult coronary artery disease in asymptomatic individuals.

    PubMed

    Song, Kyoung Doo; Kim, Sung Mok; Choe, Yeon Hyeon; Jung, Wooin; Lee, Sang-Chol; Chang, Sung-A; Choi, Yoon Ho; Sung, Jidong

    2015-06-01

    To evaluate the feasibility of using coronary magnetic resonance angiography (CMRA) with stress-perfusion and delayed-enhancement MRI as a screening tool for the detection of coronary artery disease (CAD) in asymptomatic subjects. Three hundred and forty-one self-referred asymptomatic subjects were enrolled in this study. Cardiac MR imaging was performed using a 1.5-T scanner with a 32-channel cardiac coil. Coronary artery stenosis, regional wall motion abnormalities, myocardial perfusion abnormalities, and delayed myocardial enhancement were analyzed. The occurrence of new chest pain and cardiac events was assessed in 332 subjects (97.3 %) over an average 29 ± 6 months (range, 18-39 months) follow-up period. A total of 3296 (82.4 %) of 4000 coronary artery segments examined exhibited diagnostic image quality on combined whole-heart and volume-targeted CMRA. Combined MRI detected significant CADs in 13 (3.8 %) of 341 subjects. Among these, 11 subjects (84.6 %) had both coronary artery stenosis (≥50 % by diameter) on CMRA and stress-perfusion defects in corresponding areas. Five of the 13 subjects showed evidence of old myocardial infarctions on delayed-enhancement MRI. Three subjects (0.9 %) underwent percutaneous coronary intervention after CAD was detected on cardiac MRI. There were no cardiac events during the follow-up period in subjects who complied with follow-up. Normal stress-perfusion and delayed-enhancement MRI lead to excellent outcomes when used to predict future cardiac events in asymptomatic subjects. Coronary MRA correlates well with stress-perfusion MRI for detecting significant CAD and helps exclude CAD in asymptomatic individuals.

  5. Stress-first protocol for myocardial perfusion SPECT imaging with semiconductor cameras: high diagnostic performances with significant reduction in patient radiation doses.

    PubMed

    Perrin, Mathieu; Djaballah, Wassila; Moulin, Frédéric; Claudin, Marine; Veran, Nicolas; Imbert, Laetitia; Poussier, Sylvain; Morel, Olivier; Besseau, Cyril; Verger, Antoine; Boutley, Henri; Karcher, Gilles; Marie, Pierre-Yves

    2015-06-01

    Effective doses of 14 mSv or higher are currently being attained in patients having stress and rest myocardial perfusion imaging (MPI) single photon emission computed tomography (SPECT) performed on the same day with conventional protocols. This study aimed to assess the actual reduction in effective doses as well as diagnostic performances for MPI routinely planned with: (1) high-sensitivity cadmium zinc telluride (CZT) cameras, (2) very low injected activities and (3) a stress-first protocol where the normality of stress images may lead to avoiding rest imaging. During a 1-year period, 2,845 patients had MPI on a CZT camera, a single-day stress-first protocol and low injected activities (120 MBq of (99m)Tc-sestamibi at stress for 75 kg body weight and threefold higher at rest). The ability to detect > 50% coronary stenosis was assessed in a subgroup of 149 patients who also had coronary angiography, while the normalcy rate was assessed in a subgroup of 128 patients with a low pretest likelihood of coronary artery disease (<10%). Overall, 33% of patients had abnormal MPI of which 34% were women and 34% were obese. The mean effective doses and the percentage of exams involving only stress images were: (1) 3.53 ± 2.10 mSv and 37% in the overall population, (2) 4.83 ± 1.56 mSv and 5% in the subgroup with angiography and (3) 1.96 ± 1.52 mSv and 71 % in the low-probability subgroup. Sensitivity and global accuracy for identifying the 106 patients with coronary stenosis were 88 and 80%, respectively, while the normalcy rate was 97 %. When planned with a low-dose stress-first protocol on a CZT camera, MPI provides high diagnostic performances and a dramatic reduction in patient radiation doses. This reduction is even greater in low-risk subgroups with high rates of normal stress images, thus allowing the mean radiation dose to be balanced against cardiac risk in targeted populations.

  6. Quantitative myocardial perfusion with stress dual-energy CT: iodine concentration differences between normal and ischemic or necrotic myocardium. Initial experience.

    PubMed

    Delgado Sánchez-Gracián, Carlos; Oca Pernas, Roque; Trinidad López, Carmen; Santos Armentia, Eloísa; Vaamonde Liste, Antonio; Vázquez Caamaño, María; Tardáguila de la Fuente, Gonzalo

    2016-09-01

    To determine whether the quantification of iodine with stress dual-energy computed tomography (DECT-S) allows for the discrimination between a normal and an ischemic or necrotic myocardium using magnetic resonance (MR) as a reference. This retrospective study was approved by the institutional review board, with waiver of informed consent. Thirty-six cardiac MR and DECT-S images from patients with suspected coronary artery disease were evaluated. Perfusion defects were visually determined, and myocardial iodine concentration was calculated by two observers using DECT colour-coded iodine maps. Iodine concentration differences were calculated using parametric tests. Receiver operating characteristic (ROC) curve analysis was conducted to estimate the optimal iodine concentration threshold for discriminating pathologic myocardium. In total, 576 cardiac segments were evaluated. There were differences in mean iodine concentration (p < 0.001) between normal (2.56 ± 0.66 mg/mL), ischemic (1.98 ± 0.36 mg/dL) and infarcted segments (1.35 ± 0.57 mg/mL). A myocardium iodine concentration of 2.1 mg/mL represented the optimal threshold to discriminate between normal and pathologic myocardium (sensitivity 75 %, specificity 73.6 %, area under the curve 0.806). Excellent agreement was found in measured myocardium iodine concentration (intraclass correlation coefficient 0.814). Cardiac DECT-S with iodine quantification may be useful to differentiate healthy and ischemic or necrotic myocardium. • DECT-S allows for determination of myocardial iodine concentration as a quantitative perfusion parameter. • A high interobserver correlation exists in measuring myocardial iodine concentration with DECT-S. • Myocardial iodine concentration may be useful in the assessment of patients with CAD.

  7. Complementary Prognostic Values of Stress Myocardial Perfusion and Late Gadolinium Enhancement Imaging by Cardiac Magnetic Resonance in Patients with Known or Suspected Coronary Artery Disease

    PubMed Central

    Steel, Kevin; Broderick, Ryan; Gandla, Vijay; Larose, Eric; Resnic, Frederick; Jerosch-Herold, Michael; Brown, Kenneth A.; Kwong, Raymond Y.

    2009-01-01

    BACKGROUND Recent studies have demonstrated the significant prognostic value of stress CMR myocardial perfusion imaging (CMRMPI). Apart from characterizing reversible perfusion defect (RevPD) from flow-limiting coronary stenosis, CMR late enhancement imaging (LGE) is currently the most sensitive method in detecting subendocardial infarction (MI). We therefore tested the hypothesis that, characterization of these 2 processes from coronary artery disease (CAD) by CMR can provide complementary prognostic values. Methods and Results We performed CMRMPI followed by LGE imaging on 254 patients referred with symptoms of myocardial ischemia. At a median follow up of 17 months, 49 cardiac events (MACE) occurred including 12 cardiac deaths, 16 acute myocardial infarction (MI), and 21 cardiac hospitalizations. RevPD and LGE both maintained a > 3-fold association with cardiac death or acute MI (Death/MI) when adjusted to each other and to the effects of patient age and gender (adjusted HR 3.31, P=0.02 and 3.43, P=0.01, respectively). In patients without a history of MI who had negative RevPD, LGE presence was associated with >11-fold hazards increase to Death/MI. Patients with neither RevPD nor LGE had a 98.1% negative annual event rate for Death/MI. For association with MACE, RevPD was the strongest multivariable variable in the best overall model (HR 10.92, P<0.0001). Conclusions CMR imaging provides robust risk-stratification of patients who presents with symptoms of ischemia. Characterization of RevPD and LGE by CMR provides strong and complementary prognostic implication towards cardiac death or acute MI. PMID:19770399

  8. Estimation of skeletal muscle interstitial adenosine during forearm dynamic exercise in humans

    NASA Technical Reports Server (NTRS)

    Costa, F.; Heusinkveld, J.; Ballog, R.; Davis, S.; Biaggioni, I.

    2000-01-01

    It has been proposed that adenosine is a metabolic signal that triggers activation of muscle afferents involved in the exercise pressor reflex. Furthermore, exogenous adenosine induces sympathetic activation that mimics the exercise pressor reflex, and blockade of adenosine receptors inhibits sympathetic activation induced by exercise. Thus, we hypothesize that adenosine is released locally by the muscle during exercise. We used microdialysis probes, placed in the flexor digitorium superficialis muscle, to estimate muscle interstitial adenosine levels in humans. We estimated resting in vivo muscle interstitial adenosine concentrations (0.292+/-0.058 micromol/L, n=4) by perfusing increasing concentrations of adenosine to determine the gradient produced in the dialysate. Muscle interstitial adenosine concentrations increased from 0.23+/-0.04 to 0.82+/-0.14 micromol/L (n=14, P<0.001) during intermittent dynamic exercise at 50% of maximal voluntary contraction. Lactate increased from 0.8+/-0.1 to 2.3+/-0.3 mmol/L (P<0.001). Lower intensity (15% maximal voluntary contraction) intermittent dynamic exercise increased adenosine concentrations from 0.104+/-0.02 to 0.42+/-0.16 micromol/L (n=7). The addition of ischemia to this low level of exercise produced a greater increase in adenosine (from 0.095+/-0.02 to 0.48+/-0.2 micromol/L) compared with nonischemic exercise (0. 095+/-0.02 to 0.25+/-0.12 micromol/L). These results indicate that microdialysis is useful in estimating adenosine concentrations and in reflecting changes in muscle interstitial adenosine during dynamic exercise in humans.

  9. Estimation of skeletal muscle interstitial adenosine during forearm dynamic exercise in humans

    NASA Technical Reports Server (NTRS)

    Costa, F.; Heusinkveld, J.; Ballog, R.; Davis, S.; Biaggioni, I.

    2000-01-01

    It has been proposed that adenosine is a metabolic signal that triggers activation of muscle afferents involved in the exercise pressor reflex. Furthermore, exogenous adenosine induces sympathetic activation that mimics the exercise pressor reflex, and blockade of adenosine receptors inhibits sympathetic activation induced by exercise. Thus, we hypothesize that adenosine is released locally by the muscle during exercise. We used microdialysis probes, placed in the flexor digitorium superficialis muscle, to estimate muscle interstitial adenosine levels in humans. We estimated resting in vivo muscle interstitial adenosine concentrations (0.292+/-0.058 micromol/L, n=4) by perfusing increasing concentrations of adenosine to determine the gradient produced in the dialysate. Muscle interstitial adenosine concentrations increased from 0.23+/-0.04 to 0.82+/-0.14 micromol/L (n=14, P<0.001) during intermittent dynamic exercise at 50% of maximal voluntary contraction. Lactate increased from 0.8+/-0.1 to 2.3+/-0.3 mmol/L (P<0.001). Lower intensity (15% maximal voluntary contraction) intermittent dynamic exercise increased adenosine concentrations from 0.104+/-0.02 to 0.42+/-0.16 micromol/L (n=7). The addition of ischemia to this low level of exercise produced a greater increase in adenosine (from 0.095+/-0.02 to 0.48+/-0.2 micromol/L) compared with nonischemic exercise (0. 095+/-0.02 to 0.25+/-0.12 micromol/L). These results indicate that microdialysis is useful in estimating adenosine concentrations and in reflecting changes in muscle interstitial adenosine during dynamic exercise in humans.

  10. Soft tissue attenuation patterns in stress myocardial perfusion SPECT images: a comparison between supine and upright acquisition systems.

    PubMed

    Chawla, David; Rahaby, Mouyyad; Amin, Amit P; Vashistha, Raj; Alyousef, Tareq; Martinez, Hector X; Doukky, Rami

    2011-04-01

    Soft tissue attenuation patterns and their interaction with body habitus and gender in Single Photon Emission Computed Tomography (SPECT)-myocardial perfusion imaging (MPI) of upright patient-position acquisition systems are not well described. In a retrospective cross-sectional study, we compared the prevalence and patterns of soft tissue attenuation in two groups of normal SPECT-MPI studies acquired by supine (n = 263) vs upright (n = 212) acquisition systems. Attenuation patterns observed in the study population were: anterior (22.3%), inferior (51.6%) and lateral (18.1%). Anterior attenuation was significantly less in those imaged upright (6.1% vs 35.4%), P < .001; particularly among women (9.5% vs 50.7%), P < .001. Inferior attenuation was more common among women imaged upright (49.5% vs 13.5%), P < .001; but was not affected by imaging position among men. Lateral attenuation was more prevalent in the upright group (24.1% vs 13.3%), P = .002; and had a strong association with female gender (P < .001) and BMI ≥ 30 (P < .001). Upright SPECT-MPI acquisition is associated with a unique attenuation pattern which is vastly different than the supine position. Female gender strongly impacted this attenuation pattern, particularly obese women. Our study is the first to describe, in details, the attenuation patterns with upright imaging and is critical for the accurate interpretation of SPECT-MPI acquired with upright systems.

  11. Transport stress in broilers. II. Superoxide production, adenosine phosphate concentrations, and mRNA levels of avian uncoupling protein, avian adenine nucleotide translocator, and avian peroxisome proliferator-activated receptor-gamma coactivator-1alpha in skeletal muscles.

    PubMed

    Zhang, L; Yue, H Y; Wu, S G; Xu, L; Zhang, H J; Yan, H J; Cao, Y L; Gong, Y S; Qi, G H

    2010-03-01

    The effect of transport stress on superoxide production and adenosine phosphate concentration in addition to avian uncoupling protein (avUCP), avian adenine nucleotide translocator, and avian peroxisome proliferator-activated receptor-gamma coactivator-1alpha mRNA levels of skeletal muscles in broilers was investigated. Arbor Acres chicks (n = 360, 46 d old, males) were randomly allotted to 1 of 5 treatments: unstressed control, 45-min (short-term) transport with 45-min (short-term) recovery, 45-min transport with 3-h (long-term) recovery, 3-h (long-term) transport with 45-min recovery, and 3-h transport with 3-h recovery. Each treatment consisted of 6 replicates with 12 birds each. All birds (except control group) were transported according to a designed protocol. Transport time affected reactive oxygen species production in the thigh muscle (P < 0.05), adenosine triphosphate (ATP) content and energy charge (EC) in both breast and thigh muscles (P < 0.05 for all 4 comparisons), ATP:adenosine diphosphate (ADP) ratio in the breast muscle (P < 0.05), and avUCP mRNA levels in the thigh muscle (P < 0.05). Long-term transport increased (P < 0.05) reactive oxygen species production, ATP content, ATP:ADP ratio, and EC in the thigh muscle, but it decreased ATP content, ATP:ADP ratio, and EC in the breast muscle. Long-term transport increased avUCP mRNA in the thigh muscle (P < 0.05). Long-term recovery increased the ATP (P < 0.05) and ADP (P < 0.05) concentrations, avian adenine nucleotide translocator mRNA (P < 0.05), and avian peroxisome proliferator-activated receptor-gamma coactivator-1alpha mRNA (P < 0.05) in the thigh muscle, whereas EC decreased (P < 0.05) in the breast muscle. There were interactions between transport and recovery time on ATP (P < 0.05), EC (P < 0.05), and avUCP mRNA level (P < 0.05) in the thigh muscle. This study suggests that long-term transport accelerates muscle energy metabolism and lipid peroxidation. A long-term recovery may help alleviate

  12. Rat cardiac myocyte adenosine transport and metabolism

    SciTech Connect

    Ford, D.A.; Rovetto, M.J.

    1987-01-01

    Based on the importance of myocardial adenosine and adenine nucleotide metabolism, the adenosine salvage pathway in ventricular myocytes was studied. Accurate estimates of transport rates, separate from metabolic fllux, were determined. Adenosine influx was constant between 3 and 60 s. Adenosine metabolism maintained intracellular adenosine concentrations < 10% of the extracellular adenosine concentrations and thus unidirectional influx could be measured. Myocytes transported adenosine via saturable and nonsaturable processes. A minimum estimate of the V/sub max/ of myocytic adenosine kinase indicated the saturable component of adenosine influx was independent of adenosine kinase activity. Saturable transport was inhibited by nitrobenzylthioinosine and verapamil. Extracellular adenosine taken up myocytes was rapidly phosphorylated to adenine taken up by myocytes was rapidly phosphorylated to adenine nucleotides. Not all extracellular adenosine, though, was phosphorylated on entering myocytes, since free, as opposed to protein-bound, intracellular adenosine was detected after digitonin extraction of cells in the presence of 1 mM ethylene-diaminetetraacetic acid.

  13. [Study of efficacy and safety of pharmacological stress tests in nuclear cardiology].

    PubMed

    Baskot, Branislav; Rafajlovski, Saso; Ristić-Angelkov, Andelka; Obradović, Slobodan; Gligić, Branko; Orozović, Vjekoslav; Agbaba, Nikola

    2009-03-01

    Treadmill test combined with myocardial perfusion scintigraphy (MPS) is a commonly used technique in the assessment of coronary artery disease. Many patients who cannot adequately perform exercise stress testing may nevertheless undergo pharmacological tests, most commonly with the vasodilator agents (adenosine and dipyridamole), as well as the positive inotropic agent dobutamine. Patients undergoing vasodilators stress testing with either dipyridamole or adenosine also perform simultaneous low-intensity exercise. The aim of this study was to compare various pharmacological stress tests alone or in combination with low intensity exercise as preparation for MPS in regard to incidence of adverse effects, quality of diagnostic image and the acquisition initial time. A total of 2 205 patients underwent pharmacological stress tests. Pharmacological stress test with adenosine was applied in 493 patients. In 405 of them we performed concomitant low level exercise (50 W) by bicycle ergometar (AdenoEX). In 88 of them we performed adenosine abbreviated protocol (AdenoSCAN). In 1 526 patients we performed pharmacological stress test with dipyridamole. In 871 of them we performed concomitant low level exercise (50 W) by bicycle ergometar (DipyEX), and in 775 we used only dipyridamole protocol (DipySCAN). In 186 patients we used pharmacological stress test with dobutamine. We followed side effects of adenosine, dipyiridamole and dobutamine, compared results between protocols with concomitant low level exercise and vasodilatators only. We also compared image quality, and suggested time of acquisition after stress test. We found numerous side effects especially with adenosine, but these effects were short-lived and not required active interventions. Benefit with concomitant exercise in booth AdenoEX and DipyEX included decreased side effects (AdenoEX vs AdenoSCAN 620% vs 87%, respectively, and DipyEX vs DipySCAN 37% vs 59%, respectively) improved safety and patients tolerance

  14. Feasibility and safety of exercise stress testing using an anti-gravity treadmill with Tc-99m tetrofosmin single-photon emission computed tomography (SPECT) myocardial perfusion imaging: A pilot non-randomized controlled study.

    PubMed

    Daly, Patrick; Kayse, Regina; Rudick, Steven; Robbins, Nathan; Scheler, Jennifer; Harris, David; O'Donnell, Robert; Dwivedi, Alok K; Gerson, Myron C

    2017-08-31

    Exercise is the AHA/ACC guideline-recommended stress modality for myocardial perfusion imaging, but many patients are unable to exercise to target heart rate on a conventional treadmill. We examined the feasibility and safety of stress imaging using an anti-gravity treadmill in patients with perceived poor exercise capacity. 49 patients were recruited for stress testing by anti-gravity treadmill (n = 29) or to a regadenoson control group (n = 20). Seventeen anti-gravity test patients (59%) reached target heart rate obviating the need for a pharmacologic stress agent. Adverse effects of the anti-gravity treadmill were limited to minor muscle aches in 5 subjects. Stress myocardial perfusion image quality judged by 3 blinded readers on a 5-point scale was comparable for the anti-gravity treadmill (4.30 ± SD 0.87) vs pharmacologic stress (4.28 ± SD 0.66). Stress testing using an anti-gravity treadmill is feasible and may help some patients safely achieve target heart rate.

  15. Intracellular adenosine formation and release by freshly-isolated vascular endothelial cells from rat skeletal muscle: effects of hypoxia and/or acidosis.

    PubMed

    Le, G Y; Essackjee, H C; Ballard, H J

    2014-07-18

    Previous studies suggested indirectly that vascular endothelial cells (VECs) might be able to release intracellularly-formed adenosine. We isolated VECs from the rat soleus muscle using collagenase digestion and magnetic-activated cell sorting (MACS). The VEC preparation had >90% purity based on cell morphology, fluorescence immunostaining, and RT-PCR of endothelial markers. The kinetic properties of endothelial cytosolic 5'-nucleotidase suggested it was the AMP-preferring N-I isoform: its catalytic activity was 4 times higher than ecto-5'nucleotidase. Adenosine kinase had 50 times greater catalytic activity than adenosine deaminase, suggesting that adenosine removal in VECs is mainly through incorporation into adenine nucleotides. The maximal activities of cytosolic 5'-nucleotidase and adenosine kinase were similar. Adenosine and ATP accumulated in the medium surrounding VECs in primary culture. Hypoxia doubled the adenosine, but ATP was unchanged; AOPCP did not alter medium adenosine, suggesting that hypoxic VECs had released intracellularly-formed adenosine. Acidosis increased medium ATP, but extracellular conversion of ATP to AMP was inhibited, and adenosine remained unchanged. Acidosis in the buffer-perfused rat gracilis muscle elevated AMP and adenosine in the venous effluent, but AOPCP abolished the increase in adenosine, suggesting that adenosine is formed extracellularly by non-endothelial tissues during acidosis in vivo. Hypoxia plus acidosis increased medium ATP by a similar amount to acidosis alone and adenosine 6-fold; AOPCP returned the medium adenosine to the level seen with hypoxia alone. These data suggest that VECs release intracellularly formed adenosine in hypoxia, ATP during acidosis, and both under simulated ischaemic conditions, with further extracellular conversion of ATP to adenosine. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Cardiac energetics, oxygenation, and perfusion during increased workload in patients with type 2 diabetes mellitus.

    PubMed

    Levelt, Eylem; Rodgers, Christopher T; Clarke, William T; Mahmod, Masliza; Ariga, Rina; Francis, Jane M; Liu, Alexander; Wijesurendra, Rohan S; Dass, Saira; Sabharwal, Nikant; Robson, Matthew D; Holloway, Cameron J; Rider, Oliver J; Clarke, Kieran; Karamitsos, Theodoros D; Neubauer, Stefan

    2016-12-07

    Patients with type 2 diabetes mellitus (T2DM) are known to have impaired resting myocardial energetics and impaired myocardial perfusion reserve, even in the absence of obstructive epicardial coronary artery disease (CAD). Whether or not the pre-existing energetic deficit is exacerbated by exercise, and whether the impaired myocardial perfusion causes deoxygenation and further energetic derangement during exercise stress, is uncertain. Thirty-one T2DM patients, on oral antidiabetic therapies with a mean HBA1c of 7.4 ± 1.3%, and 17 matched controls underwent adenosine stress cardiovascular magnetic resonance for assessment of perfusion [myocardial perfusion reserve index (MPRI)] and oxygenation [blood-oxygen level-dependent (BOLD) signal intensity change (SIΔ)]. Cardiac phosphorus-MR spectroscopy was performed at rest and during leg exercise. Significant CAD (>50% coronary stenosis) was excluded in all patients by coronary computed tomographic angiography. Resting phosphocreatine to ATP (PCr/ATP) was reduced by 17% in patients (1.74 ± 0.26, P = 0.001), compared with controls (2.07 ± 0.35); during exercise, there was a further 12% reduction in PCr/ATP (P = 0.005) in T2DM patients, but no change in controls. Myocardial perfusion and oxygenation were decreased in T2DM (MPRI 1.61 ± 0.43 vs. 2.11 ± 0.68 in controls, P = 0.002; BOLD SIΔ 7.3 ± 7.8 vs. 17.1 ± 7.2% in controls, P < 0.001). Exercise PCr/ATP correlated with MPRI (r = 0.50, P = 0.001) and BOLD SIΔ (r = 0.32, P = 0.025), but there were no correlations between rest PCr/ATP and MPRI or BOLD SIΔ. The pre-existing energetic deficit in diabetic cardiomyopathy is exacerbated by exercise; stress PCr/ATP correlates with impaired perfusion and oxygenation. Our findings suggest that, in diabetes, coronary microvascular dysfunction exacerbates derangement of cardiac energetics under conditions of increased workload. © The Author 2015. Published by Oxford University Press on behalf of the European Society of

  17. Effects of Static Cold Storage and Hypothermic Machine Perfusion on Oxidative Stress Factors, Adhesion Molecules, and Zinc Finger Transcription Factor Proteins Before and After Liver Transplantation.

    PubMed

    Zhao, De-Fang; Dong, Qin; Zhang, Tong

    2017-02-17

    BACKGROUND This study aimed to investigate the effects of static cold storage (SCS) and hypothermic machine perfusion (HMP) on the oxidative stress factors (OSF), adhesion molecules (AM), and zinc finger transcription factor (Snail) before and after liver transplantation. MATERIAL AND METHODS Experimental dogs were randomly divided into donor (group A), SCS (group B), and HMP (group C) (n=30) groups. Livers retrieved from group A were transplanted into group B after SCS, and the livers sampled from group B were transplanted into group C after HMP. The dogs in group A were euthanized and discarded, and the livers sampled from group C were used for other experiments. Twenty dogs with successful liver transplants were randomly selected from groups B and C for analysis. RESULTS During the liver sampling process, the levels of OSF, AM, and Snail between the 2 groups showed no significant differences (P>0.05); before the transplantation, the levels of chemokine CXCL14 and Snail between the 2 groups showed no significant differences (P>0.05), and compared with group B, HIF-1α and P-selectin in group C were lower (P<0.01); 60 min after the transplantation, HIF-1α, chemokine CXCL14, P-selectin, and Snail in group C were lower than that in group B (P<0.01). CONCLUSIONS HMP can significantly reduce the levels of OSF and inflammatory factors, which is conducive for liver transplantation.

  18. Cardiac shock wave therapy and myocardial perfusion in severe coronary artery disease.

    PubMed

    Kaller, M; Faber, L; Bogunovic, N; Horstkotte, D; Burchert, W; Lindner, Oliver

    2015-10-01

    Ultrasound guided cardiac shock wave therapy (CSWT) is a noninvasive therapeutic option in the treatment of chronic-refractory angina. Clinical trials have shown that CSWT reduces angina symptoms, improves regional systolic function, LV ejection fraction, myocardial perfusion and quality of life parameters. Absolute measurements of myocardial perfusion before and after CSWT have not been performed so far. We studied a total of 21 CCS III patients with history of CAD and multiple interventions who suffered from disabling angina despite individually optimized medical therapy. An N-13 NH3 PET perfusion scan under adenosine was performed before and after CSWT treatment. CSWT was well tolerated in all patients. Absolute perfusion under adenosine of the global left-ventricular myocardium did not change under therapy or minimal coronary resistance. The treated segments, however, showed in terms of both perfusion and resistance a mild but significant improvement, by 11 and 15 %, respectively, whereas no change could be observed in the remote segments. Considering a threshold of increased perfusion of 5 %, 10 (77 %) out of 13 patients with a better target perfusion improved in their CCS class, whereas 3 (43 %) out of 7 patients without improved target perfusion improved in their CCS class too. Standard CSWT has the potential to improve myocardial perfusion of the therapy zone and clinical CAD symptomatology without affecting global myocardial perfusion. As a noninvasive and well tolerated therapeutic option, these data suggest the use of CSWT in patients with end-stage CAD.

  19. Thallium-201 washout rate of stress myocardial perfusion imaging as a predictor of mortality in diabetic kidney disease patients initiating hemodialysis: an observational, follow-up study.

    PubMed

    Hayashi, Toshihide; Joki, Nobuhiko; Tanaka, Yuri; Iwasaki, Masaki; Kubo, Shun; Matsukane, Ai; Takahashi, Yasunori; Imamura, Yoshihiko; Hirahata, Koichi; Hase, Hiroki

    2017-04-21

    Thallium-201 washout rate of stress myocardial perfusion imaging (MPI) has been reported to correlate with coronary flow reserve which is a parameter of myocardial microcirculation. However, the evidence for its use in diabetic kidney disease (DKD) has been lacking, and the association between thallium-201 washout rate and adverse outcomes including death is unknown. Therefore, the present study was conducted to evaluate the predictive ability of thallium-201 washout rate for mortality in DKD patients initiating hemodialysis. A total of 96 patients with type 2 diabetes who had been started on maintenance hemodialysis undergoing stress MPI with thallium-201 within 1 year, 72 men and 24 women, with a median age of 67 years, were studied. The endpoint was defined as all-cause death. The Cox proportional hazards model was used to calculate hazard ratios (HR) and 95% confidence intervals (CI). During the mean follow-up period of 3.4 ± 2.1 years, 18 (18.8%) deaths occurred. Cumulative survival rates during the follow-up period, with thallium-201 washout rate levels in the lowest tertile (3.1-36.2%), the middle tertile (36.5-46.3%), and the highest tertile (46.4-66.2%), were 51.0, 86.5, and 85.3%, respectively. Overall, the multivariate Cox regression analysis revealed that thallium-201 washout rate remained an independent predictor of death after adjusting by confounding variables (HR 0.91, 95% CI 0.85-0.97). Among DKD patients initiating hemodialysis, thallium-201 washout rate seems to be useful for predicting death.

  20. Possible mechanism of adenosine protection in carbon tetrachloride acute hepatotoxicity. Role of adenosine by-products and glutathione peroxidase.

    PubMed

    Chagoya de Sánchez, V; Hernández-Muñoz, R; Yáñez, L; Vidrio, S; Díaz-Muñoz, M

    1995-02-01

    Adenosine proved to be an effective hepatoprotector increasing the survival rate of rats receiving lethal doses of CCl4. Searching for the mechanism of action, we found that adenosine transiently prevents the necrotic liver damage associated to an acute CCl4 treatment. The antilipoperoxidative action of the nucleoside was evidenced by a decrease of TBA-reactive products and the diene conjugates elicited by the hepatotoxin. Adenosine's protective effect was demonstrated by reverting the decrease of cytochrome P-450 while preserved intact the activity of the microsomal enzyme glucose-6-phosphatase. CCl4 promoted an increase in the oxidant stress through an enhancement in oxidized glutathione levels. This action was also completely counteracted by the nucleoside. Adenosine was unable to prevent CCl4 activation and, even, increased .CCl3 formation in the presence of PBN in vivo. However, in the presence of the nucleoside, irreversible binding of 14CCl4 to the microsomal lipid fraction of the treated animals was decreased. These results suggest that adenosine protective action might be exerted at the level of the propagation reaction following CCl4 activation. Two possible mechanisms were associated to the nucleoside protection: (1) the peroxide-metabolyzed enzymes, GSH-per, showed a marked increase after 30 minutes of adenosine treatment, which was potentiated by the hepatotoxin, suggesting an important role of this enzyme in the nucleoside's action; (2) the adenosine catabolism induced an increase in uric acid level, and allopurinol, a purine metabolism inhibitor, prevented such elevation as well as the antilipoperoxidative action of adenosine and the increase of GSH-per associated with the nucleoside treatment. These facts strongly suggest that the protective effect elicited by adenosine is not a direct one, but rather is related to its catabolic products, such as uric acid, which has been recognized as a free radical scavenger.

  1. Pharmacological and other nonexercise alternatives to exercise testing to evaluate myocardial perfusion and left ventricular function with radionuclides

    SciTech Connect

    DePuey, E.G.; Rozanski, A. )

    1991-04-01

    Pharmacological vasodilatation with either dipyridamole or adenosine is a safe and accurate alternative to exercise testing to diagnose coronary artery disease with thallium 201 myocardial perfusion imaging. The technique also provides important prognostic information with regard to future cardiac events in patients undergoing diagnostic testing, in those evaluated preoperatively, and in those with recent myocardial infarctions. Multigated equilibrium and first-pass radionuclide ventriculography also are well suited to evaluate the effects of interventional procedures. Success has been achieved using this methodology in a variety of interventions including conventional exercise testing, pharmacological stress testing, atrial pacing, assessment of myocardial viability with nitroglycerin, mental stress testing, and ambulatory monitoring of left ventricular ejection fraction. 67 references.

  2. Endocardial–epicardial distribution of myocardial perfusion reserve assessed by multidetector computed tomography in symptomatic patients without significant coronary artery disease: insights from the CORE320 multicentre study

    PubMed Central

    Kühl, Jørgen Tobias; George, Richard T.; Mehra, Vishal C.; Linde, Jesper J.; Chen, Marcus; Arai, Andrew E.; Di Carli, Marcelo; Kitagawa, Kakuya; Dewey, Marc; Lima, Joao A.C.; Kofoed, Klaus Fuglsang

    2016-01-01

    Aim Previous animal studies have demonstrated differences in perfusion and perfusion reserve between the subendocardium and subepicardium. 320-row computed tomography (CT) with sub-millimetre spatial resolution allows for the assessment of transmural differences in myocardial perfusion reserve (MPR) in humans. We aimed to test the hypothesis that MPR in all myocardial layers is determined by age, gender, and cardiovascular risk profile in patients with ischaemic symptoms or equivalent but without obstructive coronary artery disease (CAD). Methods and results A total of 149 patients enrolled in the CORE320 study with symptoms or signs of myocardial ischaemia and absence of significant CAD by invasive coronary angiography were scanned with static rest and stress CT perfusion. Myocardial attenuation densities were assessed at rest and during adenosine stress, segmented into 3 myocardial layers and 13 segments. MPR was higher in the subepicardium compared with the subendocardium (124% interquartile range [45, 235] vs. 68% [22,102], P < 0.001). Moreover, MPR in the septum was lower than in the inferolateral and anterolateral segments of the myocardium (55% [19, 104] vs. 89% [37, 168] and 124% [54, 270], P < 0.001). By multivariate analysis, high body mass index was significantly associated with reduced MPR in all myocardial layers when adjusted for cardiovascular risk factors (P = 0.02). Conclusion In symptomatic patients without significant coronary artery stenosis, distinct differences in endocardial–epicardial distribution of perfusion reserve may be demonstrated with static CT perfusion. Low MPR in all myocardial layers was observed specifically in obese patients. PMID:26341292

  3. Optimal thallium-201 dose in cadmium-zinc-telluride SPECT myocardial perfusion imaging.

    PubMed

    Ishihara, Masaru; Taniguchi, Yasuyo; Onoguchi, Masahisa; Shibutani, Takayuki

    2016-12-22

    We aimed to determine the optimal thallium 201 chloride (thallium-201) dose using a novel ultrafast cardiac gamma camera with cadmium-zinc-telluride (CZT) solid-state semiconductor detectors (D-SPECT). The optimal thallium-201 dose for obtaining left ventricular (LV) myocardial counts was determined from a phantom study. Consecutive 292 patients underwent stress myocardial perfusion imaging with a thallium-201 injection. Stress test comprised exercise or pharmacological (adenosine) provocation. We calculated an optimal thallium-201 dose that resulted in better LV myocardial counts during 6 minutes of acquisition time. We corrected the respective values according to the patient's age, sex, body mass index (BMI), and type of stress test. The lowest thallium-201 dose for obtaining acceptable imaging was 1.2 million counts. Radiopharmaceutical doses showed a positive correlation with the patient's age (P < .001), sex (P = .012), BMI (P < .001), and type of stress test (P < .001). Multivariate analysis revealed that the patient's BMI and the type of stress test were statistically significant factors for determining the correct radiopharmaceutical dose (P < .001 for both). For clinical use of the CZT SPECT system, the optimal individual thallium-201 doses can be determined based on the patient's BMI and type of stress test.

  4. [Myocardial perfusion scintigraphy 2012 in Germany. Results of the 6th Query].

    PubMed

    Lindner, O; Burchert, W; Schäfers, M; Schaefer, W

    2014-01-01

    The working group Cardiovascular Nuclear Medicine of the German Society of Nuclear Medicine presents the results of the 6th survey on myocardial perfusion scintigraphy (MPS) of the reporting year 2012. 278 questionnaires (177 private practices (PP), 78 hospitals (HO), 23 university hospitals (UH)) were evaluated. MPS of 105,941 patients were reported. 95% [2005 = 80%] of MPS studies were conducted with (99m)Tc perfusion radiopharmaceuticals and only 5% with 201Tl. 79% [2009 = 76%] of the MPS were performed in PP, 15% [2009 = 17%] in HO, and 6% [2009 = 7%] in UH. Data from 108 centres which participated in all surveys from 2005 to 2012 showed an increase in MPS numbers of 4.0% (PP +6.1%, HO +18.2%, UH -18.3%). 29% of all participants (27% of PP, 31% of HO, and 26% of UH) noticed no change and 26% of all participants (28% of PP, 17% of HO and 35% of UH) an increase in their MPS requests since the 2009 query. The type of stress was pharmacological in 39% [2009 = 31%]. Of these 61% with adenosine (39% with exercise), 22% with regadenoson (51% with exercise), 14% with dipyridamole (60% with exercise), and 3% with dobutamine. Gated SPECT was performed in 73% [2009 = 56%] of all rest, in 70% [2009 = 56%] of all stress and in 67% [47%] of all stress and rest MPS. Only 36% [2009 = 33%] of the centres performed a quantification of all their studies with scores, whereas 41% [2009 = 52%] did not apply any quantification. 60% [2009 = 49%] of the MPS were requested by ambulatory care cardiologists. The survey on MPS in Germany reveals a good conformity of imaging procedures with the current guideline. A positive development in MPS practice and referral can be stated. However, there is still some potential of MPS processing considering the quantitative perfusion analysis.

  5. Adenosine-associated delivery systems.

    PubMed

    Kazemzadeh-Narbat, Mehdi; Annabi, Nasim; Tamayol, Ali; Oklu, Rahmi; Ghanem, Amyl; Khademhosseini, Ali

    2015-01-01

    Adenosine is a naturally occurring purine nucleoside in every cell. Many critical treatments such as modulating irregular heartbeat (arrhythmias), regulation of central nervous system (CNS) activity and inhibiting seizural episodes can be carried out using adenosine. Despite the significant potential therapeutic impact of adenosine and its derivatives, the severe side effects caused by their systemic administration have significantly limited their clinical use. In addition, due to adenosine's extremely short half-life in human blood (<10 s), there is an unmet need for sustained delivery systems to enhance efficacy and reduce side effects. In this article, various adenosine delivery techniques, including encapsulation into biodegradable polymers, cell-based delivery, implantable biomaterials and mechanical-based delivery systems, are critically reviewed and the existing challenges are highlighted.

  6. Stress thallium-201/rest technetium-99m sequential dual-isotope high-speed myocardial perfusion imaging validation versus invasive coronary angiography.

    PubMed

    Barone-Rochette, Gilles; Leclere, Mélanie; Calizzano, Alex; Vautrin, Estelle; Céline, Gallazzini-Crepin; Broisat, Alexis; Ghezzi, Catherine; Baguet, Jean Philippe; Machecourt, Jacques; Vanzetto, Gérald; Fagret, Daniel

    2015-06-01

    Recent advances in nuclear myocardial perfusion imaging (MPI) have made it possible to develop a dual-isotope protocol for high-speed acquisition with image quality and radiation delivery comparable to that obtained with conventional single isotope protocols. So far, no study has compared dual-isotope high-speed MPI to invasive coronary angiography (ICA) in a large cohort using a Cadmium-zinc-telluride SPECT system. Over a 1-year period (May 2011 to April 2012), 1366 patients underwent dual-isotope high-speed MPI. Patients with ICA within 3 months after dual-isotope high-speed MPI were included together with patients with a low likelihood of coronary artery disease (CAD) in order to assess normalcy rate. Global summed stress score (SSS) and summed rest score (SRS) were calculated, and ICA results were analyzed independently. The main end point was a patient-based assessment of the diagnostic performance of dual-isotope high-speed MPI in detecting or ruling out significant CAD (>70% reduction in lumen diameter). Inclusion criteria were fulfilled for 214 patients (143 men; age 60 ± 14 years; ICA, n = 104; low likelihood for CAD, n = 110). An exercise stress test was performed in 62% of patients and a pharmacological stress test was performed with either dipyridamole (32%) or dobutamine (6%). Average examination duration was 22.4 ± 4.5 minutes. Mean SSS, SRS, and SDS were 8.0 ± 4.9, 3.1 ± 4.3, and 5.0 ± 3.2, respectively. Prevalence of angiographic CAD was 75%. ICA detected stenosis in the left main trunk, left anterior descending artery, left circumflex artery, and right coronary artery in 4, 33, 31, and 42 patients, respectively. Sensitivity of dual-isotope high-speed MPI was 94%, normalcy rate was 92%, and accuracy was 83% for detecting CAD. Dual-isotope high-speed MPI is reliable at detecting or ruling out CAD. NCT01785589.

  7. Comparison of the Diagnostic Performance of Four Quantitative Myocardial Perfusion Estimation Methods Used in Cardiac MR Imaging: CE-MARC Substudy.

    PubMed

    Biglands, John D; Magee, Derek R; Sourbron, Steven P; Plein, Sven; Greenwood, John P; Radjenovic, Aleksandra

    2015-05-01

    To compare the diagnostic performance of four tracer kinetic analysis methods to quantify myocardial perfusion from magnetic resonance (MR) imaging cardiac perfusion data sets in terms of their ability to lead to the diagnosis of myocardial ischemia. The study was approved by the regional ethics committee, and all patients gave written consent. A representative sample of 50 patients with suspected ischemic heart disease was retrospectively selected from the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease trial data set. Quantitative myocardial blood flow (MBF) was estimated from rest and adenosine stress MR imaging perfusion data sets by using four established methods. A matching diagnosis of both an inducible defect as assessed with single photon emission computed tomography and a luminal stenosis of 70% or more as assessed with quantitative x-ray angiography was used as the reference standard for the presence of myocardial ischemia. Diagnostic performance was evaluated with receiver operating characteristic (ROC) curve analysis for each method, with stress MBF and myocardial perfusion reserve (MPR) serving as continuous measures. Area under the ROC curve with stress MBF and MPR as the outcome measures, respectively, was 0.86 and 0.92 for the Fermi model, 0.85 and 0.87 for the uptake model, 0.85 and 0.80 for the one-compartment model, and 0.87 and 0.87 for model-independent deconvolution. There was no significant difference between any of the models or between MBF and MPR, except that the Fermi model outperformed the one-compartment model if MPR was used as the outcome measure (P = .02). Diagnostic performance of quantitative myocardial perfusion estimates is not affected by the tracer kinetic analysis method used. (©) RSNA

  8. Advances in understanding adenosine as a plurisystem modulator in sepsis and the systemic inflammatory response syndrome (SIRS).

    PubMed

    Conlon, Beth A; Ross, James D; Law, William R

    2005-09-01

    Adenosine is a ubiquitous molecule that influences every physiological system studied thus far. In this review, we consider the influence of this purine nucleoside on some of the physiological systems affected during sepsis and SIRS. In the control of perfusion and cardiac output distribution, endogenous adenosine appears to play an important role in regulating perfusion in various vascular beds. Some of this control is mediated by stimulation of adenylyl cyclase, while part occurs by stimulating the production of nitric oxide. In the heart, adenosine may act as an inhibitory modulator of TNF-alpha expression. With regard to innate immune responses the effects of adenosine vary considerably, and are complex. However, the dominant responses relevant to SIRS indicate attenuation of inflammatory responses. Many of the effects of adenosine may also involve modulating oxyradical-mediated response. This occurs via increased oxyradical production via adenosine degradation (xanthine oxidase pathway), or limiting inflammatory oxyradical generation. Attempts to exploit the beneficial responses to adenosine have met with some success, and are considered here.

  9. Intermedin1-53 attenuates vascular smooth muscle cell calcification by inhibiting endoplasmic reticulum stress via cyclic adenosine monophosphate/protein kinase A pathway.

    PubMed

    Chang, Jin-Rui; Duan, Xiao-Hui; Zhang, Bao-Hong; Teng, Xu; Zhou, Ye-Bo; Liu, Yue; Yu, Yan-Rong; Zhu, Yi; Tang, Chao-Shu; Qi, Yong-Fen

    2013-10-01

    We previously reported that endoplasmic reticulum (ER) stress-mediated apoptosis participated in vascular calcification. Importantly, a novel paracrine/autocrine peptide intermedin1-53 (IMD1-53) in the vasculature inhibited vascular calcification in rats. But the mechanisms needed to be fully elucidated. Vascular smooth muscle cells (VSMCs) calcification was induced by CaCl2 and β-glycerophosphate. Tunicamycin (Tm) or dithiothreitol (DTT) was used to induce ER stress. We found that IMD1-53 (10(-7)mol/L) treatment significantly alleviated the protein expression of ER stress hallmarks activating transcription factor 4 (ATF4), ATF6, glucose-regulated protein 78 (GRP78) and GRP94 induced by Tm or DTT. ER stress occurred in early and late calcification of VSMCs but was inhibited by IMD1-53. These inhibitory effects of IMD1-53 were abolished by treatment with the protein kinase A (PKA) inhibitor H89. Pretreatment with IMD1-53 decreased the number of apoptotic VSMCs and downregulated protein expression of cleaved caspase 12 and C/EBP homologous protein (CHOP) in calcified VSMCs. Concurrently, IMD1-53 restored the loss of VSMC lineage markers and ameliorated calcium deposition and alkaline phosphatase activity in calcified VSMCs as well. The observation was further verified by Alizarin Red S staining, which showed that IMD1-53 reduced positive red nodules among calcified VSMCs. In conclusion, IMD1-53 attenuated VSMC calcification by inhibiting ER stress through cAMP/PKA signalling.

  10. Imaging Adenosine Triphosphate (ATP)

    PubMed Central

    Rajendran, Megha; Dane, Eric; Conley, Jason; Tantama, Mathew

    2016-01-01

    Adenosine triphosphate (ATP) is a universal mediator of metabolism and signaling across unicellular and multicellular species. There is a fundamental interdependence between the dynamics of ATP and the physiology that occurs inside and outside the cell. Characterizing and understanding ATP dynamics provides valuable mechanistic insight into processes that range from neurotransmission to the chemotaxis of immune cells. Therefore, we require the methodology to interrogate both temporal and spatial components of ATP dynamics from the subcellular to organismal levels in live specimens. Over the last several decades, a number of molecular probes that are specific for ATP have been developed. These probes have been combined with imaging approaches, particularly optical microscopy, to enable qualitative and quantitative detection of this critical molecule. In this review, we survey current examples of technologies that are available to visualize ATP in living cells and identify areas where new tools and approaches are needed to expand our capabilities. PMID:27638696

  11. The clinical usefulness of electrocardiogram-gated Tc-99m methoxy-isobutyl-isonitrile images in the detection of basal wall motion abnormalities and reversibility of stress induced perfusion defects.

    PubMed

    Marzullo, P; Marcassa, C; Sambuceti, G; Parodi, O; L'Abbate, A

    1992-01-01

    Technetium-99m methoxy-isobutyl-isonitrile (SESTAMIBI) has been recently introduced to trace regional myocardial perfusion. Beyond blood flow distribution, a quantitative index of regional myocardial wall motion from SESTAMIBI electrocardiogram (ECG)-gated images was obtained, according to the assumption that changes in the detected radioactivity reflect changes in myocardial wall thickness during the cardiac cycle. As a preliminary study, 20 patients with coronary artery disease and regional wall motion abnormalities and 15 normal subjects were studied by SESTAMIBI scintigraphy and contrast ventriculography. Regional wall motion was analyzed by a radial method applied to both techniques. Absolute systolic changes in radioactivity and its ratio to reference normal values (wall thickening index, WTI) were determined in 9 anatomical cardiac regions according to the formula (endsystolic counting profile-enddiastolic counting profile/enddiastolic counting profile) x 100. The overall agreement between radioisotopic and ventriculographic techniques was 88% (158 of 180 segments). Normal, hypokinetic and akinetic ventriculographic segments showed WTI values of 1.1 +/- 0.2, 0.8 +/- 0.2 and 0.4 +/- 0.3 respectively (P less than 0.001). A second clinical study was performed in 25 patients studied by stress/rest ECG-gated SESTAMIBI scintigraphy. The assumption of this part of the study was to investigate if a preserved wall thickening in segments with stress defects might predict those areas with normal resting perfusion. Partial or total normalization of regional perfusion was observed in 90% of segments with a WTI greater than or equal to 0.8. These studies indicate the ECG-gated SESTAMIBI may represent a suitable technique for the simultaneous analysis of flow distribution and function. Analysis of post-exercise ECG-gated SESTAMIBI can predict the reversibility of transient perfusion defects.

  12. New Insights into the Cyclic Di-adenosine Monophosphate (c-di-AMP) Degradation Pathway and the Requirement of the Cyclic Dinucleotide for Acid Stress Resistance in Staphylococcus aureus*

    PubMed Central

    Bowman, Lisa; Zeden, Merve S.; Kaever, Volkhard

    2016-01-01

    Nucleotide signaling networks are key to facilitate alterations in gene expression, protein function, and enzyme activity in response to diverse stimuli. Cyclic di-adenosine monophosphate (c-di-AMP) is an important secondary messenger molecule produced by the human pathogen Staphylococcus aureus and is involved in regulating a number of physiological processes including potassium transport. S. aureus must ensure tight control over its cellular levels as both high levels of the dinucleotide and its absence result in a number of detrimental phenotypes. Here we show that in addition to the membrane-bound Asp-His-His and Asp-His-His-associated (DHH/DHHA1) domain-containing phosphodiesterase (PDE) GdpP, S. aureus produces a second cytoplasmic DHH/DHHA1 PDE Pde2. Although capable of hydrolyzing c-di-AMP, Pde2 preferentially converts linear 5′-phosphadenylyl-adenosine (pApA) to AMP. Using a pde2 mutant strain, pApA was detected for the first time in S. aureus, leading us to speculate that this dinucleotide may have a regulatory role under certain conditions. Moreover, pApA is involved in a feedback inhibition loop that limits GdpP-dependent c-di-AMP hydrolysis. Another protein linked to the regulation of c-di-AMP levels in bacteria is the predicted regulator protein YbbR. Here, it is shown that a ybbR mutant S. aureus strain has increased acid sensitivity that can be bypassed by the acquisition of mutations in a number of genes, including the gene coding for the diadenylate cyclase DacA. We further show that c-di-AMP levels are slightly elevated in the ybbR suppressor strains tested as compared with the wild-type strain. With this, we not only identified a new role for YbbR in acid stress resistance in S. aureus but also provide further insight into how c-di-AMP levels impact acid tolerance in this organism. PMID:27834680

  13. New Insights into the Cyclic Di-adenosine Monophosphate (c-di-AMP) Degradation Pathway and the Requirement of the Cyclic Dinucleotide for Acid Stress Resistance in Staphylococcus aureus.

    PubMed

    Bowman, Lisa; Zeden, Merve S; Schuster, Christopher F; Kaever, Volkhard; Gründling, Angelika

    2016-12-30

    Nucleotide signaling networks are key to facilitate alterations in gene expression, protein function, and enzyme activity in response to diverse stimuli. Cyclic di-adenosine monophosphate (c-di-AMP) is an important secondary messenger molecule produced by the human pathogen Staphylococcus aureus and is involved in regulating a number of physiological processes including potassium transport. S. aureus must ensure tight control over its cellular levels as both high levels of the dinucleotide and its absence result in a number of detrimental phenotypes. Here we show that in addition to the membrane-bound Asp-His-His and Asp-His-His-associated (DHH/DHHA1) domain-containing phosphodiesterase (PDE) GdpP, S. aureus produces a second cytoplasmic DHH/DHHA1 PDE Pde2. Although capable of hydrolyzing c-di-AMP, Pde2 preferentially converts linear 5'-phosphadenylyl-adenosine (pApA) to AMP. Using a pde2 mutant strain, pApA was detected for the first time in S. aureus, leading us to speculate that this dinucleotide may have a regulatory role under certain conditions. Moreover, pApA is involved in a feedback inhibition loop that limits GdpP-dependent c-di-AMP hydrolysis. Another protein linked to the regulation of c-di-AMP levels in bacteria is the predicted regulator protein YbbR. Here, it is shown that a ybbR mutant S. aureus strain has increased acid sensitivity that can be bypassed by the acquisition of mutations in a number of genes, including the gene coding for the diadenylate cyclase DacA. We further show that c-di-AMP levels are slightly elevated in the ybbR suppressor strains tested as compared with the wild-type strain. With this, we not only identified a new role for YbbR in acid stress resistance in S. aureus but also provide further insight into how c-di-AMP levels impact acid tolerance in this organism.

  14. Myocardial perfusion as an indicator of graft patency after coronary artery bypass surgery. [Thallium 201

    SciTech Connect

    Kolibash, A.J.; Call, T.D.; Bush, C.A.; Tetalman, M.R.; Lewis, R.P.

    1980-05-01

    Stress and resting myocardial perfusion were assessed in 38 patients who received 96 grafts. Stress perfusion was evaluated with thallium-201 and resting myocardial blood flow distribution with radiolabeled particles. When both stress and rest perfusion were normal, graft patency was 82% (51 of 62 grafts). Graft patency was also high (81%, 13 of 16) in areas where stress perfusion abnormalities resolved or become less apparent at rest. However, when stress perfusion defects remained unchanged at rest, the graf was likely to be occuluded (73%, 11 of 15). Maintenance of normal rest perfusion or improvement of rest perfusion postoperatively was also associated with a high graft patency rate (80%, 35 of 44), whereas the development of new rest perfusion defects postoperatively implied graft occlusion (86%, six of seven).

  15. Nuclear cardiology: Myocardial perfusion and function

    SciTech Connect

    Seldin, D.W. )

    1991-08-01

    Myocardial perfusion studies continue to be a major focus of research, with new investigations of the relationship of exercise-redistribution thallium imaging to diagnosis, prognosis, and case management. The redistribution phenomenon, which seemed to be fairly well understood a few years ago, is now recognized to be much more complex than originally thought, and various strategies have been proposed to clarify the meaning of persistent defects. Pharmacologic intervention with dipyridamole and adenosine has become available as an alternative to exercise, and comparisons with exercise imaging and catheterization results have been described. Thallium itself is no longer the sole single-photon perfusion radiopharmaceutical; two new technetium agents are now widely available. In addition to perfusion studies, advances in the study of ventricular function have been made, including reports of studies performed in conjunction with technetium perfusion studies, new insights into cardiac physiology, and the prognostic and case-management information that function studies provide. Finally, work has continued with monoclonal antibodies for the identification of areas of myocyte necrosis. 41 references.

  16. Quantification of myocardial perfusion using cardiac magnetic resonance imaging correlates significantly to rubidium-82 positron emission tomography in patients with severe coronary artery disease: a preliminary study.

    PubMed

    Qayyum, Abbas A; Hasbak, Philip; Larsson, Henrik B W; Christensen, Thomas E; Ghotbi, Adam A; Mathiasen, Anders B; Vejlstrup, Niels G; Kjaer, Andreas; Kastrup, Jens

    2014-07-01

    Aim was to compare absolute myocardial perfusion using cardiac magnetic resonance imaging (CMRI) based on Tikhonov's procedure of deconvolution and rubidium-82 positron emission tomography (Rb-82 PET). Fourteen patients with coronary artery stenosis underwent rest and adenosine stress imaging by 1.5-Tesla MR Scanner and a mCT/PET 64-slice Scanner. CMRI were analyzed based on Tikhonov's procedure of deconvolution without specifying an explicit compartment model using our own software. PET images were analyzed using standard clinical software. CMRI and PET data was compared with Spearman's rho and Bland-Altman analysis. CMRI results were strongly and significantly correlated with PET results for the absolute global myocardial perfusion differences (r=0.805, p=0.001) and for global myocardial perfusion reserve (MPR) (r=0.886, p<0.001). At vessel territorial level, CMRI results were also significantly correlated with absolute PET myocardial perfusion differences (r=0.737, p<0.001) and MPR (r=0.818, p<0.001). Each vessel territory had similar strong correlation for absolute myocardial perfusion differences (right coronary artery (RCA): r=0.787, p=0.001; left anterior descending artery (LAD): r=0.796, p=0.001; left circumflex artery (LCX): r=0.880, p<0.001) and for MPR (RCA: r=0.895, p<0.001; LAD: r=0.886, p<0.001; LCX: r=0.886, p<0.001). On a global and vessel territorial basis, CMRI-measured absolute myocardial perfusion differences and MPR were strongly and significantly correlated with the Rb-82 PET findings. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Purine metabolism in adenosine deaminase deficiency.

    PubMed Central

    Mills, G C; Schmalstieg, F C; Trimmer, K B; Goldman, A S; Goldblum, R M

    1976-01-01

    Purine and pyrimidine metabolites were measured in erythrocytes, plasma, and urine of a 5-month-old infant with adenosine deaminase (adenosine aminohydrolase, EC 3.5.4.4) deficiency. Adenosine and adenine were measured using newly devised ion exchange separation techniques and a sensitive fluorescence assay. Plasma adenosine levels were increased, whereas adenosine was normal in erythrocytes and not detectable in urine. Increased amounts of adenine were found in erythrocytes and urine as well as in the plasma. Erythrocyte adenosine 5'-monophosphate and adenosine diphosphate concentrations were normal, but adenosine triphosphate content was greatly elevated. Because of the possibility of pyrimidine starvation, pyrimidine nucleotides (pyrimidine coenzymes) in erythrocytes and orotic acid in urine were measured. Pyrimidine nucleotide concentrations were normal, while orotic acid was not detected. These studies suggest that the immune deficiency associated with adenosine deaminase deficiency may be related to increased amounts of adenine, adenosine, or adenine nucleotides. PMID:1066699

  18. Improved exercise myocardial perfusion during lidoflazine therapy

    SciTech Connect

    Shapiro, W.; Narahara, K.A.; Park, J.

    1983-11-01

    Lidoflazine is a synthetic drug with calcium-channel blocking effects. In a study of 6 patients with severe classic angina pectoris, single-blind administration of lidoflazine was associated with improved myocardial perfusion during exercise as determined by thallium-201 stress scintigraphy. These studies demonstrate that lidoflazine therapy is associated with relief of angina, an increased physical work capacity, and improved regional myocardial perfusion during exercise.

  19. In vitro effects of bisphenol A on the quality parameters, oxidative stress, DNA integrity and adenosine triphosphate content in sterlet (Acipenser ruthenus) spermatozoa.

    PubMed

    Hulak, Martin; Gazo, Ievgeniia; Shaliutina, Anna; Linhartova, Pavla

    2013-08-01

    Among endocrine disruptors, the xenoestrogen bisphenol A (BPA) deserves particular attention due to widespread human exposure. Besides hormonal effects, BPA has been suspected to be responsible for adverse effect on reproductive ability of various species. In the present study the effect of BPA on the quality parameters, oxidative stress, the DNA integrity and intracellular ATP content of sterlet (Acipenser ruthenus) spermatozoa were investigated in vitro. Fish spermatozoa were exposed to concentrations of BPA possibly occurring in nature (0.5, 1.75, 2.5, 5 and 10μg/L) for 2h. Results revealed that BPA significantly decreased spermatozoa motility and velocity of spermatozoa at concentration of BPA 2.5-10μg/L. Significant positive correlation (r=0.713, P<0.05) was found between percent motile spermatozoa and ATP content. Oxidative stress was observed at concentrations 1.75-10μg/L, as reflected by significantly higher levels of protein and lipid oxidation and superoxide dismutase activity. Intracellular ATP content of spermatozoa decreased with increasing concentrations of BPA. A dramatic increase in DNA fragmentation expressed as percent tail DNA (2.2%±0.46) and Olive tail moment (0.37±0.09 arbitrary units) was recorded at concentrations of 1.75μg/L and above. The present study confirms that concentrations of BPA that can be encountered in nature are capable to induce oxidative stress, leading to impaired sperm quality, DNA fragmentation and intracellular ATP content. Copyright © 2013. Published by Elsevier Inc.

  20. Adenosine-Associated Delivery Systems

    PubMed Central

    Kazemzadeh-Narbat, Mehdi; Annabi, Nasim; Tamayol, Ali; Oklu, Rahmi; Ghanem, Amyl; Khademhosseini, Ali

    2016-01-01

    Adenosine is a naturally occurring purine nucleoside in every cell. Many critical treatments such as modulating irregular heartbeat (arrhythmias), regulation of central nervous system (CNS) activity, and inhibiting seizural episodes can be carried out using adenosine. Despite the significant potential therapeutic impact of adenosine and its derivatives, the severe side effects caused by their systemic administration have significantly limited their clinical use. In addition, due to adenosine’s extremely short half-life in human blood (less than 10 s), there is an unmet need for sustained delivery systems to enhance efficacy and reduce side effects. In this paper, various adenosine delivery techniques, including encapsulation into biodegradable polymers, cell-based delivery, implantable biomaterials, and mechanical-based delivery systems, are critically reviewed and the existing challenges are highlighted. PMID:26453156

  1. Effects of adenosine, exercise, and moderate acute hypoxia on energy substrate utilization of human skeletal muscle.

    PubMed

    Heinonen, Ilkka; Kemppainen, Jukka; Kaskinoro, Kimmo; Peltonen, Juha E; Sipilä, Hannu T; Nuutila, Pirjo; Knuuti, Juhani; Boushel, Robert; Kalliokoski, Kari K

    2012-02-01

    Glucose metabolism increases in hypoxia and can be influenced by endogenous adenosine, but the role of adenosine for regulating glucose metabolism at rest or during exercise in hypoxia has not been elucidated in humans. We studied the effects of exogenous adenosine on human skeletal muscle glucose uptake and other blood energy substrates [free fatty acid (FFA) and lactate] by infusing adenosine into the femoral artery in nine healthy young men. The role of endogenous adenosine was studied by intra-arterial adenosine receptor inhibition (aminophylline) during dynamic one-leg knee extension exercise in normoxia and acute hypoxia corresponding to ∼3,400 m of altitude. Extraction and release of energy substrates were studied by arterial-to-venous (A-V) blood samples, and total uptake or release was determined by the product of A-V differences and muscle nutritive perfusion measured by positron emission tomography. The results showed that glucose uptake increased from a baseline value of 0.2 ± 0.2 to 2.0 ± 2.2 μmol·100 g(-1)·min(-1) during adenosine infusion (P < 0.05) at rest. Although acute hypoxia enhanced arterial FFA levels, it did not affect muscle substrate utilization at rest. During exercise, glucose uptake was higher (195%) during acute hypoxia compared with normoxia (P = 0.058), and aminophylline had no effect on energy substrate utilization during exercise, despite that arterial FFA levels were increased. In conclusion, exogenous adenosine at rest and acute moderate hypoxia during low-intensity knee-extension exercise increases skeletal muscle glucose uptake, but the increase in hypoxia appears not to be mediated by adenosine.

  2. Predator odor evokes sex-independent stress responses in male and female Wistar rats and reduces phosphorylation of cyclic-adenosine monophosphate response element binding protein in the male, but not the female hippocampus.

    PubMed

    Homiack, Damek; O'Cinneide, Emma; Hajmurad, Sema; Barrileaux, Brett; Stanley, Mary; Kreutz, Michael R; Schrader, Laura A

    2017-09-01

    Post-traumatic stress disorder (PTSD) is characterized by memory disturbances following trauma. Acute predator threat has emerged as an ethological model of PTSD, yet the effects of predator odor on signaling cascades associated with long-term memory remain poorly understood. In this study, we exposed male and female Wistar rats to the synthetic predator odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) to assess behavioral and physiological responses as well as rapid modulation of signal transduction cascades associated with learning and memory in the male and female hippocampus. During exposure to TMT in the homecage, both male and female animals displayed robust immobility, avoidance, and altered activity as a function of time. Physiologically, TMT exposure increased circulating corticosterone and blood glucose in both male and female rodents, suggesting that TMT evokes sex-independent behavioral and physiological responses. With respect to signal transduction, TMT exposure rapidly reduced phosphorylation of cyclic-adenosine monophosphate response element binding protein (CREB) in the male, but not the female hippocampus. Furthermore, TMT exposure reduced phosphorylation of extracellular signal-regulated kinase 1/2 and increased nuclear expression of the synapto-nuclear messenger protein Jacob in the male hippocampus, consistent with activation of the CREB shut-off pathway. In a follow-up behavioral experiment, post-training exposure to TMT did not affect spatial water maze performance of male rats. However, male rats re-introduced to the context in which TMT had previously been presented displayed avoidance and hyperactivity, but not freezing behavior or elevated corticosterone responses, suggesting that TMT exposure supports a form of contextual conditioning which is not characterized by immobility. Taken together, our findings suggest that TMT evokes similar behavioral and physiological responses in male and female Wistar rats, but affects distinct signaling

  3. Sulphur flux through the sulphate assimilation pathway is differently controlled by adenosine 5'-phosphosulphate reductase under stress and in transgenic poplar plants overexpressing gamma-ECS, SO, or APR.

    PubMed

    Scheerer, Ursula; Haensch, Robert; Mendel, Ralf R; Kopriva, Stanislav; Rennenberg, Heinz; Herschbach, Cornelia

    2010-01-01

    Sulphate assimilation provides reduced sulphur for the synthesis of cysteine, methionine, and numerous other essential metabolites and secondary compounds. The key step in the pathway is the reduction of activated sulphate, adenosine 5'-phosphosulphate (APS), to sulphite catalysed by APS reductase (APR). In the present study, [(35)S]sulphur flux from external sulphate into glutathione (GSH) and proteins was analysed to check whether APR controls the flux through the sulphate assimilation pathway in poplar roots under some stress conditions and in transgenic poplars. (i) O-Acetylserine (OAS) induced APR activity and the sulphur flux into GSH. (ii) The herbicide Acetochlor induced APR activity and results in a decline of GSH. Thereby the sulphur flux into GSH or protein remained unaffected. (iii) Cd treatment increased APR activity without any changes in sulphur flux but lowered sulphate uptake. Several transgenic poplar plants that were manipulated in sulphur metabolism were also analysed. (i) Transgenic poplar plants that overexpressed the gamma-glutamylcysteine synthetase (gamma-ECS) gene, the enzyme catalysing the key step in GSH formation, showed an increase in sulphur flux into GSH and sulphate uptake when gamma-ECS was targeted to the cytosol, while no changes in sulphur flux were observed when gamma-ECS was targeted to plastids. (ii) No effect on sulphur flux was observed when the sulphite oxidase (SO) gene from Arabidopsis thaliana, which catalyses the back reaction of APR, that is the reaction from sulphite to sulphate, was overexpressed. (iii) When Lemna minor APR was overexpressed in poplar, APR activity increased as expected, but no changes in sulphur flux were observed. For all of these experiments the flux control coefficient for APR was calculated. APR as a controlling step in sulphate assimilation seems obvious under OAS treatment, in gamma-ECS and SO overexpressing poplars. A possible loss of control under certain conditions, that is Cd treatment

  4. Adenosine A2(A) receptor gene polymorphism (1976C>T) affects coronary flow reserve response during vasodilator stress testing in patients with non ischemic-dilated cardiomyopathy.

    PubMed

    Andreassi, Maria Grazia; Laghi Pasini, Franco; Picano, Eugenio; Capecchi, Pier Leopoldo; Pompella, Gerarda; Foffa, Ilenia; Borghini, Andrea; Sicari, Rosa

    2011-08-01

    Patients with non ischemic-dilated cardiomyopathy (DCM) are characterized by an activation of the adenosinergic system and reduced coronary flow reserve (CFR) evaluated by transthoracic Doppler echocardiography during vasodilator adenosinergic stress (dipyridamole administration). The aim of this study was to assess whether genetic polymorphisms (263C>T and 1976C>T) of the A2(A) receptor gene affect CFR response in patients with DCM. We enrolled a group of 80 patients with DCM (55 male; age, 62±10.3 years) and 162 healthy volunteers (55 male; age, 45.1±9.5 years). Doppler-derived CFR (high-dose dipyridamole coronary diastolic peak flow velocity to resting coronary peak flow velocity ratio) of distal left anterior descending artery was determined in DCM. A2(A) receptor genotyping was determined in all patients by polymerase chain reaction-restriction fragment length polymorphism analysis. The expression of A2(A) protein and mRNA was also assessed in healthy controls. The genotype distribution of the 263C>T (P=0.5) and 1976C>T (P=0.8) polymorphisms was not significantly different between patients and controls. Patients with 1976TT genotype had significantly lower CFR value than 1976CC patients (2.3±0.7, 2.0±0.5 and 1.9±0.4, P<0.05 for CC, CT and TT genotypes, respectively). Controls who were heterozygous (P=0.02) or homozygous (P=0.001) for the T1976 allele showed a significant increase in A2(A) receptor protein. These data demonstrate that A2(A) 1976C>T polymorphism is associated with a blunted coronary vasodilatory response in patients with DCM, and support a direct consequences of this single nucleotide polymorphism for protein expression. Additional studies are needed to better define the functional role of this genetic variant as well as to clarify the potential clinical impact of genetics during pharmacological stress cardiac imaging.

  5. Adenosine receptor targets for pain.

    PubMed

    Sawynok, J

    2016-12-03

    The main focus for the development of adenosine targets as analgesics to date has been A1Rs due to its antinociceptive profile in various preclinical pain models. The usefulness of systemic A1R agonists may be limited by other effects (cardiovascular, motor), but enhanced selectivity for pain might occur with partial agonists, potent and highly selective agonists, or allosteric modulators. A2AR agonists exhibit some peripheral pronociceptive effects, but also act on immune cells to suppress inflammation and on spinal glia to suppress pain signaling and may be useful for inflammatory and neuropathic pain. A2BR agonists exhibit peripheral proinflammatory effects on immune cells, but also spinal antinociceptive effects similar to A2AR agonists. A3Rs are now demonstrated to produce antinociception in several preclinical neuropathic pain models, with mechanistic actions on glial cells, and may be useful for neuropathic pain. Endogenous adenosine levels can be augmented by inhibition of metabolism (via adenosine kinase) or increased generation (via nucleotidases), and these approaches have implications for pain. Endogenous adenosine contributes to antinociception by several pharmacological agents, herbal remedies, acupuncture, transcutaneous electrical nerve stimulation, exercise, joint mobilization, and water immersion via spinal and/or peripheral effects, such that this system appears to constitute a major pain regulatory system. Finally, caffeine inhibits A1-, A2A- and A3Rs with similar potency, and dietary caffeine intake will need attention in trials of: (a) agonists and/or modulators acting at these receptors, (b) some pharmacological and herbal analgesics, and (c) manipulations that enhance endogenous adenosine levels, all of which are inhibited by caffeine and/or A1R antagonists in preclinical studies. All adenosine receptors have effects on spinal glial cells in regulating nociception, and gender differences in the involvement of such cells in chronic

  6. Cochlear perfusion with a viscous fluid.

    PubMed

    Wang, Yi; Olson, Elizabeth S

    2016-07-01

    The flow of viscous fluid in the cochlea induces shear forces, which could provide benefit in clinical practice, for example to guide cochlear implant insertion or produce static pressure to the cochlear partition or wall. From a research standpoint, studying the effects of a viscous fluid in the cochlea provides data for better understanding cochlear fluid mechanics. However, cochlear perfusion with a viscous fluid may damage the cochlea. In this work we studied the physiological and anatomical effects of perfusing the cochlea with a viscous fluid. Gerbil cochleae were perfused at a rate of 2.4 μL/min with artificial perilymph (AP) and sodium hyaluronate (Healon, HA) in four different concentrations (0.0625%, 0.125%, 0.25%, 0.5%). The different HA concentrations were applied either sequentially in the same cochlea or individually in different cochleae. The perfusion fluid entered from the round window and was withdrawn from basal scala vestibuli, in order to perfuse the entire perilymphatic space. Compound action potentials (CAP) were measured after each perfusion. After perfusion with increasing concentrations of HA in the order of increasing viscosity, the CAP thresholds generally increased. The threshold elevation after AP and 0.0625% HA perfusion was small or almost zero, and the 0.125% HA was a borderline case, while the higher concentrations significantly elevated CAP thresholds. Histology of the cochleae perfused with the 0.0625% HA showed an intact Reissner's membrane (RM), while in cochleae perfused with 0.125% and 0.25% HA RM was torn. Thus, the CAP threshold elevation was likely due to the broken RM, likely caused by the shear stress produced by the flow of the viscous fluid. Our results and analysis indicate that the cochlea can sustain, without a significant CAP threshold shift, up to a 1.5 Pa shear stress. Beside these finding, in the 0.125% and 0.25% HA perfusion cases, a temporary CAP threshold shift was observed, perhaps due to the presence and

  7. Cochlear perfusion with a viscous fluid

    PubMed Central

    Wang, Yi; Olson, Elizabeth S.

    2016-01-01

    The flow of viscous fluid in the cochlea induces shear forces, which could provide benefit in clinical practice, for example to guide cochlear implant insertion or produce static pressure to the cochlear partition or wall. From a research standpoint, studying the effects of a viscous fluid in the cochlea provides data for better understanding cochlear fluid mechanics. However, cochlear perfusion with a viscous fluid may damage the cochlea. In this work we studied the physiological and anatomical effects of perfusing the cochlea with a viscous fluid. Gerbil cochleae were perfused at a rate of 2.4 μL/min with artificial perilymph (AP) and sodium hyaluronate (Healon, HA) in four different concentrations (0.0625%, 0.125%, 0.25%, 0.5%). The different HA concentrations were applied either sequentially in the same cochlea or individually in different cochleae. The perfusion fluid entered from the round window and was withdrawnfrom basal scala vestibuli, in order to perfuse the entire perilymphatic space. Compound action potentials (CAP) were measured after each perfusion. After perfusion with increasing concentrations of HA in the order of increasing viscosity, the CAP thresholds generally increased. The threshold elevation after AP and 0.0625% HA perfusion was small or almost zero, and the 0.125% HA was a borderline case, while the higher concentrations significantly elevated CAP thresholds. Histology of the cochleae perfused with the 0.0625% HA showed an intact Reissner’s membrane, while in cochleae perfused with 0.125% and 0.25% HA Reissner’s membrane (RM) was torn. Thus, the CAP threshold elevation was likely due to the broken of RM, which likely caused by the shear stress produced by the flow of the viscous fluid. Our results and analysis indicate that the cochlea can sustain, without a significant CAP threshold shift, up to a 1.5 Pa shear stress. Beside these finding, in the 0.125% and 0.25% HA perfusion cases, a temporary CAP threshold shift was observed

  8. Alkaline Phosphatase, Soluble Extracellular Adenine Nucleotides, and Adenosine Production after Infant Cardiopulmonary Bypass.

    PubMed

    Davidson, Jesse A; Urban, Tracy; Tong, Suhong; Twite, Mark; Woodruff, Alan; Wischmeyer, Paul E; Klawitter, Jelena

    2016-01-01

    Decreased alkaline phosphatase activity after infant cardiac surgery is associated with increased post-operative cardiovascular support requirements. In adults undergoing coronary artery bypass grafting, alkaline phosphatase infusion may reduce inflammation. Mechanisms underlying these effects have not been explored but may include decreased conversion of extracellular adenine nucleotides to adenosine. 1) Evaluate the association between alkaline phosphatase activity and serum conversion of adenosine monophosphate to adenosine after infant cardiac surgery; 2) assess if inhibition/supplementation of serum alkaline phosphatase modulates this conversion. Pre/post-bypass serum samples were obtained from 75 infants <4 months of age. Serum conversion of 13C5-adenosine monophosphate to 13C5-adenosine was assessed with/without selective inhibition of alkaline phosphatase and CD73. Low and high concentration 13C5-adenosine monophosphate (simulating normal/stress concentrations) were used. Effects of alkaline phosphatase supplementation on adenosine monophosphate clearance were also assessed. Changes in serum alkaline phosphatase activity were strongly correlated with changes in 13C5-adenosine production with or without CD73 inhibition (r = 0.83; p<0.0001). Serum with low alkaline phosphatase activity (≤80 U/L) generated significantly less 13C5-adenosine, particularly in the presence of high concentration 13C5-adenosine monophosphate (10.4μmol/L vs 12.9μmol/L; p = 0.0004). Inhibition of alkaline phosphatase led to a marked decrease in 13C5-adenosine production (11.9μmol/L vs 2.7μmol/L; p<0.0001). Supplementation with physiologic dose human tissue non-specific alkaline phosphatase or high dose bovine intestinal alkaline phosphatase doubled 13C5-adenosine monophosphate conversion to 13C5-adenosine (p<0.0001). Alkaline phosphatase represents the primary serum ectonucleotidase after infant cardiac surgery and low post-operative alkaline phosphatase activity leads to

  9. Myocardial Perfusion Imaging with a Solid State Camera: Simulation of a Very Low Dose Imaging Protocol

    PubMed Central

    Nakazato, Ryo; Berman, Daniel S.; Hayes, Sean W.; Fish, Mathews; Padgett, Richard; Xu, Yuan; Lemley, Mark; Baavour, Rafael; Roth, Nathaniel; Slomka, Piotr J.

    2012-01-01

    High sensitivity dedicated cardiac systems cameras provide an opportunity to lower injected doses for SPECT myocardial perfusion imaging (MPI), but the exact limits for lowering doses have not been determined. List mode data acquisition allows for reconstruction of various fractions of acquired counts, allowing a simulation of gradually lower administered dose. We aimed to determine the feasibility of very low dose MPI by exploring the minimal count level in the myocardium for accurate MPI. Methods Seventy nine patients were studied (mean body mass index 30.0 ± 6.6, range 20.2–54.0 kg/m2) who underwent 1-day standard dose 99mTc-sestamibi exercise or adenosine rest/stress MPI for clinical indications employing a Cadmium Zinc Telluride dedicated cardiac camera. Imaging time was 14-min with 803 ± 200 MBq (21.7 ± 5.4mCi) of 99mTc injected at stress. To simulate clinical scans with lower dose at that imaging time, we reframed the list-mode raw data to have count fractions of the original scan. Accordingly, 6 stress equivalent datasets were reconstructed corresponding to each fraction of the original scan. Automated QPS/QGS software was used to quantify total perfusion deficit (TPD) and ejection fraction (EF) for all 553 datasets. Minimal acceptable count was determined based on previous report with repeatability of same-day same-injection Anger camera studies. Pearson correlation coefficients and SD of differences with TPD for all scans were calculated. Results The correlations of quantitative perfusion and function analysis were excellent for both global and regional analysis on all simulated low-counts scans (all r ≥0.95, p<0.0001). Minimal acceptable count was determined to be 1.0 million counts for the left ventricular region. At this count level, SD of differences was 1.7% for TPD and 4.2% for EF. This count level would correspond to a 92.5 MBq (2.5 mCi) injected dose for the 14 min acquisition. Conclusion 1.0 million myocardial count images appear to be

  10. T2-prepared steady-state free precession blood oxygen level-dependent MR imaging of myocardial perfusion in a dog stenosis model.

    PubMed

    Shea, Steven M; Fieno, David S; Schirf, Brian E; Bi, Xiaoming; Huang, Jie; Omary, Reed A; Li, Debiao

    2005-08-01

    To assess the ability of a T2-prepared steady-state free precession blood oxygen level-dependent (BOLD) magnetic resonance (MR) imaging sequence to depict changes in myocardial perfusion during stress testing in a dog stenosis model. Study was approved by the institutional Animal Care and Use Committee. A hydraulic occluder was placed in the left circumflex coronary artery (LCX) in 10 dogs. Adenosine was administered intravenously to increase coronary blood flow, and stenosis was achieved in the LCX with the occluder. A T2-prepared two-dimensional steady-state free precession sequence was used for BOLD imaging at a spatial resolution of 1.5 x 1.2 x 5.0 mm3, and first-pass perfusion images were acquired for visual comparison. Microspheres were injected to provide regional perfusion information. Mixed-effect regression analysis was performed to assess normalized MR signal intensity ratios and microsphere-measured perfusion differences. For the same data, 95% prediction intervals were calculated to determine the smallest perfusion change detectable. Means +/- standard deviations were calculated for myocardial regional comparison data. A two-tailed Student t test was used to determine if significant differences (P < .01) existed between different myocardial regions. Under maximal adenosine stress, MR clearly depicted stenotic regions and showed regional signal differences between the left anterior descending coronary artery (LAD)-fed myocardium and the stenosed LCX-fed myocardium. Visual comparisons with first-pass images were also excellent. Regional MR signal intensity differences between LAD and LCX-fed myocardium (1.24 +/- 0.08) were significantly different (P < .01) from differences between LAD and septal-fed myocardium (1.02 +/- 0.07), which was in agreement with microsphere-measured flow differences (LAD/LCX, 3.38 +/- 0.83; LAD/septal, 1.26 +/- 0.49). The linear mixed-effect regression model showed good correlation (R = 0.79) between MR differences and

  11. Effects of Curcumin on Parameters of Myocardial Oxidative Stress and of Mitochondrial Glutathione Turnover in Reoxygenation after 60 Minutes of Hypoxia in Isolated Perfused Working Guinea Pig Hearts.

    PubMed

    Ilyas, Ermita I Ibrahim; Nur, Busjra M; Laksono, Sonny P; Bahtiar, Anton; Estuningtyas, Ari; Vitasyana, Caecilia; Kusmana, Dede; Suyatna, Frans D; Tadjudin, Muhammad Kamil; Freisleben, Hans-Joachim

    2016-01-01

    In cardiovascular surgery ischemia-reperfusion injury is a challenging problem, which needs medical intervention. We investigated the effects of curcumin on cardiac, myocardial, and mitochondrial parameters in perfused isolated working Guinea pig hearts. After preliminary experiments to establish the model, normoxia was set at 30 minutes, hypoxia was set at 60, and subsequent reoxygenation was set at 30 minutes. Curcumin was applied in the perfusion buffer at 0.25 and 0.5 μM concentrations. Cardiac parameters measured were afterload, coronary and aortic flows, and systolic and diastolic pressure. In the myocardium histopathology and AST in the perfusate indicated cell damage after hypoxia and malondialdehyde (MDA) levels increased to 232.5% of controls during reoxygenation. Curcumin protected partially against reoxygenation injury without statistically significant differences between the two dosages. Mitochondrial MDA was also increased in reoxygenation (165% of controls), whereas glutathione was diminished (35.2%) as well as glutathione reductase (29.3%), which was significantly increased again to 62.0% by 0.05 μM curcumin. Glutathione peroxidase (GPx) was strongly increased in hypoxia and even more in reoxygenation (255% of controls). Curcumin partly counteracted this increase and attenuated GPx activity independently in hypoxia and in reoxygenation, 0.25 μM concentration to 150% and 0.5 μM concentration to 200% of normoxic activity.

  12. Effects of Curcumin on Parameters of Myocardial Oxidative Stress and of Mitochondrial Glutathione Turnover in Reoxygenation after 60 Minutes of Hypoxia in Isolated Perfused Working Guinea Pig Hearts

    PubMed Central

    Ilyas, Ermita I. Ibrahim; Nur, Busjra M.; Laksono, Sonny P.; Bahtiar, Anton; Estuningtyas, Ari; Vitasyana, Caecilia; Kusmana, Dede; Suyatna, Frans D.; Tadjudin, Muhammad Kamil; Freisleben, Hans-Joachim

    2016-01-01

    In cardiovascular surgery ischemia-reperfusion injury is a challenging problem, which needs medical intervention. We investigated the effects of curcumin on cardiac, myocardial, and mitochondrial parameters in perfused isolated working Guinea pig hearts. After preliminary experiments to establish the model, normoxia was set at 30 minutes, hypoxia was set at 60, and subsequent reoxygenation was set at 30 minutes. Curcumin was applied in the perfusion buffer at 0.25 and 0.5 μM concentrations. Cardiac parameters measured were afterload, coronary and aortic flows, and systolic and diastolic pressure. In the myocardium histopathology and AST in the perfusate indicated cell damage after hypoxia and malondialdehyde (MDA) levels increased to 232.5% of controls during reoxygenation. Curcumin protected partially against reoxygenation injury without statistically significant differences between the two dosages. Mitochondrial MDA was also increased in reoxygenation (165% of controls), whereas glutathione was diminished (35.2%) as well as glutathione reductase (29.3%), which was significantly increased again to 62.0% by 0.05 μM curcumin. Glutathione peroxidase (GPx) was strongly increased in hypoxia and even more in reoxygenation (255% of controls). Curcumin partly counteracted this increase and attenuated GPx activity independently in hypoxia and in reoxygenation, 0.25 μM concentration to 150% and 0.5 μM concentration to 200% of normoxic activity. PMID:26904113

  13. Beneficial and detrimental role of adenosine signaling in diseases and therapy.

    PubMed

    Liu, Hong; Xia, Yang

    2015-11-15

    Adenosine is a major signaling nucleoside that orchestrates cellular and tissue adaptation under energy depletion and ischemic/hypoxic conditions by activation of four G protein-coupled receptors (GPCR). The regulation and generation of extracellular adenosine in response to stress are critical in tissue protection. Both mouse and human studies reported that extracellular adenosine signaling plays a beneficial role during acute states. However, prolonged excess extracellular adenosine is detrimental and contributes to the development and progression of various chronic diseases. In recent years, substantial progress has been made to understand the role of adenosine signaling in different conditions and to clarify its significance during the course of disease progression in various organs. These efforts have and will identify potential therapeutic possibilities for protection of tissue injury at acute stage by upregulation of adenosine signaling or attenuation of chronic disease progression by downregulation of adenosine signaling. This review is to summarize current progress and the importance of adenosine signaling in different disease stages and its potential therapeutic effects.

  14. Pharmacological Reconditioning of Marginal Donor Rat Lungs Using Inhibitors of Peroxynitrite and Poly (ADP-ribose) Polymerase During Ex Vivo Lung Perfusion.

    PubMed

    Wang, Xingyu; Wang, Yabo; Parapanov, Roumen; Abdelnour, Etienne; Gronchi, Fabrizio; Perentes, Jean Yannis; Piquilloud, Lise; Ris, Hans-Beat; Letovanec, Igor; Liaudet, Lucas; Krueger, Thorsten

    2016-07-01

    Donor lungs obtained after prolonged warm ischemia (WI) may be unsuitable for transplantation due to the risk of reperfusion injury, but could be reconditioned using ex-vivo lung perfusion (EVLP). Key processes of reperfusion injury include the formation of reactive oxygen species (ROS)/nitrogen species (RNS) and the activation of poly(adenosine diphosphate-ribose) polymerase (PARP). We explored whether rat lungs obtained after WI could be reconditioned during EVLP using the ROS/RNS scavenger Mn(III)-tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP) or the PARP inhibitor 3-aminobenzamide (3-AB). Rat lungs obtained after 3 hours cold ischemia (CI group, control), or 1 hour WI plus 2 hours CI (WI group) were placed in an EVLP circuit for normothermic perfusion for 3 hours. Lungs retrieved after WI were treated or not with 3-AB (1 mg/mL) or MnTBAP (0.3 mg/mL), added to the perfusate. Measurements included physiological variables (lung compliance, vascular resistance, oxygenation capacity), lung weight gain, levels of proteins, lactate dehydrogenase, protein carbonyl (marker of ROS), 3-nitrotyrosine (marker of RNS), poly(adenosine diphosphate-ribose) (PAR, marker of PARP activation) and IL-6, in the bronchoalveolar lavage or the lung tissue, and histology. In comparison to the CI group, the lungs from the WI group displayed higher protein carbonyls, 3-nitrotyrosine, PAR, lactate dehydrogenase and proteins in bronchoalveolar lavage, lung weight gain, perivascular edema, as well as reduced static compliance, but similar oxygenation. All these alterations were markedly attenuated by 3-AB and MnTBAP. After EVLP, lungs obtained after WI exhibit oxidative stress, PARP activation, and tissue injury, which are suppressed by pharmacological inhibitors of ROS/RNS and PARP.

  15. Molecular implications of adenosine in obesity.

    PubMed

    Pardo, Fabián; Villalobos-Labra, Roberto; Chiarello, Delia I; Salsoso, Rocío; Toledo, Fernando; Gutierrez, Jaime; Leiva, Andrea; Sobrevia, Luis

    2017-06-01

    Adenosine has broad activities in organisms due to the existence of multiple receptors, the differential adenosine concentrations necessary to activate these receptors and the presence of proteins able to synthetize, degrade or transport this nucleoside. All adenosine receptors have been reported to be involved in glucose homeostasis, inflammation, adipogenesis, insulin resistance, and thermogenesis, indicating that adenosine could participate in the process of obesity. Since adenosine seems to be associated with several effects, it is plausible that adenosine participates in the initiation and development of obesity or may function to prevent it. Thus, the purpose of this review was to explore the involvement of adenosine in adipogenesis, insulin resistance and thermogenesis, with the aim of understanding how adenosine could be used to avoid, treat or improve the metabolic state of obesity. Treatment with specific agonists and/or antagonists of adenosine receptors could reverse the obesity state, since adenosine receptors normalizes several mechanisms involved in obesity, such as lipolysis, insulin sensitivity and thermogenesis. Furthermore, obesity is a preventable state, and the specific activation of adenosine receptors could aid in the prevention of obesity. Nevertheless, for the treatment of obesity and its consequences, more studies and therapeutic strategies in addition to adenosine are necessary. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. In vivo assessment of coronary flow and cardiac function after bolus adenosine injection in adenosine receptor knockout mice.

    PubMed

    Teng, Bunyen; Tilley, Stephen L; Ledent, Catherine; Mustafa, S Jamal

    2016-06-01

    Bolus injections of adenosine and the A2A adenosine receptor (AR) selective agonist (regadenoson) are used clinically as a substitute for a stress test in people who cannot exercise. Using isolated tissue preparations, our lab has shown that coronary flow and cardiac effects of adenosine are mostly regulated by the AR subtypes A1, A2A, and A2B In this study, we used ultrasound imaging to measure the in vivo effects of adenosine on coronary blood flow (left coronary artery) and cardiac function in anesthetized wild-type, A1 knockout (KO), A2AKO, A2BKO, A3KO, A1, and A3 double KO (A1/3 DKO) and A2A and A2B double KO (A2A/2B DKO) mice in real time. Echocardiographic and Doppler studies were performed using a Visualsonic Vevo 2100 ultrasound system. Coronary blood flow (CBF) baseline data were obtained when animals were anesthetized with 1% isoflourane. Diameter (D) and velocity time integral (VTI) were measured on the left coronary arteries (CBF = ((π/4) × D(2) × VTI × HR)/1000). CBF changes were the highest within 2 min of injection (about 10 mg/kg). Heart rate, cardiac output, and stroke volume were measured by tracing the left ventricle long axis. Our data support a role for the A2 AR in CBF and further support our conclusions of previous studies from isolated tissues. Adenosine-mediated decreases in cardiac output and stroke volume may be A2B and/or A3 AR-mediated; however, the A1 and A2 ARs also play roles in overall cardiac function. These data further provide a powerful translational tool in studying the cardiovascular effects of adenosine in disease states.

  17. Regional Stress-Induced Ischemia in Non-fibrotic Hypertrophied Myocardium in Young HCM Patients.

    PubMed

    Jablonowski, Robert; Fernlund, Eva; Aletras, Anthony H; Engblom, Henrik; Heiberg, Einar; Liuba, Petru; Arheden, Håkan; Carlsson, Marcus

    2015-12-01

    The relationship between hypertrophy, perfusion abnormalities and fibrosis is unknown in young patients with hypertrophic cardiomyopathy (HCM). Since mounting evidence suggests causal relationship between myocardial ischemia and major adverse cardiac events, we sought to investigate whether (1) regional myocardial perfusion is decreased in young HCM patients and in individuals at risk of HCM, and (2) hypoperfused areas are larger than areas with fibrosis. HCM patients (n = 12), HCM-risk subjects (n = 15) and controls (n = 9) were imaged on a 1.5 T MRI scanner. Myocardial hypertrophy was assessed on cine images. Perfusion images were acquired during adenosine hyperemia and at rest. Maximum upslope ratios of perfusion (stress/rest) were used for semiquantitative analysis. Fibrosis was assessed by late gadolinium enhancement (LGE). Results are presented as median and range. Perfusion in HCM-risk subjects and in non-hypertrophied segments in HCM patients showed no difference compared to controls (P = ns). Hypertrophic segments in HCM patients without LGE showed decreased perfusion compared to segments without hypertrophy [1.5 (1.1-2.3) vs. 2.0 (1.8-2.6), P < 0.001], and hypertrophic segments with LGE showed even lower perfusion using a segmental analysis [0.9 (0.6-1.8), P < 0.05]. The extent of hypoperfused myocardium in HCM patients during adenosine exceeded the extent of fibrosis on LGE [20 (0-48) vs. 4 (0-7) % slice area, P < 0.05] and hypoperfused areas at rest (P < 0.001). Regional perfusion is decreased in hypertrophied compared to non-hypertrophied myocardium and is lowest in fibrotic myocardium in young HCM patients but does not discriminate HCM-risk subjects from controls. The stress-induced hypoperfused regions exceed regions with LGE, indicating that hypoperfusion precedes fibrosis and may be a more sensitive marker of diseased myocardium in HCM.

  18. Tachy-Brady Arrhythmias: The Critical Role of Adenosine-induced Sino-Atrial Conduction Block in Post-Tachycardia Pauses

    PubMed Central

    Lou, Qing; Glukhov, Alexey V.; Hansen, Brian; Hage, Lori; Vargas-Pinto, Pedro; Billman, George E.; Carnes, Cynthia A.; Fedorov, Vadim V.

    2012-01-01

    Background In patients with sinoatrial nodal (SAN) dysfunction, atrial pauses lasting several seconds may follow rapid atrial pacing or paroxysmal tachycardia (tachy-brady arrhythmias). Clinical studies suggest that adenosine may play an important role in SAN dysfunction, but the mechanism remains unclear. Objective To define the mechanism of SAN dysfunction induced by the combination of adenosine and tachycardia. Methods We studied the mechanism of SAN dysfunction produced by a combination of adenosine and rapid atrial pacing in isolated coronary-perfused canine atrial preparations using high-resolution optical mapping (n=9). Sinus cycle length (SCL) and sinoatrial conduction time (SACT) were measured during adenosine (1–100μM) and 1μM DPCPX (A1 receptor antagonist, n=7) perfusion. Sinoatrial node recovery time was measured after one minute of “slow” pacing (3.3Hz) or tachypacing (7–9Hz). Results Adenosine significantly increased SCL (477±62 vs. 778±114 ms, p<0.01), and SACT during sinus rhythm (41±11 vs. 86±16 ms, p<0.01) dose-dependently. Adenosine dramatically affected SACT of the first SAN beat after tachypacing (41±5 vs. 221±98ms, p<0.01). Moreover, at high concentrations of adenosine (10–100μM), termination of tachypacing or atrial flutter/fibrillation produced atrial pauses of 4.2±3.4 seconds (n=5) due to conduction block between the SAN and atria, despite a stable SAN intrinsic rate. Conduction block was preferentially related to depressed excitability in SAN conduction pathways. Adenosine-induced changes were reversible upon washout or DPCPX treatment. Conclusions These data directly demonstrate that adenosine contributes to post-tachycardia atrial pauses through SAN exit block rather than slowed pacemaker automaticity. Thus, these data suggest an important modulatory role of adenosine in tachy-brady syndrome. PMID:22985657

  19. Adenosine receptors mediate synergistic stimulation of glucose uptake and transport by insulin and by contractions in rat skeletal muscle.

    PubMed Central

    Vergauwen, L; Hespel, P; Richter, E A

    1994-01-01

    The role of adenosine receptors in the regulation of muscle glucose uptake by insulin and contractions was studied in isolated rat hindquarters that were perfused with a standard medium containing no insulin or a submaximal concentration of 100 microU/ml. Adenosine receptor antagonism was induced by caffeine or 8-cyclopentyl-1,3-dipropylxantine (CPDPX). Glucose uptake and transport were measured before and during 30 min of electrically induced muscle contractions. Caffeine nor CPDPX affected glucose uptake in resting hindquarters. In contrast, the contraction-induced increase in muscle glucose uptake was inhibited by 30-50% by caffeine, as well as by CPDPX, resulting in a 20-25% decrease in the absolute rate of glucose uptake during contractions, compared with control values. This inhibition was independent of the rate of perfusate flow and only occurred in hindquarters perfused with insulin added to the medium. Thus, adenosine receptor antagonism inhibited glucose uptake during simultaneous exposure to insulin and contractions only. Accordingly, caffeine inhibited 3-O-methylglucose uptake during contractions only in oxidative muscle fibers that are characterized by a high sensitivity to insulin. In conclusion, the present data demonstrate A1 receptors to regulate insulin-mediated glucose transport in contracting skeletal muscle. The findings provide evidence that stimulation of sarcolemmic adenosine receptors during contractions is involved in the synergistic stimulation of muscle glucose transport by insulin and by contractions. PMID:8132783

  20. Adenosine-5'-O-phosphorylated and adenosine-5'-O-phosphorothioylated polyols as strong inhibitors of (symmetrical) and (asymmetrical) dinucleoside tetraphosphatases.

    PubMed Central

    Guranowski, Andrzej; Starzyńska, Elzbieta; McLennan, Alexander G; Baraniak, Janina; Stec, Wojciech J

    2003-01-01

    Dinucleoside 5',5"'- P (1), P ( n )-polyphosphates, and particularly the diadenosine compounds, have been implicated in extracellular purinergic signalling and in various intracellular processes, including DNA metabolism, tumour suppression and stress responses. If permitted to accumulate, they may also be toxic. One approach to understanding their function is through the various specific degradative enzymes that regulate their levels. Eight adenosine-5'- O -phosphorylated polyols (derivatives of glycerol, erythritol and pentaerythritol) and 11 adenosine-5'- O -phosphorothioylated polyols (derivatives of glycerol, erythritol, pentaerythritol, butanediol and pentanediol) have been tested as inhibitors of specific diadenosine tetraphosphate (Ap(4)A) hydrolases. Of these two groups of novel nucleotides, the adenosine-5'- O -phosphorothioylated polyols were generally stronger inhibitors than their adenosine-5'- O -phosphorylated counterparts. 1,4-Di(adenosine-5'- O -phosphorothio) erythritol appeared to be the strongest inhibitor of ( asymmetrical ) Ap(4)A hydrolases (EC 3.6.1.17) from both lupin and human, with K (i) values of 0.15 microM and 1.5 microM respectively. Of eight adenosine-5'- O -phosphorylated polyols, 1,4-di(adenosine-5'- O -phospho) erythritol was the only compound that inhibited the lupin enzyme. Two derivatives of pentaerythritol, di(adenosine-5'- O -phosphorothio)-di(phosphorothio) pentaerythritol and tri(adenosine-5'- O -phosphorothio)-phosphorothio-pentaerythritol, proved to be the strongest inhibitors of the prokaryotic ( symmetrical ) Ap(4)A hydrolase (EC 3.6.1.41) so far reported. The estimated K (i) values were 0.04 microM and 0.08 microM respectively. All of these inhibitors were competitive with respect to Ap(4)A. These new selectively acting Ap(4)A analogues should prove to be valuable tools for further studies of Ap(4)A function and of the enzymes involved in its metabolism. PMID:12697025

  1. Coronary microvascular ischemia in hypertrophic cardiomyopathy - a pixel-wise quantitative cardiovascular magnetic resonance perfusion study

    PubMed Central

    2014-01-01

    Background Microvascular dysfunction in HCM has been associated with adverse clinical outcomes. Advances in quantitative cardiovascular magnetic resonance (CMR) perfusion imaging now allow myocardial blood flow to be quantified at the pixel level. We applied these techniques to investigate the spectrum of microvascular dysfunction in hypertrophic cardiomyopathy (HCM) and to explore its relationship with fibrosis and wall thickness. Methods CMR perfusion imaging was undertaken during adenosine-induced hyperemia and again at rest in 35 patients together with late gadolinium enhancement (LGE) imaging. Myocardial blood flow (MBF) was quantified on a pixel-by-pixel basis from CMR perfusion images using a Fermi-constrained deconvolution algorithm. Regions-of-interest (ROI) in hypoperfused and hyperemic myocardium were identified from the MBF pixel maps. The myocardium was also divided into 16 AHA segments. Results Resting MBF was significantly higher in the endocardium than in the epicardium (mean ± SD: 1.25 ± 0.35 ml/g/min versus 1.20 ± 0.35 ml/g/min, P < 0.001), a pattern that reversed with stress (2.00 ± 0.76 ml/g/min versus 2.36 ± 0.83 ml/g/min, P < 0.001). ROI analysis revealed 11 (31%) patients with stress MBF lower than resting values (1.05 ± 0.39 ml/g/min versus 1.22 ± 0.36 ml/g/min, P = 0.021). There was a significant negative association between hyperemic MBF and wall thickness (β = −0.047 ml/g/min per mm, 95% CI: −0.057 to −0.038, P < 0.001) and a significantly lower probability of fibrosis in a segment with increasing hyperemic MBF (odds ratio per ml/g/min: 0.086, 95% CI: 0.078 to 0.095, P = 0.003). Conclusions Pixel-wise quantitative CMR perfusion imaging identifies a subgroup of patients with HCM that have localised severe microvascular dysfunction which may give rise to myocardial ischemia. PMID:25160568

  2. All-Systolic Non-ECG-gated Myocardial Perfusion MRI: Feasibility of Multi-Slice Continuous First-Pass Imaging

    PubMed Central

    Sharif, Behzad; Arsanjani, Reza; Dharmakumar, Rohan; Bairey Merz, C. Noel; Berman, Daniel S.; Li, Debiao

    2015-01-01

    Purpose To develop and test the feasibility of a new method for non-ECG-gated first-pass perfusion (FPP) cardiac MR capable of imaging multiple short-axis slices at the same systolic cardiac phase. Methods A magnetization-driven pulse sequence was developed for non-ECG-gated FPP imaging without saturation-recovery preparation using continuous slice-interleaved radial sampling. The image reconstruction method, dubbed TRACE, employed self-gating based on reconstruction of a real-time image-based navigator combined with reference-constrained compressed sensing. Data from ischemic animal studies (n=5) was used in a simulation framework to evaluate temporal fidelity. Healthy subjects (n=5) were studied using both the proposed and conventional method to compare the myocardial contrast-to-noise ratio (CNR). Patients (n=2) underwent adenosine stress studies using the proposed method. Results Temporal fidelity of the developed method was shown to be sufficient at high heart-rates. The healthy volunteers studies demonstrated normal perfusion and no artifacts. Compared to the conventional scheme, myocardial CNR for the proposed method was slightly higher (8.6±0.6 vs. 8.0±0.7). Patient studies showed stress-induced perfusion defects consistent with invasive angiography. Conclusions The presented methods and results demonstrate feasibility of the proposed approach for high-resolution non-ECG-gated FPP imaging and indicate its potential for achieving desirable image quality (high CNR, no dark-rim artifacts) with a 3-slice spatial coverage, all imaged at the same systolic phase. PMID:26052843

  3. Why do premature newborn infants display elevated blood adenosine levels?

    PubMed

    Panfoli, Isabella; Cassanello, Michela; Bruschettini, Matteo; Colella, Marina; Cerone, Roberto; Ravera, Silvia; Calzia, Daniela; Candiano, Giovanni; Ramenghi, Luca

    2016-05-01

    infants may be regarded as those in which premature exposure to ambient oxygen concentrations and oxidative stress causes a premature functioning of the extra-mitochondrial oxidative phosphorylation primarily in axons and endothelium. Adenosine may become a biomarker of prematurity risk, whose implications further studies may assess.

  4. Cu2+ and acute thermal stress induce protective events via the p38-MAPK signalling pathway in the perfused Rana ridibunda heart.

    PubMed

    Gaitanaki, Catherine; Pliatska, Maria; Stathopoulou, Konstantina; Beis, Isidoros

    2007-02-01

    In the present study, we investigated the induction of the p38-MAPK signalling pathway by copper, as exemplified by CuCl(2), in the isolated perfused heart of the amphibian Rana ridibunda. We found that p38-MAPK phosphorylation by CuCl(2) occurs in a dose-dependent manner, with maximum activation (8.73+/-1.43-fold relative to control values) attained by perfusion with 500 micromol l(-1) CuCl(2) for 15 min, while this activation sustained even after 60 min of reperfusion with normal bicarbonate buffer. CuCl(2) also induced the phosphorylation of the small heat shock protein 27 (Hsp27) in a p38-MAPK dependent manner, as revealed by experiments using the p38-MAPK inhibitor SB203580. p38-MAPK and Hsp27 phosphorylations were also strongly induced by hyperthermia (42 degrees C), while the simultaneous use of hyperthermia and CuCl(2) had a synergistic effect on p38-MAPK activation. Furthermore, perfusions with the potent antioxidant L-ascorbic acid (100 micromol l(-1)), the antioxidant enzymes catalase (CAT) (150 U ml(-1)) or superoxide dismutase (SOD) (30 U ml(-1)) in the presence of 500 micromol l(-1) CuCl(2) did not attenuate the CuCl(2)-induced p38-MAPK activation, implying that at least the reactive oxygen species (ROS) scavenged by these agents are not implicated in this kinase activation. The p38-MAPK phosphorylation induced by the combined action of CuCl(2) and hyperthermia was partially inhibited by catalase, indicating that hyperthermia possibly activates the kinase through the production of H(2)O(2). Caspase-3, an effector protease of apoptosis, remained inactive in hearts perfused at normal or hyperthermic conditions, in the absence or presence of 500 micromol l(-1) CuCl(2). All the above results suggest that, in the amphibian Rana ridibunda heart, p38-MAPK activation by copper has a possible protective role through the small Hsp27.

  5. Regulation of adenosine levels during cerebral ischemia

    PubMed Central

    Chu, Stephanie; Xiong, Wei; Zhang, Dali; Soylu, Hanifi; Sun, Chao; Albensi, Benedict C; Parkinson, Fiona E

    2013-01-01

    Adenosine is a neuromodulator with its level increasing up to 100-fold during ischemic events, and attenuates the excitotoxic neuronal injury. Adenosine is produced both intracellularly and extracellularly, and nucleoside transport proteins transfer adenosine across plasma membranes. Adenosine levels and receptor-mediated effects of adenosine are regulated by intracellular ATP consumption, cellular release of ATP, metabolism of extracellular ATP (and other adenine nucleotides), adenosine influx, adenosine efflux and adenosine metabolism. Recent studies have used genetically modified mice to investigate the relative contributions of intra- and extracellular pathways for adenosine formation. The importance of cortical or hippocampal neurons as a source or a sink of adenosine under basal and hypoxic/ischemic conditions was addressed through the use of transgenic mice expressing human equilibrative nucleoside transporter 1 (hENT1) under the control of a promoter for neuron-specific enolase. From these studies, we conclude that ATP consumption within neurons is the primary source of adenosine in neuronal cultures, but not in hippocampal slices or in vivo mice exposed to ischemic conditions. PMID:23064722

  6. Role of myocardial perfusion single photon emission computed tomography in pediatric cardiology practice

    PubMed Central

    Sundaram, P Shanmuga; Padma, S

    2009-01-01

    Diagnostic and prognostic power of myocardial perfusion imaging in patients with coronary artery disease has been demonstrated with planar imaging which was further improvised with addition of gated SPECT and newer Technetium labeled myocardial perfusion tracers like SestaMIBI, Tetrofosmin. Myocardial perfusion abnormalities at rest and after stress are considered to be the best predictors of cardiac event–free survival in adults with ischemic heart disease. This article highlights various myocardial perfusion imaging (MPI) radiopharmaceuticals, exercise procedures, pharmacological stress protocols, indications for MPI and myocardial perfusion patterns in children with some of the common congenital and acquired heart diseases. PMID:20808625

  7. Perfusion preservation maintains myocardial ATP levels and reduces apoptosis in an ex vivo rat heart transplantation model.

    PubMed

    Peltz, Matthias; He, Tian-Teng; Adams, Glenn A; Koshy, Seena; Burgess, Shawn C; Chao, Robert Y; Meyer, Dan M; Jessen, Michael E

    2005-10-01

    Machine perfusion preservation improves reperfusion function of many solid organs, compared with conventional storage, but has received limited clinical attention in preserving hearts for transplantation. We evaluated representative extracellular (Celsior) and intracellular (University of Wisconsion) storage solutions using static and perfusion protective strategies over a clinically relevant preservation period. Rat hearts were preserved for 200 minutes by either static storage or perfusion preservation in Celsior or University of Wisconsin solutions. Three conditions were studied: conventional static storage; static storage using either solution with 5.5 mmol/L glucose added; and perfusion preservation using either solution with 5.5 mmol/L glucose added. Glucose was provided as U-13C-labeled glucose, and glycolysis and oxidative metabolism during preservation were quantified from incorporation of (13)C into glycolytic and tricarboxylic acid cycle intermediates. Adenosine triphosphate levels after preservation, and apoptosis and cardiac function after reperfusion were measured. Both perfusion preservation groups had higher myocardial oxygen consumption during storage and better early graft function, compared with static preservation groups (P < .05). Adenosine triphosphate levels were higher after storage in the perfusion groups (P < .01). Apoptosis was reduced in the perfusion groups (P < .01). Comparing perfusion groups, hearts preserved with Celsior had higher myocardial oxygen consumption and glucose utilization during perfusion storage and exhibited decreased reperfusion coronary vascular resistance and myocardial water content, compared with the UW perfusion group (P < .05). Perfusion preservation results in greater metabolism during storage and superior cardiac function with improved myocyte survival, compared with static storage. Extracellular preservation solutions appear more effective for perfusion preservation, possibly by augmenting cellular

  8. Hypoxic vasodilatation in isolated, perfused guinea-pig heart: an analysis of the underlying mechanisms.

    PubMed Central

    von Beckerath, N; Cyrys, S; Dischner, A; Daut, J

    1991-01-01

    1. The mechanisms underlying hypoxic dilatation of coronary arteries were studied in isolated guinea-pig hearts perfused with physiological salt solution at 37 degrees C. The hearts were perfused at a constant rate of 3-10 ml min-1; coronary perfusion pressure (CPP) and isovolumetric left ventricular pressure (LVP) were measured with piezoresistive transducers. 2. Addition of the K+ channel opener cromakalim (500 nM) to the perfusate caused a maximal vasodilatation in beating hearts, i.e. a decrease in CPP of about 50%. Switching from normal perfusate (partial pressure of O2 (PO2), 650-700 mmHg) to hypoxic perfusate (PO2, 9-10 mmHg) caused a similar vasodilatation. Both of these effects were prevented by 2 microM-glibenclamide, a blocker of ATP-sensitive potassium channels. Hypoxic vasodilatation was accompanied by a marked decrease in LVP, which was reduced by 56 +/- 22% (mean +/- S.D.) in the presence of glibenclamide. 3. In hearts arrested by increasing the K+ concentration of the perfusate to 15 mM, the addition of the adenosine-uptake inhibitor dipyridamole evoked a maximal vasodilatation and this was inhibited by 76 +/- 7% in the presence of glibenclamide. 4. The adenosine antagonist 8-phenyltheophylline (8-PT; 5 microM) inhibited the vasodilatation induced by dipyridamole by 88 +/- 10%. In contrast, hypoxic vasodilatation was unaffected by 5 microM 8-PT. This suggests that hypoxic dilatation of coronary arteries is not mediated by release of adenosine from cardiomyocytes. 5. In order to test whether release of endothelium-derived relaxing factor (EDRF) contributed to hypoxic vasodilatation we blocked EDRF synthesis with N omega-nitro-L-arginine (NNA). When applied at a perfusion rate of 10 ml min-1 to arrested hearts, 10 microM-NNA increased CPP by 35% and prolonged the delay between application of hypoxic solution and half-maximal vasodilatation from 52 +/- 9 to 129 +/- 29 s. 6. Under control conditions the relation between perfusion rate and the CPP

  9. Imaging of myocardial perfusion with magnetic resonance.

    PubMed

    Barkhausen, Jörg; Hunold, Peter; Jochims, Markus; Debatin, Jörg F

    2004-06-01

    Coronary artery disease (CAD) is currently the leading cause of death in developed nations. Reflecting the complexity of cardiac function and morphology, noninvasive diagnosis of CAD represents a major challenge for medical imaging. Although coronary artery stenoses can be depicted with magnetic resonance (MR) and computed tomography (CT) techniques, its functional or hemodynamic impact frequently remains elusive. Therefore, there is growing interest in other, target organ-specific parameters such as myocardial function at stress and first-pass myocardial perfusion imaging to assess myocardial blood flow. This review explores the pathophysiologic background, recent technical developments, and current clinical status of first-pass MR imaging (MRI) of myocardial perfusion.

  10. Abdominal perfusion computed tomography.

    PubMed

    Ogul, Hayri; Bayraktutan, Ummugulsum; Kizrak, Yesim; Pirimoglu, Berhan; Yuceler, Zeynep; Sagsoz, M Erdem; Yilmaz, Omer; Aydinli, Bulent; Ozturk, Gurkan; Kantarci, Mecit

    2013-02-01

    The purpose of this article is to provide an up to date review on the spectrum of applications of perfusion computed tomography (CT) in the abdomen. New imaging techniques have been developed with the objective of obtaining a structural and functional analysis of different organs. Recently, perfusion CT has aroused the interest of many researchers who are studying the applicability of imaging modalities in the evaluation of abdominal organs and diseases. Per-fusion CT enables fast, non-invasive imaging of the tumor vascular physiology. Moreover, it can act as an in vivo biomarker of tumor-related angiogenesis.

  11. Abdominal Perfusion Computed Tomography

    PubMed Central

    Ogul, Hayri; Bayraktutan, Ummugulsum; Kizrak, Yesim; Pirimoglu, Berhan; Yuceler, Zeynep; Sagsoz, M. Erdem; Yilmaz, Omer; Aydinli, Bulent; Ozturk, Gurkan; Kantarci, Mecit

    2013-01-01

    The purpose of this article is to provide an up to date review on the spectrum of applications of perfusion computed tomography (CT) in the abdomen. New imaging techniques have been developed with the objective of obtaining a structural and functional analysis of different organs. Recently, perfusion CT has aroused the interest of many researchers who are studying the applicability of imaging modalities in the evaluation of abdominal organs and diseases. Per-fusion CT enables fast, non-invasive imaging of the tumor vascular physiology. Moreover, it can act as an in vivo biomarker of tumor-related angiogenesis. PMID:25610249

  12. Fluorometric Determination of Adenosine Nucleotide Derivatives as Measures of the Microfouling, Detrital, and Sedimentary Microbial Biomass and Physiological Status

    PubMed Central

    Davis, William M.; White, David C.

    1980-01-01

    Adenosine, adenine, cyclic adenosine monophosphate (AMP), AMP, nicotinamide adenine dinucleotide, adenosine diphosphate, and adenosine triphosphate (ATP) were recovered quantitatively from aqueous portions of lipid extracts of microfouling, detrital, and sedimentary microbial communities. These could be detected quantitatively in the picomolar range by forming their 1-N6-etheno derivatives and analyzing by high-pressure liquid chromatography with fluorescence detection. Lipid extraction and subsequent analysis allowed the simultaneous measurement of the microbial community structure, total microbial biomass with the quantitative recovery of the adenine-containing cellular components, which were protected from enzymatic destruction. This extraction and fluorescent derivatization method showed equivalency with the luciferin-luciferase method for bacterial ATP measurements. Quick-freezing samples in the field with dry ice-acetone preserved the ATP and energy charge (a ratio of adenosine nucleotides) for analysis at remote laboratories. The metabolic lability of ATP in estuarine detrital and microfouling communities, as well as bacterial monocultures of constant biomass, showed ATP to be a precarious measure of biomass under some conditions. Combinations of adenosine and adenine nucleotides gave better correlations with microbial biomass measured as extractable lipid phosphate in the detrital and microfouling microbial communities than did ATP alone. Stresses such as anoxia or filtration are reflected in the rapid accumulation of intracellular adenosine and the excretion of adenosine and AMP into the surrounding milieu. Increases in AMP and adenosine may prove to be more sensitive indicators of metabolic status than the energy charge. PMID:16345633

  13. Diagnostic Performance of First-Pass Myocardial Perfusion Imaging without Stress with Computed Tomography (CT) Compared with Coronary CT Angiography Alone, with Fractional Flow Reserve as the Reference Standard.

    PubMed

    Osawa, Kazuhiro; Miyoshi, Toru; Miki, Takashi; Koyama, Yasushi; Sato, Shuhei; Kanazawa, Susumu; Ito, Hiroshi

    2016-01-01

    Coronary computed tomography angiography (CCTA) in combination with first-pass CT myocardial perfusion imaging (MPI) has a better diagnostic performance than CCTA alone, compared with invasive coronary angiography as the reference standard. The aim of this study was to investigate the additional diagnostic value of first-pass CT-MPI without stress for detecting hemodynamic significance of coronary stenosis, compared with invasive fractional flow reserve (FFR). We recruited 53 patients with suspected coronary artery disease undergoing both CCTA and first-pass CT-MPI without stress and invasive FFR, and 75 vessels were analyzed. We used the same raw data for CCTA and CT-MPI. First-pass CT-MPI was reconstructed by examining the diastolic signal densities as a bull's eye map. Invasive FFR <0.8 was considered as positive. On per-vessel analysis, the area under the receiver operating characteristic curve for CCTA plus first-pass CT-MPI and CCTA alone was 0.81 (0.73-0.90) and 0.70 (0.61-0.81), respectively (P = 0.036). CCTA plus first-pass CT-MPI without stress showed 0.73 sensitivity, 0.74 specificity, 0.53 positive predictive value, and 0.87 negative predictive value for detecting hemodynamically significant coronary stenosis. First-pass CT-MPI without stress correctly reclassified 38% of CCTA false-positive vessels as true negative. First-pass CT-MPI without stress combined with CCTA demonstrated excellent diagnostic accuracy, compared with invasive FFR as the reference standard. This technique could complement CCTA for diagnosis of coronary artery disease.

  14. Dutch perfusion incident survey.

    PubMed

    Groenenberg, Ingrid; Weerwind, Patrick W; Everts, Peter A M; Maessen, Jos G

    2010-09-01

    Cardiopulmonary bypass procedures remain complex, involving many potential risks. Therefore, a nationwide retrospective study was conducted to gain insight into the number of incidents and accidents in Dutch adult perfusion practice. An anonymous postal survey (85 questions about hardware, disposables, fluids and medication, air emboli, anticoagulation, practice, and safety measures) was sent to all Dutch perfusionists involved in adult cardiovascular perfusion during 2006 and 2007. To guarantee complete anonymity, respondents were asked to return the survey to a notary who discarded personal information. The net response rate was 72% and covered 23,500 perfusions. Individual respondents performed 240 ± 103 perfusions during the 2-year study period and had 13.8 ± 8.7 years of practical experience. The incident rate was 1 per 15.6 perfusions and the adverse event rate was 1 per 1,236 perfusions. The three most reported incidents were: (1) persistent inability to raise the activated coagulation time above 400s during perfusion (184 incidents); (2) an allergic or anaphylactic reaction to drugs, fluids, or blood products (114 incidents); and (3) clotting formation in the extracorporeal circuit (74 incidents). Furthermore, pre-bypass safety measures showed no statistically significant association with the reported incidents. In comparison with data from the recent literature, the reported number of incidents is high. Nevertheless, the adverse outcome rate is well matched to other published surveys. The relatively high response rate conveys the impression that the Dutch perfusionist is vigilant and willing to report incidents. Hence, a web-based Dutch perfusion incident registration system is recommended.

  15. Pathological overproduction: the bad side of adenosine.

    PubMed

    Borea, Pier Andrea; Gessi, Stefania; Merighi, Stefania; Vincenzi, Fabrizio; Varani, Katia

    2017-03-02

    Adenosine is an endogenous ubiquitous purine nucleoside, which is increased by hypoxia, ischaemia and tissue damage and mediates a number of physiopathological effects by interacting with four GPCRs, identified as A1 , A2A , A2B and A3 . Physiological and acutely increased adenosine is mostly associated with beneficial effects that include vasodilatation and a decrease in inflammation. In contrast, chronic overproduction of adenosine occurs in important pathological states, where long-lasting increases in the nucleoside levels are responsible for the bad side of adenosine associated with chronic inflammation, fibrosis and organ damage. In this review, we describe and critically discuss the pathological overproduction of adenosine and analyse when, where and how adenosine exerts its detrimental effects throughout the body.

  16. Torsades de pointes after adenosine administration.

    PubMed

    Teodorovich, Nicholay; Margolin, Elena; Kogan, Yonatan; Paz, Ofir; Swissa, Moshe

    2016-01-01

    Adenosine can produce arrhythmias, which are generally short living. It may induce PACs and PVCs, sinus bradycardia, and atrial fibrillation. There have been reports of transient polymorphic VT (torsades de pointes) in patients with LQTS and others in people with normal QT interval. We report a case of a long episode of polymorphic VT induced by adenosine. A 27 year old woman received 6 mg adenosine for PSVT, which terminated and torsades de pointes developed, persisting for 17 seconds and terminated spontaneously. This is the longest described duration of the torsades after adenosine administration in patients with normal QT interval.

  17. Arterial CO2 as a Potent Coronary Vasodilator: A Preclinical PET/MR Validation Study with Implications for Cardiac Stress Testing.

    PubMed

    Yang, Hsin-Jung; Dey, Damini; Sykes, Jane; Klein, Michael; Butler, John; Kovacs, Michael; Sobczyk, Olivia; Sharif, Behzad; Bi, Xiaoming; Kali, Avinash; Cokic, Ivan; Tang, Richard; Yumul, Roya; Conte, Antonio; Tsaftaris, Sotirios; Tighiouart, Mourad; Li, Debiao; Slomka, Piotr J; Berman, Daniel; Prato, Frank; Fisher, Joseph; Dharmakumar, Rohan

    2017-03-02

    Myocardial blood flow (MBF) is the critical determinant of cardiac function. However, its response to increases in partial pressure of arterial CO2 (PaCO2), particularly with respect to adenosine, is not well characterized due to challenges in blood gas control and limited availability of validated approaches to ascertain MBF in vivo. By prospectively and independently controlling PaCO2 and combining it with (13)N-ammonia Positron Emission Tomography (PET) measurements, we investigated whether a physiologically tolerable hypercapnic stimulus (~25-mmHg increase in PaCO2) can increase MBF to that observed with adenosine in three groups of canines: (i) without coronary stenosis; (ii) subjected to non-flow limiting coronary stenosis; and (iii) following pre-administration of caffeine. The extent of effect on MBF due to hypercapnia was compared to adenosine. Methods and Results: In the absence of stenosis, mean MBF under hypercapnia was 2.1±0.9 ml/min/g and adenosine was 2.2±1.1 ml/min/g were significantly higher than at rest (0.9±0.5 ml/min/g, P<0.05); and were not different from each other (P = 0.30). Under left-anterior descending coronary (LAD) stenosis, MBF increased in response to hypercapnia and adenosine (p<0.05, all territories) but the effect was significantly lower than in the LAD territory (with hypercapnia and adenosine; both p<0.05). Mean perfusion defect volumes measured with adenosine and hypercapnia were significantly correlated (R=0.85) and were not different (P = 0.12). Following pre- administration of caffeine, a known inhibitor of adenosine, resting MBF decreased and hypercapnia increased MBF but not adenosine (p<0.05). Conclusion: Arterial blood CO2 tension when increased by 25 mmHg can induce MBF to the same level as standard dose of adenosine. Prospectively targeted arterial CO2 has the capability to evolve as an alternative to current pharmacological vasodilators used for cardiac stress testing.

  18. Partial separation of platelet and placental adenosine receptors from adenosine A2-like binding protein

    SciTech Connect

    Zolnierowicz, S.; Work, C.; Hutchison, K.; Fox, I.H. )

    1990-04-01

    The ubiquitous adenosine A2-like binding protein obscures the binding properties of adenosine receptors assayed with 5'-N-({sup 3}H)ethylcarboxamidoadenosine (({sup 3}H)NECA). To solve this problem, we developed a rapid and simple method to separate adenosine receptors from the adenosine A2-like binding protein. Human platelet and placental membranes were solubilized with 1% 3-((3-cholamidopropyl)dimethylammonio)-1-propanesulfonate. The soluble platelet extract was precipitated with polyethylene glycol and the fraction enriched in adenosine receptors was isolated from the precipitate by differential centrifugation. The adenosine A2-like binding protein was removed from the soluble placental extract with hydroxylapatite and adenosine receptors were precipitated with polyethylene glycol. The specificity of the ({sup 3}H)NECA binding is typical of an adenosine A2 receptor for platelets and an adenosine A1 receptor for placenta. This method leads to enrichment of adenosine A2 receptors for platelets and adenosine A1 receptors for placenta. This provides a useful preparation technique for pharmacologic studies of adenosine receptors.

  19. Short fasting does not protect perfused ex vivo rat liver against ischemia-reperfusion. On the importance of a minimal cell energy charge.

    PubMed

    Papegay, Bérengère; Stadler, Michaela; Nuyens, Vincent; Kruys, Véronique; Boogaerts, Jean G; Vamecq, Joseph

    2017-03-01

    Dietary restriction or reduced food intake was supported to protect against renal and hepatic ischemic injury. In this vein, short fasting was recently shown to protect in situ rat liver against ischemia-reperfusion. Here, perfused ex vivo instead of in situ livers were exposed to ischemia-reperfusion to study the impact of disconnecting liver from extrahepatic supply in energetic substrates on the protection given by short-term fasting. Perfused ex vivo livers using short (18 h) fasted compared with fed rats were submitted to ischemia-reperfusion and studied for release of cytolysis markers in the perfusate. Energetic stores are differently available in time and cell energetic charges (ratio of adenosine triphosphate plus half of the adenosine diphosphate concentrations to the sum of adenosine triphosphate + adenosine diphosphate + adenosine monophosphate concentrations), adenosine phosphates, and glycogen, which were further measured at different time points in livers. Short fasting versus feeding failed to protect perfused ex vivo rat livers against ischemia/reperfusion, increasing the release of cytolysis markers (potassium, cytochrome c, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase) in the perfusate during reoxygenation phase. Toxicity of short fasting versus feeding was associated with lower glycogen and energetic charges in livers and lower lactate levels in the perfusate. High energetic charge, intracellular content in glycogen, and glycolytic activity may protect liver against ischemia/reperfusion injury. This work does not question how much the protective role previously demonstrated in the literature for dietary restriction and short fasting. In fact, it suggests that exceeding the energy charge threshold value of 0.3 might trigger the effectiveness of this protective role. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. The influence of lactic acid on adenosine release from skeletal muscle in anaesthetized dogs.

    PubMed Central

    Ballard, H J

    1991-01-01

    1. In anaesthetized and artificially ventilated dogs, a gracilis muscle was vascularly isolated and perfused at a constant flow rate of 11.9 +/- 2.2 ml min-1 100 g-1 (mean +/- S.E.M., n = 16; equivalent to 170.2 +/- 21.3% of its resting free flow). 2. Stimulation (3 Hz) of the obturator nerve produced twitch contractions of the gracilis muscle, reduced venous pH from 7.366 +/- 0.027 to 7.250 +/- 0.031 (n = 5), increased oxygen consumption from 0.62 +/- 0.24 to 2.76 +/- 0.46 ml min-1 100 g-1 (n = 5) and increased adenosine release from -0.40 +/- 0.14 (net uptake) to 1.36 +/- 0.50 nmol min-1 100 g-1 (n = 8). 3. Infusion of lactic acid (4.2 mM) into the artery reduced venous pH to 7.281 +/- 0.026 (n = 5) and increased adenosine release to 0.96 +/- 0.40 nmol min-1 100 g-1 (n = 8), but did not significantly alter oxygen consumption (0.80 +/- 0.19 ml min-1 100 g-1; n = 5). Stimulation (3 Hz) in the presence of lactic acid infusion produced no further significant changes in venous pH or adenosine release, but increased oxygen consumption to 2.53 +/- 0.37 ml min-1 100 g-1 (n = 5). 4. Infusion of a range of lactic acid concentrations (> or = 1.83 mM) produced dose-dependent increases in adenosine release. The maximum lactic acid concentration tested (5.95 mM) reduced venous pH to 7.249 +/- 0.023 (n = 5) and increased adenosine release to 2.64 +/- 1.26 nmol min-1 100 g-1 (n = 6). 5. A strong correlation existed between the adenosine release and the venous pH (r = -0.92); points obtained during muscle stimulation and/or lactic acid infusion fell on a single correlation line. 6. The vasoactivity of adenosine administered by close-arterial injection was unaltered by infusion of either lactic acid (7.2 mM) or saline. 7. These results suggest that the release of adenosine from skeletal muscle can be induced by a decrease in pH (probably at an intracellular site), and that this mechanism may contribute to the release of adenosine during muscle contractions. PMID:1841964

  1. Myocardial perfusion and left ventricular function indices assessed by gated myocardial perfusion SPECT in methamphetamine abusers.

    PubMed

    Dadpour, Bita; Dabbagh Kakhki, Vahid R; Afshari, Reza; Dorri-Giv, Masoumeh; Mohajeri, Seyed A R; Ghahremani, Somayeh

    2016-12-01

    Methamphetamine (MA) is associated with alterations of cardiac structure and function, although it is less known. In this study, we assessed possible abnormality in myocardial perfusion and left ventricular function using gated myocardial perfusion SPECT. Fifteen patients with MA abuse, on the basis of Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) MA dependency determined by Structured Clinical Interview for DSM-IV, underwent 2-day dipyridamole stress/rest Tc-sestamibi gated myocardial perfusion SPECT. An average daily dose of MA use was 0.91±1.1 (0.2-4) g. The duration of MA use was 3.4±2.1 (1-7) years. In visual and semiquantitative analyses, all patients had normal gated myocardial perfusion SPECT, with no perfusion defects. In all gated SPECT images, there was no abnormality in left ventricular wall motion and thickening. All summed stress scores and summed rest scores were below 3. Calculated left ventricular functional indices including the end-diastolic volume, end-systolic volume, and left ventricular ejection fraction were normal. Many cardiac findings because of MA mentioned in previous reports are less likely because of significant epicardial coronary artery stenosis.

  2. Quantitative severity of stress thallium-201 myocardial perfusion single-photon emission computed tomography defects in one-vessel coronary artery disease.

    PubMed

    Matzer, L; Kiat, H; Van Train, K; Germano, G; Papanicolaou, M; Silagan, G; Eigler, N; Maddahi, J; Berman, D S

    1993-08-01

    The relation between the quantitative myocardial perfusion defect severity of exercise thallium-201 single-photon emission computed tomography (SPECT) and the quantitative degree of coronary stenosis was examined in 18 patients with 1-vessel disease (> or = 50% diameter stenosis), and abnormal thallium-201 SPECT. A total of 26 vessels were analyzed. Thallium-201 SPECT quantitative defect severity score was derived by summing the number of pixels in a coronary territory in which counts fell below the normal mean and multiplied by the number of SDs by which they fell below the normal mean. The thallium-201 defect severity score was significantly (p < 0.001) related to the maximal percent luminal diameter narrowing (r = 0.93), percent area narrowing (r = 0.89), absolute stenotic area (r = 0.79), and absolute stenotic diameter (r = 0.81). As expected, the strongest relation between thallium-201 defect severity and quantitative angiographic indexes was in the low and high ranges of coronary stenosis, with more variability and lower correlation coefficients (percent diameter: r = 0.75, p < 0.02, percent area stenosis: r = 0.63, p < 0.05) in the middle ranges (50 to 80% diameter stenosis). This observation is likely to be due to the complex flow characteristics across stenotic lesions. The findings suggest that in a select population, thallium-201 defect severity is potentially useful for noninvasive characterization of the functional severity of coronary artery stenosis and may complement coronary angiography in predicting functionally significant stenosis.

  3. Incidence of caffeine in serum of patients undergoing dipyridamole myocardial perfusion stress test by an intensive versus routine caffeine history screening.

    PubMed

    Banko, Lesan T; Haq, Salman A; Rainaldi, Debroah A; Klem, Igor; Siegler, Jason; Fogel, Joshua; Sacchi, Terrence J; Heitner, John F

    2010-05-15

    The coronary vasodilatory effect of dipyridamole is competitively blocked by caffeine. The purposes of this study were to (1) assess the incidence of having detectable serum caffeine and (2) evaluate whether an intensive caffeine history screening strategy was superior to routine history screening before dipyridamole myocardial perfusion imaging. One hundred ninety-four patients who were randomized to an intensive or a routine screening history strategy were prospectively evaluated. Serum caffeine levels were determined in all patients. Outcomes data, including death, nonfatal myocardial infarction, and history of revascularization, were obtained at 24 months. Nearly 1 in 5 patients (19%) who screened negative by history had detectable serum caffeine. In patients who screened negative by history, there was no statistically significant difference in the percentage of caffeine seropositivity between the intensive and routine arms (16% vs 22%, respectively, p = 0.31). The incidence of combined end points of death, myocardial infarction, or revascularization was 22.9% and 7.3% in patients with and without detectable serum caffeine, respectively (p = 0.01). In conclusion, despite initial negative results on screening by history, a considerably high percentage of patients had positive serum caffeine levels. These results do not support the use of an intensive screening strategy. Detectable serum caffeine was associated with a higher incidence of adverse outcomes.

  4. Real time myocardial contrast echocardiography during supine bicycle stress and continuous infusion of contrast agent. Cutoff values for myocardial contrast replenishment discriminating abnormal myocardial perfusion.

    PubMed

    Miszalski-Jamka, Tomasz; Kuntz-Hehner, Stefanie; Schmidt, Harald; Hammerstingl, Christoph; Tiemann, Klaus; Ghanem, Alexander; Troatz, Clemens; Lüderitz, Berndt; Omran, Heyder

    2007-07-01

    Myocardial contrast echocardiography (MCE) is a new imaging modality for diagnosing coronary artery disease (CAD). The aim of our study was to evaluate feasibility of qualitative myocardial contrast replenishment (RP) assessment during supine bicycle stress MCE and find out cutoff values for such analysis, which could allow accurate detection of CAD. Forty-four consecutive patients, scheduled for coronary angiography (CA) underwent supine bicycle stress two-dimensional echocardiography (2DE). During the same session, MCE was performed at peak stress and post stress. Ultrasound contrast agent (SonoVue) was administered in continuous mode using an infusion pump (BR-INF 100, Bracco Research). Seventeen-segment model of left ventricle was used in analysis. MCE was assessed off-line in terms of myocardial contrast opacification and RP. RP was evaluated on the basis of the number of cardiac cycles required to refill the segment with contrast after its prior destruction with high-power frames. Determination of cutoff values for RP assessment was performed by means of reference intervals and receiver operating characteristic analysis. Quantitative CA was carried out using CAAS system. MCE could be assessed in 42 patients. CA revealed CAD in 25 patients. Calculated cutoff values for RP-analysis (peak-stress RP >3 cardiac cycles and difference between peak stress and post stress RP >0 cardiac cycles) provided sensitive (88%) and accurate (88%) detection of CAD. Sensitivity and accuracy of 2DE were 76% and 79%, respectively. Qualitative RP-analysis based on the number of cardiac cycles required to refill myocardium with contrast is feasible during supine bicycle stress MCE and enables accurate detection of CAD.

  5. Role of Adenosine A1 Receptor in the Perifornical-Lateral Hypothalamic Area in Sleep-Wake Regulation in Rats

    PubMed Central

    Alam, Md. Noor; Kumar, Sunil; Rai, Seema; Methippara, Melvi; Szymusiak, Ronald; McGinty, Dennis

    2009-01-01

    The perifornical-lateral hypothalamic area (PF-LHA) has been implicated in the regulation of arousal. The PF-LHA contains wake-active neurons that are quiescent during nonREM sleep and in the case of neurons expressing the peptide hypocretin (HCRT), quiescent during both nonREM and REM sleep. Adenosine is an endogenous sleep factor and recent evidence suggests that adenosine via A1 receptors may act on PF-LHA neurons to promote sleep. We examined the effects of bilateral activation as well as blockade of A1 receptors in the PF-LHA on sleep-wakefulness in freely behaving rats. The sleep-wake profiles of male Wistar rats were recorded during reverse microdialysis perfusion of artificial cerebrospinal fluid (aCSF) and two doses of adenosine A1 receptor antagonist, 1,3-dipropyl-8-phenylxanthine (CPDX; 5μM and 50μM) or A1 receptor agonist, N6-cyclopentyladenosine (CPA; 5μM and 50μM) into the PF-LHA for 2h followed by 4h of aCSF perfusion. CPDX perfused into the PF-LHA during lights-on phase produced arousal (F=7.035, p <0.001) and concomitantly decreased both nonREM (F=7.295, p<0.001) and REM sleep (F=3.456, p<0.004). In contrast, CPA perfused into the PF-LHA during lights-off phase significantly suppressed arousal (F = 7.891; p <0.001) and increased nonREM (F = 8.18; p <0.001) and REM sleep (F = 30.036; p = <0.001). These results suggest that PF-LHA is one of the sites where adenosine, acting via A1 receptors, inhibits PF-LHA neurons to promote sleep. PMID:19781535

  6. Quantitative myocardial perfusion SPECT.

    PubMed

    Tsui, B M; Frey, E C; LaCroix, K J; Lalush, D S; McCartney, W H; King, M A; Gullberg, G T

    1998-01-01

    In recent years, there has been much interest in the clinical application of attenuation compensation to myocardial perfusion single photon emission computed tomography (SPECT) with the promise that accurate quantitative images can be obtained to improve clinical diagnoses. The different attenuation compensation methods that are available create confusion and some misconceptions. Also, attenuation-compensated images reveal other image-degrading effects including collimator-detector blurring and scatter that are not apparent in uncompensated images. This article presents basic concepts of the major factors that degrade the quality and quantitative accuracy of myocardial perfusion SPECT images, and includes a discussion of the various image reconstruction and compensation methods and misconceptions and pitfalls in implementation. The differences between the various compensation methods and their performance are demonstrated. Particular emphasis is directed to an approach that promises to provide quantitative myocardial perfusion SPECT images by accurately compensating for the 3-dimensional (3-D) attenuation, collimator-detector response, and scatter effects. With advances in the computer hardware and optimized implementation techniques, quantitatively accurate and high-quality myocardial perfusion SPECT images can be obtained in clinically acceptable processing time. Examples from simulation, phantom, and patient studies are used to demonstrate the various aspects of the investigation. We conclude that quantitative myocardial perfusion SPECT, which holds great promise to improve clinical diagnosis, is an achievable goal in the near future.

  7. Involvement of NADPH oxidase in A2A adenosine receptor-mediated increase in coronary flow in isolated mouse hearts.

    PubMed

    Zhou, Zhichao; Rajamani, Uthra; Labazi, Hicham; Tilley, Stephen L; Ledent, Catherine; Teng, Bunyen; Mustafa, S Jamal

    2015-06-01

    Adenosine increases coronary flow mainly through the activation of A2A and A2B adenosine receptors (ARs). However, the mechanisms for the regulation of coronary flow are not fully understood. We previously demonstrated that adenosine-induced increase in coronary flow is in part through NADPH oxidase (Nox) activation, which is independent of activation of either A1 or A3ARs. In this study, we hypothesize that adenosine-mediated increase in coronary flow through Nox activation depends on A2A but not A2BARs. Functional studies were conducted using isolated Langendorff-perfused mouse hearts. Hydrogen peroxide (H2O2) production was measured in isolated coronary arteries from WT, A2AAR knockout (KO), and A2BAR KO mice using dichlorofluorescein immunofluorescence. Adenosine-induced concentration-dependent increase in coronary flow was attenuated by the specific Nox2 inhibitor gp91 ds-tat or reactive oxygen species (ROS) scavenger EUK134 in both WT and A2B but not A2AAR KO isolated hearts. Similarly, the A2AAR selective agonist CGS-21680-induced increase in coronary flow was significantly blunted by Nox2 inhibition in both WT and A2BAR KO, while the A2BAR selective agonist BAY 60-6583-induced increase in coronary flow was not affected by Nox2 inhibition in WT. In intact isolated coronary arteries, adenosine-induced (10 μM) increase in H2O2 formation in both WT and A2BAR KO mice was attenuated by Nox2 inhibition, whereas adenosine failed to increase H2O2 production in A2AAR KO mice. In conclusion, adenosine-induced increase in coronary flow is partially mediated by Nox2-derived H2O2, which critically depends upon the presence of A2AAR.

  8. Variability in quantitative cardiac magnetic resonance perfusion analysis

    PubMed Central

    Bratis, K.

    2013-01-01

    By taking advantage of its high spatial resolution, noninvasive and nontoxic nature first-pass perfusion cardiovascular magnetic resonance (CMR) has rendered an indispensable tool for the noninvasive detection of reversible myocardial ischemia. A potential advantage of perfusion CMR is its ability to quantitatively assess perfusion reserve within a myocardial segment, as expressed semi- quantitatively by myocardial perfusion reserve index (MPRI) and fully- quantitatively by absolute myocardial blood flow (MBF). In contrast to the high accuracy and reliability of CMR in evaluating cardiac function and volumes, perfusion CMR is adversely affected by multiple potential reasons during data acquisition as well as post-processing. Various image acquisition techniques, various contrast agents and doses as well as variable blood flow at rest as well as variable reactions to stress all influence the acquired data. Mechanisms underlying the variability in perfusion CMR post processing, as well as their clinical significance, are yet to be fully elucidated. The development of a universal, reproducible, accurate and easily applicable tool in CMR perfusion analysis remains a challenge and will substantially enforce the role of perfusion CMR in improving clinical care. PMID:23825774

  9. Adenosine modulates cell growth in the human breast cancer cells via adenosine receptors.

    PubMed

    Panjehpour, Mojtaba; Karami-Tehrani, Fatemeh

    2007-01-01

    Adenosine modulates the proliferation, survival, and apoptosis of many different cell types. The present study was performed to investigate the role of adenosine receptors in the human breast cancer cell lines MCF-7 and MDA-MB468. The biological effects of adenosine on the cells were analyzed by adenylyl cyclase and cell viability assay as well as RT-PCR of adenosine receptors. RT-PCR results show the expression of the transcript of all adenosine receptors in both cell lines. By using adenosine and selective adenosine receptor agonists or antagonists, we found that A3 stimulation reduced cell viability, which was abolished by pretreatment with A3 receptor antagonist. Moreover, we demonstrated that adenosine (natural agonist) triggers a cytotoxic signal via A3 receptor activation that was not seen for other subclasses of adenosine receptors. Intracellular cAMP concentration was changed significantly only for A3 and A2B receptor-selective agonists, which indicates the functional form of these receptors on the cell surface. In conclusion, our findings revealed the role of adenosine receptors in breast cancer cell lines on growth modulation role of A3 and functional form of A2B, although its involvement in cell growth modulation was not seen. Theses findings as well as data by others may provide a possible application of adenosine receptor agonists/antagonists in breast malignancies.

  10. Ex vivo lung perfusion.

    PubMed

    Reeb, Jeremie; Cypel, Marcelo

    2016-03-01

    Lung transplantation is an established life-saving therapy for patients with end-stage lung disease. Unfortunately, greater success in lung transplantation is hindered by a shortage of lung donors and the relatively poor early-, mid-, and long-term outcomes associated with severe primary graft dysfunction. Ex vivo lung perfusion has emerged as a modern preservation technique that allows for a more accurate lung assessment and improvement in lung quality. This review outlines the: (i) rationale behind the method; (ii) techniques and protocols; (iii) Toronto ex vivo lung perfusion method; (iv) devices available; and (v) clinical experience worldwide. We also highlight the potential of ex vivo lung perfusion in leading a new era of lung preservation.

  11. Enzymatic regeneration of adenosine triphosphate cofactor

    NASA Technical Reports Server (NTRS)

    Marshall, D. L.

    1974-01-01

    Regenerating adenosine triphosphate (ATP) from adenosine diphosphate (ADP) by enzymatic process which utilizes carbamyl phosphate as phosphoryl donor is technique used to regenerate expensive cofactors. Process allows complex enzymatic reactions to be considered as candidates for large-scale continuous processes.

  12. Endogenous adenosine and adenosine receptors localized to ganglion cells of the retina

    SciTech Connect

    Braas, K.M.; Zarbin, M.A.; Snyder, S.H.

    1987-06-01

    Using specific sensitive antisera against adenosine, we have immunocytochemically localized endogenous adenosine to specific layers of rat, guinea pig, monkey, and human retina. Highest adenosine immunoreactivity was observed in ganglion cells and their processes in the optic nerve fiber layer. Substantial staining was also found throughout the inner plexiform layer and in select cells in the inner nuclear layer. Adenosine A1 receptors, labeled with the agonists L-(/sup 3/H)phenylisopropyladenosine and /sup 125/I-labeled hydroxy-phenylisopropyladenosine, were autoradiographically localized. The highest levels of binding sites occurred in the nerve fiber, ganglion cell, and inner plexiform layers of the retina in all the species examined. The distribution of adenosine A1 receptor sites closely parallels that of retinal neurons and fibers containing immunoreactive adenosine. These results suggest a role for endogenous adenosine as a coneurotransmitter in ganglion cells and their fibers in the optic nerve.

  13. Validation of a Patient-reported Outcome (PRO) Measure and a Clinician-reported Outcome (CRO) Measure to Assess Satisfaction with Pharmacologic Stress Agents for Single-photon Emission Computed Tomography (SPECT) Myocardial Perfusion Imaging (MPI).

    PubMed

    Hudgens, Stacie; Spalding, James; Chaudhari, Paresh

    2016-05-01

    The objective of this study was to develop and validate clinician and patient measures of satisfaction for pharmacologic stress agents (PSAs) used in single-photon emission computed tomography myocardial perfusion imaging procedures. Two questionnaires were developed: the Clinician Satisfaction and Preference Questionnaire (CSPQ) and the Patient Satisfaction and Preference Questionnaire (PSPQ). Items were developed, and the content validity of the questionnaires was ensured by participants' involvement in the item generation (5 clinician and 18 patient face-to-face concept elicitation interviews) and item modification phases (5 clinician and 10 patient face-to-face cognitive debriefing interviews). Psychometric validation of the satisfaction component of the questionnaires was conducted in a sample of 9 clinicians and 90 patients. After initial patient interviews and cognitive interviews, two 8-item instruments were developed with each containing an optional PSA preference question. The PSPQ assessed patients' receptiveness and satisfaction with the PSA that they received. The CSPQ assessed clinicians' satisfaction with the time and ease of PSA preparation, administration, and monitoring of the PSA. The optional preference question in both instruments assesses preference among PSAs. In a multicenter observational study of 88 patients and 9 clinicians, the PSPQ Preparation and Reaction to Agent scales elicited reliability coefficients of 0.90 and 0.87, respectively. In addition, the test-retest reliability was acceptable for all PSPQ scales (intraclass correlation coefficient range, 0.73-0.86). Concurrent validity with the Treatment Satisfaction Questionnaire for Medication (TSQM) indicates low-to-moderate correlations between the Effectiveness, Convenience, and Global Satisfaction scales of the TSQM with the PSPQ Satisfaction with Administration, Satisfaction with Effects, and Overall Satisfaction items (range, 0.46-0.78). Analysis of the CSPQ found that both the

  14. [Portable peristaltic perfusion pumps].

    PubMed

    Magallón Pedrera, I; Soto Torres, I

    1999-11-01

    Portable peristaltic perfusion pumps allow one to administer pharmaceuticals in hospitals as well as in primary health care centers and furthermore these pumps present multiple advantages for patients and their families since they make it possible to carry out treatment in a patient's home while at the same time lowering the costs involved. The authors analyze the most out standing aspects of portable peristaltic perfusion pumps along with their characteristics, installation, programming, and how to turn them on; in addition, the authors list the maintenance care which these pumps require.

  15. Insulin/adenosine axis linked signalling.

    PubMed

    Silva, Luis; Subiabre, Mario; Araos, Joaquín; Sáez, Tamara; Salsoso, Rocío; Pardo, Fabián; Leiva, Andrea; San Martín, Rody; Toledo, Fernando; Sobrevia, Luis

    2017-06-01

    Regulation of blood flow depends on systemic and local release of vasoactive molecules such as insulin and adenosine. These molecules cause vasodilation by activation of plasma membrane receptors at the vascular endothelium. Adenosine activates at least four subtypes of adenosine receptors (A1AR, A2AAR, A2BAR, A3AR), of which A2AAR and A2BAR activation leads to increased cAMP level, generation of nitric oxide, and relaxation of the underlying smooth muscle cell layer. Vasodilation caused by adenosine also depends on plasma membrane hyperpolarization due to either activation of intermediate-conductance Ca(2+)-activated K(+) channels in vascular smooth muscle or activation of ATP-activated K(+) channels in the endothelium. Adenosine also causes vasoconstriction via a mechanism involving A1AR activation resulting in lower cAMP level and increased thromboxane release. Insulin has also a dual effect causing NO-dependent vasodilation, but also sympathetic activity- and increased endothelin 1 release-dependent vasoconstriction. Interestingly, insulin effects require or are increased by activation or inactivation of adenosine receptors. This is phenomenon described for d-glucose and l-arginine transport where A2AAR and A2BAR play a major role. Other studies show that A1AR activation could reduce insulin release from pancreatic β-cells. Whether adenosine modulation of insulin biological effect is a phenomenon that depends on co-localization of adenosine receptors and insulin receptors, and adenosine plasma membrane transporters is something still unclear. This review summarizes findings addressing potential involvement of adenosine receptors to modulate insulin effect via insulin receptors with emphasis in the human vasculature. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Halobacterial adenosine triphosphatases and the adenosine triphosphatase from Halobacterium saccharovorum

    NASA Technical Reports Server (NTRS)

    Kristjansson, Hordur; Sadler, Martha H.; Hochstein, Lawrence I.

    1986-01-01

    Membranes prepared from various members of the genus Halobacterium contained a Triton X-l00 activated adenosine triphosphatase. The enzyme from Halobacterium saccharovorum was unstable in solutions of low ionic strength and maximally active in the presence of 3.5 M NaCl. A variety of nucleotide triphosphates was hydrolyzed. MgADP, the product of ATP hydrolysis, was not hydrolyzed and was a competitive inhibitor with respect to MgATP. The enzyme from H. saccharovorum was composed of at least 2 and possibly 4 subunits. The 83-kDa and 60-kDa subunits represented about 90 percent of total protein. The 60-kDa subunit reacted with dicyclohexyl-carbodiimide when inhibition was carried out in an acidic medium. The enzyme from H. saccharovorum, possesses properties of an F(1)F(0) as well as an E(1)E(2) ATPase.

  17. Halobacterial adenosine triphosphatases and the adenosine triphosphatase from Halobacterium saccharovorum

    NASA Technical Reports Server (NTRS)

    Kristjansson, Hordur; Sadler, Martha H.; Hochstein, Lawrence I.

    1986-01-01

    Membranes prepared from various members of the genus Halobacterium contained a Triton X-l00 activated adenosine triphosphatase. The enzyme from Halobacterium saccharovorum was unstable in solutions of low ionic strength and maximally active in the presence of 3.5 M NaCl. A variety of nucleotide triphosphates was hydrolyzed. MgADP, the product of ATP hydrolysis, was not hydrolyzed and was a competitive inhibitor with respect to MgATP. The enzyme from H. saccharovorum was composed of at least 2 and possibly 4 subunits. The 83-kDa and 60-kDa subunits represented about 90 percent of total protein. The 60-kDa subunit reacted with dicyclohexyl-carbodiimide when inhibition was carried out in an acidic medium. The enzyme from H. saccharovorum, possesses properties of an F(1)F(0) as well as an E(1)E(2) ATPase.

  18. Intravenous adenosine (adenoscan) versus exercise in the noninvasive assessment of coronary artery disease by SPECT

    SciTech Connect

    LaManna, M.M.; Mohama, R.; Slavich, I.L. 3d.; Lumia, F.J.; Cha, S.D.; Rambaran, N.; Maranhao, V. )

    1990-11-01

    Fifteen patients at a mean age of 58 underwent adenosine and maximal exercise thallium SPECT imaging. All scans were performed 1 week apart and within 4 weeks of cardiac catheterization. SPECT imaging was performed after the infusion of 140 micrograms/kg/min of adenosine for 6 minutes. Mean heart rate increment during adenosine administration was 67 +/- 3.7 to 77 +/- 4.1. Mean blood pressure was 136 +/- 7.2 to 135 +/- 6.2 systolic and 78 +/- 1.8 to 68 +/- 2.6 diastolic. No adverse hemodynamic effects were observed. There were no changes in PR or QRS in intervals. Five stress ECGs were ischemic. No ST changes were observed with adenosine. Although 68% of the patients had symptoms of flushing, light-headedness, and dizziness during adenosine infusion, symptoms resolved within 1 minute of dosage adjustment or termination of the infusion in all but one patient, who required theophylline. Sensitivity for coronary artery detection was 77% and specificity 100%. Concordance between adenoscans and exercise thallium scintigraphy was high (13/15 = 87%). In two patients, there were minor scintigraphic differences. The authors conclude that adenosine is a sensitive, specific, and safe alternative to exercise testing in patients referred for thallium imaging and may be preferable to dipyridamole.

  19. The interaction of exercise ability and body mass index upon long-term outcomes among patients undergoing stress-rest perfusion single-photon emission computed tomography imaging.

    PubMed

    Uretsky, Seth; Supariwala, Azhar; Gurram, Srinivasa; Bonda, Sri Lakshmi Kala; Thota, Naganath; Bezwada, Prema; Manchireddy, Seema; Nair, Subu; Cohen, Randy; Rozanski, Alan

    2013-07-01

    The obesity paradox has been reported in several populations of patients with cardiovascular disease. Recent data have shown that physical fitness may attenuate the obesity paradox. Patients who undergo pharmacologic stress testing are known to have a higher risk of mortality than those who can exercise. The purpose of this study is to determine the interaction of obesity and exercise ability on survival among patients with a normal stress-rest single-photon emission computed tomography (SPECT). A total of 5,203 (60 ± 13 years, male 37%) patients without a history of heart disease and a normal stress-rest SPECT between the years 1995 and 2010 were included in this analysis. Body mass index categories were defined according to the World Health Organization classification: normal weight, 18.5 to 24.9 kg/m(2); overweight, 25 to 29.9 kg/m(2); and obese, ≥30 kg/m(2). Patients were divided into 3 groups based on their ability to exercise: those who reached ≥6 METs on exercise, those who attained a level of <6 METs, and those who required pharmacologic stress. Patients in each of these fitness groups were further divided into 3 subgroups based on their body mass index. There were 939 (18%) deaths during a mean follow-up of 8.1 ± 4.1 years, for an overall event rate of 2.3%/y. Both exercise to ≥6 METs and being obese were associated with lower mortality. Adjusted multivariate analysis using the obese high-fit patients as the reference showed a wide heterogeneity in annualized mortality rates according to exercise and weight status, with annualized event rates which varied from 0.6%/y in the obese subjects who were physically fit to 5.3%/y among healthy subjects who underwent pharmacologic stress testing (P < .001). Stress mode and body weight impacted long-term survival in patients with a normal stress SPECT. The benefit of being physically fit was evident in all weight groups, as was the adverse effect of being unable to exercise. However, with regard to body

  20. Defect images in stress thallium-201 myocardial scintigraphy in patients with complete left bundle branch block: comparison of exercise stress and pharmacological stress.

    PubMed

    Sasaki, Hideki; Shimizu, Mitsuyuki; Ogawa, Kazuhiko; Okazaki, Fumiko; Mizokami, Tsuneo; Kusaka, Masafumi; Uehara, Yoshiki; Taniguchi, Ikuo; Mochizuki, Seibu

    2007-04-01

    Stress thallium-201 (201Tl) myocardial scintigraphy can demonstrate perfusion abnormalities, especially in the septum in patients with complete left bundle branch block (CLBBB) even with angiographically normal coronary arteries. Differences in the images between exercise and pharmacological stress 201Tl myocardial scintigraphy were evaluated in patients with CLBBB and normal coronary arteries. Forty-five patients with CLBBB underwent exercise stress using treadmill or pharmacological (adenosine triphosphate) stress 201Tl myocardial scintigraphy from October 1997 to February 2003. Patients with myocardial diseases were excluded, such as cardiomyopathy and coronary artery diseases detected by echocardiography and/or cardiac catheterization. The myocardial segment was classified according to the American Heart Association style for coronary artery disease. Peak blood pressure levels and heart rates were significantly higher in the exercise stress group than in the pharmacological stress group (p < 0.001). The rate of defects in stress images was significantly higher in the exercise stress group (72.4%; 21/29 cases) than in the pharmacological stress group (18.8%; 3/16 cases) (p < 0.01). The rate of redistribution of observed defects in delayed images was 76.2% (16/21 cases) in the exercise stress group, and 0% (0/3 cases)in the pharmacological stress group (p < 0.01). The myocardial segments showing defects were different between the exercise stress group and the pharmacological stress group. Patients with CLBBB showed different frequencies of defects by stress 201Tl myocardial scintigraphy according to the stress method. Moreover, defects also occured in areas other than the septum. Blood pressure and heart rate were involved in the mechanisms of defects in left bundle branch block.

  1. k-t SENSE-accelerated Myocardial Perfusion MR Imaging at 3.0 Tesla - comparison with 1.5 Tesla

    PubMed Central

    Plein, Sven; Schwitter, Juerg; Suerder, Daniel; Greenwood, John P.; Boesiger, Peter; Kozerke, Sebastian

    2008-01-01

    Purpose To determine the feasibility and diagnostic accuracy of high spatial resolution myocardial perfusion MR at 3.0 Tesla using k-space and time domain undersampling with sensitivity encoding (k-t SENSE). Materials and Methods The study was reviewed and approved by the local ethic review board. k-t SENSE perfusion MR was performed at 1.5 Tesla and 3.0 Tesla (saturation recovery gradient echo pulse sequence, repetition time/echo time 3.0ms/1.0ms, flip angle 15°, 5x k-t SENSE acceleration, spatial resolution 1.3×1.3×10mm3). Fourteen volunteers were studied at rest and 37 patients during adenosine stress. In volunteers, comparison was also made with standard-resolution (2.5×2.5×10mm3) 2x SENSE perfusion MR at 3.0 Tesla. Image quality, artifact scores, signal-to-noise ratios (SNR) and contrast-enhancement ratios (CER) were derived. In patients, diagnostic accuracy of visual analysis to detect >50% diameter stenosis on quantitative coronary angiography was determined by receiver-operator-characteristics (ROC). Results In volunteers, image quality and artifact scores were similar for 3.0 Tesla and 1.5 Tesla, while SNR was higher (11.6 vs. 5.6) and CER lower (1.1 vs. 1.5, p=0.012) at 3.0 Tesla. Compared with standard-resolution perfusion MR, image quality was higher for k-t SENSE (3.6 vs. 3.1, p=0.04), endocardial dark rim artifacts were reduced (artifact thickness 1.6mm vs. 2.4mm, p<0.001) and CER similar. In patients, area under the ROC curve for detection of coronary stenosis was 0.89 and 0.80, p=0.21 for 3.0 Tesla and 1.5 Tesla, respectively. Conclusions k-t SENSE accelerated high-resolution perfusion MR at 3.0 Tesla is feasible with similar artifacts and diagnostic accuracy as at 1.5 Tesla. Compared with standard-resolution perfusion MR, image quality is improved and artifacts are reduced. PMID:18936311

  2. Distribution of perfusion.

    PubMed

    Glenny, Robb; Robertson, H Thomas

    2011-01-01

    Local driving pressures and resistances within the pulmonary vascular tree determine the distribution of perfusion in the lung. Unlike other organs, these local determinants are significantly influenced by regional hydrostatic and alveolar pressures. Those effects on blood flow distribution are further magnified by the large vertical height of the human lung and the relatively low intravascular pressures in the pulmonary circulation. While the distribution of perfusion is largely due to passive determinants such as vascular geometry and hydrostatic pressures, active mechanisms such as vasoconstriction induced by local hypoxia can also redistribute blood flow. This chapter reviews the determinants of regional lung perfusion with a focus on vascular tree geometry, vertical gradients induced by gravity, the interactions between vascular and surrounding alveolar pressures, and hypoxic pulmonary vasoconstriction. While each of these determinants of perfusion distribution can be examined in isolation, the distribution of blood flow is dynamically determined and each component interacts with the others so that a change in one region of the lung influences the distribution of blood flow in other lung regions. © 2011 American Physiological Society.

  3. Perfusion vector-a new method to quantify myocardial perfusion scintigraphy images: a simulation study with validation in patients.

    PubMed

    Minarik, David; Senneby, Martin; Wollmer, Per; Mansten, Alva; Sjöstrand, Karl; Edenbrandt, Lars; Trägårdh, Elin

    2015-12-01

    The interpretation of myocardial perfusion scintigraphy (MPS) largely relies on visual assessment by the physician of the localization and extent of a perfusion defect. The aim of this study was to introduce the concept of the perfusion vector as a new objective quantitative method for further assisting the visual interpretation and to test the concept using simulated MPS images as well as patients. The perfusion vector is based on calculating the difference between the anatomical centroid and the perfusion center of gravity of the left ventricle. Simulated MPS images were obtained using the SIMIND Monte Carlo program together with XCAT phantom. Four different-sized anterior and four lateral defects were simulated, and perfusion vector components x-, y-, and z-axes were calculated. For the patient study, 40 normal and 80 abnormal studies were included. Perfusion vectors were compared between normal and abnormal (apical, inferior, anterior, and lateral ischemia or infarction) studies and also correlated to the defect size. For simulated anterior defects, the stress perfusion vector component on the y-axis (anterior-inferior direction) increased in proportion to the defect size. For the simulated lateral defects, the stress perfusion vector component on the x-axis (septal-lateral direction) decreased in proportion to the defect size. When comparing normal and abnormal patients, there was a statistically significant difference for the stress perfusion vector on the x-axis for apical and lateral defects; on the y-axis for apical, inferior, and lateral defects; and on the z-axis (basal-apical direction) for apical, anterior, and lateral defects. A significant difference was shown for the difference vector magnitude (stress/rest) between normal and ischemic patients (p = 0.001) but not for patients with infarction. The correlation between the defect size and stress vector magnitude was also found to be significant (p < 0.001). The concept of the perfusion vector

  4. Homeostatic control of synaptic activity by endogenous adenosine is mediated by adenosine kinase.

    PubMed

    Diógenes, Maria José; Neves-Tomé, Raquel; Fucile, Sergio; Martinello, Katiuscia; Scianni, Maria; Theofilas, Panos; Lopatár, Jan; Ribeiro, Joaquim A; Maggi, Laura; Frenguelli, Bruno G; Limatola, Cristina; Boison, Detlev; Sebastião, Ana M

    2014-01-01

    Extracellular adenosine, a key regulator of neuronal excitability, is metabolized by astrocyte-based enzyme adenosine kinase (ADK). We hypothesized that ADK might be an upstream regulator of adenosine-based homeostatic brain functions by simultaneously affecting several downstream pathways. We therefore studied the relationship between ADK expression, levels of extracellular adenosine, synaptic transmission, intrinsic excitability, and brain-derived neurotrophic factor (BDNF)-dependent synaptic actions in transgenic mice underexpressing or overexpressing ADK. We demonstrate that ADK: 1) Critically influences the basal tone of adenosine, evaluated by microelectrode adenosine biosensors, and its release following stimulation; 2) determines the degree of tonic adenosine-dependent synaptic inhibition, which correlates with differential plasticity at hippocampal synapses with low release probability; 3) modulates the age-dependent effects of BDNF on hippocampal synaptic transmission, an action dependent upon co-activation of adenosine A2A receptors; and 4) influences GABAA receptor-mediated currents in CA3 pyramidal neurons. We conclude that ADK provides important upstream regulation of adenosine-based homeostatic function of the brain and that this mechanism is necessary and permissive to synaptic actions of adenosine acting on multiple pathways. These mechanistic studies support previous therapeutic studies and implicate ADK as a promising therapeutic target for upstream control of multiple neuronal signaling pathways crucial for a variety of neurological disorders.

  5. Halogenated pyrrolopyrimidine analogues of adenosine from marine organisms: pharmacological activities and potent inhibition of adenosine kinase.

    PubMed

    Davies, L P; Jamieson, D D; Baird-Lambert, J A; Kazlauskas, R

    1984-02-01

    Two novel halogenated pyrrolopyrimidine analogues of adenosine, isolated from marine sources, have been examined for pharmacological and biochemical activities. 4-Amino-5-bromo-pyrrolo[2,3-d]pyrimidine, from a sponge of the genus Echinodictyum, had bronchodilator activity at least as potent as theophylline but with a different biochemical profile; unlike theophylline it had no antagonist activity at CNS adenosine receptors and it was quite a potent inhibitor of adenosine uptake and adenosine kinase in brain tissue. 5'-Deoxy-5-iodotubercidin, isolated from the red alga Hypnea valentiae, caused potent muscle relaxation and hypothermia when injected into mice. This compound was a very potent inhibitor of adenosine uptake into rat and guinea-pig brain slices and an extremely potent inhibitor of adenosine kinase from guinea-pig brain and rat brain and liver. Neither of these two pyrrolopyrimidine analogues was a substrate for, or an inhibitor of, adenosine deaminase. Neither compound appeared to have any direct agonist activity on guinea-pig brain adenosine-stimulated adenylate cyclase (A2 adenosine receptors). 5'-Deoxy-5-iodotubercidin is unique in two respects: it appears to be the first naturally-occurring example of a 5'-deoxyribosyl nucleoside and is the first example of a specifically iodinated nucleoside from natural sources. It may be the most potent adenosine kinase inhibitor yet described and, by virtue of its structure, may prove to be the most specific.

  6. Optical Aptasensors for Adenosine Triphosphate

    PubMed Central

    Ng, Stella; Lim, Hui Si; Ma, Qian; Gao, Zhiqiang

    2016-01-01

    Nucleic acids are among the most researched and applied biomolecules. Their diverse two- and three-dimensional structures in conjunction with their robust chemistry and ease of manipulation provide a rare opportunity for sensor applications. Moreover, their high biocompatibility has seen them being used in the construction of in vivo assays. Various nucleic acid-based devices have been extensively studied as either the principal element in discrete molecule-like sensors or as the main component in the fabrication of sensing devices. The use of aptamers in sensors - aptasensors, in particular, has led to improvements in sensitivity, selectivity, and multiplexing capacity for a wide verity of analytes like proteins, nucleic acids, as well as small biomolecules such as glucose and adenosine triphosphate (ATP). This article reviews the progress in the use of aptamers as the principal component in sensors for optical detection of ATP with an emphasis on sensing mechanism, performance, and applications with some discussion on challenges and perspectives. PMID:27446501

  7. The adenosine neuromodulation system in schizophrenia.

    PubMed

    Rial, Daniel; Lara, Diogo R; Cunha, Rodrigo A

    2014-01-01

    The management of schizophrenia endophenotypes, namely positive, negative, and cognitive symptoms is still an open goal, justifying the search of novel therapeutic avenues. We now review the evidence supporting the interest in targeting the adenosine modulation system to counteract the core features of schizophrenia. This interest is forwarded by the combined ability of strategies aimed at bolstering adenosine levels together with the increasingly recognized impact of adenosine A2A receptors to control dopaminergic signaling, working memory, and behavioral sensitization; this is further heralded by the suggested clinical effectiveness of therapies increasing extracellular adenosine such as dipyridamole and allopurinol and the emergent recognition of a role for adenosine in neurodevelopment. Finally, the combined role of A1 and A2A receptors in assisting the implementation of adaptive changes and encoding of information salience in neuronal circuits together with the adaptive alterations of A1 and A2A receptor density upon brain dysfunction prompts the novel working hypothesis that the parallel imbalance of adenosine formation and of A1 and A2A receptors blurs the adequate encoding of information salience in neuronal circuits, which we propose to be a core pathogenic feature in the development of schizophrenia endophenotypes. This proposal should also provide a rationale to assist the design of future therapeutic intervention targeting the adenosine modulation system to manage schizophrenia endophenotypes: these should not be based only on an attempt to target adenosine kinase-A1 receptors or only A2A receptors, but should instead simultaneously target these two arms of the adenosine modulation system. © 2014 Elsevier Inc. All rights reserved.

  8. Adenosine Kinase: Exploitation for Therapeutic Gain

    PubMed Central

    2013-01-01

    Adenosine kinase (ADK; EC 2.7.1.20) is an evolutionarily conserved phosphotransferase that converts the purine ribonucleoside adenosine into 5′-adenosine-monophosphate. This enzymatic reaction plays a fundamental role in determining the tone of adenosine, which fulfills essential functions as a homeostatic and metabolic regulator in all living systems. Adenosine not only activates specific signaling pathways by activation of four types of adenosine receptors but it is also a primordial metabolite and regulator of biochemical enzyme reactions that couple to bioenergetic and epigenetic functions. By regulating adenosine, ADK can thus be identified as an upstream regulator of complex homeostatic and metabolic networks. Not surprisingly, ADK dysfunction is involved in several pathologies, including diabetes, epilepsy, and cancer. Consequently, ADK emerges as a rational therapeutic target, and adenosine-regulating drugs have been tested extensively. In recent attempts to improve specificity of treatment, localized therapies have been developed to augment adenosine signaling at sites of injury or pathology; those approaches include transplantation of stem cells with deletions of ADK or the use of gene therapy vectors to downregulate ADK expression. More recently, the first human mutations in ADK have been described, and novel findings suggest an unexpected role of ADK in a wider range of pathologies. ADK-regulating strategies thus represent innovative therapeutic opportunities to reconstruct network homeostasis in a multitude of conditions. This review will provide a comprehensive overview of the genetics, biochemistry, and pharmacology of ADK and will then focus on pathologies and therapeutic interventions. Challenges to translate ADK-based therapies into clinical use will be discussed critically. PMID:23592612

  9. Myocardial perfusion SPECT 2015 in Germany. Results of the 7(th) survey.

    PubMed

    Lindner, Oliver; Burchert, Wolfgang; Schäfer, Wolfgang; Hacker, Marcus

    2017-02-14

    The working group Cardiovascular Nuclear Medicine of the German Society of Nuclear Medicine presents the results of the 7th survey of myocardial perfusion SPECT (MPS) of the reporting year 2015. 268 questionnaires (173 practices [PR], 67 hospitals [HO], 28 university hospitals [UH]) were evaluated. Results of the last survey from 2012 are set in squared brackets. MPS of 121 939 [105 941] patients were reported. 98 % [95 %] of all MPS were performed with Tc-99m radiopharmaceuticals and 2 % [5 %] with Tl-201. 78 % [79 %] of all patients were studied in PR, 14 % [15 %] in HO, and 8 % [6 %] in UH. A pharmacological stress test was performed in 43 % [39 %] (22 % [24 %] adenosine, 20 % [9 %] regadenoson, 1 % [6 %] dipyridamole or dobutamine). Attenuation correction was applied in 25 % [2009: 10 %] of MPS. Gated SPECT was performed in 78 % [70 %] of all rest MPS, in 80 % [73 %] of all stress and in 76 % [67 %] of all stress and rest MPS. 53 % [33 %] of all nuclear medicine departments performed MPS scoring by default, whereas 24 % [41 %] did not apply any quantification. 31 % [26 %] of all departments noticed an increase in their counted MPS and 29 % [29 %] no changes. Data from 89 departments which participated in all surveys showed an increase in MPS count of 11.1 % (PR: 12.2 %, HO: 4.8 %, UH: 18.4 %). 70 % [60 %] of the MPS were requested by ambulatory care cardiologists. The 2015 MPS survey reveals a high-grade adherence of routine MPS practice to current guidelines. The positive trend in MPS performance and number of MPS already observed in 2012 continues. Educational training remains necessary in the field of SPECT scoring.

  10. Influence of proton-pump inhibitors on stomach wall uptake of 99mTc-tetrofosmin in cadmium-zinc-telluride SPECT myocardial perfusion imaging.

    PubMed

    Mouden, Mohamed; Rijkee, Karlijn S; Schreuder, Nanno; Timmer, Jorik R; Jager, Pieter L

    2015-02-01

    Proton-pump inhibitors (PPIs) induce potentially interfering stomach wall activity in single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) with technetium-99m ((99m)Tc)-sestamibi. However, no data are available for (99m)Tc-tetrofosmin. We assessed the influence of prolonged (>2 weeks) PPI use on the stomach wall uptake of (99m)Tc-tetrofosmin in patients referred for stress MPI with a cadmium-zinc-telluride-based SPECT camera and its relation with dyspepsia symptoms. Consecutive patients (n=127) underwent a 1-day adenosine stress-first SPECT-MPI with (99m)Tc-tetrofosmin, of whom 54 (43%) patients had been on PPIs for more than 2 weeks. Stomach wall activity was identified on stress SPECT using computed tomographic attenuation maps and was scored using a four-point grading scale into clinically relevant (scores 2 or 3) or nonrelevant (scores 0 or 1).Patients on PPIs had stomach wall uptake more frequently as compared with patients not using PPIs (22 vs. 7%, P=0.017). Dyspepsia was similar in both groups. Prolonged use of PPIs is associated with stomach wall uptake of (99m)Tc-tetrofosmin in stress cadmium-zinc-telluride-SPECT images. Gastric symptoms were not associated with stomach wall uptake.

  11. Comparison of effects of ATP-MgCl/sub 2/ and adenosine-MgCl/sub 2/ on renal function following ischemia

    SciTech Connect

    Sumpio, B.E.; Hull, M.J.; Baue, A.E.; Chaudry, I.H.

    1987-02-01

    ATO-MgCl/sub 2/ administration had been shown to accelerate the recovery of renal function following warm ischemia. However, since the major breakdown product of ATP is adenosine, the relative contribution of ATP vs. adenosine in improving renal function following ischemia remains to be determined. To study this, kidneys were subjected to 45 min of normothermic ischemia and then perfused at 100 mmHg with oxygenated Krebs-HCO/sub 3/ buffer containing albumin, (/sub 3/H)inulin, substrates, and either 0.3 mM ATP-MgCl/sub 2/ or adenosine-MgCl/sub 2/ for 110 min. Perfusate and timed urine samples were collected and analyzed for radioactivity and (Na/sup +/). The functional parameters indicated that although adenosine-MgCl/sub 2/ treatment provided a transient improvement, it failed to provided a sustained improvement in renal function or attain control valued compared with ATP-MgCl/sub 2/ treatment. Thus, the salutary effects of ATP-MgCl/sub 2/ following warm ischemia in the kidney are not mediated by adenosine.

  12. 99mTc sestamibi myocardial perfusion scintigraphy with the novel use of metamizol for the detection of perfusion reversibility.

    PubMed

    Ergün, Eser Lay; Caglar, Meltem; Bozkurt, Murat Fani; Ergün, Hakan

    2008-08-01

    This study aims to investigate whether induction with metamizol, an analgesic-antipyretic drug having spasmolitic activity, could be used to increase the detectability of ischemic/jeopardized myocardium during MPS (myocardial perfusion scintigraphy). Metamizol-enhanced rest MPS (45 min after administration of 1 g metamizol orally, 740 MBq (99m)Tc sestamibi was injected, MPS was acquired 45 min later) was performed in 21 patients who had perfusion defects on their previous stress-rest (99m)Tc sestamibi MPS. Blood pressure was monitored at 15-min intervals. Stress, rest, metamizol-rest MPS images were interpreted on the model of 20 segments using a visual uptake score (VUS; 0 = normal, 1 = mild, 2 = moderate, 3 = significant decreases, 4 = no uptake). (99m)Tc sestamibi uptake ratios (MIBI-UR; mean counts in the region of the perfusion defect/mean counts in the region of the normal-perfused wall) were obtained on each MPS and compared with each other. Average MIBI-UR in each scintigraphic examination was calculated. MPS were compared with coronary angiography results. VUS and MIBI-UR results showed that metamizol-rest MPS displayed the defect reversibility better than rest MPS. Of the 14 segments with fixed perfusion defects on stress-rest MPS, 8 showed improvement of perfusion after metamizol induction. In 33 segments, lesion reversibility was better delineated on metamizol-rest MPS. Metamizol-induced sestamibi uptake was significantly higher (p < 0.001) than stress/baseline rest examinations as calculated by the MIBI-UR. Blood pressure remained unaltered. Coronary angiography results were in concordance with metamizol induced MPS. Metamizol-enhanced rest MPS increases detectability of ischemic/viable myocardium during MPS. Metamizol should be discontinued like nitrates before stress MPS since it may mask the visualization of ischemic perfusion defects.

  13. Some aspects of adenosine triphosphate synthesis from adenine and adenosine in human red blood cells

    PubMed Central

    Whittam, R.; Wiley, J. S.

    1968-01-01

    1. The synthesis of ATP has been studied in human erythrocytes. Fresh cells showed no net synthesis of ATP when incubated with adenine or adenosine, although labelled adenine was incorporated into ATP in small amounts. 2. Cold-stored cells (3-6 weeks old) became progressively depleted of adenine nucleotides but incubation with adenosine or adenine plus inosine restored the ATP concentration to normal within 4 hr. Incorporation of labelled adenine or adenosine into the ATP of incubated stored cells corresponded to net ATP synthesis by these cells. 3. Synthesis of ATP from adenosine plus adenine together was 75% derived from adenine and only 25% from adenosine, indicating that nucleotide synthesis from adenine inhibits the simultaneous synthesis of nucleotide from adenosine. PMID:5723519

  14. Early impairment of coronary microvascular perfusion capacity in rats on a high fat diet.

    PubMed

    van Haare, Judith; Kooi, M Eline; Vink, Hans; Post, Mark J; van Teeffelen, Jurgen W G E; Slenter, Jos; Munts, Chantal; Cobelens, Hanneke; Strijkers, Gustav J; Koehn, Dennis; van Bilsen, Marc

    2015-11-17

    It remains to be established if, and to what extent, the coronary microcirculation becomes compromised during the development of obesity and insulin resistance. Recent studies suggest that changes in endothelial glycocalyx properties contribute to microvascular dysfunction under (pre-)diabetic conditions. Accordingly, early effects of diet-induced obesity on myocardial perfusion and function were studied in rats under baseline and hyperaemic conditions. Rats were fed a high fat diet (HFD) for 6 weeks and myocardial microvascular perfusion was determined using first-pass perfusion MRI before and after adenosine infusion. The effect of HFD on microcirculatory properties was also assessed by sidestream darkfield (SDF) imaging of the gastrocnemius muscle. HFD-fed rats developed central obesity and insulin sensitivity was reduced as evidenced by the marked reduction in insulin-induced phosphorylation of Akt in both cardiac and gastrocnemius muscle. Early diet-induced obesity did not lead to hypertension or cardiac hypertrophic remodeling. In chow-fed, control rats a robust increase in cardiac microvascular perfusion was observed upon adenosine infusion (+40%; p < 0.05). In contrast, the adenosine response was abrogated in rats on a HFD (+8%; N.S.). HFD neither resulted in rarefaction or loss of glycocalyx integrity in skeletal muscle, nor reduced staining intensity of the glycocalyx of cardiac capillaries. Alterations in coronary microcirculatory function as assessed by first-pass perfusion MRI represent one of the earliest obesity-related cardiac adaptations that can be assessed non-invasively. In this early stage of insulin resistance, disturbances in glycocalyx barrier properties appeared not to contribute to the observed changes in coronary microvascular function.

  15. Activation of A1, A2A, or A3 adenosine receptors attenuates lung ischemia-reperfusion injury

    PubMed Central

    Gazoni, Leo M.; Walters, Dustin M.; Unger, Eric B.; Linden, Joel; Kron, Irving L.; Laubach, Victor E.

    2010-01-01

    Objective Adenosine and the activation of specific adenosine receptors are implicated in the attenuation of inflammation and organ ischemia-reperfusion (IR) injury. We hypothesized that activation of A1, A2A, or A3 adenosine receptors would provide protection against lung IR injury. Methods Using an isolated, ventilated, blood-perfused rabbit lung model, lungs underwent 18 hours cold ischemia followed by 2 hours reperfusion. Lungs were administered either vehicle, adenosine, or selective A1, A2A, or A3 receptor agonists (CCPA, ATL-313, or IB-MECA, respectively) alone or with their respective antagonists (DPCPX, ZM241385, or MRS1191) during reperfusion. Results Compared to the vehicle-treated control group, treatment with A1, A2A, or A3 agonists significantly improved function (increased lung compliance and oxygenation and decreased pulmonary artery pressure), decreased neutrophil infiltration by myeloperoxidase activity, decreased edema, and reduced TNF-α production. Adenosine treatment was also protective but not to the level of the agonists. When each agonist was paired with its respective antagonist, all protective effects were blocked. The A2A agonist reduced pulmonary artery pressure and myeloperoxidase activity and increased oxygenation to a greater degree than the A1 or A3 agonists. Conclusions Selective activation of A1, A2A, or A3 adenosine receptors provides significant protection against lung IR injury. The decreased elaboration of the potent proinflammatory cytokine, TNF-α, and decreased neutrophil sequestration likely contribute to the overall improvement in pulmonary function. These results provide evidence for the therapeutic potential of specific adenosine receptor agonists in lung transplant recipients. PMID:20398911

  16. [Stress echocardiography--an evaluation of current status].

    PubMed

    Schartl, M; Beckmann, S; Bocksch, W

    1994-08-01

    Exercise echocardiography, a versatile, noninvasive diagnostic test of left ventricular wall motion performed at rest and under induced stress, enables the cardiologist to detect and assess coronary artery disease. Stress-induced ischemia is thereby expressed as left ventricular regional wall motion abnormality. By using various physical (bicycle or treadmill exercise) and pharmacological (dipyridamole, dobutamine, adenosine) stress inducers, the test provides information about the localization and extent of coronary artery disease in addition to detecting stress-induced coronary insufficiency. As regards diagnostic accuracy in detecting coronary artery disease, stress echocardiography is superior to exercise electrocardiography and, according to the available data, it is comparable to perfusion scintigraphic testing. Studies have demonstrated the clinical value of stress echocardiography in detecting residual stenosis after angioplasty, for diagnosing bypass dysfunction after heart surgery, for preoperative risk assessment in noncardiac surgeries, and for obtaining prognostic information, e.g., after myocardial infarction. Preliminary studies have shown that pharmacological exercise echocardiography is able to identify viable myocardium in the early phases after acute myocardial infarction. Furthermore, it is able to predict the functional success of revascularization in chronic regional left ventricular dysfunction. In addition to the wide range of diagnostic possibilities in coronary artery disease, other notable applications include stress testing for assessment of global left ventricular pump function in patients with aortic regurgitation or cardiomyopathy.

  17. Involvement of A(1) adenosine receptors in osmotic volume regulation of retinal glial cells in mice.

    PubMed

    Wurm, Antje; Lipp, Stephan; Pannicke, Thomas; Linnertz, Regina; Färber, Katrin; Wiedemann, Peter; Reichenbach, Andreas; Bringmann, Andreas

    2009-09-12

    Osmotic swelling of Müller glial cells has been suggested to contribute to retinal edema. We determined the role of adenosine signaling in the inhibition of Müller cell swelling in the murine retina. The size of Müller cell somata was recorded before and during perfusion of retinal sections and isolated Müller cells with a hypoosmolar solution. Retinal tissues were freshly isolated from wild-type mice and mice deficient in A(1) adenosine receptors (A(1)AR(-/-)), or cultured as whole-mounts for three days. The potassium conductance of Müller cells was recorded in isolated cells, and retinal slices were immunostained against Kir4.1. Hypotonic exposure for 4 min induced a swelling of Müller cell bodies in retinal slices from A(1)AR(-/-) mice but not wild-type mice. Pharmacological inhibition of A(1) receptors or of the ecto-5'-nucleotidase induced hypoosmotic swelling of Müller cells from wild-type mice. Exogenous adenosine prevented the swelling of Müller cells from wild-type but not A(1)AR(-/-) mice. The antiinflammatory corticosteroid, triamcinolone acetonide, inhibited the swelling of Müller cells from wild-type mice; this effect was blocked by an antagonist of A(1) receptors. The potassium conductance of Müller cells and the Kir4.1 immunolabeling of retinal slices were not different between A(1)AR(-/-) and wild-type mice, both in freshly isolated tissues and retinal organ cultures. The data suggest that autocrine activation of A(1) receptors by extracellularly generated adenosine mediates the volume homeostasis of Müller cells in the murine retina. The swelling-inhibitory effect of triamcinolone is mediated by enhancement of endogenous adenosine signaling.

  18. Involvement of A1 adenosine receptors in osmotic volume regulation of retinal glial cells in mice

    PubMed Central

    Wurm, Antje; Lipp, Stephan; Pannicke, Thomas; Linnertz, Regina; Färber, Katrin; Wiedemann, Peter; Reichenbach, Andreas

    2009-01-01

    Purpose Osmotic swelling of Müller glial cells has been suggested to contribute to retinal edema. We determined the role of adenosine signaling in the inhibition of Müller cell swelling in the murine retina. Methods The size of Müller cell somata was recorded before and during perfusion of retinal sections and isolated Müller cells with a hypoosmolar solution. Retinal tissues were freshly isolated from wild-type mice and mice deficient in A1 adenosine receptors (A1AR−/−), or cultured as whole-mounts for three days. The potassium conductance of Müller cells was recorded in isolated cells, and retinal slices were immunostained against Kir4.1. Results Hypotonic exposure for 4 min induced a swelling of Müller cell bodies in retinal slices from A1AR−/− mice but not wild-type mice. Pharmacological inhibition of A1 receptors or of the ecto-5′-nucleotidase induced hypoosmotic swelling of Müller cells from wild-type mice. Exogenous adenosine prevented the swelling of Müller cells from wild-type but not A1AR−/− mice. The antiinflammatory corticosteroid, triamcinolone acetonide, inhibited the swelling of Müller cells from wild-type mice; this effect was blocked by an antagonist of A1 receptors. The potassium conductance of Müller cells and the Kir4.1 immunolabeling of retinal slices were not different between A1AR−/− and wild-type mice, both in freshly isolated tissues and retinal organ cultures. Conclusions The data suggest that autocrine activation of A1 receptors by extracellularly generated adenosine mediates the volume homeostasis of Müller cells in the murine retina. The swelling-inhibitory effect of triamcinolone is mediated by enhancement of endogenous adenosine signaling. PMID:19756184

  19. Adenosine receptors as drug targets — what are the challenges?

    PubMed Central

    Chen, Jiang-Fan; Eltzschig, Holger K.; Fredholm, Bertil B.

    2014-01-01

    Adenosine signalling has long been a target for drug development, with adenosine itself or its derivatives being used clinically since the 1940s. In addition, methylxanthines such as caffeine have profound biological effects as antagonists at adenosine receptors. Moreover, drugs such as dipyridamole and methotrexate act by enhancing the activation of adenosine receptors. There is strong evidence that adenosine has a functional role in many diseases, and several pharmacological compounds specifically targeting individual adenosine receptors — either directly or indirectly — have now entered the clinic. However, only one adenosine receptor-specific agent — the adenosine A2A receptor agonist regadenoson (Lexiscan; Astellas Pharma) — has so far gained approval from the US Food and Drug Administration (FDA). Here, we focus on the biology of adenosine signalling to identify hurdles in the development of additional pharmacological compounds targeting adenosine receptors and discuss strategies to overcome these challenges. PMID:23535933

  20. Thallium-201 scintigraphy perfusion defect with dipyridamole in a patient with a myocardial bridge

    SciTech Connect

    Bennett, J.M.; Blomerus, P.

    1988-04-01

    A patient with myocardial bridging and a thallium-201 scintigraphy perfusion defect after the administration of intravenous dipyridamole is presented. The same patient had a normal perfusion study on exercise stress testing. The effects of coronary vasodilators and dipyridamole on coronary artery flow patterns in patients with myocardial bridging are discussed. We suggest that coronary vasodilators may induce perfusion defects in patients with myocardial bridging and should be avoided in such patients.

  1. Adenosine receptor inhibition attenuates the decrease in cutaneous vascular conductance during whole-body cooling from hyperthermia.

    PubMed

    Swift, Brendan; McGinn, Ryan; Gagnon, Daniel; Crandall, Craig G; Kenny, Glen P

    2014-01-01

    Adenosine has both vasodilatory and vasoconstrictive properties, yet its influence on cutaneous vascular conductance (CVC) during whole-body cooling remains unknown. The present study evaluated the influence of adenosine on reflex cutaneous vasoconstriction. Four microdialysis probes were inserted into the dorsal forearm skin of eight subjects and infused with the following solutions: (i) lactated Ringer solution (CON); (ii) 4 mm theophylline (Theo), a non-selective adenosine receptor antagonist; (iii) 10 mm l-NAME, an inhibitor of nitric oxide synthase; and (iv) combined 4 mm theophylline and 10 mm l-NAME (Theo + l-NAME). Subjects subsequently donned a water-perfusion garment. Following a thermoneutral baseline period, the suit was perfused with water at 10°C for 20 min (Cooling 1). The suit was then perfused with water at 49°C for 45 min (Heating), followed by a second cooling period of 20 min using 10°C water (Cooling 2). Cutaneous blood flow (laser-Doppler) was measured over each microdialysis probe and used to calculate CVC as a percentage of the maximum determined by sodium nitroprusside infusion and local heating. Cutaneous vascular conductance was significantly elevated at the Theo site relative to CON following Cooling 1 (18 ± 6 versus 8 ± 2%; P = 0.01) and Cooling 2 (27 ± 11 versus 14 ± 5%; P = 0.022). Likewise, CVC at the Theo + l-NAME site remained greater compared with l-NAME after Cooling 1 (13 ± 4 versus 7 ± 3%; P = 0.030) and Cooling 2 (15 ± 3 versus 9 ± 2%; P = 0.009). The present findings demonstrate that non-selective antagonism of adenosine receptors attenuates the decrease in cutaneous vascular conductance during whole-body cooling from hyperthermia.

  2. Genetics Home Reference: adenosine deaminase 2 deficiency

    MedlinePlus

    ... This Page Bras J, Guerreiro R, Santo GC. Mutant ADA2 in vasculopathies. N Engl J Med. 2014 ... M, Anikster Y, King MC, Levy-Lahad E. Mutant adenosine deaminase 2 in a polyarteritis nodosa vasculopathy. ...

  3. [Adenosine deaminase in experimental trypanosomiasis: future implications].

    PubMed

    Pérez-Aguilar, Mary Carmen; Rondón-Mercado, Rocío

    2015-09-01

    The adenosine deaminase represents a control point in the regulation of extracellular adenosine levels, thus playing a critical role in the modulation of purinergic responses to certain pathophysiological events. Several studies have shown that serum and plasma enzyme levels are elevated in some diseases caused by microorganisms, which may represent a compensatory mechanism due to the elevated levels of adenosine and the release of inflammatory mediators. Recent research indicates that adenosine deaminase activity decreases and affects hematological parameters of infected animals with Trypanosoma evansi, so that such alterations could have implications in the pathogenesis of the disease. In addition, the enzyme has been detected in this parasite; allowing the inference that it could be associated with the vital functions of the same, similar to what occurs in mammals. This knowledge may be useful in the association of chemotherapy with specific inhibitors of the enzyme in future studies.

  4. Perfusion abnormalities in hemimegalencephaly.

    PubMed

    Wintermark, P; Roulet-Perez, E; Maeder-Ingvar, M; Moessinger, A C; Gudinchet, F; Meuli, R

    2009-04-01

    Cerebrovascular changes are rarely discussed in patients with hemimegalencephaly. These alterations have previously been associated with epileptical activity. We report the case of a 36-week gestation neonate presenting with total right hemimegalencephaly, as demonstrated by a magnetic resonance imaging (MRI) performed in the first days of life. Perfusion-weighted imaging displayed a clear hypervascularization of the right hemisphere. Diffusion-tensor imaging showed an arrangement of white matter fibers concentrically around the ventricle on the right hemisphere. AngioMRI showed an obvious asymmetry in the size of the middle cerebral arteries, with the right middle cerebral artery being prominent. The baby was free of clinical seizures during his first week of life. An electroencephalogram at that time displayed an asymmetric background activity, but no electrical seizures. Perfusion anomalies in hemimegalencephaly may not necessarily be related to epileptical activity, but may be related to vessel alterations. (c) Georg Thieme Verlag KG Stuttgart, New York.

  5. Metabolic changes in patients with aneurysmal subarachnoid hemorrhage apart from perfusion deficits: neuronal mitochondrial injury?

    PubMed

    Wagner, M; Jurcoane, A; Hildebrand, C; Güresir, E; Vatter, H; Zanella, F E; Berkefeld, J; Pilatus, U; Hattingen, E

    2013-08-01

    Neuronal damage in aSAH apart from perfusion deficits has been widely discussed. We aimed to test if cerebral injury occurs in aSAH independently from visible perfusion deficit by measuring cerebral metabolites in patients with aSAH without infarction or impaired perfusion. We performed 3T MR imaging including (1)H-MR spectroscopy, DWI, and MR perfusion in 58 patients with aSAH and 11 age-matched and sex-matched control patients with incidental aneurysm. We compared changes of NAA, Cho, Glx, Lac, and Cr between all patients with aSAH and controls, between patients with and without visible perfusion deficit or infarction and controls, and between patients with and without visible perfusion deficit or infarction by using the Wilcoxon signed-rank test. We found that NAA significantly (P < .005) decreased in all patients with aSAH. Cho was significantly increased in all patients compared with controls (P < .05). In patients without impaired perfusion or infarction, Glx was significantly decreased compared with both controls (P = .005) and patients with impaired perfusion or infarction (P = .006). The significant decrease of NAA and Glx in patients with aSAH but without impaired perfusion or infarction strongly suggests global metabolic changes independent from visible perfusion deficits that might reflect neuronal mitochondrial injury. Further, impaired perfusion in aSAH seems to induce additional metabolic changes from increasing neuronal stress that might, to some extent, mask the global metabolic changes.

  6. Role of adenosine receptors in caffeine tolerance

    SciTech Connect

    Holtzman, S.G.; Mante, S.; Minneman, K.P. )

    1991-01-01

    Caffeine is a competitive antagonist at adenosine receptors. Receptor up-regulation during chronic drug treatment has been proposed to be the mechanism of tolerance to the behavioral stimulant effects of caffeine. This study reassessed the role of adenosine receptors in caffeine tolerance. Separate groups of rats were given scheduled access to drinking bottles containing plain tap water or a 0.1% solution of caffeine. Daily drug intake averaged 60-75 mg/kg and resulted in complete tolerance to caffeine-induced stimulation of locomotor activity, which could not be surmounted by increasing the dose of caffeine. 5'-N-ethylcarboxamidoadenosine (0.001-1.0 mg/kg) dose dependently decreased the locomotor activity of caffeine-tolerant rats and their water-treated controls but was 8-fold more potent in the latter group. Caffeine (1.0-10 mg/kg) injected concurrently with 5-N-ethylcarboxamidoadenosine antagonized the decreases in locomotor activity comparably in both groups. Apparent pA2 values for tolerant and control rats also were comparable: 5.05 and 5.11. Thus, the adenosine-antagonist activity of caffeine was undiminished in tolerant rats. The effects of chronic caffeine administration on parameters of adenosine receptor binding and function were measured in cerebral cortex. There were no differences between brain tissue from control and caffeine-treated rats in number and affinity of adenosine binding sites or in receptor-mediated increases (A2 adenosine receptor) and decreases (A1 adenosine receptor) in cAMP accumulation. These results are consistent with theoretical arguments that changes in receptor density should not affect the potency of a competitive antagonist. Experimental evidence and theoretical considerations indicate that up-regulation of adenosine receptors is not the mechanism of tolerance to caffeine-induced stimulation of locomotor activity.

  7. Control of basal extracellular adenosine concentration in rat cerebellum

    PubMed Central

    Wall, Mark J; Atterbury, Alison; Dale, Nicholas

    2007-01-01

    To re-examine how the basal extracellular concentration of adenosine is regulated in acutely isolated cerebellar slices we have combined electrophysiological and microelectrode biosensor measurements. In almost all cases, synaptic transmission was tonically inhibited by adenosine acting via A1 receptors. By contrast, in most slices, the biosensors did not measure an adenosine tone but did record a spatially non-uniform extracellular tone of the downstream metabolites (inosine and hypoxanthine). Most of the extracellular hypoxanthine arose from the metabolism of inosine by ecto-purine nucleoside phosphorylase (PNP). Adenosine kinase was the major determinant of adenosine levels, as its inhibition increased both adenosine concentration and A1 receptor-mediated synaptic inhibition. Breakdown of adenosine by adenosine deaminase was the major source of the inosine/hypoxanthine tone. However adenosine deaminase played a minor role in determining the level of adenosine at synapses, suggesting a distal location. Blockade of adenosine transport (by NBTI/dipyridamole) had inconsistent effects on basal levels of adenosine and synaptic transmission. Unexpectedly, application of NBTI/dipyridamole prevented the efflux of adenosine resulting from block of adenosine kinase at only a subset of synapses. We conclude that there is spatial variation in the functional expression of NBTI/dipyridamole-sensitive transporters. The increased spatial and temporal resolution of the purine biosensor measurements has revealed the complexity of the control of adenosine and purine tone in the cerebellum. PMID:17446223

  8. Modulation of ischemia-evoked release of excitatory and inhibitory amino acids by adenosine A1 receptor agonist.

    PubMed

    Goda, H; Ooboshi, H; Nakane, H; Ibayashi, S; Sadoshima, S; Fujishima, M

    1998-09-18

    Adenosine has been reported to have beneficial effects against ischemic brain damage, although the mechanisms are not fully clarified. To examine the role of adenosine on the ischemia-evoked release of neurotransmitters, we applied a highly selective agonist for adenosine A1 receptor, 2-chloro-N6-cyclopentyladenosine (CCPA), into the ischemic brain using in vivo brain dialysis, which directly delivered the agonist to the local brain area. Concentrations of extracellular amino acids (glutamate, aspartate, gamma-aminobutyric acid (GABA) and taurine) and regional blood flow in the striatum of spontaneously hypertensive rats (SHRs) were monitored during cerebral ischemia elicited by bilateral carotid artery occlusion for 40 min and recirculation. Striatal blood flow and basal levels of amino acids were not affected by direct perfusion of CCPA (10 microM or 100 microM). During ischemia, concentrations of glutamate, aspartate, GABA and taurine increased up to 37-, 30-, 96- and 31-fold, respectively, when vehicle alone was administered. Administration of CCPA did not affect the changes in regional blood flow during ischemia and reperfusion. Perfusion of CCPA (100 microM), however, significantly attenuated the ischemia-evoked release of aspartate (by 70%) and glutamate (by 73%). The ischemia-induced increase of GABA tended to be decreased by CCPA, although it was not statistically significant. In contrast, both low and high concentrations of CCPA had little effect on the release of taurine during ischemia. These results suggest that stimulation of adenosine A1 receptors selectively attenuated the ischemia-evoked release of excitatory amino acids, but not of inhibitory amino acids without affecting blood flow. This modulation of the release of amino acids by adenosine A1 receptor agonists may play a protective role against ischemic neuronal damage.

  9. Termination of idiopathic sustained monomorphic ventricular tachycardia by intravenous adenosine in a pregnant woman.

    PubMed

    Hasdemir, Can; Musayev, Oktay; Alkan, Mustafa B; Can, Levent H; Kultursay, Hakan

    2009-11-01

    A 34-year-old pregnant woman presented to the emergency department with the complaints of palpitations at 32 weeks gestation. The diagnosis of right ventricular outflow tract ventricular tachycardia (VT) was made. Intravenous 5 mg of metoprolol and 25 mg of diltiazem did not terminate the VT. Ten milligrams of adenosine were administered. Within 10 s of adenosine administration, sustained VT converted to repetitive monomorphic VT and within 30 s to normal sinus rhythm. The mother and the foetus tolerated the medications well. Non-stress test for the assessment of the foetal well-being was normal.

  10. Adenosine Kinase of Trypanosoma brucei and Its Role in Susceptibility to Adenosine Antimetabolites▿ †

    PubMed Central

    Lüscher, Alexandra; Önal, Pinar; Schweingruber, Anne-Marie; Mäser, Pascal

    2007-01-01

    Trypanosoma brucei cannot synthesize purines de novo and relies on purine salvage from its hosts to build nucleic acids. With adenosine being a preferred purine source of bloodstream-form trypanosomes, adenosine kinase (AK; EC 2.7.1.20) is likely to be a key player in purine salvage. Adenosine kinase is also of high pharmacological interest, since for many adenosine antimetabolites, phosphorylation is a prerequisite for activity. Here, we cloned and functionally characterized adenosine kinase from T. brucei (TbAK). TbAK is a tandem gene, expressed in both procyclic- and bloodstream-form trypanosomes, whose product localized to the cytosol of the parasites. The RNA interference-mediated silencing of TbAK suggested that the gene is nonessential under standard growth conditions. Inhibition or downregulation of TbAK rendered the trypanosomes resistant to cordycepin (3′-deoxyadenosine), demonstrating a role for TbAK in the activation of adenosine antimetabolites. The expression of TbAK in Saccharomyces cerevisiae complemented a null mutation in the adenosine kinase gene ado1. The concomitant expression of TbAK with the T. brucei adenosine transporter gene TbAT1 allowed S. cerevisiae ado1 ade2 double mutants to grow on adenosine as the sole purine source and, at the same time, sensitized them to adenosine antimetabolites. The coexpression of TbAK and TbAT1 in S. cerevisiae ado1 ade2 double mutants proved to be a convenient tool for testing nucleoside analogues for uptake and activation by T. brucei adenosine salvage enzymes. PMID:17698621

  11. Relationship between caffeine-induced changes in resting cerebral perfusion and blood oxygenation level-dependent signal.

    PubMed

    Laurienti, Paul J; Field, Aaron S; Burdette, Jonathan H; Maldjian, Joseph A; Yen, Yi-Fen; Moody, Dixon M

    2003-09-01

    Recent interest has emerged in the use of pharmacologic methods to maximize blood oxygenation level-dependent (BOLD) signal intensity changes in functional MR imaging (fMRI). Adenosine antagonists, such as caffeine and theophylline, have been identified as potential agents for this purpose. The present study was designed to determine whether caffeine-induced decreases in cerebral perfusion result in enhanced BOLD responses to visual and auditory stimuli. MR imaging was used to measure resting cerebral perfusion and stimulus-induced BOLD signal intensity changes in 19 patients. We evaluated the relationship between resting cerebral perfusion and the magnitude of BOLD signal intensity induced by visual and auditory stimulation under caffeine and placebo conditions. The data showed that changes in resting cerebral perfusion produced by caffeine are not a consistent predictor of BOLD signal intensity magnitude. Although all cerebral perfusion was reduced in all study participants in response to caffeine, only 47% of the participants experienced BOLD signal intensity increase. This finding was independent of the participants' usual caffeine consumption. The data presented herein show that the relationship between resting cerebral perfusion and the magnitude of BOLD signal intensity is complex. It is not possible to consistently enhance BOLD signal intensity magnitude by decreasing resting perfusion with caffeine. Future studies aimed at evaluating the relationship between perfusion and BOLD signal intensity changes should seek a means to selectively modulate known components of the neural and vascular responses independently.

  12. Subnormothermic machine perfusion for ex vivo preservation and recovery of the human liver for transplantation.

    PubMed

    Bruinsma, B G; Yeh, H; Ozer, S; Martins, P N; Farmer, A; Wu, W; Saeidi, N; Op den Dries, S; Berendsen, T A; Smith, R N; Markmann, J F; Porte, R J; Yarmush, M L; Uygun, K; Izamis, M-L

    2014-06-01

    To reduce widespread shortages, attempts are made to use more marginal livers for transplantation. Many of these grafts are discarded for fear of inferior survival rates or biliary complications. Recent advances in organ preservation have shown that ex vivo subnormothermic machine perfusion has the potential to improve preservation and recover marginal livers pretransplantation. To determine the feasibility in human livers, we assessed the effect of 3 h of oxygenated subnormothermic machine perfusion (21°C) on seven livers discarded for transplantation. Biochemical and microscopic assessment revealed minimal injury sustained during perfusion. Improved oxygen uptake (1.30 [1.11-1.94] to 6.74 [4.15-8.16] mL O2 /min kg liver), lactate levels (4.04 [3.70-5.99] to 2.29 [1.20-3.43] mmol/L) and adenosine triphosphate content (45.0 [70.6-87.5] pmol/mg preperfusion to 167.5 [151.5-237.2] pmol/mg after perfusion) were observed. Liver function, reflected by urea, albumin and bile production, was seen during perfusion. Bile production increased and the composition of bile (bile salts/phospholipid ratio, pH and bicarbonate concentration) became more favorable. In conclusion, ex vivo subnormothermic machine perfusion effectively maintains liver function with minimal injury and sustains or improves various hepatobiliary parameters postischemia.

  13. Perfusion Based Cell Culture Chips

    NASA Astrophysics Data System (ADS)

    Heiskanen, A.; Emnéus, J.; Dufva, M.

    Performing cell culture in miniaturized perfusion chambers gives possibilities to experiment with cells under near in vivo like conditions. In contrast to traditional batch cultures, miniaturized perfusion systems provide precise control of medium composition, long term unattended cultures and tissue like structuring of the cultures. However, as this chapter illustrates, many issues remain to be identified regarding perfusion cell culture such as design, material choice and how to use these systems before they will be widespread amongst biomedical researchers.

  14. Real-time vascular mechanosensation through ex vivo artery perfusion

    PubMed Central

    2014-01-01

    Background Cell-based perfusion studies have provided great insight into fluid-sensing mechanisms, such as primary cilia in the renal and vascular systems. However, the intrinsic limitations of in vitro cell culture, such as the inability to reflect cellular organization within tissues, has distanced observed paradigms from possible clinical developments. Here we describe a protocol that applies ex vivo artery perfusion and calcium imaging to observe real-time cellular responses to fluid-shear stress. Results Through our ex vivo artery perfusion method, we were able to simulate physiological flow and initiate distinct fluid shear stress mechanosensory responses, as well as induced acetylcholine responses in mouse aortic tissue. The observed calcium profiles confirm results found through previous in vitro cell culture experiments. The overall procedure, including dissection, sample preparation and perfusion, takes around 3 hours to complete. Conclusion Through our unique method, we are able to induce laminar flow within intact mouse aortic tissue and illicit subsequent cellular responses. This method of ex vivo artery perfusion provides the opportunity to bridge the novel findings of in vitro studies with subsequent physiological models of fluid-shear stress mechanosensation in vascular tissues. PMID:24685068

  15. Electrophysiological and cable parameters of perfused beetle malpighian tubules.

    PubMed

    Isaacson, L C; Nicolson, S W; Fisher, D W

    1989-11-01

    Isolated perfused Malpighian tubules of the desert beetle Onymacris plana (Coleoptera: Tenebrionidae) have been subjected to cable analysis under the following conditions: control, adenosine 3',5'-cyclic monophosphate (cAMP), corpora cardiaca homogenate (CCH), and high ambient K (130 mM). In addition, we investigated possible effects of perfusate composition on proximal transtubular potential (Vo) by reducing K, Na, or Cl or by adding ouabain, furosemide, or dinitrophenol. The effects of cAMP, CCH, and high K on Vo and cable parameters were consistent with increased fluid secretion, i.e., diminished input and core resistances and increased virtual short-circuit current, length constant, and luminal diameter. They differed in that CCH had variable effects on Vo and high K did not reduce transepithelial resistance. In terms of their effects on the parameters of a simple equivalent electrical circuit, the responses to cAMP, CCH, and a high ambient K concentration appear to be mediated by different mechanisms. Alterations in perfusate composition were almost without effect.

  16. Adenosine Monophosphate (AMP)-Activated Protein Kinase: A New Target for Nutraceutical Compounds

    PubMed Central

    Marín-Aguilar, Fabiola; Pavillard, Luis E.; Giampieri, Francesca; Bullón, Pedro; Cordero, Mario D.

    2017-01-01

    Adenosine monophosphate-activated protein kinase (AMPK) is an important energy sensor which is activated by increases in adenosine monophosphate (AMP)/adenosine triphosphate (ATP) ratio and/or adenosine diphosphate (ADP)/ATP ratio, and increases different metabolic pathways such as fatty acid oxidation, glucose transport and mitochondrial biogenesis. In this sense, AMPK maintains cellular energy homeostasis by induction of catabolism and inhibition of ATP-consuming biosynthetic pathways to preserve ATP levels. Several studies indicate a reduction of AMPK sensitivity to cellular stress during aging and this could impair the downstream signaling and the maintenance of the cellular energy balance and the stress resistance. However, several diseases have been related with an AMPK dysfunction. Alterations in AMPK signaling decrease mitochondrial biogenesis, increase cellular stress and induce inflammation, which are typical events of the aging process and have been associated to several pathological processes. In this sense, in the last few years AMPK has been identified as a very interesting target and different nutraceutical compounds are being studied for an interesting potential effect on AMPK induction. In this review, we will evaluate the interaction of the different nutraceutical compounds to induce the AMPK phosphorylation and the applications in diseases such as cancer, type II diabetes, neurodegenerative diseases or cardiovascular diseases. PMID:28146060

  17. Mucosal adenosine stimulates chloride secretion in canine tracheal epithelium

    SciTech Connect

    Pratt, A.D.; Clancy, G.; Welsh, M.J.

    1986-08-01

    Adenosine is a local regulator of a variety of physiological functions in many tissues and has been observed to stimulate secretion in several Cl-secreting epithelia. In canine tracheal epithelium the authors found that adenosine stimulates Cl secretion from both the mucosal and submucosal surfaces. Addition of adenosine, or its analogue 2-chloroadenosine, to the mucosal surface potently stimulated Cl secretion with no effect on the rate of Na absorption. Stimulation resulted from an interaction of adenosine with adenosine receptors, because it was blocked by the adenosine receptor blocker, 8-phenyltheophylline. The adenosine receptor was a stimulatory receptor as judged by the rank-order potency of adenosine and its analogues and by the increase in cellular adenosine 3',5'-cyclic monophosphate levels produced by 2-chloroadenosine. Adenosine also stimulated Cl secretion when it was added to the submucosal surface, although the maximal increase in secretion was less and it was much less potent. The observation that mucosal 8-phenyletheophylline blocked the effect of submucosal 2-chloroadenosine, whereas submucosal 8-phenyltheophylline did not prevent a response to mucosal or submucosal 2-chloroadenosine, suggests that adenosine receptors are located on the mucosal surface. Thus submucosal adenosine may stimulate secretion by crossing the epithelium and interacting with receptors located on the mucosal surface. Because adenosine can be released from mast cells located in the airway lumen in response to inhaled material, and because adenosine stimulated secretion from the mucosal surface, it may be in a unique position to control the epithelium on a regional level.

  18. Prediction of reversible perfusion defects by quantitative analysis of post-exercise electrocardiogram-gated acquisition of technetium-99m 2-methoxyisobutylisonitrile myocardial perfusion scintigraphy.

    PubMed

    Marcassa, C; Marzullo, P; Sambuceti, G; Parodi, O

    1992-01-01

    The aim of this study was to assess the reliability of the quantitative analysis of regional wall thickening with electrocardiographic-gated technetium-99m 2-methoxyisobutylisonitrile (SESTAMIBI) in predicting the reversibility of stress-induced perfusion defects. The assumption was that a preserved resting wall thickening in a segment with stress-induced perfusion defect would predict normal resting perfusion. Twenty-five patients with suspected coronary artery disease underwent planar stress-rest SESTAMIBI scintigraphy. The wall thickening was quantitatively evaluated as percentage increase in counts from diastole to systole; a ratio defined as the wall thickening index (WTI) between patient and normal profile (mean - 2 SD) below 1 was considered abnormal. Improvement of the perfusion pattern at rest was observed in 76% (54/71) of segments with a stress-induced perfusion defect; 90% of these segments had a (WTI) greater than 0.8. Five segments (9%) showed fixed perfusion defects despite a WTI value greater than 0.8. In conclusion, quantitative analysis of regional wall thickening by electrocardiographic-gated SESTAMIBI identifies segments with reversible perfusion defects; this may overcome the need for studies at rest and may direct the detection of hypoperfused but viable myocardium.

  19. End-ischemic machine perfusion reduces bile duct injury in donation after circulatory death rat donor livers independent of the machine perfusion temperature.

    PubMed

    Westerkamp, Andrie C; Mahboub, Paria; Meyer, Sophie L; Hottenrott, Maximilia; Ottens, Petra J; Wiersema-Buist, Janneke; Gouw, Annette S H; Lisman, Ton; Leuvenink, Henri G D; Porte, Robert J

    2015-10-01

    A short period of oxygenated machine perfusion (MP) after static cold storage (SCS) may reduce biliary injury in donation after cardiac death (DCD) donor livers. However, the ideal perfusion temperature for protection of the bile ducts is unknown. In this study, the optimal perfusion temperature for protection of the bile ducts was assessed. DCD rat livers were preserved by SCS for 6 hours. Thereafter, 1 hour of oxygenated MP was performed using either hypothermic machine perfusion, subnormothermic machine perfusion, or with controlled oxygenated rewarming (COR) conditions. Subsequently, graft and bile duct viability were assessed during 2 hours of normothermic ex situ reperfusion. In the MP study groups, lower levels of transaminases, lactate dehydrogenase (LDH), and thiobarbituric acid reactive substances were measured compared to SCS. In parallel, mitochondrial oxygen consumption and adenosine triphosphate (ATP) production were significantly higher in the MP groups. Biomarkers of biliary function, including bile production, biliary bicarbonate concentration, and pH, were significantly higher in the MP groups, whereas biomarkers of biliary epithelial injury (biliary gamma-glutamyltransferase [GGT] and LDH), were significantly lower in MP preserved livers. Histological analysis revealed less injury of large bile duct epithelium in the MP groups compared to SCS. In conclusion, compared to SCS, end-ischemic oxygenated MP of DCD livers provides better preservation of biliary epithelial function and morphology, independent of the temperature at which MP is performed. End-ischemic oxygenated MP could reduce biliary injury after DCD liver transplantation. © 2015 American Association for the Study of Liver Diseases.

  20. Nuclear myocardial perfusion imaging using thallium-201 with a novel multifocal collimator SPECT/CT: IQ-SPECT versus conventional protocols in normal subjects.

    PubMed

    Matsuo, Shinro; Nakajima, Kenichi; Onoguchi, Masahisa; Wakabayash, Hiroshi; Okuda, Koichi; Kinuya, Seigo

    2015-06-01

    A novel multifocal collimator, IQ-SPECT (Siemens) consists of SMARTZOOM, cardio-centric and 3D iterative SPECT reconstruction and makes it possible to perform MPI scans in a short time. The aims are to delineate the normal uptake in thallium-201 ((201)Tl) SPECT in each acquisition method and to compare the distribution between new and conventional protocol, especially in patients with normal imaging. Forty patients (eight women, mean age of 75 years) who underwent myocardial perfusion imaging were included in the study. All patients underwent one-day protocol perfusion scan after an adenosine-stress test and at rest after administering (201)Tl and showed normal results. Acquisition was performed on a Symbia T6 equipped with a conventional dual-headed gamma camera system (Siemens ECAM) and with a multifocal SMARTZOOM collimator. Imaging was performed with a conventional system followed by IQ-SPECT/computed tomography (CT). Reconstruction was performed with or without X-ray CT-derived attenuation correction (AC). Two nuclear physicians blinded to clinical information interpreted all myocardial perfusion images. A semi-quantitative myocardial perfusion was analyzed by a 17-segment model with a 5-point visual scoring. The uptake of each segment was measured and left ventricular functions were analyzed by QPS software. IQ-SPECT provided good or excellent image quality. The quality of IQ-SPECT images without AC was similar to those of conventional LEHR study. Mid-inferior defect score (0.3 ± 0.5) in the conventional LEHR study was increased significantly in IQ-SPECT with AC (0 ± 0). IQ-SPECT with AC improved the mid-inferior decreased perfusion shown in conventional images. The apical tracer count in IQ-SPECT with AC was decreased compared to that in LEHR (0.1 ± 0.3 vs. 0.5 ± 0.7, p < 0.05). The left ventricular ejection fraction from IQ-SPECT was significantly higher than that from the LEHR collimator (p = 0.0009). The images of IQ-SPECT acquired in a

  1. Neurabin scaffolding of adenosine receptor and RGS4 regulates anti-seizure effect of endogenous adenosine

    PubMed Central

    Chen, Yunjia; Liu, Yin; Cottingham, Christopher; McMahon, Lori; Jiao, Kai; Greengard, Paul; Wang, Qin

    2012-01-01

    Endogenous adenosine is an essential protective agent against neural damage by various insults to the brain. However, the therapeutic potential of adenosine receptor-directed ligands for neuroprotection is offset by side effects in peripheral tissues and organs. An increase in adenosine receptor responsiveness to endogenous adenosine would enhance neuroprotection while avoiding the confounding effects of exogenous ligands. Here we report novel regulation of adenosine-evoked responses by a neural tissue-specific protein, neurabin. Neurabin attenuated adenosine A1 receptor (A1R) signaling by assembling a complex between the A1R and the regulator of G protein signaling 4 (RGS4), a protein known to turn off G protein signaling. Inactivation of the neurabin gene enhanced A1R signaling and promoted the protective effect of adenosine against excitotoxic seizure and neuronal death in mice. Furthermore, administration of a small molecule inhibitor of RGS4 significantly attenuated seizure severity in mice. Notably, the dose of kainate capable of inducing an ~50% rate of death in WT mice did not affect neurabin null mice or WT mice co-treated with an RGS4 inhibitor. The enhanced anti-seizure and neuroprotective effect achieved by disruption of the A1R/neurabin/RGS4 complex is elicited by the on-site and on-demand release of endogenous adenosine, and does not require administration of A1R ligands. These data identify neurabin-RGS4 as a novel tissue-selective regulatory mechanism for fine-tuning adenosine receptor function in the nervous system. Moreover, these findings implicate the A1R/neurabin/RGS4 complex as a valid therapeutic target for specifically manipulating the neuroprotective effects of endogenous adenosine. PMID:22357852

  2. Neurabin scaffolding of adenosine receptor and RGS4 regulates anti-seizure effect of endogenous adenosine.

    PubMed

    Chen, Yunjia; Liu, Yin; Cottingham, Christopher; McMahon, Lori; Jiao, Kai; Greengard, Paul; Wang, Qin

    2012-02-22

    Endogenous adenosine is an essential protective agent against neural damage by various insults to the brain. However, the therapeutic potential of adenosine receptor-directed ligands for neuroprotection is offset by side effects in peripheral tissues and organs. An increase in adenosine receptor responsiveness to endogenous adenosine would enhance neuroprotection while avoiding the confounding effects of exogenous ligands. Here we report novel regulation of adenosine-evoked responses by a neural tissue-specific protein, neurabin. Neurabin attenuated adenosine A(1) receptor (A1R) signaling by assembling a complex between the A1R and the regulator of G-protein signaling 4 (RGS4), a protein known to turn off G-protein signaling. Inactivation of the neurabin gene enhanced A1R signaling and promoted the protective effect of adenosine against excitotoxic seizure and neuronal death in mice. Furthermore, administration of a small molecule inhibitor of RGS4 significantly attenuated seizure severity in mice. Notably, the dose of kainate capable of inducing an ∼50% rate of death in wild-type (WT) mice did not affect neurabin-null mice or WT mice cotreated with an RGS4 inhibitor. The enhanced anti-seizure and neuroprotective effect achieved by disruption of the A1R/neurabin/RGS4 complex is elicited by the on-site and on-demand release of endogenous adenosine, and does not require administration of A1R ligands. These data identify neurabin-RGS4 as a novel tissue-selective regulatory mechanism for fine-tuning adenosine receptor function in the nervous system. Moreover, these findings implicate the A1R/neurabin/RGS4 complex as a valid therapeutic target for specifically manipulating the neuroprotective effects of endogenous adenosine.

  3. Perfusion Bioreactor Module

    NASA Technical Reports Server (NTRS)

    Morrison, Dennis R.

    1990-01-01

    Perfusion bioreactor module, self-contained, closed-loop cell-culture system that operates in microgravity or on Earth. Equipment supports growth or long-term maintenance of cultures of human or other fragile cells for experiments in basic cell biology or process technology. Designed to support proliferation (initially at exponential rates of growth) of cells in complex growth medium and to maintain confluent cells in defined medium under conditions optimized to permit or encourage selected functions of cells, including secretion of products of cells into medium.

  4. The adenosine kinase hypothesis of epileptogenesis

    PubMed Central

    Boison, Detlev

    2008-01-01

    Current therapies for epilepsy are largely symptomatic and do not affect the underlying mechanisms of disease progression, i.e. epileptogenesis. Given the large percentage of pharmacoresistant chronic epilepsies, novel approaches are needed to understand and modify the underlying pathogenetic mechanisms. Although different types of brain injury (e.g. status epilepticus, traumatic brain injury, stroke) can trigger epileptogenesis, astrogliosis appears to be a homotypic response and hallmark of epilepsy. Indeed, recent findings indicate that epilepsy might be a disease of astrocyte dysfunction. This review focuses on the inhibitory neuromodulator and endogenous anticonvulsant adenosine, which is largely regulated by astrocytes and its key metabolic enzyme adenosine kinase (ADK). Recent findings support the “ADK hypothesis of epileptogenesis”: (i) Mouse models of epileptogenesis suggest a sequence of events leading from initial downregulation of ADK and elevation of ambient adenosine as an acute protective response, to changes in astrocytic adenosine receptor expression, to astrocyte proliferation and hypertrophy (i.e. astrogliosis), to consequential overexpression of ADK, reduced adenosine and – finally – to spontaneous focal seizure activity restricted to regions of astrogliotic overexpression of ADK. (ii) Transgenic mice overexpressing ADK display increased sensitivity to brain injury and seizures. (iii) Inhibition of ADK prevents seizures in a mouse model of pharmacoresistant epilepsy. (iv) Intrahippocampal implants of stem cells engineered to lack ADK prevent epileptogenesis. Thus, ADK emerges both as a diagnostic marker to predict, as well as a prime therapeutic target to prevent, epileptogenesis. PMID:18249058

  5. MOLECULAR PROBES FOR EXTRACELLULAR ADENOSINE RECEPTORS

    PubMed Central

    Jacobson, Kenneth A.; Ukena, Dieter; Padgett, William; Kirk, Kenneth L.; Daly, John W.

    2012-01-01

    Derivatives of adenosine receptor agonists (N6-phenyladenosines) and antagonists (1,3-dialkyl-8-phenylxanthines) bearing functionalized chains suitable for attachment to other molecules have been reported [Jacobson et al., J. med. Chem. 28, 1334 and 1341 (1985)]. The “functionalized congener” approach has been extended to the synthesis of spectroscopic and other probes for adenosine receptors that retain high affinity (Ki ~ 10−9 −10−8 M) in A1-receptor binding. The probes have been synthesized from an antagonist xanthine amine congener (XAC) and an adenosine amine congener (ADAC). [3H]ADAC has been synthesized and found to bind highly specifically to A1-adenosine receptors of rat and calf cerebral cortical membranes with KD values of 1.4 and 0.34 nM respectively. The higher affinity in the bovine brain, seen also with many of the probes derived from ADAC and XAC, is associated with phenyl substituents. The spectroscopic probes contain a reporter group attached at a distal site of the functionalized chain. These bifunctional ligands may contain a spin label (e.g. the nitroxyl radical TEMPO) for electron spin resonance spectroscopy, or a fluorescent dye, including fluorescein and 4-nitrobenz-2-oxa-1,3-diazole (NBD), or labels for 19F nuclear magnetic resonance spectroscopy. Potential applications of the spectroscopic probes in characterization of adenosine receptors are discussed. PMID:3036153

  6. Radioimmunochemical quantitation of human adenosine deaminase.

    PubMed Central

    Daddona, P E; Frohman, M A; Kelley, W N

    1979-01-01

    Markedly reduced or absent adenosine deaminase activity in man is associated with an autosomal recesive form of severe conbined immunodeficiency disease. To further define the genetic nature of this enzyme defect, we have quantitated immunologically active adenosine deaminase (CRM) in the hemolysate of homozygous deficient patients and their heterozygous parents. A highly specific radioimmunoassay was developed capable of detecting 0.05% of normal erythrocyte adenosine deaminase. Hemolysates from nine heterozygotes (five families) showed a wide range in CRM (32--100% of normal) and variable absolute specific activities with several being at least 1 SD BELOW THE NORMAL MEAN. Hemolysates from four unrelated patients showed less than 0.09% adenosine deaminase activity with CRM ranging from less than 0.06 to 5.6% of the normal mean. In conclusion, heterozygote and homozygote hemolysates from five of the eight families analyzed revealed variable levels of CRM suggesting heterogeneous genetic alteration or expression of the silent or defective allele(s) of adenosine deaminase. PMID:468994

  7. Adenosine receptor targeting in health and disease.

    PubMed

    Gessi, Stefania; Merighi, Stefania; Fazzi, Debora; Stefanelli, Angela; Varani, Katia; Borea, Pier Andrea

    2011-12-01

    The adenosine receptors A(1), A(2A), A(2B) and A(3) are important and ubiquitous mediators of cellular signaling that play vital roles in protecting tissues and organs from damage. In particular, adenosine triggers tissue protection and repair by different receptor-mediated mechanisms, including increasing the oxygen supply:demand ratio, pre-conditioning, anti-inflammatory effects and the stimulation of angiogenesis. The state of the art of the role of adenosine receptors which have been proposed as targets for drug design and discovery, in health and disease, and an overview of the ligands for these receptors in clinical development. Selective ligands of A(1), A(2A), A(2B) and A(3) adenosine receptors are likely to find applications in the treatment of pain, ischemic conditions, glaucoma, asthma, arthritis, cancer and other disorders in which inflammation is a feature. The aim of this review is to provide an overview of the present knowledge regarding the role of these adenosine receptors in health and disease.

  8. Caffeine, adenosine receptors, and synaptic plasticity.

    PubMed

    Costenla, Ana Rita; Cunha, Rodrigo A; de Mendonça, Alexandre

    2010-01-01

    Few studies to date have looked at the effects of caffeine on synaptic plasticity, and those that did used very high concentrations of caffeine, whereas the brain concentrations attained by regular coffee consumption in humans should be in the low micromolar range, where caffeine exerts pharmacological actions mainly by antagonizing adenosine receptors. Accordingly, rats drinking caffeine (1 g/L) for 3 weeks, displayed a concentration of caffeine of circa 22 microM in the hippocampus. It is known that selective adenosine A1 receptor antagonists facilitate, whereas selective adenosine A2A receptor antagonists attenuate, long term potentiation (LTP) in the hippocampus. Although caffeine is a non-selective antagonist of adenosine receptors, it attenuates frequency-induced LTP in hippocampal slices in a manner similar to selective adenosine A2A receptor antagonists. These effects of low micromolar concentration of caffeine (30 microM) are maintained in aged animals, which is important when a possible beneficial effect for caffeine in age-related cognitive decline is proposed. Future studies will still be required to confirm and detail the involvement of A1 and A2A receptors in the effects of caffeine on hippocampal synaptic plasticity, using both pharmacological and genetic approaches.

  9. Differential A1 adenosine receptor reserve for two actions of adenosine on guinea pig atrial myocytes.

    PubMed

    Srinivas, M; Shryock, J C; Dennis, D M; Baker, S P; Belardinelli, L

    1997-10-01

    Adenosine activates adenosine-induced inwardly rectifying K+ current (IKAdo) and inhibits isoproterenol (100 nM)-stimulated L-type Ca2+ current (beta-ICa,L) of guinea pig atrial myocytes with EC50 values of 2.17 and 0.20 microM, respectively. We determined whether this 11-fold difference in potency of adenosine is due to the existence of a greater A1 adenosine receptor reserve for the inhibition of beta-ICa,L than for the activation of IKAdo. Atrial myocytes were pretreated with vehicle (control) or the irreversible A1 adenosine receptor antagonist 8-cyclopentyl-3-[3-[[4-(fluorosulfonyl)benzoyl]oxy]propyl]-1-propylxa nthine (FSCPX) (10 and 50 nM) for 30 min, and after a 60-min washout period, concentration-response curves were determined for the adenosine-induced activation of IKAdo and inhibition of beta-ICa,L. Pretreatment of atrial myocytes with 10 nM FSCPX reduced the maximal activation of IKAdo by 60% (7.9 +/- 0.2 to 3.2 +/- 0.1 pA/pF). In contrast, a higher concentration of FSCPX (50 nM) was required to reduce the maximal inhibition of beta-ICa,L by 39% (95 +/- 4% to 58. 7 +/- 5.6%) and caused a 15-fold increase in the EC50 value of adenosine. Values of the equilibrium dissociation constant (KA) for adenosine to activate IKAdo and inhibit beta-ICa,L, estimated according to the method of Furchgott, were 2.7 and 5.6 microM, respectively. These values were used to determine the relationship between adenosine receptor occupancy and response. Half-maximal and maximal activations of IKAdo required occupancies of 40% and 98% of A1 adenosine receptors, respectively. In contrast, occupancies of only 4% and 70%, respectively, of A1 adenosine receptors were sufficient to cause half-maximal and maximal inhibitions of beta-ICa, L. Consistent with this result, a partial agonist of the A1 adenosine receptor SHA040 inhibited beta-ICa,L by 60 +/- 3.5% but activated IKAdo by only 18.1 +/- 2.5%. The results indicate that the A1 adenosine receptor is coupled more efficiently to

  10. Role of adenosine signaling in penile erection and erectile disorders.

    PubMed

    Phatarpekar, Prasad V; Wen, Jiaming; Xia, Yang

    2010-11-01

    Penile erection is a hemodynamic process, which results from increased flow and retention of blood in the penile organ due to the relaxation of smooth muscle cells. Adenosine, a physiological vasorelaxant, has been shown to be a modulator of penile erection. To summarize the research on the role of adenosine signaling in normal penile erection and erectile disorders. Evidence in the literature on the association between adenosine signaling and normal and abnormal penile erection, i.e., erectile dysfunction (ED) and priapism. The article reviews the literature on the role of endogenous and exogenous adenosine in normal penile erection, as well as in erectile disorders namely, ED and priapism. Adenosine has been shown to relax corpus cavernosum from various species including human in both in vivo and in vitro studies. Neuromodulatory role of adenosine in corpus cavernosum has also been demonstrated. Impaired adenosine signaling through A(2B) receptor causes partial resistance of corpus cavernosum, from men with organic ED, to adenosine-mediated relaxation. Increased level of adenosine has been shown to be a causative factor for priapism. Overall, the research reviewed here suggests a general role of exogenous and endogenous adenosine signaling in normal penile erection. From this perspective, it is not surprising that impaired adenosine signaling is associated with ED, and excessive adenosine signaling is associated with priapism. Adenosine signaling represents a potentially important diagnostic and therapeutic target for the treatment of ED and priapism. © 2009 International Society for Sexual Medicine.

  11. Role of Adenosine Signaling in Penile Erection and Erectile Disorders

    PubMed Central

    Phatarpekar, Prasad V.; Wen, Jiaming; Xia, Yang

    2010-01-01

    Introduction Penile erection is a hemodynamic process, which results from increased flow and retention of blood in the penile organ due to the relaxation of smooth muscle cells. Adenosine, a physiological vasorelaxant, has been shown to be a modulator of penile erection. Aim To summarize the research on the role of adenosine signaling in normal penile erection and erectile disorders. Main Outcome Measures Evidence in the literature on the association between adenosine signaling and normal and abnormal penile erection, i.e., erectile dysfunction (ED) and priapism. Methods The article reviews the literature on the role of endogenous and exogenous adenosine in normal penile erection, as well as in erectile disorders namely, ED and priapism. Results Adenosine has been shown to relax corpus cavernosum from various species including human in both in vivo and in vitro studies. Neuromodulatory role of adenosine in corpus cavernosum has also been demonstrated. Impaired adenosine signaling through A2B receptor causes partial resistance of corpus cavernosum, from men with organic ED, to adenosine-mediated relaxation. Increased level of adenosine has been shown to be a causative factor for priapism. Conclusion Overall, the research reviewed here suggests a general role of exogenous and endogenous adenosine signaling in normal penile erection. From this perspective, it is not surprising that impaired adenosine signaling is associated with ED, and excessive adenosine signaling is associated with priapism. Adenosine signaling represents a potentially important diagnostic and therapeutic target for the treatment of ED and priapism. PMID:19889148

  12. Evaluation of Short- and Long-Term Efficacy of Combined Intracoronary Administration of High-Dose Adenosine and Tirofiban during Primary Percutaneous Coronary Intervention

    PubMed Central

    Li, Yanbing; Li, Qiang; Li, Feiou; Zong, Min; Miao, Guobin; Yang, Xinchun; Tong, Zichuan; Zhang, Jianjun

    2016-01-01

    Background To assess the influence of combined intracoronary application of high-dose adenosine and tirofiban in primary percutaneous coronary intervention (PCI) on clinical events and cardiac function. Methods Our study evaluated consecutive patients with acute ST-segment elevation myocardial infarction undergoing primary PCI, who were randomly divided into adenosine group (n = 130) and control group (n = 128). Combined with thrombus aspiration and then intracoronary tirofiban, the adenosine group received intracoronary adenosine (2 mg) through the aspiration catheter 2 times. After thrombus aspiration and stenting of the infarct- related artery, the control group received placebo. The primary endpoint of our investigation was major adverse cardiac events (MACE) at the 1-year and 3-year marks. The secondary endpoint comprised left ventricular remodeling (LVR) at 6 months, myocardial blush grade (MBG), thrombolysis in myocardial infarction (TIMI) flow grade and corrected TIMI frame count (CTFC) after PCI. Results Our study found that TIMI flow grade post-PCI did not differ significantly between the 2 groups, while CTFC favored the adenosine-treated patients (21.6 ± 6.5 vs. 25.1 ± 7.8, p = 0.001). Although the adenosine group achieved a higher rate of MBG 3 (45.1% vs. 32.0%, p = 0.035) and MBG 2-3 (76.2% vs. 62.3%, p = 0.018) than the control group, the incidences of MACE at 1 year (20.0% vs. 25.0%, p = 0.373) and 3 years (26.9% vs. 32.0%, p = 0.413) were comparable. LVR occurred in 23.1% (27/117) of adenosine-treated patients and in 29.8% (43/114) of the controls (p = 0.296). Conclusions Intracoronary administration of high-dose adenosine combined with intracoronary tirofiban and thrombus aspiration may further improve myocardial perfusion after primary PCI. PMID:27899850

  13. Harmonic analysis of perfusion pumps.

    PubMed

    Dougherty, F Carroll; Donovan, F M; Townsley, Mary I

    2003-12-01

    The controversy over the use of nonpulsatile versus pulsatile pumps for maintenance of normal organ function during ex vivo perfusion has continued for many years, but resolution has been limited by lack of a congruent mathematical definition of pulsatility. We hypothesized that the waveform frequency and amplitude, as well as the underlying mean distending pressure are all key parameters controlling vascular function. Using discrete Fourier Analysis, our data demonstrate the complexity of the pulmonary arterial pressure waveform in vivo and the failure of commonly available perfusion pumps to mimic in vivo dynamics. In addition, our data show that the key harmonic signatures are intrinsic to the perfusion pumps, are similar for flow and pressure waveforms, and are unchanged by characteristics of the downstream perfusion circuit or perfusate viscosity.

  14. Adenine and adenosine salvage in Leishmania donovani.

    PubMed

    Boitz, Jan M; Ullman, Buddy

    2013-08-01

    6-aminopurine metabolism in Leishmania is unique among trypanosomatid pathogens since this genus expresses two distinct routes for adenine salvage: adenine phosphoribosyltransferase (APRT) and adenine deaminase (AAH). To evaluate the relative contributions of APRT and AAH, adenine salvage was evaluated in Δaprt, Δaah, and Δaprt/Δaah null mutants of L. donovani. The data confirm that AAH plays the dominant role in adenine metabolism in L. donovani, although either enzyme alone is sufficient for salvage. Adenosine salvage was also evaluated in a cohort of null mutants. Adenosine is also primarily converted to hypoxanthine, either intracellularly or extracellularly, but can also be phosphorylated to the nucleotide level by adenosine kinase when the predominant pathways are genetically or pharmacologically blocked. These data provide genetic verification for the relative contributions of 6-aminopurine metabolizing pathways in L. donovani and demonstrate that all of the pathways can function under appropriate conditions of genetic or pharmacologic perturbation.

  15. Validation of minimally invasive measurement of myocardial perfusion using electron beam computed tomography and application in human volunteers

    PubMed Central

    Bell, M; Lerman, L; Rumberger, J

    1999-01-01

    OBJECTIVES—To measure myocardial perfusion using an estimate of intramyocardial vascular volume obtained by electron beam computed tomography (EBCT) in an animal model; to assess the feasibility and validity of measuring regional myocardial perfusion in human volunteers using the techniques developed and validated in the animal studies.
METHODS—Measurements of myocardial perfusion with EBCT employing intravenous contrast injections were compared with radioactive microsphere measurements (flow 57 to 346 ml/100 g/min) in seven closed chest dogs. Fourteen human volunteers then underwent EBCT scans using intravenous contrast injections.
RESULTS—Mean (SEM) global intramyocardial vascular volume by EBCT was 7.6 (1.1)%. The correlation between global EBCT (y) and microsphere (x) perfusion was y = 0.59x + 15.56 (r = 0.86) before, and y = 0.72x + 6.06 (r = 0.88) after correcting for intramyocardial vascular volume. Regional perfusion correlation was y = 0.75x + 23.84 (r = 0.82). Corresponding improvements in agreement between the two techniques were also seen using Bland-Altman plots. In the human subjects, mean resting global myocardial flow was 98 (6) ml/100 g/min, with homogeneous flow across all regions. In 10 of these subjects, perfusion was studied during coronary vasodilatation using intravenous adenosine. Global flow increased from 93 (5) ml/100 g/min at rest to 250 (19) ml/100 g/min during adenosine (p < 0.001), with an average perfusion reserve ratio of 2.8 (0.2). Similar changes in regional perfusion were observed and were uniform throughout all regions, with a mean regional perfusion reserve ratio of 2.8 (0.3).
CONCLUSIONS—Accounting for intramyocardial vascular volume improves the accuracy of EBCT measurements of myocardial perfusion when using intravenous contrast injections. The feasibility of providing accurate measurements of global and regional myocardial perfusion and perfusion reserve in people using this

  16. Human adenosine deaminase. Distribution and properties.

    PubMed

    Van der Weyden, M B; Kelley, W N

    1976-09-25

    Adenosine deaminase exists in multiple molecular forms in human tissue. One form of the enzyme appears to be "particulate". Three forms of the enzyme are soluble and interconvertible with apparent molecular weights of approximately 36,000, 114,000, and 298,000 (designated small, intermediate, and large, respectively). The small form of adenosine deaminase is convertible to the large form only in the presence of a protein, which has an apparent molecular weight of 200,000 and has no adenosine deaminase activity. This conversion of the small form of the enzyme to the large form occurs at 4 degrees, exhibits a pH optimum of 5.0 to 8.0, and is associated with a loss of conversion activity. The small form of the enzyme predominates in tissue preparations exhibiting the higher enzyme-specific activities and no detectable conversion activity. The large form of adenosine deaminase predominates in tissue extracts exhibiting the lower enzyme specific activities and abundant conversion activity. The small form of adenosine deaminase shows several electrophoretic variants by isoelectric focusing. The electrophoretic heterogeneity observed with the large form of the enzyme is similar to that observed with the small form, with the exception that several additional electrophoretic variants are uniformly identified. No organ specificity is demonstrable for the different electrophoretic forms. The kinetic characteristics of the three soluble molecular species of adenosine deaminase are identical except for pH optimum, which is 5.5 for the intermediate species and 7.0 to 7.4 for the large and small forms.

  17. Hypoxia/reoxygenation impairs memory formation via adenosine-dependent activation of caspase 1.

    PubMed

    Chiu, Gabriel S; Chatterjee, Diptaman; Darmody, Patrick T; Walsh, John P; Meling, Daryl D; Johnson, Rodney W; Freund, Gregory G

    2012-10-03

    After hypoxia, a critical adverse outcome is the inability to create new memories. How anterograde amnesia develops or resolves remains elusive, but a link to brain-based IL-1 is suggested due to the vital role of IL-1 in both learning and brain injury. We examined memory formation in mice exposed to acute hypoxia. After reoxygenation, memory recall recovered faster than memory formation, impacting novel object recognition and cued fear conditioning but not spatially cued Y-maze performance. The ability of mice to form new memories after hypoxia/reoxygenation was accelerated in IL-1 receptor 1 knockout (IL-1R1 KO) mice, in mice receiving IL-1 receptor antagonist (IL-1RA), and in mice given the caspase 1 inhibitor Ac-YVAD-CMK. Mechanistically, hypoxia/reoxygenation more than doubled caspase 1 activity in the brain, which was localized to the amygdala compared to the hippocampus. This reoxygenation-dependent activation of caspase 1 was prevented by broad-spectrum adenosine receptor (AR) antagonism with caffeine and by targeted A1/A2A AR antagonism with 8-cyclopentyl-1,3-dipropylxanthine plus 3,7-dimethyl-1-propargylxanthine. Additionally, perfusion of adenosine activated caspase 1 in the brain, while caffeine blocked this action by adenosine. Finally, resolution of anterograde amnesia was improved by both caffeine and by targeted A1/A2A AR antagonism. These findings indicate that amygdala-based anterograde amnesia after hypoxia/reoxygenation is sustained by IL-1β generated through adenosine-dependent activation of caspase 1 after reoxygenation.

  18. Hypoxia/reoxygenation impairs memory formation via adenosine-dependent activation of caspase 1

    PubMed Central

    Chiu, Gabriel S.; Chatterjee, Diptaman; Darmody, Patrick T.; Walsh, John P.; Meling, Daryl D.; Johnson, Rodney W.; Freund, Gregory G.

    2012-01-01

    After hypoxia, a critical adverse outcome is the inability to create new memories. How anterograde amnesia develops or resolves remains elusive, but a link to brain-based IL-1 is suggested due to the vital role of IL-1 in both learning and brain injury. We examined memory formation in mice exposed to acute hypoxia. After reoxygenation, memory recall recovered faster than memory formationimpacting novel object recognition and cued fear conditioning but not spatially cued Y-maze performance. The ability of mice to form new memories after hypoxia/reoxygenation was accelerated in IL-1 receptor 1 knockout (IL-1R1 KO) mice, in mice receiving IL-1 receptor antagonist (IL-1RA) and in mice given the caspase 1 inhibitor, Ac-YVAD-CMK. Mechanistically, hypoxia/reoxygenation more than doubled caspase 1 activity in the brain which was localized to the amygdala compared to the hippocampus. This reoxygenation-dependent activation of caspase 1 was prevented by broad-spectrum adenosine receptor (AR) antagonism with caffeine and by targeted A1/A2A AR antagonism with 8-cyclopentyl-1, 3-dipropylxanthine + 3, 7-dimethyl-1-propargylxanthine. Additionally, perfusion of adenosine activated caspase 1 in the brain while caffeine blocked this action by adenosine. Finally, resolution of anterograde amnesia was improved by both caffeine and by targeted A1/A2A AR antagonism. These findings indicate that amygdala-based anterograde amnesia after hypoxia/reoxygenation is sustained by IL-1β generated through adenosine-dependent activation of caspase 1 after reoxygenation. PMID:23035103

  19. Diastolic time fraction as a determinant of subendocardial perfusion.

    PubMed

    Fokkema, Dirk S; VanTeeffelen, Jurgen W G E; Dekker, Simone; Vergroesen, Isabelle; Reitsma, Johannes B; Spaan, Jos A E

    2005-05-01

    Diastolic time fraction (DTF) has been recognized as an important determinant for subendocardial perfusion, but microsphere studies in which DTF was the independent variable are practically absent. In 21 anesthetized goats, the left coronary main stem was artificially perfused at controlled pressure. DTF was varied by pacing the heart, vagus stimulation, or administration of dobutamine. Regional coronary flow was measured with fluorescent microspheres under full adenosine dilation. Perfusion pressure (P(c)) was defined as mean coronary arterial pressure minus minimal left ventricular pressure. Regional flow conductances (flow/P(c)) were as follows: for the subendocardium, C(endo) = -0.103 + 0.197 DTF + 0.00074 P(c) (P < 0.001); for the midmyocardium, conductance = -0.048 + 0.126 DTF + 0.00049 P(c) (P < 0.001); and for the subepicardium, C(epi) was not significant. C(endo)-DTF relations demonstrated a finite value for DTF at which flow is zero, implying that, at physiological pressures, systolic subendocardial flow limitation extends into diastole. The DTF corresponding to an equal conductance in subendocardium and subepicardium (DTF1) was inversely related to P(c): DTF1 = 0.78 - 0.003 P(c) (P < 0.01). When heart rate and P(c) were held constant and dobutamine was administered (5 goats), contractility doubled and DTF increased by 39%, resulting in an increase of C(endo) of 40%. It is concluded that 1) DTF is a determinant of subendocardial perfusion, 2) systolic compression exerts a flow-limiting effect into diastole, and 3) corresponding to clinical findings on inducible ischemia we predict that, under hyperemic conditions, C(endo) < C(epi) if P(c) is lower than approximately 75% of a normal aortic pressure and heart rate >80 beats/min.

  20. Numerical simulation of blood flow in femoral perfusion: comparison between side-armed femoral artery perfusion and direct femoral artery perfusion.

    PubMed

    Kitamura, Shingo; Shirota, Minori; Fukuda, Wakako; Inamura, Takao; Fukuda, Ikuo

    2016-12-01

    Computational numerical analysis was performed to elucidate the flow dynamics of femoral artery perfusion. Numerical simulation of blood flow was performed from the right femoral artery in an aortic model. An incompressible Navier-Stokes equation and continuity equation were solved using computed flow dynamics software. Three different perfusion models were analyzed: a 4.0-mm cannula (outer diameter 15 French size), a 5.2-mm cannula (18 French size) and an 8-mm prosthetic graft. The cannula was inserted parallel to the femoral artery, while the graft was anastomosed perpendicular to the femoral artery. Shear stress was highest with the 4-mm cannula (172 Pa) followed by the graft (127 Pa) and the 5.2-mm cannula (99 Pa). The cannula exit velocity was high, even when the 5.2-mm cannula was used. Although side-armed perfusion with an 8-mm graft generated a high shear stress area near the point of anastomosis, flow velocity at the external iliac artery was decreased. The jet speed decreased due to the Coanda effect caused by the recirculation behind sudden expansion of diameter, and the flow velocity maintains a constant speed after the reattachment length of the flow. This study showed that iliac artery shear stress was lower with the 5.2-mm cannula than with the 4-mm cannula when used for femoral perfusion. Side-armed graft perfusion generates a high shear stress area around the anastomotic site, but flow velocity in the iliac artery is slower in the graft model than in the 5.2-mm cannula model.

  1. Cardiac myocyte–secreted cAMP exerts paracrine action via adenosine receptor activation

    PubMed Central

    Sassi, Yassine; Ahles, Andrea; Truong, Dong-Jiunn Jeffery; Baqi, Younis; Lee, Sang-Yong; Husse, Britta; Hulot, Jean-Sébastien; Foinquinos, Ariana; Thum, Thomas; Müller, Christa E.; Dendorfer, Andreas; Laggerbauer, Bernhard; Engelhardt, Stefan

    2014-01-01

    Acute stimulation of cardiac β-adrenoceptors is crucial to increasing cardiac function under stress; however, sustained β-adrenergic stimulation has been implicated in pathological myocardial remodeling and heart failure. Here, we have demonstrated that export of cAMP from cardiac myocytes is an intrinsic cardioprotective mechanism in response to cardiac stress. We report that infusion of cAMP into mice averted myocardial hypertrophy and fibrosis in a disease model of cardiac pressure overload. The protective effect of exogenous cAMP required adenosine receptor signaling. This observation led to the identification of a potent paracrine mechanism that is dependent on secreted cAMP. Specifically, FRET-based imaging of cAMP formation in primary cells and in myocardial tissue from murine hearts revealed that cardiomyocytes depend on the transporter ABCC4 to export cAMP as an extracellular signal. Extracellular cAMP, through its metabolite adenosine, reduced cardiomyocyte cAMP formation and hypertrophy by activating A1 adenosine receptors while delivering an antifibrotic signal to cardiac fibroblasts by A2 adenosine receptor activation. Together, our data reveal a paracrine role for secreted cAMP in intercellular signaling in the myocardium, and we postulate that secreted cAMP may also constitute an important signal in other tissues. PMID:25401477

  2. A new class of adenosine receptors in brain: Characterization by 2-chloro( sup 3 H)adenosine binding

    SciTech Connect

    Chin, Jerome Hsicheng.

    1988-01-01

    Considerable evidence has accumulated in recent years to support a role for adenosine as an important physiological modulator in many mammalian tissues. In brain, adenosine is a potent depressant of neuronal firing and synaptic transmission. The exact mechanisms by which adenosine analogs depress nerve cell activity in the brain are not clear. Despite considerable investigation, neither the A1 nor the A2 adenosine receptors associated with adenylate cyclase have been able to account adequately for the actions of adenosine in brain. It has been proposed that additional adenosine receptors, possibly linked to calcium channels, are present in the central nervous system and are responsible for the physiological actions of adenosine. In this thesis, evidence is provided for the existence of a novel class of adenosine receptors in rat brain. The methods used to identify this new class of receptors involved radioligand binding techniques which have been successfully employed to characterize the properties of many neurotransmitter and drug receptors. 2-Chloro({sup 3}H)adenosine (Cl({sup 3}H)Ado) was selected as the ligand for these experiments since is a water-soluble, metabolically-stable analog of adenosine and a potent depressant of synaptic transmission in brain. The results demonstrate the presence of a distinct class of 2-chloro({sup 3}H)adenosine binding sites in rat forebrain membranes with an apparent K{sub D} of about 10 {mu}M and a B{sub max} of about 60 pmol per mg of protein. Specific 2-chloro ({sup 3}H)adenosine binding is highly specific for adenosine agonists and antagonists. Inhibition of binding by adenosine agonists exhibits an order of potency 2-chloroadenosine > 5{prime}-N-ethylcarboxamide adenosine > ({minus})-N{sup 6}-(R-phenylisopropyl)adenosine, which differs from that of both A1 and A2 adenosine receptors.

  3. Pain-relieving prospects for adenosine receptors and ectonucleotidases

    PubMed Central

    Zylka, Mark J.

    2010-01-01

    Adenosine receptor agonists have potent antinociceptive effects in diverse preclinical models of chronic pain. In contrast, the efficacy of adenosine or adenosine receptor agonists at treating pain in humans is unclear. Two ectonucleotidases that generate adenosine in nociceptive neurons were recently identified. When injected spinally, these enzymes have long-lasting adenosine A1 receptor (A1R)-dependent antinociceptive effects in inflammatory and neuropathic pain models. Furthermore, recent findings indicate that spinal adenosine A2A receptor activation can enduringly inhibit neuropathic pain symptoms. Collectively, these studies suggest the possibility of treating chronic pain in humans by targeting specific adenosine receptor subtypes in anatomically defined regions with agonists or with ectonucleotidases that generate adenosine. PMID:21236731

  4. Coronary microembolization does not induce acute preconditioning against infarction in pigs-the role of adenosine.

    PubMed

    Skyschally, Andreas; Schulz, Rainer; Gres, Petra; Konietzka, Ina; Martin, Claus; Haude, Michael; Erbel, Raimund; Heusch, Gerd

    2004-08-01

    After coronary microembolization (ME) adenosine is released from ischemic areas of the microembolized myocardium. This adenosine dilates vessels in adjacent nonembolized myocardium and increases coronary blood flow. For ischemic preconditioning (IP) to protect the myocardium against infarction, an increase in the interstitial adenosine concentration (iADO) prior to the subsequent ischemia/reperfusion is necessary. We hypothesized that the adenosine release after ME is sufficient to increase iADO and protect the myocardium against infarction from subsequent ischemia/reperfusion. We have therefore compared myocardial protection by either coronary microembolization or ischemic preconditioning prior to ischemia/reperfusion. In anesthetized pigs, the left anterior descending (LAD) was cannulated and perfused from an extracorporeal circuit. In 11 pigs, sustained ischemia was induced by 85% inflow reduction for 90 min (controls). Two other groups of pigs were subjected either to IP (n = 8; 10-min ischemia/15-min reperfusion) or coronary ME (n = 9; i.c. microspheres; 42 microm Ø; 3000 x ml(-1) x min inflow) prior to sustained ischemia. Coronary venous adenosine concentration (vADO) and iADO (microdialysis) were measured. Infarct size was determined after 2-h reperfusion by triphenyl tetrazolium chloride staining. In pigs subjected to IP, infarct size was reduced to 2.6 +/- 1.1% (mean +/- S.E.M.) vs. 17.0 +/- 3.2% in controls. iADO was increased from 2.4 +/- 1.3 to 13.1 +/- 5.8 micromol x l(-1) during the reperfusion following IP. In pigs subjected to ME, at 10 min after ME, coronary blood flow (38.6 +/- 3.6 to 53.6 +/- 4.3 ml x min(-1)) and vADO (0.25 +/- 0.04 to 0.48 +/- 0.07 micromol x l(-1)) were increased. However, iADO (2.0 +/- 0.5 at baseline vs. 2.3 +/- 0.6 micromol x l(-1) at 10 min after ME) did not increase. Infarct size induced by sustained ischemia following ME (22.5 +/- 5.2%) was above that of controls for any given subendocardial blood flow. ME released

  5. Ligands and therapeutic perspectives of adenosine A(2A) receptors.

    PubMed

    Diniz, C; Borges, F; Santana, L; Uriarte, E; Oliveira, J M A; Gonçalves, J; Fresco, P

    2008-01-01

    Adenosine A(2A) receptors are members of the G protein-coupled receptor family and mediate multiple physiological effects of adenosine, both at the central nervous system (CNS) and at peripheral tissues, by activating several pathways or interacting with other receptors or proteins. Increasing evidence relate A(2A) receptors with pharmacological stress testing, neurodegenerative disorders (such as Parkinson's disease) and inflammation, renewing the interest in these receptors, increasingly viewed as promising therapeutic targets. Series of agonists and antagonists have been developed by medicinal chemistry artwork either by structure activity relationship (SAR) or quantitative structure activity relationship (QSAR) studies. These studies have allowed identification of the structural and electrostatic requirements for high affinity A(2A) receptor binding and, therefore, contributing to the rational design of A(2A) receptor ligands. Additional rational chemical modifications of the existing A(2A) receptor ligands may further improve their affinity/selectivity. The purpose of this review is to analize and summarize aspects related to the medicinal chemistry of A(2A) receptor ligands, their present and potencial therapeutic applications by exploring the molecular structure and physiological and pathophysiological roles of A(2A) receptors.

  6. Evaluating acellular versus cellular perfusate composition during prolonged ex vivo lung perfusion after initial cold ischaemia for 24 hours.

    PubMed

    Becker, Simon; Steinmeyer, Jasmin; Avsar, Murat; Höffler, Klaus; Salman, Jawad; Haverich, Axel; Warnecke, Gregor; Ochs, Matthias; Schnapper, Anke

    2016-01-01

    Normothermic ex vivo lung perfusion (EVLP) has developed as a powerful technique to evaluate particularly marginal donor lungs prior to transplantation. In this study, acellular and cellular perfusate compositions were compared in an identical experimental setting as no consensus has been reached on a preferred technique yet. Porcine lungs underwent EVLP for 12 h on the basis of an acellular or a cellular perfusate composition after 24 h of cold ischaemia as defined organ stress. During perfusion, haemodynamic and respiratory parameters were monitored. After EVLP, the lung condition was assessed by light and transmission electron microscopy. Aerodynamic parameters did not show significant differences between groups and remained within the in vivo range during EVLP. Mean oxygenation indices were 491 ± 39 in the acellular group and 513 ± 53 in the cellular group. Groups only differed significantly in terms of higher pulmonary artery pressure and vascular resistance in the cellular group. Lung histology and ultrastructure were largely well preserved after prolonged EVLP and showed only minor structural alterations which were similarly present in both groups. Prolonged acellular and cellular EVLP for 12 h are both feasible with lungs prechallenged by ischaemic organ stress. Physiological and ultrastructural analysis showed no superiority of either acellular or cellular perfusate composition.

  7. Rationale and Design of the Dual Energy Computed Tomography for Ischemia Determination Compared to “Gold Standard” Non-invasive and Invasive Techniques (DECIDE-Gold): A Multicenter International Efficacy Diagnostic Study of Rest-Stress Dual-Energy Computed Tomography Angiography with Perfusion

    PubMed Central

    Truong, Quynh A.; Knaapen, Paul; Pontone, Gianluca; Andreini, Daniele; Leipsic, Jonathon; Carrascosa, Patricia; Lu, Bin; Branch, Kelley; Raman, Subha; Bloom, Stephen; Min, James K.

    2014-01-01

    BACKGROUND Dual-energy CT (DECT) has potential to improve myocardial perfusion for physiologic assessment of coronary artery disease (CAD). Diagnostic performance of rest-stress DECT perfusion (DECTP) is unknown. OBJECTIVE DECIDE-Gold is a prospective multicenter study to evaluate the accuracy of DECT to detect hemodynamic (HD) significant CAD, as compared to fractional flow reserve (FFR) as a reference standard. METHODS Eligible participants are subjects with symptoms of CAD referred for invasive coronary angiography (ICA). Participants will undergo DECTP, which will be performed by pharmacological stress, and participants will subsequently proceed to ICA and FFR. HD-significant CAD will be defined as FFR ≥ 0.80. In those undergoing myocardial stress imaging (MPI) by positron emission tomography (PET), single photon emission computed tomography (SPECT) or cardiac magnetic resonance (CMR) imaging, ischemia will be graded by % ischemic myocardium. Blinded core laboratory interpretation will be performed for CCTA, DECTP, MPI, ICA and FFR. RESULTS Primary endpoint is accuracy of DECTP to detect ≥ 1 HD-significant stenosis at the subject-level when compared to FFR. Secondary and tertiary endpoints are accuracies of combinations of DECTP at the subject and vessel levels compared to FFR and MPI. CONCLUSION DECIDE-Gold will determine the performance of DECTP for diagnosing ischemia. PMID:25549826

  8. Ex vivo lung perfusion

    PubMed Central

    Machuca, Tiago N.

    2014-01-01

    Lung transplantation (LTx) is an established treatment option for eligible patients with end-stage lung disease. Nevertheless, the imbalance between suitable donor lungs available and the increasing number of patients considered for LTx reflects in considerable waitlist mortality. Among potential alternatives to address this issue, ex vivo lung perfusion (EVLP) has emerged as a modern preservation technique that allows for more accurate lung assessment and also improvement of lung function. Its application in high-risk donor lungs has been successful and resulted in safe expansion of the donor pool. This article will: (I) review the technical details of EVLP; (II) the rationale behind the method; (III) report the worldwide clinical experience with the EVLP, including the Toronto technique and others; (IV) finally, discuss the growing literature on EVLP application for donation after cardiac death (DCD) lungs. PMID:25132972

  9. Adenosine A1 and A3 receptors protect astrocytes from hypoxic damage.

    PubMed

    Björklund, Olga; Shang, Mingmei; Tonazzini, Ilaria; Daré, Elisabetta; Fredholm, Bertil B

    2008-10-31

    Brain levels of adenosine are elevated during hypoxia. Through effects on adenosine receptors (A(1), A(2A), A(2B) and A(3)) on astrocytes, adenosine can influence functions such as glutamate uptake, reactive gliosis, swelling, as well as release of neurotrophic and neurotoxic factors having an impact on the outcome of metabolic stress. We have studied the roles of these receptors in astrocytes by evaluating their susceptibility to damage induced by oxygen deprivation or exposure to the hypoxia mimic cobalt chloride (CoCl(2)). Hypoxia caused ATP breakdown and purine release, whereas CoCl(2) (0.8 mM) mainly reduced ATP by causing cell death in human D384 astrocytoma cells. Further experiments were conducted in primary astrocytes prepared from specific adenosine receptor knock-out (KO) and wild type (WT) mice. In WT cells purine release following CoCl(2) exposure was mainly due to nucleotide release, whereas hypoxia-induced intracellular ATP breakdown followed by nucleoside efflux. N-ethylcarboxamidoadenosine (NECA), an unselective adenosine receptor agonist, protected from cell death following hypoxia. Cytotoxicity was more pronounced in A(1)R KO astrocytes and tended to be higher in WT cells in the presence of the A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Genetic deletion of A(2A) receptor resulted in less prominent effects. A(3)R KO glial cells were more affected by hypoxia than WT cells. Accordingly, the A(3) receptor agonist 2-chloro-N(6)-(3-iodobenzyl)-N-methyl-5'-carbamoyladenosine (CL-IB-MECA) reduced ATP depletion caused by hypoxic conditions. It also reduced apoptosis in human astroglioma D384 cells after oxygen deprivation. In conclusion, the data point to a cytoprotective role of adenosine mediated by both A(1) and A(3) receptors in primary mouse astrocytes.

  10. Regulation of adenosine transport by acute and chronic ethanol exposure

    SciTech Connect

    Nagy, L.E.; Casso, D.; Diamond, I.; Gordon, A.S. )

    1989-02-09

    Chronic exposure to ethanol results in a desensitization of adenosine receptor-stimulated cAMP production. Since adenosine is released by cells and is known to desensitize its own as well as other receptors, it may be involved in ethanol-induced desensitization of adenosine receptor function. Therefore, we have examine the acute and chronic effects of ethanol on the transport of adenosine via the nucleoside transport. Acute exposure to ethanol caused an inhibition of adenosine uptake in S49 lymphoma cells. This decrease in uptake resulted in accumulation of extracellular adenosine after ethanol exposure. The effect of ethanol was specific to nucleoside transport. Uptake of uridine, also transported by the nucleoside transporter, was inhibited by ethanol to the same degree as adenosine uptake, while neither isoleucine nor deoxyglucose uptake was altered by ethanol treatment. Inhibition of adenosine uptake by ethanol was non-competitive and dependent on the concentration of ethanol. After chronic exposure to ethanol, cells became tolerant to the acute effects of ethanol. There was no longer an acute inhibition of adenosine uptake, nor was these accumulation of extracellular adenosine. Chronic ethanol exposure also resulted in a decrease in the absolute rate of adenosine uptake. Binding studies using a high affinity lignad for the nucleoside transporter, nitrobenzylthioinosine (NBMPR), indicate that this decreased uptake was due to a decrease in the maximal number of binding sites. These ethanol-induced changes in adenosine transport may be important for the acute and chronic effects of ethanol.

  11. A1 adenosine receptors inhibit chloride transport in the shark rectal gland. Dissociation of inhibition and cyclic AMP.

    PubMed Central

    Kelley, G G; Poeschla, E M; Barron, H V; Forrest, J N

    1990-01-01

    In the in vitro perfused rectal gland of the dogfish shark (Squalus acanthias), the adenosine analogue 2-chloroadenosine (2Clado) completely and reversibly inhibited forskolin-stimulated chloride secretion with an IC50 of 5 nM. Other A1 receptor agonists including cyclohexyladenosine (CHA), N-ethylcarboxamideadenosine (NECA) and R-phenylisopropyl-adenosine (R-PIA) also completely inhibited forskolin stimulated chloride secretion. The "S" stereoisomer of PIA (S-PIA) was a less potent inhibitor of forskolin stimulated chloride secretion, consistent with the affinity profile of PIA stereoisomers for an A1 receptor. The adenosine receptor antagonists 8-phenyltheophylline and 8-cyclopentyltheophylline completely blocked the effect of 2Clado to inhibit forskolin-stimulated chloride secretion. When chloride secretion and tissue cyclic (c)AMP content were determined simultaneously in perfused glands, 2Clado completely inhibited secretion but only inhibited forskolin stimulated cAMP accumulation by 34-40%, indicating that the mechanism of inhibition of secretion by 2Clado is at least partially cAMP independent. Consistent with these results, A1 receptor agonists only modestly inhibited (9-15%) forskolin stimulated adenylate cyclase activity and 2Clado markedly inhibited chloride secretion stimulated by a permeant cAMP analogue, 8-chlorophenylthio cAMP (8CPT cAMP). These findings provide the first evidence for a high affinity A1 adenosine receptor that inhibits hormone stimulated ion transport in a model epithelia. A major portion of this inhibition occurs by a mechanism that is independent of the cAMP messenger system. PMID:1970583

  12. Retinal research using the perfused mammalian eye.

    PubMed

    Niemeyer, G

    2001-05-01

    The effort to isolate and maintain alive in vitro an intact mammalian eye is rewarded by the full control provided over the arterial input and exclusion of systemic regulatory or compensatory mechanisms. Electrical recording of typical light-evoked field potentials from retina and optic nerve can be complemented by single-cell recording. Thus, light-induced electrical activity reflects the function of the retinal pigment epithelium, of the layers of the retina and of the ganglion cells or their axons. Retinal function in vitro is documented by electrophysiological and morphological methods revealing subtle features of retinal information processing as well as optic nerve signals that approach-at threshold stimulus intensity-the human psychophysical threshold. Such sensitivity of third-order retinal neurons is described for the first time. This well controlled in vitro preparation has been used successfully for biophysical, metabolic and pharmacological studies. Examples are provided that demonstrate the marked sensibility of the rod system to changes in glucose supply. Moreover, histochemical identification of glycogen stores revealed labeling of the second- and third-order neurons subserving the rod system, in addition to labeling of Müller (glial) cells in the cat retina. The glycogen content of the cat retina is augmented by prolonged anesthesia, largely depleted by ischemia after enucleation and enhanced by insulin. Pharmacological experiments using agonists and antagonists of putative retinal neurotransmitters are summarized and outlined using the muscarinic cholinergic agonist QNB as an example. Actions and uptake of the neuromodulator adenosine are presented in detail, including inhibitory effects on physiologically characterized ganglion cells. Neuronal effects of adenosine are distinguished from those resulting from vasodilatation and from glycogenolysis induced by the neuromodulator. To open the blood-retina barrier, a hyperosmotic challenge can be

  13. Perfusion measurement in acute pancreatitis using dynamic perfusion MDCT.

    PubMed

    Bize, Pierre E; Platon, Alexandra; Becker, Christoph D; Poletti, Pierre-Alexandre

    2006-01-01

    Our objective was to determine whether MDCT with perfusion imaging could help in assessing the severity of acute pancreatitis in the initial phase of the disease. One hundred six patients with abdominal pain were prospectively enrolled in this study. Patients were separated into two groups: P1 (severe) and P2 (mild) acute pancreatitis. Mean perfusion value was 24.8 mL/100 mL/min in the P1 group and 50.5 mL/100 mL/min in the P2 group (p = 0.0016, significant). Our preliminary data suggest that pancreatic perfusion measurement using MDCT with perfusion imaging could help in assessing the severity of acute pancreatitis.

  14. Cerebral-Body Perfusion Model

    DTIC Science & Technology

    1990-07-01

    compared to the 0.5g curve) fall in flow. Fig. 9b, showing the 5g case, strongly suggests a possible, so-called, " luxury perfusion ", in which natural...as the luxury perfusion situation which bypasses the flow with the nutrients it carries (through newly opened collaterals) and result in a "blackout...89-0054 CEREBRAL-BODY PERFUSION MODEL S. Sorek’, J. Bear2, and M., Feinsod3 in Collaboration with K. Allen4, L. Bunt5 and S. Ben-IHaiM6 July 1990

  15. The role of adenosine in Alzheimer's disease.

    PubMed

    Rahman, Anisur

    2009-09-01

    Alzheimer's disease (AD) is a neurodegenerative disorder of the central nervous system manifested by cognitive and memory deterioration, a variety of neuropsychiatric symptoms, behavioral disturbances, and progressive impairment of daily life activities. Current pharmacotherapies are restricted to symptomatic interventions but do not prevent progressive neuronal degeneration. Therefore, new therapeutic strategies are needed to intervene with these progressive pathological processes. In the past several years adenosine, a ubiquitously released purine ribonucleoside, has become important for its neuromodulating capability and its emerging positive experimental effects in neurodegenerative diseases. Recent research suggests that adenosine receptors play important roles in the modulation of cognitive function. The present paper attempts to review published reports and data from different studies showing the evidence of a relationship between adenosinergic function and AD-related cognitive deficits. Epidemiological studies have found an association between coffee (a nonselective adenosine receptor antagonist) consumption and improved cognitive function in AD patients and in the elderly. Long-term administration of caffeine in transgenic animal models showed a reduced amyloid burden in brain with better cognitive performance. Antagonists of adenosine A2A receptors mimic these beneficial effects of caffeine on cognitive function. Neuronal cell cultures with amyloid beta in the presence of an A2A receptor antagonist completely prevented amyloid beta-induced neurotoxicity. These findings suggest that the adenosinergic system constitutes a new therapeutic target for AD, and caffeine and A2A receptor antagonists may have promise to manage cognitive dysfunction in AD.

  16. Distributed Perfusion Educational Model: A Shift in Perfusion Economic Realities

    PubMed Central

    Austin, Jon W.; Evans, Edward L.; Hoerr, Harry R.

    2005-01-01

    Abstract: In recent years, a steady decline in the number of perfusion education programs in the United States has been noted. At the same time, there has been a parallel decline in the number of students graduated from perfusion educational programs in the United States. Also, as noted by several authors, there has been an increase in demand for perfusion graduates. The decline in programs and graduates has also been noted in anesthesia and surgical residency programs. The shift is caused by a combination of economic and clinical factors. First, decreased reimbursement has led to reallocation of hospital resources. Second, the original enthusiasm for beating heart coronary artery bypass surgery was grossly overestimated and has led to further reallocation of hospital resources and denigration of cardiopulmonary bypass. This paper describes two models of perfusion education programs: serial perfusion education model (SPEM) and the distributed perfusion education model (DPEM). Arguments are presented that the SPEM has some serious limitations and challenges for long-term economic survival. The authors feel the DPEM along with dependence on tuition funding can survive the current clinical and economic conditions and allow the profession to adapt to changes in scope of practice. PMID:16524152

  17. A Novel Method for Screening Adenosine Receptor Specific Agonists for Use in Adenosine Drug Development

    PubMed Central

    Jones, Karlie R.; Choi, Uimook; Gao, Ji-Liang; Thompson, Robert D.; Rodman, Larry E.; Malech, Harry L.; Kang, Elizabeth M.

    2017-01-01

    Agonists that target the A1, A2A, A2B and A3 adenosine receptors have potential to be potent treatment options for a number of diseases, including autoimmune diseases, cardiovascular disease and cancer. Because each of these adenosine receptors plays a distinct role throughout the body, obtaining highly specific receptor agonists is essential. Of these receptors, the adenosine A2AR and A2BR share many sequence and structural similarities but highly differ in their responses to inflammatory stimuli. Our laboratory, using a combination of specially developed cell lines and calcium release analysis hardware, has created a new and faster method for determining specificity of synthetic adenosine agonist compounds for the A2A and A2B receptors in human cells. A2A receptor expression was effectively removed from K562 cells, resulting in the development of a distinct null line. Using HIV-lentivector and plasmid DNA transfection, we also developed A2A and A2B receptor over-expressing lines. As adenosine is known to cause changes in intracellular calcium levels upon addition to cell culture, calcium release can be determined in these cell lines upon compound addition, providing a functional readout of receptor activation and allowing us to isolate the most specific adenosine agonist compounds. PMID:28317879

  18. Cardiac endothelial transport and metabolism of adenosine and inosine

    PubMed Central

    Schwartz, Lisa M.; Bukowski, Thomas R.; Revkin, James H.; Bassingthwaighte, James B.

    2010-01-01

    The influence of transmembrane flux limitations on cellular metabolism of purine nucleosides was assessed in whole organ studies. Transcapillary transport of the purine nucleosides adenosine (Ado) and inosine (Ino) via paracellular diffusion through interendothelial clefts in parallel with carrier-mediated transendothelial fluxes was studied in isolated, Krebs-Henseleit-perfused rabbit and guinea pig hearts. After injection into coronary inflow, multiple-indicator dilution curves were obtained from coronary outflow for 90 s for 131I-labeled albumin (intravascular reference tracer), [3H]arabinofuranosyl hypoxanthine (AraH; extracellular reference tracer and nonreactive adenosine analog), and either [14C]Ado or [14C]Ino. Ado or Ino was separated from their degradative products, hypoxanthine, xanthine, and uric acid, in each outflow sample by HPLC and radioisotope counting. Ado and Ino, but not AraH, permeate the luminal membrane of endothelial cells via a saturable transporter with permeability-surface area product PSecl and also diffuse passively through interendothelial clefts with the same conductance (PSg) as AraH. These parallel conductances were estimated via fitting with an axially distributed, multi-pathway, four-region blood-tissue exchange model. PSg for AraH were ~4 and 2.5 ml · g−1 · min−1 in rabbits and guinea pigs, respectively. In contrast, transplasmalemmal conductances (endothelial PSecl) were ~0.2 ml · g−1 · min−1 for both Ado and Ino in rabbit hearts but ~2 ml · g−1 · min−1 in guinea pig hearts, an order of magnitude different. Purine nucleoside metabolism also differs between guinea pig and rabbit cardiac endothelium. In guinea pig heart, 50% of the tracer Ado bolus was retained, 35% was washed out as Ado, and 15% was lost as effluent metabolites; 25% of Ino was retained, 50% washed out, and 25% was lost as metabolites. In rabbit heart, 45% of Ado was retained and 5% lost as metabolites, and 7% of Ino was retained and 3% lost as

  19. Adenosine receptors and the central nervous system.

    PubMed

    Sebastião, Ana M; Ribeiro, Joaquim A

    2009-01-01

    The adenosine receptors (ARs) in the nervous system act as a kind of "go-between" to regulate the release of neurotransmitters (this includes all known neurotransmitters) and the action of neuromodulators (e.g., neuropeptides, neurotrophic factors). Receptor-receptor interactions and AR-transporter interplay occur as part of the adenosine's attempt to control synaptic transmission. A(2A)ARs are more abundant in the striatum and A(1)ARs in the hippocampus, but both receptors interfere with the efficiency and plasticity-regulated synaptic transmission in most brain areas. The omnipresence of adenosine and A(2A) and A(1) ARs in all nervous system cells (neurons and glia), together with the intensive release of adenosine following insults, makes adenosine a kind of "maestro" of the tripartite synapse in the homeostatic coordination of the brain function. Under physiological conditions, both A(2A) and A(1) ARs play an important role in sleep and arousal, cognition, memory and learning, whereas under pathological conditions (e.g., Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, stroke, epilepsy, drug addiction, pain, schizophrenia, depression), ARs operate a time/circumstance window where in some circumstances A(1)AR agonists may predominate as early neuroprotectors, and in other circumstances A(2A)AR antagonists may alter the outcomes of some of the pathological deficiencies. In some circumstances, and depending on the therapeutic window, the use of A(2A)AR agonists may be initially beneficial; however, at later time points, the use of A(2A)AR antagonists proved beneficial in several pathologies. Since selective ligands for A(1) and A(2A) ARs are now entering clinical trials, the time has come to determine the role of these receptors in neurological and psychiatric diseases and identify therapies that will alter the outcomes of these diseases, therefore providing a hopeful future for the patients who suffer from these diseases.

  20. Pulmonary ventilation/perfusion scan

    MedlinePlus

    ... JavaScript. A pulmonary ventilation/perfusion scan involves two nuclear scan tests to measure breathing (ventilation) and circulation ( ... In: Mettler FA, Guiberteau MJ, eds. Essentials of Nuclear Medicine Imaging . 6th ed. Philadelphia, PA: Elsevier Saunders; ...