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Sample records for adenosine stress myocardial

  1. Adenosine triphosphate stress echocardiography in the detection of myocardial ischemia.

    PubMed

    Fukai, T; Koyanagi, S; Tashiro, H; Ichiki, T; Tsutsui, H; Matsumoto, T; Takeshita, A

    1995-10-01

    The purpose of this study was to assess feasibility and safety in the diagnosis of coronary artery in the diagnosis of coronary artery disease and myocardial ischemia using adenosine triphosphate (ATP) stress echocardiography. ATP, a product of human myocardial tissue, is more potent than adenosine in increasing coronary blood flow. Like adenosine, ATP also has a short half-life (<10 s). Left ventricular echocardiograms were recorded during step-wise infusions of ATP in 86 patients who underwent coronary angiography and stress thallium 201 scintigraphy. No serious complications occurred with ATP infusion and most of the side effects were mild and transient. Significant coronary artery disease (>75% diameter stenosis) was present in 34 of 48 patients who had normal echocardiograms at rest. The sensitivity and specificity of ATP-induced wall motion abnormalities for coronary artery disease was 65% (22 of 34) and 100% (14 of 14), respectively. The sensitivity was 50% (10 of 20) in those with one-vessel disease and 86% (12 of 14) in those with multivessel disease (P < .05). In patients with normal echocardiograms at rest and without prior myocardial infarction, the sensitivity of ATP stress echocardiography for the detection of myocardial ischemia assessed by 201Tl single proton emission computed tomography was 58%, with a specificity of 76%, and a diagnostic accuracy of 66%. The sensitivity was 43% in those with one-vessel disease, and 86% in those with multivessel disease (P = .05). In patients with prior myocardial infarction, the sensitivity of ATP stress echocardiography for the detection of viable but jeopardized myocardium was 81%, with a specificity of 91%. The patients with well-developed collateral circulation had a higher incidence of developing wall motion abnormality than those without collaterals (70% v 40%, P < .01). ATP stress echocardiography is valuable for the assessment of coronary artery disease in patients with multivessel disease, coronary

  2. 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. PMID:27473274

  3. [Detection of coronary artery disease by adenosine triphosphate stress echocardiography: comparison with adenosine triphosphate stress thallium myocardial scintigraphy and coronary angiography].

    PubMed

    Harada, M; Okura, K; Nishizawa, S; Inoue, T; Sakai, H; Lee, T; Sugiyama, Y; Suzuki, M; Hirai, H; Yamaguchi, T

    1998-09-01

    The clinical feasibility and usefulness of adenosine triphosphate-2Na (ATP) stress echocardiography for the detection of coronary artery disease (CAD) were assessed. Two-dimensional echocardiography and thallium-201 single photon emission computed tomography (SPECT) during ATP infusion were performed simultaneously in 58 consecutive patients (41 men and 17 women; mean age 66 +/- 12 years) with suspected CAD. ATP was infused intravenously at 0.16 mg/kg/min for 5 min and thallium was injected at 4 min. All patients underwent coronary angiography within 2 weeks of ATP echocardiography and ATP SPECT. An ischemic response during ATP infusion was detected by echocardiography as the development or worsening of a wall motion abnormality compared with the baseline and by SPECT as a perfusion defect that filled totally or partially during redistribution. Significant coronary artery stenosis was defined as > or = 75% diameter stenosis in a major epicardial vessel. The severity of the stenosis was classified as follows: Group A, lesions with significant coronary artery stenosis (> or = 75%, < 90%); Group B, lesions with severe coronary artery stenosis (> or = 90%) without collateral circulation; Group C, lesions with severe coronary artery stenosis (> or = 90%) with collateral circulation. Significant CAD was present in 43 of 58 patients. The overall sensitivity, specificity and accuracy of ATP echocardiography for detecting significant CAD were 70%, 100% and 78%, respectively, and those of ATP SPECT were 98%, 87% and 95%, respectively. In patients without previous myocardial infarction, the sensitivity of ATP echocardiography was 67%. The sensitivity of ATP echocardiography and ATP SPECT for detecting myocardial ischemia were 59% and 95% in patients with 1-vessel disease, 75% and 100% in those with 2-vessel disease, and 88% and 100% in those with 3-vessel disease, respectively. The induction of wall motion abnormality by ATP echocardiography was highly concordant with ATP

  4. 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.

  5. Qualitative and Quantitative Assessment of Adenosine Triphosphate Stress Whole-Heart Dynamic Myocardial Perfusion Imaging Using 256-Slice Computed Tomography

    PubMed Central

    Kurata, Akira; Kawaguchi, Naoto; Kido, Teruhito; Inoue, Katsuji; Suzuki, Jun; Ogimoto, Akiyoshi; Funada, Jun-ichi; Higaki, Jitsuo; Miyagawa, Masao; Vembar, Mani; Mochizuki, Teruhito

    2013-01-01

    Background The aim of this study was to investigate the correlation of the qualitative transmural extent of hypoperfusion areas (HPA) using stress dynamic whole-heart computed tomography perfusion (CTP) imaging by 256-slice CT with CTP-derived myocardial blood flow (MBF) for the estimation of the severity of coronary artery stenosis. Methods and Results Eleven patients underwent adenosine triphosphate (0.16 mg/kg/min, 5 min) stress dynamic CTP by 256-slice CT (coverage: 8 cm, 0.27 s/rotation), and 9 of the 11 patients underwent coronary angiography (CAG). Stress dynamic CTP (whole–heart datasets over 30 consecutive heart beats in systole without spatial and temporal gaps) was acquired with prospective ECG gating (effective radiation dose: 10.4 mSv). The extent of HPAs was visually graded using a 3-point score (normal, subendocardial, transmural). MBF (ml/100g/min) was measured by deconvolution. Differences in MBF (mean ± standard error) according to HPA and CAG results were evaluated. In 27 regions (3 major coronary territories in 9 patients), 11 coronary stenoses (> 50% reduction in diameter) were observed. In 353 myocardial segments, HPA was significantly related to MBF (P < 0.05; normal 295 ± 94; subendocardial 186 ± 67; and transmural 80 ± 53). Coronary territory analysis revealed a significant relationship between coronary stenosis severity and MBF (P < 0.05; non-significant stenosis [< 50%], 284 ± 97; moderate stenosis [50–70%], 184 ± 74; and severe stenosis [> 70%], 119 ± 69). Conclusion The qualitative transmural extent of HPA using stress whole-heart dynamic CTP imaging by 256-slice CT exhibits a good correlation with quantitative CTP-derived MBF and may aid in assessing the hemodynamic significance of coronary artery disease. PMID:24376774

  6. Relation between QT dispersion and adenosine triphosphate stress thallium-201 single-photon emission computed tomographic imaging for detecting myocardial ischemia and scar.

    PubMed

    Teragawa, H; Hirao, H; Muraoka, Y; Yamagata, T; Matsuura, H; Kajiyama, G

    1999-04-15

    It is not known if QT dispersion is useful for detecting coronary artery disease. We investigated whether QT dispersion at baseline and during adenosine triphosphate (ATP) infusion correlate with the imaging patterns obtained from ATP stress thallium-201 single-photon emission computed tomography (ATP-SPECT). QT dispersion was determined in 169 patients who underwent ATP-SPECT from 12-lead electrocardiograms obtained at baseline and 3 minutes after the beginning of ATP infusion. Based on the results of ATP-SPECT, patients were divided into 4 groups: normal (n = 55), ischemia (n = 38), ischemia and scar (n = 42), and scar (n = 34). Baseline QT dispersions (mean +/- SD) in the normal, ischemia, ischemia and scar, and scar groups were 48 +/- 15, 50 +/- 17, 69 +/- 25, and 70 +/- 24 ms, respectively. Baseline QT dispersion was significantly greater in the groups with myocardial scar. QT dispersions during ATP infusion were 43 +/- 16, 63 +/- 20, 76 +/- 20, and 62 +/- 25 ms in the normal, ischemia, ischemia and scar, and scar groups, respectively. QT dispersion increased with ATP infusion in patients with myocardial ischemia. QT dispersion at baseline and during ATP infusion correlated with the ATP-SPECT imaging pattern. These findings suggest that baseline QT dispersion and ATP-induced changes in QT dispersion may help detect the presence of myocardial ischemia and scar. PMID:10215275

  7. Functional assessment of sequential coronary artery fistula and coronary artery stenosis with fractional flow reserve and stress adenosine myocardial perfusion imaging.

    PubMed

    Yew, Kuan Leong; Ooi, Poh Siang; Law, Chiong Soon

    2015-10-01

    Coronary artery fistula is an abnormal connection between one coronary artery to another coronary artery or cardiac chambers. The coronary artery fistula may cause significant shunting of blood and cause "pseudo-stenosis" or "steal phenomenon". This will also accentuate pre-existing mild-moderate de novo coronary lesions with resultant greater pressure gradient difference across the lesions. Thus, fractional flow reserve can be a useful tool to guide intervention decision on the coronary artery fistula. There are very few published reports regarding the use of FFR to assess coronary artery fistula. In fact, there is no outcome data regarding the deferment of coronary artery fistula intervention when the FFR is not physiologically significant. This case highlighted the use of FFR to evaluate the functional significance of coronary fistula in the setting of ischemia evaluation and it was proven to be safe to defer intervention with good 3 year clinical outcome. Stress adenosine myocardial perfusion imaging correlated with the FFR result.

  8. Assessment of myocardial perfusion by harmonic power doppler imaging at rest and during adenosine triphosphate stress: comparison with coronary flow velocity reserve in the left anterior descending coronary arter.

    PubMed

    Takeuchi, Masaaki; Yoshitani, Hidetoshi; Miyazaki, Chinami; Otani, Shinichiro; Sakamoto, Kazuo; Yoshikawa, Junichi

    2002-02-01

    To clarify whether the myocardial perfusion abnormalities observed on harmonic power Doppler imaging (HPDI) during hyperemia are related to a decrease in coronary flow velocity reserve (CFVR), HPDI and CFVR were measured in the left anterior descending coronary artery (LAD) territory of 75 patients. During continuous infusion of Levovist, dual-frame triggered apical 4-chamber views were obtained at rest and during adenosine triphosphate (ATP) infusion. The persistence of perfusion defects during ATP infusion or stress-induced defects in the LAD territory was defined as abnormal. Both HPDI and coronary flow velocity recordings of adequate quality were successfully obtained in 73 patients, and 37 patients showed abnormal myocardial perfusion. CFVR was significantly lower in patients with abnormal perfusion than in patients who had normal findings (1.38+/-0.38 vs 2.60+/-0.76, p<0.001). A CFVR less than 1.9 had a sensitivity of 89% (33/37) and a specificity of 89% (32/36) for predicting the presence of abnormal myocardial perfusion. This study demonstrates that myocardial perfusion abnormalities observed during HPDI using ATP stress are closely correlated to a decrease in CFVR and may reflect significant stenosis or microvascular damage in the LAD territory. PMID:11999642

  9. d-Propranolol prevents adenosine formation associated with myocardial hypoperfusion.

    PubMed

    Wangler, R D; Peterson, W P; Sparks, H V

    1989-03-01

    d-Propranolol eliminates the increased adenine nucleoside release from hypoperfused hearts [R. D. Wangler, D. F. DeWitt, and H. V. Sparks, Am. J. Physiol. 247 (Heart Circ. Physiol. 16): H330-H336, 1984]. To determine whether d-propranolol reduces adenosine formation or adenosine release into the vascular compartment, we measured myocardial tissue adenosine (TADO). Decreased formation would lower TADO, whereas decreased release would elevate TADO. Reduction of perfusion pressure by 50% reduced coronary flow (CF), venous oxygen tension (PVO2), and myocardial oxygen consumption (MVO2) by approximately 40, 25, and 35%, respectively. Total adenosine and inosine released during 30 min of hypoperfusion increased 10- and 5-fold, respectively. Also, TADO increased from 2.68 +/- 0.37 to 5.17 +/- 0.67 nmol/g (P less than 0.05). In the presence of d-propranolol, the same reduction in perfusion pressure caused a similar decrease in CF and MVO2. d-Propranolol eliminated the release of adenosine and inosine associated with hypoperfusion. TADO after 30 min of hypoperfusion plus d-propranolol was not significantly increased (3.27 +/- 0.40 nmol/g) and was significantly less than hypoperfused hearts. When severe hypoperfusion was created by reducing perfusion pressure 75%, adenosine release still did not increase if d-propranolol was present. When adenosine release was plotted as a function of oxygen supply-consumption, they were related in a hyperbolic fashion. Despite the severity of hypoperfusion, in the presence of d-propranolol the supply-to-consumption ratio was similar to that of the control perfusion group (no drug). We conclude that d-propranolol blocks nucleoside formation during hypoperfusion by reducing oxygen demand such that a reduction of oxygen supply no longer stimulates adenosine formation. PMID:2923237

  10. Role of adenosine as adjunctive therapy in acute myocardial infarction.

    PubMed

    Forman, Mervyn B; Stone, Gregg W; Jackson, Edwin K

    2006-01-01

    Although early reperfusion and maintained patency is the mainstay therapy for ST elevation myocardial infarction, experimental studies demonstrate that reperfusion per se induces deleterious effects on viable ischemic cells. Thus "myocardial reperfusion injury" may compromise the full potential of reperfusion therapy and may account for unfavorable outcomes in high-risk patients. Although the mechanisms of reperfusion injury are complex and multifactorial, neutrophil-mediated microvascular injury resulting in a progressive decrease in blood flow ("no-reflow" phenomenon) likely plays an important role. Adenosine is an endogenous nucleoside found in large quantities in myocardial and endothelial cells. It activates four well-characterized receptors producing various physiological effects that attenuate many of the proposed mechanisms of reperfusion injury. The cardio-protective effects of adenosine are supported by its role as a mediator of pre- and post-conditioning. In experimental models, administration of adenosine in the peri-reperfusion period results in a marked reduction in infarct size and improvement in ventricular function. The cardioprotective effects in the canine model have a narrow time window with the drug losing its effect following three hours of ischemia. Several small clinical studies have demonstrated that administration of adenosine with reperfusion therapy reduces infarct size and improves ventricular function. In the larger AMISTAD and AMISTAD II trials a 3-h infusion of adenosine as an adjunct to reperfusion resulted in a striking reduction in infarct size (55-65%). Post hoc analysis of AMISTAD II showed that this was associated with significantly improved early and late mortality in patients treated within 3.17 h of symptoms. An intravenous infusion of adenosine for 3 h should be considered as adjunctive therapy in high risk-patients undergoing reperfusion therapy. PMID:16961725

  11. [The accuracy and side effects of pharmacologic stress thallium myocardial scintigraphy with adenosine triphosphate disodium (ATP) infusion in the diagnosis of coronary artery disease].

    PubMed

    Kinoshita, S; Suzuki, S; Shindou, A; Watanabe, K; Muramatsu, T; Ide, M; Dohi, Y; Yamashita, S; Suzuki, T; Nishimura, K

    1994-08-01

    The diagnostic accuracy and side effects of pharmacologic stress thallium myocardial scintigraphy with ATP infusion were studied in 172 patients with or without coronary artery disease. ATP was infused for five minutes at a rate of 0.16 mg/kg/min (group A) or 0.18 mg/kg/min (group B) via antecubital vein. One hundred and eleven (67 of group A, 44 of group B) of 172 patients underwent coronary arteriography (CAG). In 111 patients received CAG, overall sensitivity, specificity and accuracy of this method were 88%, 84% and 87%, respectively. In 67 patients of group A, these were 92%, 81% and 90%. In 44 patients of group B, 79%, 87% and 82% were documented (NS, between group A and B). Chest pain, flushing, bradycardia and ST depression were included in side effects caused by ATP infusion. At least one of these side effects were observed in 84% of the all 172 patients, 89% of group A and 75% of group B (NS). But, all of the side effects were spontaneously alleviated within two minutes without any therapy. In conclusion, pharmacologic stress myocardial scintigraphy with ATP infusion is very accurate and safe, and infusion rate of 0.16 mg/kg/min is optimal for this purpose. PMID:7933682

  12. High Concordance Between Mental Stress–Induced and Adenosine-Induced Myocardial Ischemia Assessed Using SPECT in Heart Failure Patients: Hemodynamic and Biomarker Correlates

    PubMed Central

    Wawrzyniak, Andrew J.; Dilsizian, Vasken; Krantz, David S.; Harris, Kristie M.; Smith, Mark F.; Shankovich, Anthony; Whittaker, Kerry S.; Rodriguez, Gabriel A.; Gottdiener, John; Li, Shuying; Kop, Willem; Gottlieb, Stephen S.

    2016-01-01

    Mental stress can trigger myocardial ischemia, but the prevalence of mental stress–induced ischemia in congestive heart failure (CHF) patients is unknown. We characterized mental stress–induced and adenosine-induced changes in myocardial perfusion and neurohormonal activation in CHF patients with reduced left-ventricular function using SPECT to precisely quantify segment-level myocardial perfusion. Methods Thirty-four coronary artery disease patients (mean age ± SD, 62 ± 10 y) with CHF longer than 3 mo and ejection fraction less than 40% underwent both adenosine and mental stress myocardial perfusion SPECT on consecutive days. Mental stress consisted of anger recall (anger-provoking speech) followed by subtraction of serial sevens. The presence and extent of myocardial ischemia was quantified using the conventional 17-segment model. Results Sixty-eight percent of patients had 1 ischemic segment or more during mental stress and 81% during adenosine. On segment-by-segment analysis, perfusion with mental stress and adenosine were highly correlated. No significant differences were found between any 2 time points for B-type natriuretic peptide, tumor necrosis factor-α, IL-1b, troponin, vascular endothelin growth factor, IL-17a, matrix metallopeptidase-9, or C-reactive protein. However, endothelin-1 and IL-6 increased, and IL-10 decreased, between the stressor and 30 min after stress. Left-ventricular end diastolic dimension was 179 ± 65 mL at rest and increased to 217 ± 71 after mental stress and 229 ± 86 after adenosine (P < 0.01 for both). Resting end systolic volume was 129 ± 60 mL at rest and increased to 158 ± 66 after mental stress (P < 0.05) and 171 ± 87 after adenosine (P < 0.07), with no significant differences between adenosine and mental stress. Ejection fraction was 30 ± 12 at baseline, 29 ± 11 with mental stress, and 28 ± 10 with adenosine (P = not significant). Conclusion There was high concordance between ischemic perfusion defects induced

  13. 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

  14. [99mTc-MIBI myocardial tomography with intravenous infusion of adenosine triphosphate in the diagnosis of coronary artery disease].

    PubMed

    Kumano, S

    1996-02-01

    To evaluate its feasibility, safety and diagnostic accuracy, 99mTc-MIBI myocardial tomography with adenosine triphosphate (ATP) infusion (0.16 mg/kg/min for 5 min) was performed 100 consecutive patients using the stress/rest one day protocol. None of the patients required treatment with aminophylline during the study. The sensitivity and specificity for detecting patients with coronary artery disease were 97% and 71%, respectively. Those for detecting individual coronary lesion (> or = 75% stenosis) were 92% and 89%, respectively. The high hepatic uptake of 99mTc-MIBI causes artifactual perfusion defects in the inferior myocardial wall, particularly on ATP stress images. In order to reduce this artifactual phenomenon, the interval time between injection and stress imaging must be increased. PMID:8721103

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

    PubMed Central

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

    2016-01-01

    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 (99mTc-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/m2. 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

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

    PubMed Central

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

    2016-01-01

    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 (99mTc-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/m2. 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

  17. Oxidant stress and damage in post-ischemic mouse hearts: effects of adenosine.

    PubMed

    Hack, Benjamin; Witting, Paul K; Rayner, Benjamin S; Stocker, Roland; Headrick, John P

    2006-07-01

    Despite the general understanding that ischemia-reperfusion (I/R) promotes oxidant stress, specific contributions of oxidant stress or damage to myocardial I/R injury remain poorly defined. Moreover, whether endogenous 'cardioprotectants' such as adenosine act via limiting this oxidant injury is unclear. Herein we characterized effects of 20 min ischemia and 45 min reperfusion on cardiovascular function, oxidative stress and damage in isolated perfused mouse hearts (with glucose or pyruvate as substrate), and examined whether 10 microM adenosine modified these processes. In glucose-perfused hearts post-ischemic contractile function was markedly impaired (< 50% of pre-ischemia), cell damage assessed by lactate dehydrogenase (LDH) release was increased (12 +/- 2 IU/g vs. 0.2 +/- 0.1 IU/g in normoxic hearts), endothelial-dependent dilation in response to ADP was impaired while endothelial-independent dilation in response to nitroprusside was unaltered. Myocardial oxidative stress increased significantly, based on decreased glutathione redox status ([GSSG]/[GSG + GSSH] = 7.8 +/- 0.3% vs. 1.3 +/- 0.1% in normoxic hearts). Tissue cholesterol, native cholesteryl esters (CE) and the lipid-soluble antioxidant alpha-tocopherol (alpha-TOH, the most biologically active form of vitamin E) were unaffected by I/R, whereas markers of primary lipid peroxidation (CE-derived lipid hydroperoxides and hydroxides; CE-O(O)H) increased significantly (14 +/- 2 vs. 2 +/- 1 pmol/mg in normoxic hearts). Myocardial alpha -tocopherylquinone (alpha-TQ; an oxidation product of alpha -TOH) also increased (10.3 +/- 1.0 vs. 1.7 +/- 0.2 pmol/mg in normoxic hearts). Adenosine treatment improved functional recovery and vascular function, and limited LDH efflux. These effects were associated with an anti-oxidant effect of adenosine, as judged by inhibition of I/R-mediated changes in glutathione redox status (by 60%), alpha-TQ (80%) and CE-O(O)H (100%). Provision of 10 mM pyruvate as sole substrate (to

  18. 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.

  19. 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. PMID:26081145

  20. Myocardial blood flow and adenosine A2A receptor density in endurance athletes and untrained men

    PubMed Central

    Heinonen, Ilkka; Nesterov, Sergey V; Liukko, Kaisa; Kemppainen, Jukka; Någren, Kjell; Luotolahti, Matti; Virsu, Pauliina; Oikonen, Vesa; Nuutila, Pirjo; Kujala, Urho M; Kainulainen, Heikki; Boushel, Robert; Knuuti, Juhani; Kalliokoski, Kari K

    2008-01-01

    Previous human studies have shown divergent results concerning the effects of exercise training on myocardial blood flow (MBF) at rest or during adenosine-induced hyperaemia in humans. We studied whether these responses are related to alterations in adenosine A2A receptor (A2AR) density in the left-ventricular (LV) myocardium, size and work output of the athlete's heart, or to fitness level. MBF at baseline and during intravenous adenosine infusion, and A2AR density at baseline were measured using positron emission tomography, and by a novel A2AR tracer in 10 healthy male endurance athletes (ET) and 10 healthy untrained (UT) men. Structural LV parameters were measured with echocardiography. LV mass index was 71% higher in ET than UT (193 ± 18 g m−2versus 114 ± 13 g m−2, respectively). MBF per gram of tissue was significantly lower in the ET than UT at baseline, but this was only partly explained by reduced LV work load since MBF corrected for LV work was higher in ET than UT, as well as total MBF. The MBF during adenosine-induced hyperaemia was reduced in ET compared to UT, and the fitter the athlete was, the lower was adenosine-induced MBF. A2AR density was not different between the groups and was not coupled to resting or adenosine-mediated MBF. The novel findings of the present study show that the adaptations in the heart of highly trained endurance athletes lead to relative myocardial ‘overperfusion’ at rest. On the other hand hyperaemic perfusion is reduced, but is not explained by A2AR density. PMID:18772204

  1. [Occupational stress and myocardial infarction].

    PubMed

    Consoli, Silla M

    2015-01-01

    Besides the best-known role of depressed mood, occupational stress deserves to be taken as a coronary risk factor. There are two basic models to define occupational stress: Karasek's model (high job psychological demands associated with low decision latitude, or even low social support at work) and Siegrist's model (imbalance between efforts and rewards received). The combination of the two models better reflects the coronary risk than each model alone. Occupational stress appears both as a risk factor and a prognostic factor after the occurrence of myocardial infarction. The relevance of the models is best in men or in younger age subjects. In women, role conflicts (occupational/domestic), the existence of excessive "intrinsic" efforts (job over investment) and association with marital stress provide more specific information. Burnout, particularly among health professionals, and bullying at work are also linked to cardiovascular risk. Occupational stress is a collective indicator of health at work, valuable to the employer. At an individual level, it can lead to therapeutic preventive approaches. PMID:26150284

  2. [Occupational stress and myocardial infarction].

    PubMed

    Consoli, Silla M

    2015-01-01

    Besides the best-known role of depressed mood, occupational stress deserves to be taken as a coronary risk factor. There are two basic models to define occupational stress: Karasek's model (high job psychological demands associated with low decision latitude, or even low social support at work) and Siegrist's model (imbalance between efforts and rewards received). The combination of the two models better reflects the coronary risk than each model alone. Occupational stress appears both as a risk factor and a prognostic factor after the occurrence of myocardial infarction. The relevance of the models is best in men or in younger age subjects. In women, role conflicts (occupational/domestic), the existence of excessive "intrinsic" efforts (job over investment) and association with marital stress provide more specific information. Burnout, particularly among health professionals, and bullying at work are also linked to cardiovascular risk. Occupational stress is a collective indicator of health at work, valuable to the employer. At an individual level, it can lead to therapeutic preventive approaches.

  3. Pharmacological prevention of reperfusion injury in acute myocardial infarction. A potential role for adenosine as a therapeutic agent.

    PubMed

    Quintana, Miguel; Kahan, Thomas; Hjemdahl, Paul

    2004-01-01

    The concept of reperfusion injury, although first recognized from animal studies, is now recognized as a clinical phenomenon that may result in microvascular damage, no-reflow phenomenon, myocardial stunning, myocardial hibernation and ischemic preconditioning. The final consequence of this event is left ventricular (LV) systolic dysfunction leading to increased morbidity and mortality. The typical clinical case of reperfusion injury occurs in acute myocardial infarction (MI) with ST segment elevation in which an occlusion of a major epicardial coronary artery is followed by recanalization of the artery. This may occur either spontaneously or by means of thrombolysis and/or by primary percutaneous coronary intervention (PCI) with efficient platelet inhibition by aspirin (acetylsalicylic acid), clopidogrel and glycoprotein IIb/IIIa inhibitors. Although the pathophysiology of reperfusion injury is complex, the major role that neutrophils play in this process is well known. Neutrophils generate free radicals, degranulation products, arachidonic acid metabolites and platelet-activating factors that interact with endothelial cells, inducing endothelial injury and neutralization of nitrous oxide vasodilator capacity. Adenosine, through its multi-targeted pharmacological actions, is able to inhibit some of the above-mentioned detrimental effects. The net protective of adenosine in in vivo models of reperfusion injury is the reduction of the infarct size, the improvement of the regional myocardial blood flow and of the regional function of the ischemic area. Additionally, adenosine preserves the post-ischemic coronary flow reserve, coronary blood flow and the post-ischemic regional contractility. In small-scale studies in patients with acute MI, treatment with adenosine has been associated with smaller infarcts, less no-reflow phenomenon and improved LV function. During elective PCI adenosine reduced ST segment shifts, lactate production and ischemic symptoms. During the

  4. Adenosine induced coronary spasm – A rare presentation

    PubMed Central

    Arora, P.; Bhatia, V.; Arora, M.; Kaul, U.

    2014-01-01

    Adenosine is commonly used as a pharmacological agent in myocardial perfusion imaging, as an antiarrhythmic agent, and in Cath Lab. during PCI for treating no reflow phenomenon. Coronary spasm has been reported following adenosine injection during stress imaging. We report a rare complication with ST segment elevation, following adenosine injection, given for treatment of supraventricular tachycardia. PMID:24581102

  5. Temporal analysis of regional strain rate during adenosine triphosphate stress before and after percutaneous coronary interventions.

    PubMed

    Gunji, Kazue; Takagi, Atsushi; Arai, Kotaro; Ashihara, Kyomi; Hagiwara, Nobuhisa

    2015-05-01

    Regional myocardial ischemia is thought to be characterized by diastolic dysfunction. We aimed to clarify whether temporal analysis of strain rate (SR) index derived from two-dimensional speckle-tracking echocardiography (2DTE) can assess the regional myocardial ischemia or not. Forty-two patients with significant coronary stenoses were referred for percutaneous coronary intervention (PCI). 2DTE was performed before and a day after PCI. Time from aortic valve closure to peak early diastolic longitudinal SR ∆(TAVC-E SR) was measured both at baseline and during adenosine triphosphate (ATP) infusion. TAVC-E SR was calculated as TAVC-E SR during ATP infusion subtracted by TAVC-E SR at baseline. In forty-five target ischemic regions, TAVC-E SR at baseline was significantly longer than that of control regions (166 ± 28 vs. 136 ± 32 ms, P < 0.0001). TAVC-E SR in target ischemic regions significantly prolonged during ATP stress to 221 ± 37 ms (P < 0.0001), while it did not change in control regions. Immediately after PCI, TAVC-E SR in target regions significantly decreased to 135 ± 27 ms, P < 0.0001 without prolongation during ATP stress. Receiver operating characteristic curves demonstrated that ∆TAVC-E SR could assess regional myocardial ischemia by a cutoff criterion of 14 ms with sensitivity of 93% and specificity of 95%. 2DTE-derived TAVC-E SR significantly increased during ATP stress only in ischemic myocardium. This phenomenon disappeared immediately after PCI. Temporal analysis of TAVC-E SR appeared to be useful to assess the regional myocardial ischemia. PMID:24633495

  6. Predictors and Diagnostic Significance of the Adenosine Related Side Effects on Myocardial Perfusion SPECT/CT Imaging

    PubMed Central

    Yıldırım Poyraz, Nilüfer; Özdemir, Elif; Poyraz, Barış Mustafa; Kandemir, Zuhal; Keskin, Mutlay; Türkölmez, Şeyda

    2014-01-01

    Objective: The aim of this study was to investigate the relationship between patient characteristics and adenosine-related side-effects during stress myocard perfusion imaging (MPI). The effect of presence of adenosine-related side-effects on the diagnostic value of MPI with integrated SPECT/CT system for coronary artery disease (CAD), was also assessed in this study. Methods: Total of 281 patients (109 M, 172 F; mean age:62.6±10) who underwent standard adenosine stress protocol for MPI, were included in this study. All symptoms during adenosine infusion were scored according to the severity and duration. For the estimation of diagnostic value of adenosine MPI with integrated SPECT/CT system, coronary angiography (CAG) or clinical follow-up were used as gold standard. Results: Total of 173 patients (61.6%) experienced adenosine-related side-effects (group 1); flushing, dyspnea, and chest pain were the most common. Other 108 patients completed pharmacologic stress (PS) test without any side-effects (group 2). Test tolerability were similar in the patients with cardiovascular or airway disease to others, however dyspnea were observed significantly more common in patients with mild airway disease. Body mass index (BMI) ≥30 kg/m2 and age ≤45 years were independent predictors of side-effects. The diagnostic value of MPI was similar in both groups. Sensitivity of adenosine MPI SPECT/CT was calculated to be 86%, specificity was 94% and diagnostic accuracy was 92% for diagnosis of CAD. Conclusion: Adenosine MPI is a feasible and well tolerated method in patients who are not suitable for exercise stress test as well as patients with cardiopulmonary disease. However age ≤45 years and BMI ≥30 kg/m2 are the positive predictors of adenosine-related side-effects, the diagnostic value of adenosine MPI SPECT/CT is not affected by the presence of adenosine related side-effects. PMID:25541932

  7. 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. PMID:18000974

  8. 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.

  9. Adenosine Stress and Rest T1 Mapping Can Differentiate Between Ischemic, Infarcted, Remote, and Normal Myocardium Without the Need for Gadolinium Contrast Agents

    PubMed Central

    Liu, Alexander; Wijesurendra, Rohan S.; Francis, Jane M.; Robson, Matthew D.; Neubauer, Stefan; Piechnik, Stefan K.; Ferreira, Vanessa M.

    2016-01-01

    Objectives The aim of this study was to evaluate the potential of T1 mapping at rest and during adenosine stress as a novel method for ischemia detection without the use of gadolinium contrast. Background In chronic coronary artery disease (CAD), accurate detection of ischemia is important because targeted revascularization improves clinical outcomes. Myocardial blood volume (MBV) may be a more comprehensive marker of ischemia than myocardial blood flow. T1 mapping using cardiac magnetic resonance (CMR) is highly sensitive to changes in myocardial water content, including MBV. We propose that T1 mapping at rest and during adenosine vasodilatory stress can detect MBV changes in normal and diseased myocardium in CAD. Methods Twenty normal controls (10 at 1.5-T; 10 at 3.0-T) and 10 CAD patients (1.5-T) underwent conventional CMR to assess for left ventricular function (cine), infarction (late gadolinium enhancement [LGE]) and ischemia (myocardial perfusion reserve index [MPRI] on first-pass perfusion imaging during adenosine stress). These were compared to novel pre-contrast stress/rest T1 mapping using the Shortened Modified Look-Locker Inversion recovery technique, which is heart rate independent. T1 values were derived for normal myocardium in controls and for infarcted, ischemic, and remote myocardium in CAD patients. Results Normal myocardium in controls (normal wall motion, MPRI, no LGE) showed normal resting T1 (954 ± 19 ms at 1.5-T; 1,189 ± 34 ms at 3.0-T) and significant positive T1 reactivity during adenosine stress compared to baseline (6.2 ± 0.5% at 1.5-T; 6.3 ± 1.1% at 3.0-T; all p < 0.0001). Infarcted myocardium showed the highest resting T1 of all tissue classes (1,442 ± 84 ms), without significant T1 reactivity (0.2 ± 1.5%). Ischemic myocardium showed elevated resting T1 compared to normal (987 ± 17 ms; p < 0.001) without significant T1 reactivity (0.2 ± 0.8%). Remote myocardium, although having comparable resting T1 to normal (955 ± 17 ms

  10. Clinical benefit of adenosine as an adjunct to reperfusion in ST-elevation myocardial infarction patients: An updated meta-analysis of randomized controlled trials

    PubMed Central

    Bulluck, Heerajnarain; Sirker, Alex; Loke, Yoon K.; Garcia-Dorado, David; Hausenloy, Derek J.

    2016-01-01

    Background Adenosine administered as an adjunct to reperfusion can reduce coronary no-reflow and limit myocardial infarct (MI) size in ST-segment elevation myocardial infarction (STEMI) patients. Whether adjunctive adenosine therapy can improve clinical outcomes in reperfused STEMI patients is not clear and is investigated in this meta-analysis of 13 randomized controlled trials (RCTs). Methods We performed an up-to-date search for all RCTs investigating adenosine as an adjunct to reperfusion in STEMI patients. We calculated pooled relative risks using a fixed-effect meta-analysis assessing the impact of adjunctive adenosine therapy on major clinical endpoint including all-cause mortality, non-fatal myocardial infarction, and heart failure. Surrogate markers of reperfusion were also analyzed. Results 13 RCTs (4273 STEMI patients) were identified and divided into 2 subgroups: intracoronary adenosine versus control (8 RCTs) and intravenous adenosine versus control (5 RCTs). In patients administered intracoronary adenosine, the incidence of heart failure was significantly lower (risk ratio [RR] 0.44 [95% CI 0.25–0.78], P = 0.005) and the incidence of coronary no-reflow was reduced (RR for TIMI flow<3 postreperfusion 0.68 [95% CI 0.47–0.99], P = 0.04). There was no difference in heart failure incidence in the intravenous adenosine group but most RCTs in this subgroup were from the thrombolysis era. There was no difference in non-fatal MI or all-cause mortality in both subgroups. Conclusion We find evidence of improved clinical outcome in terms of less heart failure in STEMI patients administered intracoronary adenosine as an adjunct to reperfusion. This finding will need to be confirmed in a large adequately powered prospective RCT. PMID:26402450

  11. New method of intracoronary adenosine injection to prevent microvascular reperfusion injury in patients with acute myocardial infarction undergoing percutaneous coronary intervention.

    PubMed

    Grygier, Marek; Araszkiewicz, Aleksander; Lesiak, Maciej; Janus, Magdalena; Kowal, Jadwiga; Skorupski, Wlodzimierz; Pyda, Malgorzata; Mitkowski, Przemyslaw; Grajek, Stefan

    2011-04-15

    The aim of our study was to examine the role of a new, simple protocol of intracoronary adenosine administration performed during primary angioplasty on the immediate angiographic results and clinical course. A prospective, single-center, randomized, placebo-controlled trial of 70 consecutive patients (64 ± 14 years, 54 men) with acute myocardial infarction with ST-segment elevation undergoing primary percutaneous coronary intervention (PCI) was conducted. Patients were randomized to 2 groups. Group 1 (n = 35) received intracoronary adenosine (1 to 2 mg) with a hand injection through the guiding catheter 2 times: immediately after crossing the lesion of the infarct-related artery with guidewire and then after the first balloon inflation. Group 2 (n = 35) received placebo. The baseline clinical and angiographic characteristics of the 2 groups were similar. Percutaneous coronary intervention resulted in Thrombolysis In Myocardial Infarction grade 3 flow after PCI in 32 patients (91.4%) in the adenosine group and 27 patients (77.1%) in the placebo group (p = 0.059). Myocardial blush grade 3 was observed at the end of PCI in 23 patients (65.7%) in the adenosine group and 13 (37.1%) in the placebo group (p < 0.05). Resolution of ST-segment elevation (> 50%) was more frequently observed in the adenosine than in the placebo group: 27 (77%) versus 15 (43%), respectively (p < 0.01). In conclusion, intracoronary adenosine administration improved the angiographic and electrocardiographic results in patients with acute myocardial infarction with ST-segment elevation undergoing PCI. Adenosine administration seemed to be associated with a more favorable clinical course. PMID:21310372

  12. Pharmacologic stress dual-isotope myocardial perfusion single-photon emission computed tomography.

    PubMed

    Matzer, L; Kiat, H; Wang, F P; Van Train, K; Germano, G; Friedman, J; Berman, D S

    1994-12-01

    Separate-acquisition rest thallium-201/exercise technetium-99m sestamibi (sestamibi) dual-isotope single-photon emission computed tomography (SPECT) has been shown to be effective for assessment of myocardial perfusion and viability. The present study was designed to validate the dual-isotope approach when used in conjunction with pharmacologic stress. All patients had rest 201TI SPECT followed immediately by adenosine (n = 82) or dipyridamole (n = 50) infusion and sestamibi injection. Sestamibi SPECT was performed 1 hour later. The entire study lasted < 2.5 hours. The patient population was categorized into three groups: 51 consecutive patients with coronary angiography and no previous myocardial infarction (group I), 58 consecutive patients with a low prescintigraphic test likelihood of coronary artery disease (group II), and 23 consecutive catheterized patients with remote Q-wave myocardial infarction (group III). For group I patients, the sensitivity and specificity for dual-isotope SPECT were 92% (35 of 38) and 85% (11 of 13), respectively, when > or = 50% coronary artery narrowing was considered significant and were 97% (34 of 35) and 81% (13 of 16) respectively, when > or = 70% narrowing was considered significant. The normalcy rate among the 58 patients of group II was 96%. Comparisons for pattern of stress-defect reversibility demonstrated that of the 97 stress defects within the infarct zones (group III), 15% were reversible and 85% were nonreversible. In contrast, of the 227 stress defects within the diseased (> or = 50% stenosis) vessel zones of the group I patients, 93% were reversible and 7% were noreversible (p < 0.001 vs group III). In conclusion, separate acquisition rest 201-TI/pharmacologic stress sestamibi dual-isotope SPECT is an efficient myocardial perfusion imaging protocol with high accuracy for detection and assessment of angiographically significant coronary artery disease.

  13. Adenosine A2(A) receptor modulates the oxidative stress response of primed polymorphonuclear leukocytes after parabolic flight.

    PubMed

    Kaufmann, Ines; Feuerecker, Matthias; Salam, Alex; Schelling, Gustav; Thiel, Manfred; Choukèr, Alexander

    2011-07-01

    Space flight and gravitational stress can alter innate immune function. Parabolic flights (PFs) as a model for short-term gravitational changes prime the cytotoxic capability of polymorphonuclear leukocytes (PMNs). In view of the emerging role of adenosine in the regulation of innate immune responses, we examined the potency of adenosine to control the release of cytotoxic H(2)O(2) by primed PMNs via the adenosine receptor system. During PFs, microgravity conditions (<10(-2) G) are generated for approximately 22 seconds, followed by a hypergravity (1.8 G) phase resulting in gravitational stress. We studied the ex vivo effects of adenosine on the production of H(2)O(2) by stimulated PMNs and determined adenosine plasma levels and adenosine A2(A) receptor transcripts of leukocytes of PF participants (n = 15). Increasing concentrations of adenosine dose dependently reduced tissue-toxic H(2)O(2) production by PMNs with a half-maximal inhibitory concentration (IC(50)) of 19.5 nM before takeoff and 7.6 nM at 48 hours after PF. This increase in the adenosine-mediated inhibition of PMNs' H(2)O(2) production was completely reversed by addition of the A2(A) receptor antagonist ZM241385. PF induced a nonsignificant elevation in adenosine plasma levels; A2(A) receptor mRNA from leukocytes remained almost unchanged. Adenosine limits the oxidative stress response of PMNs after PFs through an upregulation of the adenosine A2(A) receptor function. This stop signal on inflammation is stronger than that under normal physiologic states and may limit further cytotoxic damage. Pharmacologic manipulation of the adenosine A2(A) receptor pathway could be a potential target for control of unwanted exacerbations of cytotoxic PMN functions.

  14. Depressive Symptoms Are Associated with Mental Stress-Induced Myocardial Ischemia after Acute Myocardial Infarction

    PubMed Central

    Wei, Jingkai; Pimple, Pratik; Shah, Amit J.; Rooks, Cherie; Bremner, J. Douglas; Nye, Jonathon A.; Ibeanu, Ijeoma; Murrah, Nancy; Shallenberger, Lucy; Raggi, Paolo; Vaccarino, Viola

    2014-01-01

    Objectives Depression is an adverse prognostic factor after an acute myocardial infarction (MI), and an increased propensity toward emotionally-driven myocardial ischemia may play a role. We aimed to examine the association between depressive symptoms and mental stress-induced myocardial ischemia in young survivors of an MI. Methods We studied 98 patients (49 women and 49 men) age 38–60 years who were hospitalized for acute MI in the previous 6 months. Patients underwent myocardial perfusion imaging at rest, after mental stress (speech task), and after exercise or pharmacological stress. A summed difference score (SDS), obtained with observer-independent software, was used to quantify myocardial ischemia under both stress conditions. The Beck Depression Inventory-II (BDI-II) was used to measure depressive symptoms, which were analyzed as overall score, and as separate somatic and cognitive depressive symptom scores. Results There was a significant positive association between depressive symptoms and SDS with mental stress, denoting more ischemia. After adjustment for demographic and lifestyle factors, disease severity and medications, each incremental depressive symptom was associated with 0.14 points higher SDS. When somatic and cognitive depressive symptoms were examined separately, both somatic [β = 0.17, 95% CI: (0.04, 0.30), p = 0.01] and cognitive symptoms [β = 0.31, 95% CI: (0.07, 0.56), p = 0.01] were significantly associated with mental stress-induced ischemia. Depressive symptoms were not associated with ischemia induced by exercise or pharmacological stress. Conclusion Among young post-MI patients, higher levels of both cognitive and somatic depressive symptoms are associated with a higher propensity to develop myocardial ischemia with mental stress, but not with physical (exercise or pharmacological) stress. PMID:25061993

  15. Relationship between post-cardiac arrest myocardial oxidative stress and myocardial dysfunction in the rat

    PubMed Central

    2014-01-01

    Background Reperfusion after resuscitation from cardiac arrest (CA) is an event that increases reactive oxygen species production leading to oxidative stress. More specifically, myocardial oxidative stress may play a role in the severity of post-CA myocardial dysfunction. This study investigated the relationship between myocardial oxidative stress and post-CA myocardial injury and dysfunction in a rat model of CA and cardiopulmonary resuscitation (CPR). Ventricular fibrillation was induced in 26 rats and was untreated for 6 min. CPR, including mechanical chest compression, ventilation, and epinephrine, was then initiated and continued for additional 6 min prior to defibrillations. Resuscitated animals were sacrificed at two h (n = 9), 4 h (n = 6) and 72 h (n = 8) following resuscitation, and plasma collected for assessment of: high sensitivity cardiac troponin T (hs-cTnT), as marker of myocardial injury; isoprostanes (IsoP), as marker of lipid peroxidation; and 8-hydroxyguanosine (8-OHG), as marker of DNA oxidative damage. Hearts were also harvested for measurement of tissue IsoP and 8-OHG. Myocardial function was assessed by echocardiography at the corresponding time points. Additional 8 rats were not subjected to CA and served as baseline controls. Results Compared to baseline, left ventricular ejection fraction (LVEF) was reduced at 2 and 4 h following resuscitation (p < 0.01), while it was similar at 72 h. Inversely, plasma hs-cTnT increased, compared to baseline, at 2 and 4 h post-CA (p < 0.01), and then recovered at 72 h. Similarly, plasma and myocardial tissue IsoP and 8-OHG levels increased at 2 and 4 h post-resuscitation (p < 0.01 vs. baseline), while returned to baseline 72 h later. Myocardial IsoP were directly related to hs-cTnT levels (r = 0.760, p < 0.01) and inversely related to LVEF (r = -0.770, p < 0.01). Myocardial 8-OHG were also directly related to hs-cTnT levels (r = 0.409, p < 0.05) and

  16. 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. PMID:27374982

  17. 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.

  18. 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. PMID:26774540

  19. Two-dimensional strain combined with adenosine stress echocardiography assessment of viable myocardium.

    PubMed

    Fang, Ling-Ling; Zhang, Ping-Yang; Wang, Chong; Wang, Li-Ming; Ma, Xiao-Wu; Shi, Hong-Wei; Feng, Xue-Hong

    2011-03-01

    The objective of this study was to explore a new method for the identification of viable myocardium by means of two-dimensional (2D) strain imaging combined with adenosine stress echocardiography. A total of 15 anesthetized open-chest healthy mongrel dogs underwent left anterior descending coronary artery occlusion for 90 min followed by 120-min reperfusion. Adenosine was infused at 140 μg kg(-1) min(-1) over a period of 6 min. Images were acquired at baseline (when pericardial cradle was made), after reperfusion (when reperfusion finished) and after adenosine administration (while administration stopped). Measurements of the regional peak-systolic strain in radial, circumferential, and longitudinal motion on anterior wall and anterior septum were, respectively, performed under different conditions. The dogs were killed after the echocardiographic studies finished and then the area of infracted myocardium was defined by triphenyltetrazolium chloride histology. A segment with equal or less than 50% area of infracted myocardium was considered to be viable. As a result, 37 regions were viable whereas 53 were non-viable among 90 regions in 15 dogs. At baseline, there was no significant difference in peak-systolic radial strain (Rs), circumferential strain (Cs), and longitudinal strain (Ls) between the viable and non-viable groups. After reperfusion, Rs, Cs, and Ls in absolute value decreased compared to those at baseline in both groups, although there was no significant difference between these groups. Rs and Ls increased after adenosine administration compared to reperfusion (p < 0.01; p < 0.05) in viable group while there were no changes in non-viable group. Compared with non-viable group Rs, Cs and Ls in viable group increased significantly (p < 0.01; 0.05) after adenosine administration. There was a negative correlation between Rs and infarct size (r = -0.72). Cs and Ls correlated well with infarct size, respectively (r = 0.40; 0.67). A change of Rs more than 13

  20. Regional left ventricular myocardial contractility and stress in a finite element model of posterobasal myocardial infarction.

    PubMed

    Wenk, Jonathan F; Sun, Kay; Zhang, Zhihong; Soleimani, Mehrdad; Ge, Liang; Saloner, David; Wallace, Arthur W; Ratcliffe, Mark B; Guccione, Julius M

    2011-04-01

    Recently, a noninvasive method for determining regional myocardial contractility, using an animal-specific finite element (FE) model-based optimization, was developed to study a sheep with anteroapical infarction (Sun et al., 2009, "A Computationally Efficient Formal Optimization of Regional Myocardial Contractility in a Sheep With Left Ventricular Aneurysm," ASME J. Biomech. Eng., 131(11), p. 111001). Using the methodology developed in the previous study (Sun et al., 2009, "A Computationally Efficient Formal Optimization of Regional Myocardial Contractility in a Sheep With Left Ventricular Aneurysm," ASME J. Biomech. Eng., 131(11), p. 111001), which incorporates tagged magnetic resonance images, three-dimensional myocardial strains, left ventricular (LV) volumes, and LV cardiac catheterization pressures, the regional myocardial contractility and stress distribution of a sheep with posterobasal infarction were investigated. Active material parameters in the noninfarcted border zone (BZ) myocardium adjacent to the infarct (T(max_B)), in the myocardium remote from the infarct (T(max_R)), and in the infarct (T(max_I)) were estimated by minimizing the errors between FE model-predicted and experimentally measured systolic strains and LV volumes using the previously developed optimization scheme. The optimized T(max_B) was found to be significantly depressed relative to T(max_R), while T(max_I) was found to be zero. The myofiber stress in the BZ was found to be elevated, relative to the remote region. This could cause further damage to the contracting myocytes, leading to heart failure.

  1. Acute Stress Decreases but Chronic Stress Increases Myocardial Sensitivity to Ischemic Injury in Rodents

    PubMed Central

    Eisenmann, Eric D.; Rorabaugh, Boyd R.; Zoladz, Phillip R.

    2016-01-01

    Cardiovascular disease (CVD) is the largest cause of mortality worldwide, and stress is a significant contributor to the development of CVD. The relationship between acute and chronic stress and CVD is well evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia–reperfusion injury (IRI). Conversely, chronic stress is arrhythmogenic and increases sensitivity to myocardial IRI. Few studies have examined the impact of validated animal models of stress-related psychological disorders on the ischemic heart. This review examines the work that has been completed using rat models to study the effects of stress on myocardial sensitivity to ischemic injury. Utilization of animal models of stress-related psychological disorders is critical in the prevention and treatment of cardiovascular disorders in patients experiencing stress-related psychiatric conditions. PMID:27199778

  2. Efficacy of Adenosine in Patients With Acute Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: A PRISMA-Compliant Meta-Analysis.

    PubMed

    Gao, Qijun; Yang, Bo; Guo, Yi; Zheng, Feng

    2015-08-01

    Whether adenosine offers cardioprotective effects when used as an adjunctive therapy for patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) remains controversial.To evaluate, via meta-analysis, the efficacy of adenosine in patients with AMI undergoing PCI.Randomized controlled trials (RCTs) published in Medline, Embase, and the Cochrane Central Register of Controlled Trials.RCTs of patients with AMI undergoing primary PCI, comparing adenosine treatment and placebo groups and reporting mortality, thrombolysis in myocardial infarction (TIMI) flow grade, myocardial blush grade (MBG), re-infarction, left-ventricular ejection fraction (LVEF), ST-segment elevation resolution (STR), recurrent angina, or heart failure (HF).Risk of bias was assessed by the Cochrane guidelines and publication bias by Egger's test. For studies reported in multiple publications, the most complete publication was used. Arms using different dosing schedules were merged. Mean differences (MDs) or risk ratios (RRs) were determined.Data were extracted from 15 RCTs involving 1736 patients. Compared with placebo, adenosine therapy was associated with fewer occurrences of heart failure (RR: 0.65, 95% confidence interval [CI]: 0.43-0.97, P[REPLACEMENT CHARACTER]=[REPLACEMENT CHARACTER]0.03) and no-reflow (TIMI flow grade <3, RR: 0.62, 95% CI: 0.45-0.85, P[REPLACEMENT CHARACTER]=[REPLACEMENT CHARACTER]0.003; MBG[REPLACEMENT CHARACTER]=[REPLACEMENT CHARACTER]0-1, RR: 0.81; 95% CI: 0.67-0.98, P[REPLACEMENT CHARACTER]=[REPLACEMENT CHARACTER]0.03), more occurrences of STR (RR: 1.19, 95% CI: 1.07-1.31, P[REPLACEMENT CHARACTER]<[REPLACEMENT CHARACTER]0.00001), but no overall improvement of LVEF (MD: 2.29, 95% CI: -0.09 to 4.67, P[REPLACEMENT CHARACTER]=[REPLACEMENT CHARACTER]0.06). Adenosine improved LVEF in the intravenous subgroup and the regular-dose intracoronary (IC) subgroup (0.24-2.25[REPLACEMENT CHARACTER]mg) compared with placebo (MD: 2.68, 95

  3. Acute Anteroseptal Myocardial Infarction after a Negative Exercise Stress Test.

    PubMed

    Al-Alawi, Abdullah M; Janardan, Jyotsna; Peck, Kah Y; Soward, Alan

    2016-05-01

    A myocardial infarction is a rare complication which can occur after an exercise stress test. We report a 48-year-old male who was referred to the Mildura Cardiology Practice, Victoria, Australia, in August 2014 with left-sided chest pain. He underwent an exercise stress test which was negative for myocardial ischaemia. However, the patient presented to the Emergency Department of the Mildura Base Hospital 30 minutes after the test with severe retrosternal chest pain. An acute anteroseptal ST segment elevation myocardial infarction was observed on electrocardiography. After thrombolysis, he was transferred to a tertiary hospital where coronary angiography subsequently revealed significant left anterior descending coronary artery stenosis. Thrombus aspiration and a balloon angioplasty were performed. The patient was discharged three days after the surgical procedure in good health.

  4. Association between Anger and Mental Stress-Induced Myocardial Ischemia

    PubMed Central

    Pimple, Pratik; Shah, Amit; Rooks, Cherie; Bremner, J. Douglas; Nye, Jonathon; Ibeanu, Ijeoma; Murrah, Nancy; Shallenberger, Lucy; Kelley, Mary; Raggi, Paolo; Vaccarino, Viola

    2014-01-01

    Background Mental stress-induced myocardial ischemia is associated with adverse prognosis in coronary artery disease patients. Anger is thought to be a trigger of acute coronary syndromes and is associated with increased cardiovascular risk; however, little direct evidence exists for a link between anger and myocardial ischemia. Methods [99mTc]sestamibi single-photon emission tomography was performed at rest, after mental stress (a social stressor with a speech task), and after exercise/pharmacological stress. Summed scores of perfusion abnormalities were obtained by observer-independent software. A summed difference score, the difference between stress and rest scores, was used to quantify myocardial ischemia under both stress conditions. The Spielberger's State-Trait Anger Expression Inventory was used to assess different anger dimensions. Results The mean age was 50 years, 50% were female and 60% were non-white. After adjusting for demographic factors, smoking, coronary artery disease severity, depressive and anxiety symptoms, each interquartile range increment in state-anger score was associated with 0.36 units adjusted increase in ischemia as measured by the summed difference score (95% CI: 0.14-0.59); the corresponding association for trait-anger was 0.95 (95% CI: 0.21-1.69). Anger expression scales were not associated ischemia. None of the anger dimensions were related to ischemia during exercise/pharmacological stress. Conclusion Anger, both as an emotional state and as a personality trait, is significantly associated with propensity to develop myocardial ischemia during mental stress, but not during exercise/pharmacological stress. Patients with this psychological profile may be at increased risk for silent ischemia induced by emotional stress and this may translate into worse prognosis. PMID:25497256

  5. Role of adenosine A2B receptor signaling in contribution of cardiac mesenchymal stem-like cells to myocardial scar formation.

    PubMed

    Ryzhov, Sergey; Sung, Bong Hwan; Zhang, Qinkun; Weaver, Alissa; Gumina, Richard J; Biaggioni, Italo; Feoktistov, Igor

    2014-09-01

    Adenosine levels increase in ischemic hearts and contribute to the modulation of that pathological environment. We previously showed that A2B adenosine receptors on mouse cardiac Sca1(+)CD31(-) mesenchymal stromal cells upregulate secretion of paracrine factors that may contribute to the improvement in cardiac recovery seen when these cells are transplanted in infarcted hearts. In this study, we tested the hypothesis that A2B receptor signaling regulates the transition of Sca1(+)CD31(-) cells, which occurs after myocardial injury, into a myofibroblast phenotype that promotes myocardial repair and remodeling. In vitro, TGFβ1 induced the expression of the myofibroblast marker α-smooth muscle actin (αSMA) and increased collagen I generation in Sca1(+)CD31(-) cells. Stimulation of A2B receptors attenuated TGFβ1-induced collagen I secretion but had no effect on αSMA expression. In vivo, myocardial infarction resulted in a rapid increase in the numbers of αSMA-positive cardiac stromal cells by day 5 followed by a gradual decline. Genetic deletion of A2B receptors had no effect on the initial accumulation of αSMA-expressing stromal cells but hastened their subsequent decline; the numbers of αSMA-positive cells including Sca1(+)CD31(-) cells remained significantly higher in wild type compared with A2B knockout hearts. Thus, our study revealed a significant contribution of cardiac Sca1(+)CD31(-) cells to the accumulation of αSMA-expressing cells after infarction and implicated A2B receptor signaling in regulation of myocardial repair and remodeling by delaying deactivation of these cells. It is plausible that this phenomenon may contribute to the beneficial effects of transplantation of these cells to the injured heart.

  6. 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.

  7. Oxidative Stress Biomarkers and Adenosine Deaminase over the Alopecic Area of the Patients with Alopecia Areata

    PubMed Central

    Öztürk, Perihan; Arıcan, Özer; Kurutaş, Ergül Belge; Mülayim, Kamil

    2016-01-01

    Background: Alopecia areata (AA) is an autoimmune, T-cell mediated, and chronic inflammatory disorder. The pathological mechanisms of disease are unclear, but oxidative stress may be involved. To our knowledge, no studies have examined the oxidative stress levels or biomarkers within the lesional area and skin surface in patients with AA. Similarly, adenosine deaminase (ADA) has not been characterized in AA. Aims: Therefore, we aimed to define ADA levels and the factors involved in oxidative stress from scalp-scrapes of patients with AA. Study Design: Case-control study. Method: A total of 60 patients (30 diagnosed AA patients and 30 healthy controls) were included in the study. ADA as well as oxidative stress factors, including malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were analyzed from scalp-scrapes in both groups and quantified by spectrophotometry. Results: Activities of SOD (p=0.000), CAT (p=0.033), and ADA (p=0.004) as well as levels of GSH (p=0.000) and MDA (p=0.032) in patients with AA were higher than the controls statistically significant. Conclusion: Based on these results, factors associated with oxidative stress were elevated in AA patient scalp-scrapes compared to controls and may have a defined role the disease pathogenesis. Alterations in the activities of antioxidant enzymes from AA patient scraping samples may be a local effect of elevated oxidative stress levels. In this disease, oxidative stress may affect not only hair follicle but also any layers of the skin. PMID:27403388

  8. Cardiac oxidative stress and inflammatory cytokines response after myocardial infarction.

    PubMed

    Neri, Margherita; Fineschi, Vittorio; Di Paolo, Marco; Pomara, Cristoforo; Riezzo, Irene; Turillazzi, Emanuela; Cerretani, Daniela

    2015-01-01

    Oxidative stress in heart failure or during ischemia/reperfusion occurs as a result of the excessive generation or accumulation of free radicals or their oxidation products. Free radicals formed during oxidative stress can initiate lipid peroxidation, oxidize proteins to inactive states and cause DNA strand breaks. Oxidative stress is a condition in which oxidant metabolites exert toxic effects because of their increased production or an altered cellular mechanism of protection. In the early phase of acute heart ischemia cytokines have the feature to be functional pleiotropy and redundancy, moreover, several cytokines exert similar and overlapping actions on the same cell type and one cytokine shows a wide range of biological effects on various cell types. Activation of cytokine cascades in the infarcted myocardium was established in numerous studies. In experimental models of myocardial infarction, induction and release of the pro-inflammatory cytokines like TNF-α (Tumor Necrosis Factor α), IL-1β (Interleukin- 1β) and IL-6 (Interleukin-6) and chemokines are steadily described. The current review examines the role of oxidative stress and pro-inflammatory cytokines response following acute myocardial infarction and explores the inflammatory mechanisms of cardiac injury.

  9. Role of endothelium in ischaemia-induced myocardial dysfunction of isolated working hearts: cardioprotection by activation of adenosine A(2A) receptors.

    PubMed

    Maddock, H L; Broadley, K J; Bril, A; Khandoudi, N

    2001-01-01

    1 This study aimed to determine the role of the vascular endothelium on recovery of contractile function following global low-flow ischaemia of guinea-pig isolated working hearts and the effects of adenosine analogues on this recovery. 2 Guinea-pig isolated spontaneously beating or paced working hearts were set up and coronary flow (CF), aortic output (AO) (as an index of cardiac function), heart rate (HR), left ventricular pressure (LVP) and dP/dt max recorded. The endothelium was either intact or removed by a blast of oxygen. 3 In spontaneously beating hearts, low-flow ischaemia for 30 min reduced CF and cardiac contractility (LVP, dP/dt max) but not AO. On reperfusion, CF, LVP and dP/dt max recovered, while AO fell precipitously followed by a gradual recovery, indicative of myocardial stunning. The effects of ischaemia did not differ between endothelium-intact and -denuded hearts, indicating no role of the endothelium in the changes observed. 4 The adenosine analogues, N6-cyclopentyladenosine (CPA, A1 selective), 5'-N-ethylcarboxamidoadenosine (NECA, two-fold A2 selective over A1) and 2-p-((carboxyethyl)-phenethylamino)-5'carboxamidoadenosine (CGS21680, A2A selective) were infused (3 x 10-7 M) from 10 min into the 30-min low-flow ischaemia of denuded hearts and during reperfusion. 5 CGS21680 increased CF and improved the postischaemic functional recovery, as measured by the AO. NECA and CPA were not cardioprotective. The A2A selective antagonist, ZM241385, attenuated the coronary vasodilatation by CGS21680 and abolished the improved recovery of AO on reperfusion. 6 Reperfusion of paced working hearts caused a dramatic fall in AO which failed to recover. Infusion of CGS21680 from 15 min into the ischaemic period produced vasodilatation but failed to restore AO, presumably because the ischaemic damage was irreversible. 7 Thus, the endothelium plays no role in myocardial dysfunction following low-flow global ischaemia and reperfusion of guinea-pig working hearts

  10. Reclassification of cardiovascular risk in patients with normal myocardial perfusion imaging using heart rate response to vasodilator stress.

    PubMed

    Iqbal, Fahad M; Al Jaroudi, Wael; Sanam, Kumar; Sweeney, Aaron; Heo, Jaekyeong; Iskandrian, Ami E; Hage, Fadi G

    2013-01-15

    Previous studies have shown that patients with normal vasodilator myocardial perfusion imaging (MPI) findings remain at a greater risk of future cardiac events than patients with normal exercise MPI findings. The aim was to assess improvement in risk classification provided by the heart rate response (HRR) in patients with normal vasodilator MPI findings when added to traditional risk stratification. We retrospectively studied 2,000 patients with normal regadenoson or adenosine MPI findings. Risk stratification was performed using Adult Treatment Panel III framework. Patients were stratified by HRR (percentage of increase from baseline) into tertiles specific to each vasodilator. All-cause mortality and cardiac death/nonfatal myocardial infarction (MI) ≤2 years from the index MPI were recorded. During follow-up, 11.8% patients died and 2.7% patients experienced cardiac death/nonfatal MI in the adenosine and regadenoson groups, respectively. The patients who died had a greater Framingham risk score (12 ± 4 vs 11 ± 4, p = 0.009) and lower HRR (22 ± 16 vs 32 ± 21, p <0.0001). In an adjusted Cox model, the lowest tertile HRR was associated with an increased risk of mortality (hazard ratio 2.1) and cardiac death/nonfatal MI (hazard ratio 2.9; p <0.01). Patients in the highest HRR tertile, irrespective of the Adult Treatment Panel III category, were at low risk. When added to the Adult Treatment Panel III categories, the HRR resulted in net reclassification improvement in mortality of 18% and cardiac death/nonfatal MI of 22%. In conclusion, a blunted HRR to vasodilator stress was independently associated with an increased risk of cardiac events and overall mortality in patients with normal vasodilator MPI findings. The HRR correctly reclassified a substantial proportion of these patients in addition to the traditional risk classification models and identified patients with normal vasodilator MPI findings, who had a truly low risk of events.

  11. Psychological Stress in Wives of Patients with Myocardial Infarction

    PubMed Central

    Skelton, M.; Dominian, J.

    1973-01-01

    In a study of the psychological consequences of myocardial infarction on 65 wives of husbands admitted to a coronary care unit feelings of loss, depression, and guilt were common at the time of infarction. Many wives (38%) found the period of convalescence after discharge very stressful, attributing this to fears of a recurrent infarct and marital tension owing to their husbands' increased irritability and dependency. These anxieties and tensions gradually diminished and at one year after the initial illness only eight wives whose husbands had made a good physical recovery still showed considerable psychological disturbance. It is suggested that unnecessary emotional distress, particularly in the initial period after discharge from hospital, can be alleviated by increased help and support from the hospital and family doctor. PMID:4700299

  12. [Tissue Doppler in the assessment of myocardial function in stress echocardiography].

    PubMed

    Citro, Rodolfo; Salustri, Alessandro; Trambaiolo, Paolo; Gregorio, Giovanni

    2002-02-01

    Recently, stress echocardiography has emerged as a valuable tool for the diagnosis and evaluation of coronary artery disease, but its interpretation still remains subjective, relying on image quality and reader's experience. These problems could be overcome by quantitative analysis of wall motion. Tissue Doppler provides quantitative information on regional myocardial systolic and diastolic velocities that can be displayed either in spectral mode or color coded, reflecting the peak velocity increment induced by exercise or dobutamine administration. Pulsed wave tissue Doppler allows to measure regional instantaneous myocardial velocities with high temporal resolution and has been shown valuable for detecting stress-induced changes of both myocardial systolic and diastolic function. This method may also identify myocardial viability by measuring increase in systolic peak velocity at low-dose of dobutamine in dysfunctional myocardial segments. Color coded tissue Doppler resolves mean velocities with higher spatial resolution, and post-processing analysis of digital acquired images has been shown feasible and reproducible. Myocardial velocity gradient is a more sensitive parameter compared to the simple measurement of the peak endocardial systolic velocity for evaluating myocardial ischemia during dobutamine echocardiography. From the raw data, it is also possible to measure strain and strain rate. These new parameters have the potential to differentiate between wall motion and contractility, with obvious implications when applied to stress echocardiography. In conclusion, tissue Doppler is able to quantify regional myocardial function. After a large scale validation, this technique will be incorporated with stress echocardiography in clinical practice.

  13. [Thallium-201 myocardial scintigraphy after intravenous infusion of adenosine triphosphate disodium: a preliminary study in the diagnosis of coronary artery disease].

    PubMed

    Kinoshita, S; Yamashita, S; Suzuki, T; Muramatsu, T; Ide, M; Dohi, Y; Nishimura, K; Miyamae, T

    1991-12-01

    The feasibility and safety of thallium-201 myocardial scintigraphy after the intravenous infusion of adenosine triphosphate disodium (ATP) (Adetphos, Kowa) were studied in eight patients with angina pectoris and/or old myocardial infarction. Coronary arteriography (CAG) was performed by the conventional method in all patients. ATP was infused for 5 min and thallium was injected at 3 min after the start of ATP infusion. ATP was given at 0.12 mg/min/kg in two patients (group A), 0.16 mg/min/kg in three patients (group B), 0.20 mg/min/kg in one patient (group C) and 0.28 mg/min/kg in two patients (group D). SPECT images were obtained at 10 min and 180 min after thallium injection. No significant hemodynamic changes were observed in group A and B. Severe hypotension was observed in group C and one member of group D. Chest pain was experienced by one patient in group A, two in group B, one in group C, and both of the two in group D. ST depression on the electrocardiogram (ECG) was documented in one patient each of groups B and C. In one group D patient, the study was discontinued because of complete atrioventricular block persistent for 5 beats. The correlation between thallium imaging and CAG was unclear in group A, reasonable in groups B and C, and obscure in group D because of side effects. None of the patients who developed side effects of ATP were administered sublingual nitroglycerin or intravenous aminophylline. Their symptoms or ECG changes improved spontaneously within 2 min and disappeared within 5 min after termination of infusion. In conclusion, the optimal ATP regimen for this purpose was considered to be a 5 min infusion at 0.16 mg/kg/min and this method was found to be feasible and safe. PMID:1784093

  14. Oxidative stress and myocardial injury in the diabetic heart

    PubMed Central

    Ansley, David M.; Wang, Baohua

    2013-01-01

    Reactive oxygen or nitrogen species play an integral role in both myocardial injury and repair. This dichotomy is differentiated at the level of species type, amount, duration of free radical generated. Homeostatic mechanisms designed to prevent free radical generation in the first instance, scavenge, or enzymatically convert them to less toxic forms and water, play crucial roles in maintenance of cellular structure and function. The outcome between functional recovery and dysfunction is dependent upon the inherent ability of these homeostatic antioxidant defenses to withstand acute free radical generation, in the order of seconds to minutes. Alternatively, pre-existent antioxidant capacity (from intracellular and extracellular sources) may regulate the degree of free radical generation. This converts reactive oxygen and nitrogen species to the role of second messenger involved in cell signalling. The adaptive capacity of the cell is altered by the balance between death or survival signal converging at the level of the mitochondria, with distinct pathophysiologic consequences that extends the period of injury from hours to days and weeks. Hyperglycemia, hyperlipidemia, and insulin resistance enhance oxidative stress in diabetic myocardium that cannot adapt to ischemia reperfusion. Altered glucose flux, mitochondrial derangements and nitric oxide synthase uncoupling in the presence of decreased antioxidant defense and impaired prosurvival cell signalling may render the diabetic myocardium more vulnerable to injury, remodelling and heart failure. PMID:23011912

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

    PubMed Central

    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.

    2016-01-01

    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

  16. 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

  17. Molecular Mechanisms of Stress-Induced Myocardial Injury in a Rat Model Simulating Posttraumatic Stress Disorder

    PubMed Central

    Liu, Mi; Xu, Feifei; Tao, Tianqi; Song, Dandan; Li, Dong; Li, Yuzhen; Guo, Yucheng; Liu, Xiuhua

    2016-01-01

    ABSTRACT Objective Posttraumatic stress disorder (PTSD) is an independent risk factor for cardiovascular diseases. This study investigated the molecular mechanisms underlying myocardial injury induced by simulated PTSD. Methods Sprague-Dawley rats were randomly divided into two groups: control group (n = 18) and PTSD group (n = 30). The PTSD model was replicated using the single prolonged stress (SPS) method. On the 14th day poststress, the apoptotic cells in myocardium were assessed using both TUNEL method and transmission electron microscopy; the protein levels of the endoplasmic reticulum stress (ERS) molecules were measured by using Western blotting analysis. Results Exposure to SPS resulted in characteristic morphologic changes of apoptosis in cardiomyocytes assessed by transmission electron microscopy. Moreover, TUNEL staining was also indicative of the elevated apoptosis rate of cardiomyocytes from the SPS rats (30.69% versus 7.26%, p < .001). Simulated PTSD also induced ERS in myocardium, demonstrated by up-regulation of protein levels of glucose-regulated protein 78 (0.64 versus 0.26, p = .017), calreticulin (p = .040), and CCAAT/enhancer-binding protein-homologous protein (0.95 versus 0.43, p = .047), phosphorylation of protein kinase RNA–like ER kinase (p = .003), and caspase 12 activation (0.30 versus 0.06, p < .001) in myocardium from the SPS rats. The ratio of Bcl-2 to Bax decreased significantly in myocardium from the SPS rats (p = .005). Conclusions The ERS-related apoptosis mediated by the protein kinase RNA–like ER kinase/CCAAT/enhancer-binding protein-homologous protein and caspase 12 pathways may be associated with myocardial injury in a rat model simulating PTSD. This study may advance our understanding of how PTSD contributes to myocardial injury on a molecular level. PMID:27359173

  18. Adenosine and the Auditory System

    PubMed Central

    Vlajkovic, Srdjan M; Housley, Gary D; Thorne, Peter R

    2009-01-01

    Adenosine is a signalling molecule that modulates cellular activity in the central nervous system and peripheral organs via four G protein-coupled receptors designated A1, A2A, A2B, and A3. This review surveys the literature on the role of adenosine in auditory function, particularly cochlear function and its protection from oxidative stress. The specific tissue distribution of adenosine receptors in the mammalian cochlea implicates adenosine signalling in sensory transduction and auditory neurotransmission although functional studies have demonstrated that adenosine stimulates cochlear blood flow, but does not alter the resting and sound-evoked auditory potentials. An interest in a potential otoprotective role for adenosine has recently evolved, fuelled by the capacity of A1 adenosine receptors to prevent cochlear injury caused by acoustic trauma and ototoxic drugs. The balance between A1 and A2A receptors is conceived as critical for cochlear response to oxidative stress, which is an underlying mechanism of the most common inner ear pathologies (e.g. noise-induced and age-related hearing loss, drug ototoxicity). Enzymes involved in adenosine metabolism, adenosine kinase and adenosine deaminase, are also emerging as attractive targets for controlling oxidative stress in the cochlea. Other possible targets include ectonucleotidases that generate adenosine from extracellular ATP, and nucleoside transporters, which regulate adenosine concentrations on both sides of the plasma membrane. Developments of selective adenosine receptor agonists and antagonists that can cross the blood-cochlea barrier are bolstering efforts to develop therapeutic interventions aimed at ameliorating cochlear injury. Manipulations of the adenosine signalling system thus hold significant promise in the therapeutic management of oxidative stress in the cochlea. PMID:20190966

  19. Comparison of stress-only vs. stress/rest with technetium-99m methoxyisobutylisonitrile myocardial perfusion imaging.

    PubMed

    Worsley, D F; Fung, A Y; Coupland, D B; Rexworthy, C G; Sexsmith, G P; Lentle, B C

    1992-01-01

    Unlike conventional thallium-201 myocardial imaging, technetium-99m methoxyisobutylisonitrile (MIBI) requires separate stress and rest injections. We prospectively studied 148 consecutive patients referred for myocardial perfusion studies to determine the diagnostic value of rest images once normal exercise or dipyridamole tomographic images had been obtained. In patients referred with no history of previous myocardial infarction in whom the diagnosis of coronary artery disease was suspected, 45 of 109 (41%) patients had normal stress tomographic images. Obtaining rest images did not alter the final interpretation in any of these cases. From this we infer that in patients with normal images after exercise or dipyridamole administration and no past history of myocardial infarction, 99mTc-MIBI rest images are not required. This provides several advantages including increased speed of diagnosis, decreased patient radiation exposure, improved cost efficiency and decreased demand on tomographic camera time.

  20. 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. PMID:27114365

  1. Sex Differences in Mental Stress-Induced Myocardial Ischemia in Young Survivors of an Acute Myocardial Infarction

    PubMed Central

    Vaccarino, Viola; Shah, Amit J.; Rooks, Cherie; Ibeanu, Ijeoma; Nye, Jonathon A.; Pimple, Pratik; Salerno, Amy; D'Marco, Luis; Karohl, Cristina; Bremner, J. Douglas; Raggi, Paolo

    2014-01-01

    Objectives Emotional stress may disproportionally affect young women with ischemic heart disease. We sought to examine whether mental stress-induced myocardial ischemia (MSIMI), but not exercise-induced ischemia, is more common in young women with previous myocardial infarction (MI) than men. Methods We studied 98 post-MI patients (49 women and 49 men) aged 38-60 years. Women and men were matched for age, MI type, and months since MI. Patients underwent [99mTc]sestamibi perfusion imaging at rest, after mental stress, and after exercise/pharmacological stress. Perfusion defect scores were obtained with observer-independent software. A summed difference score (SDS), the difference between stress and rest scores, was used to quantify ischemia under both stress conditions. Results Women aged 50 or younger, but not older women, showed a more adverse psychosocial profile than age-matched men, but did not differ for conventional risk factors and tended to have less angiographic coronary artery disease (CAD). Compared with age-matched men, women aged 50 or younger exhibited a higher SDS with mental stress (3.1 vs. 1.5, p=0.029) and had twice the rate of MSIMI (SDS ≥3), 52% vs. 25%, while ischemia with physical stress did not differ (36% vs 25%). In older patients there were no sex differences in MSIMI. The higher prevalence of MSIMI in young women persisted when adjusting for sociodemographic and lifestyle factors, CAD severity and depression. Conclusions MSIMI post-MI is more common in women aged 50 or younger compared to age-matched men. These sex differences are not observed in post-MI patients who are older than 50 years. PMID:24608039

  2. 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.

  3. 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. PMID:26056314

  4. Adiposity Is Associated with Gender-Specific Reductions in Left Ventricular Myocardial Perfusion during Dobutamine Stress

    PubMed Central

    Hall, Michael E.; Brinkley, Tina E.; Chughtai, Haroon; Morgan, Timothy M.; Hamilton, Craig A.; Jordan, Jennifer H.; Stacey, R. Brandon; Soots, Sandra; Hundley, W. Gregory

    2016-01-01

    Background Obesity and visceral adiposity are increasingly recognized risk factors for cardiovascular disease. Visceral fat may reduce myocardial perfusion by impairing vascular endothelial function. Women experience more anginal symptoms compared to men despite less severe coronary artery stenosis, as assessed by angiography. Women and men have different fat storage patterns which may account for the observed differences in cardiovascular disease. Therefore, our objective was to evaluate the relationship between visceral adipose tissue distributions and myocardial perfusion in men and women. Methods Visceral and subcutaneous fat distributions and myocardial perfusion were measured in 69 men and women without coronary artery disease using magnetic resonance imaging techniques. Myocardial perfusion index was quantified after first-pass perfusion with gadolinium contrast at peak dose dobutamine stress. Results We observed inverse relationships between female gender (r = -0.35, p = 0.003), pericardial fat (r = -0.36, p = 0.03), intraperitoneal fat (r = -0.37, p = 0.001), and retroperitoneal fat (r = -0.36, p = 0.002) and myocardial perfusion index. Visceral fat depots were not associated with reduced myocardial perfusion at peak dose dobutamine in men. However, in women, BMI (r = -0.33, p = 0.04), pericardial fat (r = -0.53, p = 0.02), subcutaneous fat (r = -0.39, p = 0.01) and intraperitoneal fat (r = -0.30, p = 0.05) were associated with reduced myocardial perfusion during dobutamine stress. Conclusions Higher visceral fat volumes are associated with reduced left ventricular myocardial perfusion at peak dose dobutamine stress in women but not in men. These findings suggest that visceral fat may contribute to abnormal microcirculatory coronary artery perfusion syndromes, explaining why some women exhibit more anginal symptoms despite typically lower grade epicardial coronary artery stenoses than men. PMID:26751789

  5. Thymol, a dietary monoterpene phenol abrogates mitochondrial dysfunction in β-adrenergic agonist induced myocardial infarcted rats by inhibiting oxidative stress.

    PubMed

    Nagoor Meeran, M F; Jagadeesh, G S; Selvaraj, P

    2016-01-25

    Mitochondrial dysfunction has been suggested to be one of the important pathological events in isoproterenol (ISO), a synthetic catecholamine and β-adrenergic agonist induced myocardial infarction (MI). In this context, we have evaluated the impact of thymol against ISO induced oxidative stress and calcium uniporter malfunction involved in the pathology of mitochondrial dysfunction in rats. Male albino Wistar rats were pre and co-treated with thymol (7.5 mg/kg body weight) daily for 7 days. Isoproterenol (100 mg/kg body weight) was subcutaneously injected into rats on 6th and 7th day to induce MI. To explore the extent of cardiac mitochondrial damage, the activities/levels of cardiac marker enzymes, mitochondrial lipid peroxidation products, antioxidants, lipids, calcium, adenosine triphosphate and multi marker enzymes were evaluated. Isoproterenol induced myocardial infarcted rats showed a significant increase in the activities of cardiac diagnostic markers, heart mitochondrial lipid peroxidation, lipids, calcium, and a significant decrease in the activities/levels of heart mitochondrial superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, isocitrate, malate, α-ketoglutarate and NADH-dehydrogenases, cytochrome-C-oxidase, and adenosine triphosphate. Thymol pre and co-treatment showed near normalized effects on all the biochemical parameters studied. Transmission electron microscopic findings and mitochondrial swelling studies confirmed our biochemical findings. The in vitro study also revealed the potent free-radical scavenging activity of thymol. Thus, thymol attenuates the involvement of ISO against oxidative stress and calcium uniporter malfunction associated with mitochondrial dysfunction in rats. PMID:26721194

  6. Complex Signaling Network in Regulation of Adenosine 5′-Phosphosulfate Reductase by Salt Stress in Arabidopsis Roots1[W

    PubMed Central

    Koprivova, Anna; North, Kathryn Anne; Kopriva, Stanislav

    2008-01-01

    Sulfur-containing compounds play an important role in plant stress defense; however, only a little is known about the molecular mechanisms of regulation of sulfate assimilation by stress. Using known Arabidopsis (Arabidopsis thaliana) mutants in signaling pathways, we analyzed regulation of the key enzyme of sulfate assimilation, adenosine 5′-phosphosulfate reductase (APR), by salt stress. APR activity and mRNA levels of all three APR isoforms increased 3-fold in roots after 5 h of treatment with 150 mm NaCl. The regulation of APR was not affected in mutants deficient in abscisic acid (ABA) synthesis and treatment of the plants with ABA did not affect the mRNA levels of APR isoforms, showing that APR is regulated by salt stress in an ABA-independent manner. In mutants deficient in jasmonate, salicylate, or ethylene signaling, APR mRNA levels were increased upon salt exposure similar to wild-type plants. Surprisingly, however, APR enzyme activity was not affected by salt in these plants. The same result was obtained in mutants affected in cytokinin and auxin signaling. Signaling via gibberellic acid, on the other hand, turned out to be essential for the increase in APR mRNA by salt treatment. These results demonstrate an extensive posttranscriptional regulation of plant APR and reveal that the sulfate assimilation pathway is controlled by a complex network of multiple signals on different regulatory levels. PMID:18218969

  7. Adenosine protects Sprague Dawley rats from high-fat diet and repeated acute restraint stress-induced intestinal inflammation and altered expression of nutrient transporters.

    PubMed

    Lee, C Y

    2015-04-01

    This study investigated the effect of repeated acute restraint stress and high-fat diet (HFD) on intestinal expression of nutrient transporters, concomitant to intestinal inflammation. The ability of adenosine to reverse any change was examined. Six-week-old male Sprague Dawley rats were divided into eight groups: control or non-stressed (C), rats exposed to restraint stress for 6 h per day for 14 days (S), control rats fed with HFD (CHF) and restraint-stressed rats fed with HFD (SHF); four additional groups received the same treatments and were also given 50 mg/l adenosine dissolved in drinking water. Fasting blood glucose, plasma insulin, adiponectin and corticosterone were measured. Intestinal expression of SLC5A1, SLC2A2, NPC1L1 and TNF-α was analysed. Histological evaluation was conducted to observe for morphological and anatomical changes in the intestinal tissues. Results showed that HFD feeding increased glucose and insulin levels, and repeated acute restraint stress raised the corticosterone level by 22%. Exposure to both stress and HFD caused a further increase in corticosterone to 41%, while decreasing plasma adiponectin level. Restraint stress altered intestinal expression of SLC5A1, SLC2A2 and NPC1L1. These changes were enhanced in SHF rats. Adenosine was found to alleviate HFD-induced increase in glucose and insulin levels, suppress elevation of corticosterone in S rats and improve the altered nutrient transporters expression profiles. It also prevented upregulation of TNF-α in the intestine of SHF rats. In summary, a combination of stress and HFD exaggerated stress- and HFD-induced pathophysiological changes in the intestine, and biochemical parameters related to obesity. Adenosine attenuated the elevation of corticosterone and altered expression of SLC5A1, NPC1L1 and TNF-α.

  8. Features of adenosine metabolism of mouse heart.

    PubMed

    Deussen, Andreas; Weichsel, Johannes; Pexa, Annette

    2006-11-01

    Adenosine metabolism and transport were evaluated in the isolated perfused mouse heart and compared with the well-established model of isolated perfused guinea pig heart. Coronary venous release of adenosine under well-oxygenated conditions in the mouse exceeds that in the guinea pig threefold when related to tissue mass. Total myocardial adenosine production rate under this condition was approximately 2 nmol/min per gramme and similar in both species. Coronary resistance vessels of mice are highly sensitive to exogenous adenosine, and the threshold for adenosine-induced vasodilation is approximately 30 nmol/l. Adenosine membrane transport was largely insensitive to nitrobenzyl-thioinosine (NBTI) in mouse heart, which is in contrast to guinea pig and several other species. This indicates the dominance of NBTI-insensitive transporters in mouse heart. For future studies, the assessment of cytosolic and extracellular adenosine metabolism and its relationship with coronary flow will require the use of more effective membrane transport blockers.

  9. Chronic intermittent mental stress promotes atherosclerotic plaque vulnerability, myocardial infarction and sudden death in mice.

    PubMed

    Roth, Lynn; Rombouts, Miche; Schrijvers, Dorien M; Lemmens, Katrien; De Keulenaer, Gilles W; Martinet, Wim; De Meyer, Guido R Y

    2015-09-01

    Vulnerable atherosclerotic plaques are prone to plaque rupture leading to acute cardiovascular syndromes and death. Elucidating the risk of plaque rupture is important to define better therapeutic or preventive strategies. In the present study, we investigated the effect of chronic intermittent mental stress on atherosclerotic plaque stability and cardiovascular mortality in apolipoprotein E-deficient (ApoE(-/-)) mice with a heterozygous mutation in the fibrillin-1 gene (Fbn1(C1039G+/)(-)). This mouse model displays exacerbated atherosclerosis with spontaneous plaque ruptures, myocardial infarction and sudden death, when fed a Western-type diet (WD). Female ApoE(-/-)Fbn1(C1039G+/-) mice were fed a WD for up to 25 weeks. After 10 weeks WD, mice were divided in a control (n = 27) and mental stress (n = 29) group. The chronic intermittent mental stress protocol consisted of 3 triggers: water avoidance, damp bedding and restraint stress, in a randomly assigned order lasting 6 h every weekday for 15 weeks. Chronic intermittent mental stress resulted in a significant increase in the amount of macrophages in atherosclerotic plaques of the proximal ascending aorta, whereas type I collagen and fibrous cap thickness were decreased. The coronary arteries of mental stress-treated mice showed larger plaques, more stenosis, and an increased degree of perivascular fibrosis. Moreover, myocardial infarctions occurred more frequently in the mental stress group. As compared to the control group, the survival of stressed ApoE(-/-)Fbn1(C1039G+/-) mice decreased from 67% to 52% at 25 weeks WD, presumably due to myocardial infarctions. In conclusion, chronic intermittent mental stress promotes plaque instability, myocardial infarctions, and mortality of ApoE(-/-)Fbn1(C1039G+/-) mice. PMID:26233915

  10. Family Stress Management Following Acute Myocardial Infarction: An Educational and Skills Training Intervention Program.

    ERIC Educational Resources Information Center

    Nelson, David V.; Cleveland, Sidney E.; Baer, Paul E.

    1998-01-01

    Provides a conceptual background for specific behavioral-therapy approach to family stress management in dealing with the sequelae of acute myocardial infarction for all family members with the goal of reducing morbidity for all family members as they cope with ongoing survivorship issues. Describes the program and discusses its pilot…

  11. The Role of Oxidative Stress in Myocardial Ischemia and Reperfusion Injury and Remodeling: Revisited

    PubMed Central

    Kurian, Gino A.; Rajagopal, Rashmi; Vedantham, Srinivasan; Rajesh, Mohanraj

    2016-01-01

    Oxidative and reductive stress are dual dynamic phases experienced by the cells undergoing adaptation towards endogenous or exogenous noxious stimulus. The former arises due to the imbalance between the reactive oxygen species production and antioxidant defenses, while the latter is due to the aberrant increase in the reducing equivalents. Mitochondrial malfunction is the common denominator arising from the aberrant functioning of the rheostat that maintains the homeostasis between oxidative and reductive stress. Recent experimental evidences suggest that the maladaptation during oxidative stress could play a pivotal role in the pathophysiology of major cardiovascular diseases such as myocardial infraction, atherosclerosis, and diabetic cardiovascular complications. In this review we have discussed the role of oxidative and reductive stress pathways in the pathogenesis of myocardial ischemia/reperfusion injury and diabetic cardiomyopathy (DCM). Furthermore, we have provided impetus for the development of subcellular organelle targeted antioxidant drug therapy for thwarting the deterioration of the failing myocardium in the aforementioned cardiovascular conditions. PMID:27313825

  12. The Role of Oxidative Stress in Myocardial Ischemia and Reperfusion Injury and Remodeling: Revisited.

    PubMed

    Kurian, Gino A; Rajagopal, Rashmi; Vedantham, Srinivasan; Rajesh, Mohanraj

    2016-01-01

    Oxidative and reductive stress are dual dynamic phases experienced by the cells undergoing adaptation towards endogenous or exogenous noxious stimulus. The former arises due to the imbalance between the reactive oxygen species production and antioxidant defenses, while the latter is due to the aberrant increase in the reducing equivalents. Mitochondrial malfunction is the common denominator arising from the aberrant functioning of the rheostat that maintains the homeostasis between oxidative and reductive stress. Recent experimental evidences suggest that the maladaptation during oxidative stress could play a pivotal role in the pathophysiology of major cardiovascular diseases such as myocardial infraction, atherosclerosis, and diabetic cardiovascular complications. In this review we have discussed the role of oxidative and reductive stress pathways in the pathogenesis of myocardial ischemia/reperfusion injury and diabetic cardiomyopathy (DCM). Furthermore, we have provided impetus for the development of subcellular organelle targeted antioxidant drug therapy for thwarting the deterioration of the failing myocardium in the aforementioned cardiovascular conditions. PMID:27313825

  13. ST-Elevation Myocardial Infarction after Pharmacologic Persantine Stress Test in a Patient with Wellens' Syndrome

    PubMed Central

    Alattar, Fady; Koneru, Jayanth; Shamoon, Fayez

    2014-01-01

    Wellens' syndrome, also known as LAD coronary T-wave inversion syndrome, is a characteristic ECG pattern that highly suggests critical stenosis of the proximal left anterior descending (LAD) coronary artery. 75% of patients with this finding go on to develop acute anterior wall myocardial infarction within one week unless prevented by early intervention on the culprit lesion. Most instances of ST-elevation occurring during cardiac stress testing have been observed with exercise, with only seven cases reported in the literature with pharmacologic stress. We present a case of a patient with no known cardiac disease who presented with chest pain and an ECG consistent with Wellens' syndrome that developed an acute anterior wall ST-elevation myocardial infarction after pharmacologic stress test. PMID:25161778

  14. 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

  15. Safety of guidewire-based measurement of fractional flow reserve and the index of microvascular resistance using intravenous adenosine in patients with acute or recent myocardial infarction

    PubMed Central

    Ahmed, Nadeem; Layland, Jamie; Carrick, David; Petrie, Mark C.; McEntegart, Margaret; Eteiba, Hany; Hood, Stuart; Lindsay, Mitchell; Watkins, Stuart; Davie, Andrew; Mahrous, Ahmed; Carberry, Jaclyn; Teng, Vannesa; McConnachie, Alex; Curzen, Nick; Oldroyd, Keith G.; Berry, Colin

    2016-01-01

    Aims Coronary guidewire-based diagnostic assessments with hyperemia may cause iatrogenic complications. We assessed the safety of guidewire-based measurement of coronary physiology, using intravenous adenosine, in patients with an acute coronary syndrome. Methods We prospectively enrolled invasively managed STEMI and NSTEMI patients in two simultaneously conducted studies in 6 centers (NCT01764334; NCT02072850). All of the participants underwent a diagnostic coronary guidewire study using intravenous adenosine (140 μg/kg/min) infusion for 1–2 min. The patients were prospectively assessed for the occurrence of serious adverse events (SAEs) and symptoms and invasively measured hemodynamics were also recorded. Results 648 patients (n = 298 STEMI patients in 1 hospital; mean time to reperfusion 253 min; n = 350 NSTEMI in 6 hospitals; median time to angiography from index chest pain episode 3 (2, 5) days) were included between March 2011 and May 2013. Two NSTEMI patients (0.3% overall) experienced a coronary dissection related to the guidewire. No guidewire dissections occurred in the STEMI patients. Chest symptoms were reported in the majority (86%) of patient's symptoms during the adenosine infusion. No serious adverse events occurred during infusion of adenosine and all of the symptoms resolved after the infusion ceased. Conclusions In this multicenter analysis, guidewire-based measurement of FFR and IMR using intravenous adenosine was safe in patients following STEMI or NSTEMI. Self-limiting symptoms were common but not associated with serious adverse events. Finally, coronary dissection in STEMI and NSTEMI patients was noted to be a rare phenomenon. PMID:26418191

  16. 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.

  17. 5'-Adenosine monophosphate and adenosine metabolism, and adenosine responses in mouse, rat and guinea pig heart.

    PubMed

    Headrick, J P; Peart, J; Hack, B; Garnham, B; Matherne, G P

    2001-11-01

    We examined myocardial 5'-adenosine monophosphate (5'-AMP) catabolism, adenosine salvage and adenosine responses in perfused guinea pig, rat and mouse heart. MVO(2) increased from 71+/-8 microl O(2)/min per g in guinea pig to 138+/-17 and 221+/-15 microl O(2)/min per g in rat and mouse. VO(2)/beat was 0.42+/-0.03, 0.50+/-0.03 and 0.55+/-0.04 microl O(2)/g in guinea pig, rat and mouse, respectively. Resting and peak coronary flows were highest in mouse vs. rat and guinea pig, and peak ventricular pressures and Ca(2+) sensitivity declined as heart mass increased. Net myocardial 5'-AMP dephosphorylation increased significantly as mass declined (3.8+/-0.5, 9.0+/-1.4 and 11.0+/-1.6 nmol/min per g in guinea pig, rat and mouse, respectively). Despite increased 5'-AMP catabolism, coronary venous [adenosine] was similar in guinea pig, rat and mouse (45+/-8, 69+/-10 and 57+/-14 nM, respectively). Comparable venous [adenosine] was achieved by increased salvage vs. deamination: 64%, 41% and 39% of adenosine formed was rephosphorylated while 23%, 46%, and 50% was deaminated in mouse, rat and guinea pig, respectively. Moreover, only 35-45% of inosine and its catabolites derive from 5'-AMP (vs. IMP) dephosphorylation in all species. Although post-ischemic purine loss was low in mouse (due to these adaptations), functional tolerance to ischemia decreased with heart mass. Cardiovascular sensitivity to adenosine also differed between species, with A(1) receptor sensitivity being greatest in mouse while A(2) sensitivity was greatest in guinea pig. In summary: (i) cardiac 5'-AMP dephosphorylation, VO(2), contractility and Ca(2+) sensitivity all increase as heart mass falls; (ii) adaptations in adenosine salvage vs. deamination limit purine loss and yield similar adenosine levels across species; (iii) ischemic tolerance declines with heart mass; and (iv) cardiovascular sensitivity to adenosine varies, with increasing A(2) sensitivity relative to A(1) sensitivity in larger hearts.

  18. 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

  19. Platelet Aggregation and Mental Stress Induced Myocardial Ischemia: Results from the REMIT Study

    PubMed Central

    Jiang, Wei; Boyle, Stephen H.; Ortel, Thomas L.; Samad, Zainab; Velazquez, Eric J.; Harrison, Robert W.; Wilson, Jennifer; Kuhn, Cynthia; Williams, Redford B.; O’Connor, Christopher M.; Becker, Richard C.

    2015-01-01

    BACKGROUND Mental stress-induced myocardial ischemia (MSIMI) is common in patients with ischemic heart disease (IHD) and associated with a poorer cardiovascular prognosis. Platelet hyperactivity is an important factor in acute coronary syndrome. This study examined associations between MSIMI and resting and mental stress-induced platelet activity. METHODS Eligible patients with clinically stable IHD underwent a battery of 3 mental stress tests during the recruitment phase of REMIT (Responses of Myocardial Ischemia to Escitalopram Treatment) study. MSIMI was assessed by echocardiography and electrocardiography. Ex vivo platelet aggregation in response to ADP, epinephrine, collagen, serotonin, and combinations of serotonin plus ADP, epinephrine, and collagen were evaluated as was platelet serotonin transporter expression. RESULTS Of the 270 participants who completed mental stress testing, and had both resting and post-stress platelet aggregation evaluation, 43.33% (N=117) met criteria for MSIMI and 18.15% (N=49) had normal left ventricular response to stress (NLVR). The MSIMI group, relative to the NLVR groups, demonstrated heightened mental stress-induced aggregation responses, as measured by area under the curve, to collagen 10 μM (6.95[5.54] vs. −14.23[8.75].; p=0.045), epinephrine 10 μM (12.84[4.84] vs. −6.40[7.61].; p=0.037) and to serotonin 10 μM plus ADP 1 μM (6.64[5.29] vs. −27.34[8.34]; p < .001). The resting platelet aggregation and serotonin transporter expression, however, were not different between the two groups. CONCLUSIONS These findings suggest that the dynamic change of platelet aggregation caused by mental stress may underlie MSIMI. While the importance of these findings requires additional investigation, they raise concern given the recognized relationship between mental stress-induced platelet hyperactivity and cardiovascular events in patients with IHD. PMID:25819856

  20. Oxidative stress and myocardial dysfunction in young rabbits after short term anabolic steroids administration.

    PubMed

    Germanakis, Ioannis; Tsarouhas, Konstantinos; Fragkiadaki, Persefoni; Tsitsimpikou, Christina; Goutzourelas, Nikolaos; Champsas, Maria Christakis; Stagos, Demetrios; Rentoukas, Elias; Tsatsakis, Aristidis M

    2013-11-01

    The present study focuses on the short term effects of repeated low level administration of turinabol and methanabol on cardiac function in young rabbits (4 months-old). The experimental scheme consisted of two oral administration periods, lasting 1 month each, interrupted by 1-month wash-out period. Serial echocardiographic evaluation at the end of all three experimental periods was performed in all animals. Oxidative stress markers have also been monitored at the end of each administration period. Treated animals originally showed significantly increased myocardial mass and systolic cardiac output, which normalized at the end of the wash out period. Re-administration led to increased cardiac output, at the cost though of a progressive myocardial mass reduction. A dose-dependent trend towards impaired longitudinal systolic, diastolic and global myocardial function was also observed. The adverse effects were more pronounced in the methanabol group. For both anabolic steroids studied, the low dose had no significant effects on oxidative stress markers monitored, while the high dose created a hostile oxidative environment. In conclusion, anabolic administration has been found to create a possible deleterious long term effect on the growth of the immature heart and should be strongly discouraged especially in young human subjects. PMID:23537599

  1. Oxidative stress and myocardial dysfunction in young rabbits after short term anabolic steroids administration.

    PubMed

    Germanakis, Ioannis; Tsarouhas, Konstantinos; Fragkiadaki, Persefoni; Tsitsimpikou, Christina; Goutzourelas, Nikolaos; Champsas, Maria Christakis; Stagos, Demetrios; Rentoukas, Elias; Tsatsakis, Aristidis M

    2013-11-01

    The present study focuses on the short term effects of repeated low level administration of turinabol and methanabol on cardiac function in young rabbits (4 months-old). The experimental scheme consisted of two oral administration periods, lasting 1 month each, interrupted by 1-month wash-out period. Serial echocardiographic evaluation at the end of all three experimental periods was performed in all animals. Oxidative stress markers have also been monitored at the end of each administration period. Treated animals originally showed significantly increased myocardial mass and systolic cardiac output, which normalized at the end of the wash out period. Re-administration led to increased cardiac output, at the cost though of a progressive myocardial mass reduction. A dose-dependent trend towards impaired longitudinal systolic, diastolic and global myocardial function was also observed. The adverse effects were more pronounced in the methanabol group. For both anabolic steroids studied, the low dose had no significant effects on oxidative stress markers monitored, while the high dose created a hostile oxidative environment. In conclusion, anabolic administration has been found to create a possible deleterious long term effect on the growth of the immature heart and should be strongly discouraged especially in young human subjects.

  2. Right Ventricular Dysfunction Secondary to Myocardial Ischemia Provoked by Stress Testing.

    PubMed

    Obeid, Anis I.; Battaglia, Joseph; Lozner, Eugene

    1998-07-01

    We present the cases of two patients, aged 59 and 85 years, who were evaluated with stress echocardiography for chest pain. Both patients developed dramatic echocardiographic findings consisting of severe right ventricular enlargement and hypokinesis, as well as enlargement of the right atrium at relatively low-level exercise. One patient collapsed with severe sinus bradycardia, junctional rhythm, ST elevation in the inferior leads, marked hypotension, and neck vein congestion. The other patient developed staggering and symptoms of hypoperfusion. In both patients, correction of critical proximal right coronary artery stenosis by angioplasty resulted in complete resolution of the right ventricular dysfunction on repeat stress testing. We conclude that in some patients, stress-induced myocardial ischemia may involve primarily the right ventricle with little or no evidence of ischemic changes in the left ventricle. An assessment of right ventricular function should be included in stress echocardiographic studies. PMID:11175063

  3. Mechanisms of oxidative stress and myocardial protection during open-heart surgery

    PubMed Central

    Baikoussis, Nikolaos G.; Papakonstantinou, Nikolaos A.; Verra, Chrysoula; Kakouris, Georgios; Chounti, Maria; Hountis, Panagiotis; Dedeilias, Panagiotis; Argiriou, Michalis

    2015-01-01

    Cold heart protection via cardioplegia administration, limits the amount of oxygen demand. Systemic normothermia with warm cardioplegia was introduced due to the abundance of detrimental effects of hypothermia. A temperature of 32–33°C in combination with tepid blood cardioplegia of the same temperature appears to be protective enough for both; heart and brain. Reduction of nitric oxide (NO) concentration is in part responsible for myocardial injury after the cardioplegic cardiac arrest. Restoration of NO balance with exogenous NO supplementation has been shown useful to prevent inflammation and apoptosis. In this article, we discuss the “deleterious” effects of the oxidative stress of the extracorporeal circulation and the up-to-date theories of “ideal” myocardial protection. PMID:26440242

  4. Sex-dependent effects of chronic psychosocial stress on myocardial sensitivity to ischemic injury.

    PubMed

    Rorabaugh, Boyd R; Krivenko, Anna; Eisenmann, Eric D; Bui, Albert D; Seeley, Sarah; Fry, Megan E; Lawson, Joseph D; Stoner, Lauren E; Johnson, Brandon L; Zoladz, Phillip R

    2015-01-01

    Individuals with post-traumatic stress disorder (PTSD) experience many debilitating symptoms, including intrusive memories, persistent anxiety and avoidance of trauma-related cues. PTSD also results in numerous physiological complications, including increased risk for cardiovascular disease (CVD). However, characterization of PTSD-induced cardiovascular alterations is lacking, especially in preclinical models of the disorder. Thus, we examined the impact of a psychosocial predator-based animal model of PTSD on myocardial sensitivity to ischemic injury. Male and female Sprague-Dawley rats were exposed to psychosocial stress or control conditions for 31 days. Stressed rats were given two cat exposures, separated by a period of 10 days, and were subjected to daily social instability throughout the paradigm. Control rats were handled daily for the duration of the experiment. Rats were tested on the elevated plus maze (EPM) on day 32, and hearts were isolated on day 33 and subjected to 20 min ischemia and 2 h reperfusion on a Langendorff isolated heart system. Stressed male and female rats gained less body weight relative to controls, but only stressed males exhibited increased anxiety on the EPM. Male, but not female, rats exposed to psychosocial stress exhibited significantly larger infarcts and attenuated post-ischemic recovery of contractile function compared to controls. Our data demonstrate that predator stress combined with daily social instability sex-dependently increases myocardial sensitivity to ischemic injury. Thus, this manipulation may be useful for studying potential mechanisms underlying cardiovascular alterations in PTSD, as well as sex differences in the cardiovascular stress response. PMID:26458179

  5. Sex-dependent effects of chronic psychosocial stress on myocardial sensitivity to ischemic injury.

    PubMed

    Rorabaugh, Boyd R; Krivenko, Anna; Eisenmann, Eric D; Bui, Albert D; Seeley, Sarah; Fry, Megan E; Lawson, Joseph D; Stoner, Lauren E; Johnson, Brandon L; Zoladz, Phillip R

    2015-01-01

    Individuals with post-traumatic stress disorder (PTSD) experience many debilitating symptoms, including intrusive memories, persistent anxiety and avoidance of trauma-related cues. PTSD also results in numerous physiological complications, including increased risk for cardiovascular disease (CVD). However, characterization of PTSD-induced cardiovascular alterations is lacking, especially in preclinical models of the disorder. Thus, we examined the impact of a psychosocial predator-based animal model of PTSD on myocardial sensitivity to ischemic injury. Male and female Sprague-Dawley rats were exposed to psychosocial stress or control conditions for 31 days. Stressed rats were given two cat exposures, separated by a period of 10 days, and were subjected to daily social instability throughout the paradigm. Control rats were handled daily for the duration of the experiment. Rats were tested on the elevated plus maze (EPM) on day 32, and hearts were isolated on day 33 and subjected to 20 min ischemia and 2 h reperfusion on a Langendorff isolated heart system. Stressed male and female rats gained less body weight relative to controls, but only stressed males exhibited increased anxiety on the EPM. Male, but not female, rats exposed to psychosocial stress exhibited significantly larger infarcts and attenuated post-ischemic recovery of contractile function compared to controls. Our data demonstrate that predator stress combined with daily social instability sex-dependently increases myocardial sensitivity to ischemic injury. Thus, this manipulation may be useful for studying potential mechanisms underlying cardiovascular alterations in PTSD, as well as sex differences in the cardiovascular stress response.

  6. 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

  7. Oxidative-Nitrosative Stress and Myocardial Dysfunctions in Sepsis: Evidence from the Literature and Postmortem Observations

    PubMed Central

    Neri, M.; Riezzo, I.; Pomara, C.; Schiavone, S.; Turillazzi, E.

    2016-01-01

    Background. Myocardial depression in sepsis is common, and it is associated with higher mortality. In recent years, the hypothesis that the myocardial dysfunction during sepsis could be mediated by ischemia related to decreased coronary blood flow waned and a complex mechanism was invoked to explain cardiac dysfunction in sepsis. Oxidative stress unbalance is thought to play a critical role in the pathogenesis of cardiac impairment in septic patients. Aim. In this paper, we review the current literature regarding the pathophysiology of cardiac dysfunction in sepsis, focusing on the possible role of oxidative-nitrosative stress unbalance and mitochondria dysfunction. We discuss these mechanisms within the broad scenario of cardiac involvement in sepsis. Conclusions. Findings from the current literature broaden our understanding of the role of oxidative and nitrosative stress unbalance in the pathophysiology of cardiac dysfunction in sepsis, thus contributing to the establishment of a relationship between these settings and the occurrence of oxidative stress. The complex pathogenesis of septic cardiac failure may explain why, despite the therapeutic strategies, sepsis remains a big clinical challenge for effectively managing the disease to minimize mortality, leading to consideration of the potential therapeutic effects of antioxidant agents. PMID:27274621

  8. Myocardial autophagic energy stress responses—macroautophagy, mitophagy, and glycophagy

    PubMed Central

    Mellor, Kimberley M.; Taylor, David J. R.; Gottlieb, Roberta A.

    2015-01-01

    An understanding of the role of autophagic processes in the management of cardiac metabolic stress responses is advancing rapidly and progressing beyond a conceptualization of the autophagosome as a simple cell recycling depot. The importance of autophagy dysregulation in diabetic cardiomyopathy and in ischemic heart disease - both conditions comprising the majority of cardiac disease burden - has now become apparent. New findings have revealed that specific autophagic processes may operate in the cardiomyocyte, specialized for selective recognition and management of mitochondria and glycogen particles in addition to protein macromolecular structures. Thus mitophagy, glycophagy, and macroautophagy regulatory pathways have become the focus of intensive experimental effort, and delineating the signaling pathways involved in these processes offers potential for targeted therapeutic intervention. Chronically elevated macroautophagic activity in the diabetic myocardium is generally observed in association with structural and functional cardiomyopathy; yet there are also numerous reports of detrimental effect of autophagy suppression in diabetes. Autophagy induction has been identified as a key component of protective mechanisms that can be recruited to support the ischemic heart, but in this setting benefit may be mitigated by adverse downstream autophagic consequences. Recent report of glycophagy upregulation in diabetic cardiomyopathy opens up a novel area of investigation. Similarly, a role for glycogen management in ischemia protection through glycophagy initiation is an exciting prospect under investigation. PMID:25747748

  9. High-intensity training reduces intermittent hypoxia-induced ER stress and myocardial infarct size.

    PubMed

    Bourdier, Guillaume; Flore, Patrice; Sanchez, Hervé; Pepin, Jean-Louis; Belaidi, Elise; Arnaud, Claire

    2016-01-15

    Chronic intermittent hypoxia (IH) is described as the major detrimental factor leading to cardiovascular morbimortality in obstructive sleep apnea (OSA) patients. OSA patients exhibit increased infarct size after a myocardial event, and previous animal studies have shown that chronic IH could be the main mechanism. Endoplasmic reticulum (ER) stress plays a major role in the pathophysiology of cardiovascular disease. High-intensity training (HIT) exerts beneficial effects on the cardiovascular system. Thus, we hypothesized that HIT could prevent IH-induced ER stress and the increase in infarct size. Male Wistar rats were exposed to 21 days of IH (21-5% fraction of inspired O2, 60-s cycle, 8 h/day) or normoxia. After 1 wk of IH alone, rats were submitted daily to both IH and HIT (2 × 24 min, 15-30m/min). Rat hearts were either rapidly frozen to evaluate ER stress by Western blot analysis or submitted to an ischemia-reperfusion protocol ex vivo (30 min of global ischemia/120 min of reperfusion). IH induced cardiac proapoptotic ER stress, characterized by increased expression of glucose-regulated protein kinase 78, phosphorylated protein kinase-like ER kinase, activating transcription factor 4, and C/EBP homologous protein. IH-induced myocardial apoptosis was confirmed by increased expression of cleaved caspase-3. These IH-associated proapoptotic alterations were associated with a significant increase in infarct size (35.4 ± 3.2% vs. 22.7 ± 1.7% of ventricles in IH + sedenary and normoxia + sedentary groups, respectively, P < 0.05). HIT prevented both the IH-induced proapoptotic ER stress and increased myocardial infarct size (28.8 ± 3.9% and 21.0 ± 5.1% in IH + HIT and normoxia + HIT groups, respectively, P = 0.28). In conclusion, these findings suggest that HIT could represent a preventive strategy to limit IH-induced myocardial ischemia-reperfusion damages in OSA patients. PMID:26566725

  10. Effect of theophylline on adenosine production in the canine myocardium

    SciTech Connect

    McKenzie, J.E.; Steffen, R.P.; Haddy, F.J.

    1987-01-01

    Adenosine is thought to participate in local regulation of coronary blood flow. However, competitive antagonists of adenosine fail to block myocardial active hyperemia. The authors examined the effect of locally administered theophylline on active hyperemia and myocardial adenosine production during intracoronary isoproterenol infusion in the dog heart. Isoproterenol decreased coronary resistance and increased myocardial adenosine production. Infusion of theophylline at a rate that attenuated the vasodilator response to exogenously administered adenosine failed to attenuate the increase in coronary blood flow produced by isoproterenol. However, theophylline plus isoproterenol production greater increases in myocardial adensine production than isoproterenol alone. The curves relating resistance and adenosine in the presence of theophylline fell to the right of those in the absence of theophylline. These findings suggest that the failure of theophylline to attenuate isoproterenol hyperemia in the dog heart results at least in part from an increase in adenosine concentration at the arteriole to a level beyond that blocked by this competitive antagonist and that adenosine may in fact play a role in isoproterenol-induced active hyperemia.

  11. Myocardial function improved by electromagnetic field induction of stress protein hsp70.

    PubMed

    George, Isaac; Geddis, Matthew S; Lill, Zachary; Lin, Hana; Gomez, Teodoro; Blank, Martin; Oz, Mehmet C; Goodman, Reba

    2008-09-01

    Studies on myocardial function have shown that hsp70, stimulated by an increase in temperature, leads to improved survival following ischemia-reperfusion (I-R). Low frequency electromagnetic fields (EMFs) also induce the stress protein hsp70, but without elevating temperature. We have examined the hemodynamic changes in concert with EMF pre-conditioning and the induction of hsp70 to determine whether improved myocardial function occurs following I-R injury in Sprague-Dawley rats. Animals were exposed to EMF (60 Hz, 8 microT) for 30 min prior to I-R. Ischemia was then induced by ligation of left anterior descending coronary artery (LAD) for 30 min, followed by 30 min of reperfusion. Blood and heart tissue levels for hsp70 were determined by Western blot and RNA transcription by rtPCR. Significant upregulation of the HSP70 gene and increased hsp70 levels were measured in response to EMF pre-exposures. Invasive hemodynamics, as measured using a volume conductance catheter, demonstrated significant recovery of systolic contractile function after 30 min of reperfusion following EMF exposure. Additionally, isovolemic relaxation, a measure of ventricular diastolic function, was markedly improved in EMF-treated animals. In conclusion, non-invasive EMF induction of hsp70 preserved myocardial function and has the potential to improve tolerance to ischemic injury.

  12. Thymoquinone Protects against Myocardial Ischemic Injury by Mitigating Oxidative Stress and Inflammation

    PubMed Central

    Ojha, Shreesh; Azimullah, Sheikh; Mohanraj, Rajesh; Sharma, Charu; Yasin, Javed; Arya, Dharamvir S.; Adem, Abdu

    2015-01-01

    The present study was aimed at investigating the cardioprotective activity of thymoquinone (TMQ), an active principle of the herb, Nigella sativa, which is used for the management of various diseases. The present study examined the cardioprotective effect of TMQ in isoproterenol- (ISP-) induced myocardial infarction in rats. Myocardial infarction was induced by two subcutaneous injections of ISP (85 mg/kg) at an interval of 24 hr. TMQ (20 mg/kg) was administered orally for 21 days. ISP-treated rats showed depletion of antioxidants and marker enzymes from myocardium along with lipid peroxidation and enhanced levels of proinflammatory cytokines. ISP also induced histopathological alterations in myocardium. Treatment with TMQ prevented the depletion of endogenous antioxidants and myocyte injury marker enzymes and inhibited lipid peroxidation as well as reducing the levels of proinflammatory cytokines. TMQ pretreatment also reduced myonecrosis, edema, and infiltration of inflammatory cells and showed preservation of cardiomyocytes histoarchitecture. The present study results demonstrate that TMQ exerts cardioprotective effect by mitigating oxidative stress, augmenting endogenous antioxidants, and maintaining structural integrity. The results of the present study indicate that TMQ may serve as an excellent agent alone or as adjuvant to prevent the onset and progression of myocardial injury. PMID:26101531

  13. Urinary 1-Hydroxypyrene is Associated with Oxidative Stress and Inflammatory Biomarkers in Acute Myocardial Infarction

    PubMed Central

    Freitas, Fernando; Brucker, Natália; Durgante, Juliano; Bubols, Guilherme; Bulcão, Rachel; Moro, Angela; Charão, Mariele; Baierle, Marília; Nascimento, Sabrina; Gauer, Bruna; Sauer, Elisa; Zimmer, Marcelo; Thiesen, Flávia; Castro, Iran; Saldiva, Paulo; Garcia, Solange C.

    2014-01-01

    Several studies have associated exposure to environmental pollutants, especially polycyclic aromatic hydrocarbons (PAHs), with the development of cardiovascular diseases. Considering that 1-hydroxypyrene (1-OHP) is the major biomarker of exposure to pyrenes, the purpose of this study was to evaluate the potential association between 1-OHP and oxidative stress/inflammatory biomarkers in patients who had suffered an acute myocardial infarction (AMI). After adopting the exclusion criteria, 58 post-infarction patients and 41 controls were sub-divided into smokers and non-smokers. Urinary 1-OHP, hematological and biochemical parameters, oxidative stress biomarkers (MDA, SOD, CAT, GPx and exogenous antioxidants) and the inflammatory biomarker (hs-CRP) were analyzed. 1-OHP levels were increased in post-infarct patients compared to controls (p < 0.05) and were correlated to MDA (r = 0.426, p < 0.01), CAT (r = 0.474, p < 0.001) and β-carotene (r = −0.309; p < 0.05) in non-smokers. Furthermore, post-infarction patients had elevated hs-CRP, MDA, CAT and GPx levels compared to controls for both smokers and non-smokers. Besides, β-carotene levels and SOD activity were decreased in post-infarction patients. In summary, our findings indicate that the exposure to pyrenes was associated to lipid damage and alterations of endogenous and exogenous antioxidants, demonstrating that PAHs contribute to oxidative stress and are associated to acute myocardial infarction. PMID:25257356

  14. "Stress" hyperglycaemia during acute myocardial infarction: an indicator of pre-existing diabetes?

    PubMed

    Husband, D J; Alberti, K G; Julian, D G

    1983-07-23

    Hyperglycaemia occurring at admission in patients with suspected acute myocardial infarction is generally held to represent stress hyperglycaemia. 26 patients, not previously known to be diabetic, had blood glucose values greater than or equal to 10 mmol/l on admission to a coronary care unit. 16 survived for 2 months at which time a 75 g oral glucose tolerance test (OGTT) showed diabetes in 10 (63%) and impaired glucose tolerance in 1 (WHO criteria). All those with abnormal glucose tolerance at 2 months had had raised glycosylated haemoglobin (HbA1) (greater than 7.5%) on admission, indicating pre-existing diabetes. All those with a HbA1 level over 8% had abnormal glucose tolerance. 7 of the 10 who died or did not have an OGTT also had raised HbA1 at admission. An admission blood glucose greater than or equal to 10 mmol/l in patients with severe chest pain is more likely to indicate previously undiagnosed diabetes than "stress" hyperglycaemia. There is no evidence that myocardial infarction precipitates diabetes. The glycosylated haemoglobin concentration can be used to distinguish between stress hyperglycaemia and hyperglycaemia caused by diabetes.

  15. The triterpenoids of Ganoderma tsugae prevent stress-induced myocardial injury in mice.

    PubMed

    Kuok, Qian-Yu; Yeh, Chen-Yu; Su, Bor-Chyuan; Hsu, Pei-Ling; Ni, Hao; Liu, Ming-Yie; Mo, Fan-E

    2013-10-01

    Ganoderma mushrooms (Lingzhi in Chinese) have well-documented health benefits. Ganoderma tsugae (G. tsugae), one of the ganoderma species, has been commercially cultivated as a dietary supplement. Because G. tsugae has high antioxidant activity and because oxidative stress is often associated with cardiac injury, we hypothesized that G. tsugae protects against cardiac injury by alleviating oxidative stress. We tested the hypothesis using a work-overload-induced myocardial injury model created by challenging mice with isoproterenol (ISO). Remarkably, oral G. tsugae protected the mice from ISO-induced myocardial injury. Moreover, the triterpenoid fraction of G. tsugae, composed of a mixture of nine structurally related ganoderic acids (GAs), provided cardioprotection by inhibiting the ISO-induced expression of Fas/Fas ligand, oxidative stress, and apoptosis. The antioxidant activity of GAs was tested in cultured cardio-myoblast H9c2 cells against the insult of H₂O₂. GAs dissipated the cellular reactive oxygen species imposed by H₂O₂ and prevented cell death. Our findings uncovered the cardioprotective activity of G. tsugae and identified GAs as the bioactive components against cardiac insults.

  16. Cardioprotective Benefits of Adenosine Triphosphate: Sensitive Potassium Channel Opener Diazoxide Are Lost with Administration after the Onset of Stress in Mouse and Human Myocytes

    PubMed Central

    Janjua, M Burhan; Makepeace, Carol M; Anastacio, Melissa M; Schuessler, Richard B; Nichols, Colin G; Lawton, Jennifer S

    2014-01-01

    Background Adenosine triphosphate - sensitive (KATP) potassium channel opener diazoxide (DZX) maintains myocyte volume and contractility during stress via an unknown mechanism when administered at the onset of stress. This study was performed to investigate the cardioprotective potential of DZX when added after the onset of the stresses of hyperkalemic cardioplegia, metabolic inhibition, and hypo osmotic stress. Study Design Isolated mouse ventricular and human atrial myocytes were exposed to control Tyrode’s solution (TYR) for 10–20 min, test solution for 30 min (hypothermic hyperkalemic cardioplegia (CPG), CPG + 100uM diazoxide (CPG+DZX), metabolic inhibition (MI), MI+DZX, mild hypo osmotic stress (0.9T), or 0.9T + DZX) with DZX added after 10 or 20 min stress, followed by 20 min re-exposure to TYR (+/− DZX). Myocyte volume (human + mouse) and contractility (mouse) were compared. Results Mouse and human myocytes demonstrated significant swelling during exposure to CPG, MI, and hypo osmotic stress that was not prevented by DZX when administered either at 10 or 20 min after the onset of stress. Contractility following the stress of CPG in mouse myocytes significantly declined when DZX was administered 20 min after the onset of stress (p<0.05 vs. TYR). Contractility following hypo osmotic stress in mouse myocytes was not altered by the addition of DZX. Conclusions To maintain myocyte volume homeostasis and contractility during stress (hyperkalemic cardioplegia, metabolic inhibition, and hypo osmotic stress), KATP channel opener diazoxide requires administration at the onset of stress in this isolated myocyte model. These data have potential implications for any future clinical application of diazoxide. PMID:25158912

  17. Psychosocial Stress and Risk of Myocardial Infarction: A Case-Control Study in Belgrade (Serbia)

    PubMed Central

    Vujcic, Isidora; Vlajinac, Hristina; Dubljanin, Eleonora; Vasiljevic, Zorana; Matanovic, Dragana; Maksimovic, Jadranka; Sipetic, Sandra

    2016-01-01

    Background The purpose of this study was to investigate which psychosocial risk factors show the strongest association with occurrence of myocardial infarction (MI) in the population of Belgrade in peacetime, after the big political changes in Serbia. Methods A case-control study was conducted involving 154 consecutive newly diagnosed patients with MI, and 308 controls matched by gender, age, and place of residence. Results According to conditional logistic regression analysis, after adjustment for conventional coronary risk factors, the odds ratios (95% confidence intervals) for work-related stressful events, financial stress, deaths and diseases, and general stress were 3.78 (1.83-7.81), 3.80 (1.96-7.38), 1.69 (1.03-2.78), and 3.54 (2.01-6.22), respectively. Among individual stressful life events, the following were independently related to MI: death of a close family member, 2.21 (1.01-4.84); death of a close friend, 42.20 (3.70-481.29); major financial problems, 8.94 (1.83-43.63); minor financial problems, 4.74 (2.02-11.14); changes in working hours, 4.99 (1.64-15.22); and changes in working conditions, 30.94 (5.43-176.31). Conclusions During this political transition period , stress at work, financial stress, and stress in general as they impacted the population of Belgrade, Serbia were strongly associated with occurence of MI. PMID:27274168

  18. Hydrogen sulfide preconditioning protects against myocardial ischemia/reperfusion injury in rats through inhibition of endo/sarcoplasmic reticulum stress

    PubMed Central

    Li, Changyong; Hu, Min; Wang, Yuan; Lu, Huan; Deng, Jing; Yan, Xiaohong

    2015-01-01

    Ischemia reperfusion (I/R) injury is a major cause of myocardial damage. Hydrogen sulfide (H2S), a gaseous signal molecule, has drawn considerable attention for its role in various pathophysiological processes. Multiple lines of evidence reveal the protective effects of H2S in various models of cardiac injury, however, the exact mechanism underlying this protective effect of H2S against myocardial I/R injury is not fully understood. The present study was designed to investigate whether H2S preconditioning attenuates myocardial I/R injury in rats and whether the observed protection is associated with reduced endo/sarcoplasmic reticulum (ER/SR) stress. We found that H2S preconditioning significantly reduced myocardial infarct size, preserved left ventricular function, and inhibited I/R-induced cardiomyocyte apoptosis in vivo. Furthermore, H2S preconditioning significantly attenuated I/R-induced ER/SR stress responses, including the increased expression of glucose-regulated protein 78, C/EBP homologous protein, and activate transcription factor in myocardium. Additionally, we demonstrate that H2S preconditioning attenuates ER/SR stress and inhibits cardiomyocyte apoptosis in an in vitro model of hypoxia/reoxygenation in rat H9c2 cardiac myocytes. In conclusion, these results suggest that H2S-attenuated ER/SR stress plays an important role in its protective effects against I/R-induced myocardial injury. PMID:26339339

  19. Assessment of Myocardial Ischemia in Obese Individuals Undergoing Physical Stress Echocardiography (PSE)

    PubMed Central

    Silveira, Mara Graziele Maciel; Sousa, Antônio Carlos Sobral; Santos, Marcos Antônio Almeida; Tavares, Irlaneide da Silva; Andrade, Stephanie Macedo; Melo, Luiza Dantas; de Andrade, Loren Suyane Oliveira; Santos, Emmanuel Lima Almeida; Oliveira, Joselina Luzia Menezes

    2015-01-01

    Background Physical stress echocardiography is an established methodology for diagnosis and risk stratification of coronary artery disease in patients with physical capacity. In obese (body mass index ≥ 30 kg/m2) the usefulness of pharmacological stress echocardiography has been demonstrated; however, has not been reported the use of physical stress echocardiography in this growing population group. Objective To assess the frequency of myocardial ischemia in obese and non-obese patients undergoing physical stress echocardiography and compare their clinical and echocardiographic differences. Methods 4,050 patients who underwent treadmill physical stress echocardiography were studied according to the Bruce protocol, divided into two groups: obese (n = 945; 23.3%) and non-obese (n = 3,105; 76.6%). Results There was no difference regarding gender. Obese patients were younger (55.4 ± 10.9 vs. 57.56 ± 11.67) and had a higher frequency of hypertension (75.2% vs. 57, 2%; p < 0.0001), diabetis mellitus (15.2% vs. 10.9%; p < 0.0001), dyslipidemia (59.5% vs 51.9%; p < 0.0001), family history of coronary artery disease (59.3% vs. 55.1%; p = 0.023) and physical inactivity (71.4% vs. 52.9%, p < 0.0001). The obese had greater aortic dimensions (3.27 vs. 3.14 cm; p < 0.0001), left atrium (3.97 vs. 3.72 cm; p < 0.0001) and the relative thickness of the ventricule (33.7 vs. 32.8 cm; p < 0.0001). Regarding the presence of myocardial ischemia, there was no difference between groups (19% vs. 17.9%; p = 0.41). In adjusted logistic regression, the presence of myocardial ischemia remained independently associated with age, female gender, diabetes and hypertension. Conclusion Obesity did not behave as a predictor of the presence of ischemia and the physical stress echocardiography. The application of this assessment tool in large scale sample demonstrates the feasibility of the methodology, also in obese. PMID:25714197

  20. Flos Puerariae Extract Prevents Myocardial Apoptosis via Attenuation Oxidative Stress in Streptozotocin-Induced Diabetic Mice

    PubMed Central

    Guo, Shuang; Cheng, Hongke; Wu, Jiliang; Liu, Chao

    2014-01-01

    Background Diabetic cardiomyopathy (DCM) suggests a direct cellular insult to myocardium. Apoptosis is considered as one of the hallmarks of DCM. Oxidative stress plays a key role in the pathogenesis of DCM. In this study, we explored the prevention of myocardial apoptosis by crude extract from Flos Puerariae (FPE) in experimental diabetic mice. Methods Experimental diabetic model was induced by intraperitoneally injection of streptozotocin (STZ, 50 mg/kg/day) for five consecutive days in C57BL/6J mice. FPE (100, 200 mg/kg) was orally administrated once a day for ten weeks. Cardiac structure changes, apoptosis, superoxide production, NADPH oxidase subunits expression (gp91phox, p47phox, and p67phox), and related regulatory factors were assessed in the heart of mice. Results Diabetic mice were characterized by high blood glucose (≥11.1 mmol/L) and reduced body weight. In the end of the experiment, aberrant myofilament structure, as well as TUNEL positive cardiac cells coupled with increased Bax/Bcl-2 ratio and Caspase-3 expression was found in diabetic mice. Moreover, ROS formation, the ratio of NADP+/NADPH and NADPH oxidase subunits expression of gp91phox and p47phox, lipid peroxidation level was significantly increased, while antioxidant enzyme SOD and GSH-Px activity were reduced in the myocardial tissue of diabetic mice. In contrast, treatment with FPE resulted in a normalized glucose and weight profile. FPE administration also preserved myocardial structure and reduced apoptotic cardiac cell death in diabetic mice. The elevated markers of oxidative stress were significantly reversed by FPE supplementation. Further, FPE treatment markedly inhibited the increased Bax/Bcl-2 ratio and Caspase-3 expression, as well as suppressed JNK and P38 MAPK activation in the heart of diabetic mice. Conclusions Our data demonstrate for the first time that FPE may have therapeutic potential for STZ-induced diabetic cardiomyopathy through preventing myocardial apoptosis via

  1. Low Intensity Physical Exercise Attenuates Cardiac Remodeling and Myocardial Oxidative Stress and Dysfunction in Diabetic Rats

    PubMed Central

    Gimenes, C.; Gimenes, R.; Rosa, C. M.; Xavier, N. P.; Campos, D. H. S.; Fernandes, A. A. H.; Cezar, M. D. M.; Guirado, G. N.; Cicogna, A. C.; Takamoto, A. H. R.; Okoshi, M. P.; Okoshi, K.

    2015-01-01

    We evaluated the effects of a low intensity aerobic exercise protocol on cardiac remodeling and myocardial function in diabetic rats. Wistar rats were assigned into four groups: sedentary control (C-Sed), exercised control (C-Ex), sedentary diabetes (DM-Sed), and exercised diabetes (DM-Ex). Diabetes was induced by intraperitoneal injection of streptozotocin. Rats exercised for 9 weeks in treadmill at 11 m/min, 18 min/day. Myocardial function was evaluated in left ventricular (LV) papillary muscles and oxidative stress in LV tissue. Statistical analysis was given by ANOVA or Kruskal-Wallis. Echocardiogram showed diabetic groups with higher LV diastolic diameter-to-body weight ratio and lower posterior wall shortening velocity than controls. Left atrium diameter was lower in DM-Ex than DM-Sed (C-Sed: 5.73 ± 0.49; C-Ex: 5.67 ± 0.53; DM-Sed: 6.41 ± 0.54; DM-Ex: 5.81 ± 0.50 mm; P < 0.05 DM-Sed vs C-Sed and DM-Ex). Papillary muscle function was depressed in DM-Sed compared to C-Sed. Exercise attenuated this change in DM-Ex. Lipid hydroperoxide concentration was higher in DM-Sed than C-Sed and DM-Ex. Catalase and superoxide dismutase activities were lower in diabetics than controls and higher in DM-Ex than DM-Sed. Glutathione peroxidase activity was lower in DM-Sed than C-Sed and DM-Ex. Conclusion. Low intensity exercise attenuates left atrium dilation and myocardial oxidative stress and dysfunction in type 1 diabetic rats. PMID:26509175

  2. Effects of modified pharmacologic stress approaches on hyperemic myocardial blood flow

    SciTech Connect

    Czernin, J.; Auerbach, M.; Sun, K.T.

    1995-04-01

    Pharmacologic stress testing with 0.56 mg/kg of intravenous dipyridamole is frequently used to noninvasively detect coronary artery disease (CAD). However, high-dose dipyridamole (0.80 mg/kg) or the combination of standard-dose dipyridamole (0.56 mg/kg) with the isometric handgrip maneuver might evoke a greater coronary hyperemic response. To evaluate the effect of modified pharmacologic stress tests, myocardial blood flow was quantified in 11 male subjects (mean age: 27 {plus_minus} 7 yr) during standard-dose dipyridamole (0.56 mg/kg), high-dose dipyridamole (0.80 mg/kg) and standard-dose dipyridamole combined with the isometric handgrip exercise using dynamic PET and a two-compartment model for {sup 13}N-ammonia. Systolic blood pressure, heart rate and rate pressure product remained unchanged from standard to high-dose dipyridamole but increased with the addition of the isometric handgrip. Myocardial blood flow was unchanged from standard to high-dose dipyridamole but was lower with the addition of the isometric handgrip. The hyperemic response induced by standard-dose dipyridamole cannot be further enhanced by high-dose dipyridamole. The addition of the isometric handgrip exercise results in a modest, but significant decline in hyperemic blood flow possibly due to increased extravascular resistive forces or an increase in a mediated coronary vasoconstriction associated with exercise. 31 refs., 2 figs., 1 tab.

  3. Association of statin use and stress-induced hyperglycemia in patients with acute ST-elevation myocardial infarction

    PubMed Central

    Yan, Chen; Qin, Ma; Juan, Yang S; Tao, Li Y; dong, Gao M; Zechun, Zeng; Chun, Yang X; Liang, Cong H; Yin, Liu

    2016-01-01

    Background Only a few information is available on the risk of stress hyperglycemia following acute myocardial infarction after statin use. We investigate the association of stress-induced hyperglycemia following statin use in patients with acute myocardial infarction. Methods An observational analysis of 476 consecutive patients who suffered acute myocardial infarction was carried out. All selected patients were divided into diabetes mellitus and non-diabetes based on the presence or absence of diabetes. The cardiac incidence of in-hospital and stress-induced hyperglycemia was recorded. Results Among patients with stress hyperglycemia in non-diabetes mellitus subgroups, the average fasting plasma glucose values in statin users were higher than in non-statin users (P < 0.05). But in diabetes mellitus subgroups, the average fasting plasma glucose did not have a significant difference between statin users and non-statin users (P > 0.05). In non-diabetes mellitus patients, the incidence of stress hyperglycemia with statin therapy was significantly higher than with non-statin therapy (P = 0.003). But in diabetes mellitus patients group, there is no significant difference in incidence of stress hyperglycemia between patients with statin therapy and patients without statin therapy (P = 0.902).The incidence of heart failure and in-hospital mortality of acute myocardial infarction in patients with stress-induced hyperglycemia was significantly higher than in non-hyperglycemia patients (P < 0.05). Conclusion Statins are related to higher stress hyperglycemia and cardiac incidences after acute myocardial infarction. PMID:27158481

  4. Evaluation of the prevalence of stress and its phases in acute myocardial infarction in patients active in the labor market

    PubMed Central

    Lucinda, Luciane Boreki; Prosdócimo, Ana Claudia Merchan Giaxa; de Carvalho, Katherine Athayde Teixeira; Francisco, Julio Cesar; Baena, Cristina Pellegrino; Olandoski, Marcia; do Amaral, Vivian Ferreira; Faria, José Rocha; Guarita-Souza, Luiz César

    2015-01-01

    Introduction Acute myocardial infarction is a social health problem of epidemiological relevance, with high levels of morbidity and mortality. Stress is one of the modifiable risk factors that triggers acute myocardial infarction. Stress is a result of a set of physiological reactions, which when exaggerated in intensity or duration can lead to imbalances in one's organism, resulting in vulnerability to diseases. Objective To identify the presence of stress and its phases in hospitalized and active labor market patients with unstable myocardial infarction and observe its correlation with the life of this population with stress. Methods The methodology used was a quantitative, descriptive and transversal research approach conducted with a total of 43 patients, who were still active in the labor market, presenting or not morbidities. Data collection occurred on the fourth day of their hospitalization and patients responded to Lipp's Stress Symptom Inventory for adults. Results Thirty-one patients (72.1%) presented stress and twelve (27.8%) did not. In patients with stress, the identified phases were: alert - one patient (3.2%); resistance -twenty-two patients (71.0%); quasi-exhaustion - six patients (19.4%) and exhaustion - two patients (6.5%). All women researched presented stress. Conclusion The results suggest a high level of stress, especially in the resistance phase, in the male infarcted population, hospitalized and active in the labor market. PMID:25859863

  5. Myocardial perfusion SPECT in a case of retropulmonary looping of left coronary artery in a baby after arterial switch surgery

    PubMed Central

    Padma, Subramanyam; Sundaram, Palaniswamy Shanmuga

    2014-01-01

    Pediatric myocardial perfusion imaging (MPI) is not a routine investigation in an Indian setting due to under referrals and logistic problems. However, MPI is a frequently performed and established modality of investigation in adults for the identification of myocardial ischemia and viability. We report myocardial perfusion scintigraphy in a case of retropulmonary looping of left coronary artery in a baby after arterial switch surgery. Adenosine stress MPI revealed a large infarct involving anterior segment with moderate reversible ischemia of the lateral left ventricular segment. Coronary angiogram later confirmed left main coronary artery ostial occlusion with retrograde collateral supply from dilated right coronary artery. PMID:24761067

  6. Cardiac-Specific Overexpression of Catalase Attenuates Paraquat-Induced Myocardial Geometric and Contractile Alteration: Role of ER Stress

    PubMed Central

    Ge, We; Zhang, Yingmei; Han, Xuefeng; Ren, Jun

    2010-01-01

    Paraquat, a quarternary nitrogen herbicide, is a highly toxic prooxidant resulting in multi-organ failure including the heart via generation of reactive oxygen species although the underlying mechanism has not been well elucidated. This study examined the influence of cardiac-specific overexpression of catalase, an antioxidant detoxifying H2O2, on paraquat-induced myocardial geometric and functional alterations, with a focus on ER stress. FVB and catalase transgenic mice were administrated paraquat for 48 hrs. Myocardial geometry, contractile function, apoptosis, and ER stress were evaluated using echocardiography, edge-detection, caspase-3 activity and immunoblotting. Our results revealed that paraquat treatment significantly enlarged LV end-diastolic and systolic diameters, increased LV mass and resting myocyte length, reduced fractional shortening, cardiomyocyte peak shortening, maximal velocity of shortening/relengthening and prolonged relengthening duration in FVB group. While catalase transgene itself did not alter myocardial geometry and function, it mitigated or significantly attenuated paraquat-elicited myocardial geometric and functional changes. Paraquat promoted overt apoptosis and ER stress as evidenced by increased caspase-3 activity, apoptosis and ER stress markers including Bax, Bcl-2, GADD153, calregulin and phosphorylation of JNK, IRE1α and eIF2α, all were ablated by catalase transgene. Paraquat-induced cardiomyocyte dysfunction was mitigated by the ER stress inhibitor tauroursodeoxycholic acid. Moreover, the JNK inhibitor SP600125 reversed paraquat-induced ER stress as evidenced by enhanced GADD153 and IRE1α phosphorylation. Taken together, these data revealed that catalase may rescue paraquat-induced myocardial geometric and functional alteration possibly via alleviating JNK-mediated ER stress. PMID:20937379

  7. Myocardial perfusion of infarcted and normal myocardium in propofol-anesthetized minipigs using (82)Rubidium PET.

    PubMed

    Rasmussen, Thomas; Follin, Bjarke; Kastrup, Jens; Christensen, Thomas Emil; Hammelev, Karsten Pharao; Kjær, Andreas; Hasbak, Philip

    2016-06-01

    Cardiac Rubidium-82 ((82)Rb) positron-emission-tomography (PET) is a good method for quantification of myocardial blood flow in man. Quantification of myocardial blood flow in animals to evaluate new treatment strategies or to understand underlying disease is also of great interest but raises some challenges. Animals, which have been anesthetized during PET acquisition, might react differently to used stress medications, and therefore difficulties might exist while evaluating the resulting PET images using standard software packages from commercial vendors optimized for human hearts. Furthermore propofol, used for anesthesia, can influence myocardial perfusion and coronary flow reserve due to its vasorelaxant effect, and interactions might exist between propofol and used stress agents, potentially affecting the result of the examination. We present cardiac (82)Rb-PET studies performed in propofol-anesthetized minipigs with normal and infarcted myocardium stressed with both adenosine and dipyridamole. Despite the mentioned challenges, we were able to trace the small minipig heart with software designed for human cardiac PET and to achieve blood flow measurements comparable with results in humans with both adenosine and dipyridamole. We found dipyridamole to be a superior stress agent for this experimental setup. Finally, we were able to clearly identify the myocardial perfusion defect after an induced myocardial infarction. PMID:26931633

  8. Chronic plus binge ethanol feeding induces myocardial oxidative stress, mitochondrial and cardiovascular dysfunction, and steatosis.

    PubMed

    Matyas, Csaba; Varga, Zoltan V; Mukhopadhyay, Partha; Paloczi, Janos; Lajtos, Tamas; Erdelyi, Katalin; Nemeth, Balazs T; Nan, Mintong; Hasko, Gyorgy; Gao, Bin; Pacher, Pal

    2016-06-01

    Alcoholic cardiomyopathy in humans develops in response to chronic excessive alcohol consumption; however, good models of alcohol-induced cardiomyopathy in mice are lacking. Herein we describe mouse models of alcoholic cardiomyopathies induced by chronic and binge ethanol (EtOH) feeding and characterize detailed hemodynamic alterations, mitochondrial function, and redox signaling in these models. Mice were fed a liquid diet containing 5% EtOH for 10, 20, and 40 days (d) combined with single or multiple EtOH binges (5 g/kg body wt). Isocalorically pair-fed mice served as controls. Left ventricular (LV) function and morphology were assessed by invasive pressure-volume conductance approach and by echocardiography. Mitochondrial complex (I, II, IV) activities, 3-nitrotyrosine (3-NT) levels, gene expression of markers of oxidative stress (gp91phox, p47phox), mitochondrial biogenesis (PGC1α, peroxisome proliferator-activated receptor α), and fibrosis were examined. Cardiac steatosis and fibrosis were investigated by histological/immunohistochemical methods. Chronic and binge EtOH feeding (already in 10 days EtOH plus single binge group) was characterized by contractile dysfunction (decreased slope of end-systolic pressure-volume relationship and preload recruitable stroke work), impaired relaxation (decreased time constant of LV pressure decay and maximal slope of systolic pressure decrement), and vascular dysfunction (impaired arterial elastance and lower total peripheral resistance). This was accompanied by enhanced myocardial oxidative/nitrative stress (3-NT; gp91phox; p47phox; angiotensin II receptor, type 1a) and deterioration of mitochondrial complex I, II, IV activities and mitochondrial biogenesis, excessive cardiac steatosis, and higher mortality. Collectively, chronic plus binge EtOH feeding in mice leads to alcohol-induced cardiomyopathies (National Institute on Alcohol Abuse and Alcoholism models) characterized by increased myocardial oxidative

  9. Acetyl salicylic acid protected against heat stress damage in chicken myocardial cells and may associate with induced Hsp27 expression.

    PubMed

    Wu, Di; Xu, Jiao; Song, Erbao; Tang, Shu; Zhang, Xiaohui; Kemper, N; Hartung, J; Bao, Endong

    2015-07-01

    We investigated whether acetyl salicylic acid (ASA) protects chicken myocardial cells from heat stress-mediated damage in vivo and whether the induction of Hsp27 expression is connected with this function. Pathological changes, damage-related enzyme levels, and Hsp27 expression were studied in chickens following heat stress (40 ± 1 °C for 0, 1, 2, 3, 5, 7, 10, 15, or 24 h, respectively) with or without ASA administration (1 mg/kg BW, 2 h prior). Appearance of pathological lesions such as degenerations and karyopyknosis as well as the myocardial damage-related enzyme activation indicated that heat stress causes considerable injury to the myocardial cells in vivo. Myocardial cell injury was most serious in chickens exposed to heat stress without prior ASA administration; meanwhile, ASA pretreatment acted protective function against high temperature-induced injury. Hsp27 expression was induced under all experimental conditions but was one-fold higher in the ASA-pretreated animals (0.3138 ± 0.0340 ng/mL) than in untreated animals (0.1437 ± 0.0476 ng/mL) 1 h after heat stress exposure, and such an increase was sustained over the length of the experiment. Our findings indicate that pretreatment with ASA protects chicken myocardial cells from acute heat stress in vivo with almost no obvious side effects, and this protection may involve an enhancement of Hsp27 expression. However, the detailed mechanisms underlying this effect require further investigation.

  10. Regulation of Cardiovascular Development by Adenosine and Adenosine-Mediated Embryo Protection

    PubMed Central

    Rivkees, Scott A.; Wendler, Christopher C.

    2012-01-01

    Few signaling molecules have the potential to influence the developing mammal as the nucleoside adenosine. Adenosine levels increase rapidly with tissue hypoxia and inflammation. Adenosine antagonists include the methlyxanthines caffeine and theophylline. The receptors that transduce adenosine action are the A1, A2a, A2b, and A3 adenosine receptors (ARs). We examined how adenosine acts via A1ARs to influence embryo development. Transgenic mice were studied along with embryo cultures. Embryos lacking A1ARs were markedly growth retarded following intrauterine hypoxia exposure. Studies of mice selectively lacking A1AR in the heart identify the heart as a key site of adenosines embryo protective effects. Studies of isolated embryos showed that adenosine plays a key role in modulating embryo cardiac function, especially in the setting of hypoxia. When pregnant mice were treated during embryogenesis with the adenosine antagonist caffeine, adult mice had abnormal heart function. Adenosine acts via A1ARs to play an essential role in protecting the embryo against intra uterine stress, and adenosine antagonists, including caffeine, may be an unwelcome exposure for the embryo. PMID:22423036

  11. Oxidative stress and redox regulation of phospholipase D in myocardial disease.

    PubMed

    Tappia, Paramjit S; Dent, Melissa R; Dhalla, Naranjan S

    2006-08-01

    Oxidative stress may be viewed as an imbalance between reactive oxygen species (ROS) and oxidant production and the state of glutathione redox buffer and antioxidant defense system. Recently, a new paradigm of redox signaling has emerged whereby ROS and oxidants can function as intracellular signaling molecules, where ROS- and oxidant-induced death signal is converted into a survival signal. It is now known that oxidative stress is involved in cardiac hypertrophy and in the pathogenesis of cardiomyopathies, ischemic heart disease and congestive heart failure. Phospholipase D (PLD) is an important signaling enzyme in mammalian cells, including cardiomyocytes. PLD catalyzes the hydrolysis of phosphatidylcholine to produce phosphatidic acid (PA). Two mammalian PLD isozymes, PLD1 and PLD2 have been identified, characterized and cloned. The importance of PA in heart function is evident from its ability to stimulate cardiac sarcolemmal membrane and sarcoplasmic reticular Ca2+-related transport systems and to increase the intracellular concentration of free Ca2+ in adult cardiomyocytes and augment cardiac contractile activity of the normal heart. In addition, PA is also considered an important signal transducer in cardiac hypertrophy. Accordingly, this review discusses a role for redox signaling mediated via PLD in ischemic preconditioning and examines how oxidative stress affects PLD in normal hearts and during different myocardial diseases. In addition, the review provides a comparative account on the regulation of PLD activities in vascular smooth muscle cells under conditions of oxidative stress. PMID:16843818

  12. Reversible T-wave inversions and neurogenic myocardial stunning in a patient with recurrent stress-induced cardiomyopathy.

    PubMed

    Akutsu, Yasushi; Kaneko, Kyouichi; Kodama, Yusuke; Li, Hui-Ling; Suyama, Jumpei; Toshida, Tsutomu; Kayano, Hiroyuki; Shinozuka, Akira; Gokan, Takehiko; Kobayashi, Youichi

    2014-05-01

    A 72-year-old female was diagnosed as a stress-induced cardiomyopathy from apical ballooning pattern of left ventricular dysfunction without coronary artery stenosis after the mental stress. ECG showed the transient T-wave inversions after the ST-segment elevations. By the mental stress after 1 year, she showed a transient dysfunction with similar ECG changes again. T-wave inversions recovered earlier, and cardiac sympathetic dysfunction showed a lighter response corresponding to the less severe dysfunction than those after the first onset. Wellens' ECG pattern was associated with the degree of neurogenic myocardial stunning with sympathetic hyperinnervation caused by mental stress. PMID:24147830

  13. Prediction of single versus multivessel disease following myocardial infarction using 201-thallium scintigraphy and electrocardiographic stress testing

    SciTech Connect

    Weiss, R.J.; Morise, A.P.; Raabe, D.S. Jr.; Sbarbaro, J.A.

    1983-11-01

    Fifty patients were evaluated who suffered a single myocardial infarction with graded electrocardiographic stress testing, 201-thallium myocardial perfusion imaging and coronary angiography to assess the role of noninvasive indices as predictors of single versus multivessel coronary artery disease. Multivessel involvement was defined angiographically as the presence of two or more major coronary arteries with at least a 70% intraluminal diameter narrowing. Multivessel disease was defined scintigraphically as the presence of stress and/or redistribution perfusion defects in the distribution of more than one coronary artery. The results of stress electrocardiography were not useful in differentiating patients with single (9/16 positive) versus multivessel (22/34 positive) disease. The degree of exercise-induced ST-segment depression was also not helpful. Stress 201-thallium imaging did offer limited additional information with correct predictions of multivessel disease in 21 of 26 patients. Predictions of single-vessel disease were accurate in 11 of 24 patients. Eleven of these 13 incorrect predictions of single-vessel disease were due to the relative insensitivity of the thallium stress image to perceive defect in the anterior wall when the left anterior descending artery had significant obstruction at catheterization. Further refinements of stress perfusion imaging are needed before this method can be used to reliably separate patients with single and multivessel disease after myocardial infarction.

  14. Stress thallium-201 myocardial scintigraphy for the detection of individual coronary arterial lesions in patients with and without previous myocardial infarction

    SciTech Connect

    Rigo, P.; Bailey, I.K.; Griffith, L.S.; Pitt, B.; Wagner, H.N. Jr.; Becker, L.C.

    1981-08-01

    The value of stress thallium-201 scintigraphy for detecting individual coronary arterial stenoses was analyzed in 141 patients with angiographically proved coronary artery disease, 101 with and 40 without a previous myocardial infarction. In patients without infarction, the sensitivity for detecting greater than 50 percent narrowing in the left anterior descending, the right and the left circumflex coronary artery was 66, 53 and 24 percent, respectively. In those with a previous infarction, the sensitivity for demonstrating disease in the artery corresponding to the site of infarction was 100 percent for the left anterior descending, 79 percent for the right and 63 percent for the left circumflex coronary artery. In patients with a prior anterior infarction, concomitant right or left circumflex coronary arterial lesions were detected in only 1 of 12 cases, whereas in those with previous inferior or inferolateral infarction, the sensitivity for left anterior descending coronary artery disease was 69 percent. Because of the reasonably high sensitivity for detecting left anterior descending arterial disease, irrespective of the presence and location of previous infarction, myocardial scintigraphy was useful in identifying multivessel disease in patients with a previous inferior infarction. However, because of its relative insensitivity for right or left circumflex coronary artery disease, scintigraphy proved to be a poor predictor of multivessel disease in patients with a prior anterior infarction and in patients without previous myocardial infarction.

  15. Intravenous myocardial contrast echocardiography predicts regional and global left ventricular remodelling after acute myocardial infarction: comparison with low dose dobutamine stress echocardiography

    PubMed Central

    Abe, Y; Muro, T; Sakanoue, Y; Komatsu, R; Otsuka, M; Naruko, T; Itoh, A; Yoshiyama, M; Haze, K; Yoshikawa, J

    2005-01-01

    Objective: To assess the role of intravenous myocardial contrast echocardiography (MCE) in predicting functional recovery and regional or global left ventricular (LV) remodelling after acute myocardial infarction (AMI) compared with low dose dobutamine stress echocardiography (LDSE). Methods: 21 patients with anterior AMI and successful primary angioplasty underwent MCE and LDSE during the subacute stage (2–4 weeks after AMI). Myocardial perfusion and contractile reserve were assessed in each segment (12 segment model) with MCE and LDSE. The 118 dyssynergic segments in the subacute stage were classified as recovered, unchanged, or remodelled according to wall motion at six months’ follow up. Percentage increase in LV end diastolic volume (%ΔEDV) was also calculated. Results: The presence of perfusion was less accurate than the presence of contractile reserve in predicting regional recovery (55% v 81%, p < 0.0001). However, the absence of perfusion was more accurate than the absence of contractile reserve in predicting regional remodelling (83% v 48%, p < 0.0001). The number of segments without perfusion was an independent predictor of %ΔEDV, whereas the number of segments without contractile reserve was not. The area under the receiver operating characteristic curve showed that the number of segments without perfusion predicted substantial LV dilatation (%ΔEDV > 20%) more accurately than did the number of segments without contractile reserve (0.88 v 0.72). Conclusion: In successfully revascularised patients with AMI, myocardial perfusion assessed by MCE is predictive of regional and global LV remodelling rather than of functional recovery, whereas contractile reserve assessed by LDSE is predictive of functional recovery rather than of LV remodelling. PMID:15797931

  16. Sequential changes of endoplasmic reticulum stress and apoptosis in myocardial fibrosis of diabetes mellitus-induced rats

    PubMed Central

    YANG, QIONG; GAO, HUIKUAN; DONG, RUIQING; WU, YONG-QUAN

    2016-01-01

    The endoplasmic reticulum (ER) is an organelle in which proteins form their appropriate structures. However, several of these proteins become unfolded or misfolded when exposed to stimuli, including hyperglycemia, oxidative stress, ischemia, disturbance of calcium homeostasis and overexpression of abnormal proteins, which activates ER stress and the unfolded protein response (UPR). To date, investigations have demonstrated that ER stress is important in diabetic myocardial fibrosis by inducing cardiac cell apoptosis. Therefore, in the present study, the polymerase chain reaction, western blotting analysis and tissue staining were performed to identify the changes in UPR signaling proteins and apoptotic proteins in diabetic rats at different time points, and to determine whether the myocardial fibrosis is associated with ER-stress-mediated apoptosis using a diabetes mellitus (DM) rat model. It was found that the upregulation of ER stress markers and apoptotic molecules developed over time. It was also demonstrated that anti-apoptotic markers and proapoptotic markers were activated early following model establishment, and then decreased in months 4 and 5. The changes in myocardial fibrosis were found to accelerate in a time-dependent manner with apoptosis in the DM rats. PMID:27121167

  17. The association of Hsp90 expression induced by aspirin with anti-stress damage in chicken myocardial cells

    PubMed Central

    Zhang, Xiao-hui; Zhu, Huai-sen; Qian, Zhuang; Tang, Shu; Wu, Di; Kemper, Nicole; Hartung, Joerg

    2016-01-01

    The protective effect of aspirin during exposure to heat stress in broiler chickens was investigated. We assayed pathological damage, expression and distribution of Hsp90 protein and hsp90 mRNA expression in chicken heart tissues after oral administration of aspirin following exposure to high temperature for varying times. Heat stress induced increases in plasma aspartate aminotransferase, creatine kinase and lactate dehydrogenase activities while causing severe heart damage, which was characterized by granular and vacuolar degeneration, nuclear shrinkage and even myocardium fragmentation in cardiac muscle fibers. After aspirin administration, myocardial cells showed fewer pathological lesions than broilers treated with heat alone. A high positive Hsp90 signal was always detected in the nuclei of myocardial cells from broilers treated with aspirin, while in myocardial cells treated with heat alone, Hsp90 in the nuclei decreased, as did that in the cytoplasm. Aspirin induced rapid and significant synthesis of Hsp90 before and at the initial phase of heat stress, and significant expression of hsp90 mRNA was stimulated throughout the experiment when compared with cells exposed to heat stress alone. Thus, specific pre-induction of Hsp90 in cardiovascular tissue was useful for resisting heat stress damage because it produced stable damage-related enzymes and fewer pathologic changes. PMID:27051338

  18. Oxidative stress contributes to the impaired sonic hedgehog pathway in type 1 diabetic mice with myocardial infarction

    PubMed Central

    XIAO, QING; YANG, YA; ZHAO, XIAO-YA; HE, LI-SHAN; QIN, YUAN; HE, YAN-HUA; ZHANG, GUI-PING; LUO, JIAN-DONG

    2015-01-01

    Our previous study demonstrated that an impaired sonic hedgehog (Shh) pathway contributed to cardiac dysfunction in type 1 diabetic mice with myocardial infarction (MI). The present study aimed to test the hypothesis that oxidative stress may contribute to the impaired Shh pathway and cardiac dysfunction in type 1 diabetic mice with MI. Streptozotocin-induced type 1 diabetic mice (C57/Bl6, male) and rat neonatal cardiomyocytes were used in the present study. Mice were randomly assigned to undergo ligation of the coronary artery or pseudosurgery. A potent antioxidant Tempol was administered in vivo and in vitro. Cardiac function was assessed by echocardiography, capillary density by immunohistochemisty, percentage of myocardial infarct using Massons trichrome staining, reactive oxygen species detection using dihydroethidium dye or 2,7-dichlorofluorescein diacetate probe and protein expression levels of the Shh pathway by western blot analysis. The antioxidant Tempol was shown to significantly increase myocardial protein expression levels of Shh and patched-1 (Ptc1) at 7–18 weeks and improved cardiac function at 18 weeks in type 1 diabetic mice, as compared with mice receiving no drug treatment. Furthermore, myocardial protein expression levels of Shh and Ptc1 were significantly upregulated on day 7 after MI, and capillary density was enhanced. In addition, the percentage area of myocardial infarct was reduced, and the cardiac dysfunction and survival rate were improved on day 21 in diabetic mice treated with Tempol. In vitro, treatment of rat neonatal cardiomyocytes with a mixture of xanthine oxidase and xanthine decreased protein expression levels of Shh and Ptc1 in a concentration-dependent manner, and Tempol attenuated this effect. These results indicate that oxidative stress may contribute to an impaired Shh pathway in type 1 diabetic mice, leading to diminished myocardial healing and cardiac dysfunction. Antioxidative strategies aimed at restoring the

  19. Reduction of oxidative stress does not affect recovery of myocardial function: warm continuous versus cold intermittent blood cardioplegia.

    PubMed Central

    Biagioli, B.; Borrelli, E.; Maccherini, M.; Bellomo, G.; Lisi, G.; Giomarelli, P.; Sani, G.; Toscano, M.

    1997-01-01

    OBJECTIVE: To compare oxidative stress after cardiac surgery in patients treated with two different methods of myocardial protection: warm continuous versus cold intermittent blood cardioplegia. To correlate oxidative stress with postoperative myocardial dysfunction. DESIGN: Prospective, randomised, double blind, trial. SETTING: Institutional centre of cardiovascular surgery. PATIENTS: 20 patients were selected for coronary artery bypass surgery (CABG) on the following basis: stable angina, ejection fraction > 50%, double or triple vessel disease, no previous CABG or associated disease. Patients were randomised to two groups of 10 patients each. INTERVENTIONS: Patients underwent CABG with one of two different methods of myocardial protection and cardiopulmonary bypass. CBC group: intermittent cold blood antegrade-retrograde cardioplegia with moderate hypothermic cardiopulmonary bypass; WBC group: continuous warm blood antegrade-retrograde cardioplegia with mild hypothermic cardiopulmonary bypass. MAIN OUTCOME MEASURE: The index of oxidative stress used was the alteration of whole blood and plasma glutathione redox status. Samples were collected from the coronary sinus and peripheral vein before anaesthesia (T1), before aortic unclamping (T2), 15 minutes (T3), and 30 minutes (T4) after unclamping. Haemodynamic parameters were measured with thermodilution techniques. RESULTS: Oxidised glutathione and glutathione-cysteine mixed disulphide significantly increased in the coronary sinus plasma in the CBC group, and the overall redox balance of glutathione was decreased (P < 0.01) at T2-T4 versus T1, and compared with the WBC group. Comparable results were obtained for coronary sinus blood. There was no correlation between postoperative haemodynamic measurements and oxidative stress markers. CONCLUSIONS: Oxidative stress was significant in patients undergoing CABG using cold blood cardioplegia, while the warm technique minimised the effects of ischaemia. However

  20. 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.

  1. 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.

  2. Stress-related symptoms and positive emotions after a myocardial infarction: a longitudinal analysis

    PubMed Central

    Castilla, Cristina; Vázquez, Carmelo

    2011-01-01

    Background There is a controversy as to whether the diagnostic umbrella of post-traumatic stress reactions is directly applicable to serious health conditions like myocardial infarction (MI). Objective The principal objective of this study was to examine longitudinally the prevalence of posttraumatic stress-related symptoms, throughout three measurement periods, for patients who had suffered a first MI. In addition to the analysis of symptoms related to stress and general distress, the presence of and temporary evolution of positive emotions and optimism in these patients was also evaluated. Design A longitudinal study with three periods of evaluation after the MI (Time 1 (T1): 48–72 hours, Time 2 (T2): 5 months, and Time 3 (T3): 13 months). Results In T1 few symptoms related to the stressful event were found. The probable prevalence of PTSD was 8–11% at 5 months after the MI and 0–3% 13 months after the event. With regard to subjective severity of the infarction, although in the first instance patients did not regard the event as excessively traumatic, in the periods T2 and T3 this perception increased significantly [F (2, 32)=20.00; p=0.0001]. At all times during the measurement period the mean positive affect was significantly greater than the negative affect. Conclusions As the results show, the probable prevalence of PTSD, as well as the severity of different symptom clusters, is low at all times of the evaluation. The diagnostic implications of these findings are discussed as well as the uses and abuses of diagnostic labels to characterize the psychological experiences lived through after a potentially life-threatening health problem. PMID:22893827

  3. Resilience as a correlate of acute stress disorder symptoms in patients with acute myocardial infarction

    PubMed Central

    Meister, Rebecca E; Weber, Tania; Princip, Mary; Schnyder, Ulrich; Barth, Jürgen; Znoj, Hansjörg; Schmid, Jean-Paul; von Känel, Roland

    2015-01-01

    Objectives Myocardial infarction (MI) may be experienced as a traumatic event causing acute stress disorder (ASD). This mental disorder has an impact on the daily life of patients and is associated with the development of post-traumatic stress disorder. Trait resilience has been shown to be a protective factor for post-traumatic stress disorder, but its association with ASD in patients with MI is elusive and was examined in this study. Methods We investigated 71 consecutive patients with acute MI within 48 h of having stable haemodynamic conditions established and for 3 months thereafter. All patients completed the Acute Stress Disorder Scale and the Resilience Scale to self-rate the severity of ASD symptoms and trait resilience, respectively. Results Hierarchical regression analysis showed that greater resilience was associated with lower symptoms of ASD independent of covariates (b=−0.22, p<0.05). Post hoc analysis revealed resilience level to be inversely associated with the ASD symptom clusters of re-experiencing (b=−0.05, p<0.05) and arousal (b=−0.09, p<0.05), but not with dissociation and avoidance. Conclusions The findings suggest that patients with acute MI with higher trait resilience experience relatively fewer symptoms of ASD during MI. Resilience was particularly associated with re-experiencing and arousal symptoms. Our findings contribute to a better understanding of resilience as a potentially important correlate of ASD in the context of traumatic situations such as acute MI. These results emphasise the importance of identifying patients with low resilience in medical settings and to offer them adequate support. PMID:26568834

  4. Renin Inhibition and AT1R blockade improve metabolic signaling, oxidant stress and myocardial tissue remodeling

    PubMed Central

    Whaley-Connell, Adam; Habibi, Javad; Rehmer, Nathan; Ardhanari, Sivakumar; Hayden, Melvin R; Pulakat, Lakshmi; Krueger, Caroline; M Ferrario, Carlos; DeMarco, Vincent G; Sowers, James R

    2013-01-01

    Objective Strategies that block angiotensin II actions on its angiotensin type 1 receptor or inhibit actions of aldosterone have been shown to reduce myocardial hypertrophy and interstitial fibrosis in states of insulin resistance. Thereby, we sought to determine if combination of direct renin inhibition with angiotensin type 1 receptor blockade in vivo, through greater reductions in systolic blood pressure (SBP) and aldosterone would attenuate left ventricular hypertrophy and interstitial fibrosis to a greater extent than either intervention alone. Materials/Methods We utilized the transgenic Ren2 rat which manifests increased tissue expression of murine renin which, in turn, results in increased renin-angiotensin system activity, aldosterone secretion and insulin resistance. Ren2 rats were treated with aliskiren, valsartan, the combination (aliskiren+valsartan), or vehicle for 21 days. Results Compared to Sprague-Dawley controls, Ren2 rats displayed increased systolic blood pressure, elevated serum aldosterone levels, cardiac tissue hypertrophy, interstitial fibrosis and ultrastructural remodeling. These biochemical and functional alterations were accompanied by increases in the NADPH oxidase subunit Nox2 and 3-nitrotyrosine content along with increases in mammalian target of rapamycin and reductions in protein kinase B phosphorylation. Combination therapy contributed to greater reductions in systolic blood pressure and serum aldosterone but did not result in greater improvement in metabolic signaling or markers of oxidative stress, fibrosis or hypertrophy beyond either intervention alone. Conclusions Thereby, our data suggest that the greater impact of combination therapy on reductions in aldosterone does not translate into greater reductions in myocardial fibrosis or hypertrophy in this transgenic model of tissue renin overexpression. PMID:23352204

  5. Elevated ejection-phase myocardial wall stress in children with chronic kidney disease.

    PubMed

    Gu, Haotian; Sinha, Manish D; Li, Ye; Simpson, John; Chowienczyk, Phil J

    2015-10-01

    Myocardial wall stress (MWS) is thought to be the mechanical stimulus to ventricular hypertrophy. The objective of this study was to examine whether MWS is elevated in children with chronic kidney disease (CKD) who are at high risk of developing adverse cardiovascular events related to left ventricular (LV) hypertrophy. MWS, a function of left ventricular pressure, myocardial wall volume, and cavity volume, was obtained using carotid tonometry to estimate ventricular pressure and 2-dimensional transthoracic echocardiographic wall-tracking to obtain LV cavity and wall volumes. Ninety-two children (50 boys) aged 11.2±3.2 (mean±SD) years, including healthy controls (n=16), and those with CKD disease divided into 3 groups according to estimated glomerular filtration rate (mL/min per 1.73 m2) >90 (CKD 1, n=26), 60 to 90(CKD 2, n=23), and <60 (CKD≥3, n=27) were studied. There was no significant difference in age, height, weight, central or peripheral blood pressure, LV mass, or mass index in the 4 study groups. By contrast, peak, mean, and end-systolic MWS were higher in children with CKD and increased across stages of CKD (peak MWS, 338.8±18.5 and 397.5±14.3 s/cm2 in controls and CKD≥3, respectively; P=0.01). Higher systolic MWS was explained by a form of LV dysfunction whereby dynamic values of the ratio of wall volume/cavity size during systole were lower in children with CKD than in those without (P=0.001). Children with CKD exhibit blood pressure–independent LV dysfunction which results in increased systolic MWS and which may predispose to LV hypertrophy in later life. PMID:26324503

  6. Regadenoson and adenosine are equivalent vasodilators and are superior than dipyridamole- a study of first pass quantitative perfusion cardiovascular magnetic resonance

    PubMed Central

    2013-01-01

    Background Regadenoson, dipyridamole and adenosine are commonly used vasodilators in myocardial perfusion imaging for the detection of obstructive coronary artery disease. There are few comparative studies of the vasodilator properties of regadenoson, adenosine and dipyridamole in humans. The specific aim of this study was to determine the relative potency of these three vasodilators by quantifying stress and rest myocardial perfusion in humans using cardiovascular magnetic resonance (CMR). Methods Fifteen healthy normal volunteers, with Framingham score less than 1% underwent vasodilator stress testing with regadenoson (400 μg bolus), dipyridamole (0.56 mg/kg) and adenosine (140 μg /kg/min) on separate days. Rest perfusion imaging was performed initially. Twenty minutes later, stress imaging was performed at peak vasodilation, i.e. 70 seconds after regadenoson, 4 minutes after dipyridamole infusion and between 3–4 minutes of the adenosine infusion. Myocardial blood flow (MBF) in ml/min/g and myocardial perfusion reserve (MPR) were quantified using a fully quantitative model constrained deconvolution. Results Regadenoson produced higher stress MBF than dipyridamole and adenosine (3.58 ± 0.58 vs. 2.81 ± 0.67 vs. 2.78 ± 0.61 ml/min/g, p = 0.0009 and p = 0.0008 respectively). Regadenoson had a much higher heart rate response than adenosine and dipyridamole respectively (95 ± 11 vs. 76 ± 13 vs. 86 ± 12 beats/ minute) When stress MBF was adjusted for heart rate, there were no differences between regadenoson and adenosine (37.8 ± 6 vs. 36.6 ± 4 μl/sec/g, p = NS), but differences between regadenoson and dipyridamole persisted (37.8 ± 6 vs. 32.6 ± 5 μl/sec/g, p = 0.03). The unadjusted MPR was higher with regadenoson (3.11 ± 0.63) when compared with adenosine (2.7 ± 0.61, p = 0.02) and when compared with dipyridamole (2.61 ± 0.57, p = 0.04). Similar to stress MBF, these differences in MPR between regadenoson and adenosine were abolished when adjusted

  7. [Early stress tests following an uncomplicated myocardial infarct: a comparison between symptom-limited and submaximal tests].

    PubMed

    López, J; Carrasco, H A; Portillo, S; Maldonado, Z; Monzón de Briceño, Y

    1991-01-01

    To compare the diagnostic and prognostic usefulness of symptom-limited versus load-limited submaximal stress testing, 76 patients, during the first week post acute non-complicated myocardial infarction, were submitted to a symptom-limited Naughton-modified protocol stress test. At 2 METs, 3 METs and maximal effort levels, the tests were classified as positive or negative following the currently used criteria. After a mean follow-up of 15 months, the symptom-limited protocol showed the best sensitivity (95%), specificity (78%), positive (64%) and negative (98%) predictive value, and also the highest risk ratio (27.4) for prediction of subsequent coronary events (2p less than 0.01 vs 2 METs, 3 METs and 2D-Echocardiogram results). Forward stepped multiple correlation analysis indicated independent prognostic value for the results of the symptom-limited stress test (R2: .52 p less than 0.01) and for the location of the myocardial infarction (R2: .05 p less than 0.05) only. In addition, the discriminant prognostic power of the symptom-limited protocol was significant after the fourth month of follow-up (2p less than 0.05 vs submaximal tests and 2D-Echo). Therefore, we recommend the performance of a symptom-limited stress test during the first week post acute non-complicated myocardial infarction, provided that all coronary active medication has been withheld 24 hours before the test.

  8. 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

  9. 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.

  10. Investigating real-time activation of adenosine receptors by bioluminescence resonance energy transfer technique

    NASA Astrophysics Data System (ADS)

    Huang, Yimei; Yang, Hongqin; Zheng, Liqin; Chen, Jiangxu; Wang, Yuhua; Li, Hui; Xie, Shusen

    2013-02-01

    Adenosine receptors play important roles in many physiological and pathological processes, for example regulating myocardial oxygen consumption and the release of neurotransmitters. The activations of adenosine receptors have been studied by some kinds of techniques, such as western blot, immunohistochemistry, etc. However, these techniques cannot reveal the dynamical response of adenosine receptors under stimulation. In this paper, bioluminescence resonance energy transfer technique was introduced to study the real-time activation of adenosine receptors by monitoring the dynamics of cyclic adenosine monophosphate (cAMP) level. The results showed that there were significant differences between adenosine receptors on real-time responses under stimulation. Moreover, the dynamics of cAMP level demonstrated that competition between adenosine receptors existed. Taken together, our study indicates that monitoring the dynamics of cAMP level using bioluminescence resonance energy transfer technique could be one potential approach to investigate the mechanism of competitions between adenosine receptors.

  11. INCREASED PULMONARY PRESSURES AND MYOCARDIAL WALL STRESS IN CHILDREN WITH SEVERE MALARIA*

    PubMed Central

    Janka, Jacqueline J.; Koita, Ousmane A.; Traoré, Broulaye; Traoré, Josépha M.; Mzayek, Fawaz; Sachdev, Vandana; Wang, Xunde; Sanogo, Kassoum; Sangaré, Lansana; Mendelsohn, Laurel; Masur, Henry; Kato, Gregory J.; Gladwin, Mark T.; Krogstad, Donald J.

    2011-01-01

    Background Chronic intravascular hemolysis leads to nitric oxide (NO) depletion and pulmonary hypertension in sickle cell disease. To test whether this pathophysiology occurs in malaria, we examined 53 children admitted to hospital with severe malaria (excluding cerebral malaria) and 31 age-matched controls in Mali. Methods Severity of hemolysis was assessed from plasma free hemoglobin (Hb) and arginase-1 levels. NO metabolism was assessed by whole blood nitrite levels and plasma NO consumption. Effects on the cardiovascular system and endothelial function were assessed by using echocardiography to measure peak tricuspid regurgitant jet velocity (TRV) and from plasma levels of N-terminal prohormone brain natriuretic peptide (NT-proBNP) and soluble vascular cell adhesion molecule-1 (sVCAM-1). Results Children with severe malaria had higher plasma Hb and arginase-1 levels, reduced whole blood nitrite levels and increased NO consumption relative to controls. They also had increased pulmonary arterial pressures (p < 0.05) with elevated levels of NT-proBNP and sVCAM-1 (p < 0.001). Conclusions Children with severe malaria have increased pulmonary pressures and myocardial wall stress. These complications are consistent with NO depletion from intravascular hemolysis, and indicate that the pathophysiologic cascade from intravascular hemolysis to NO depletion and its cardiopulmonary effects is activated in children with severe malaria. PMID:20662718

  12. Posttraumatic Stress and Myocardial Infarction Risk Perceptions in Hospitalized Acute Coronary Syndrome Patients

    PubMed Central

    Edmondson, Donald; Shaffer, Jonathan A.; Denton, Ellen-Ge; Shimbo, Daichi; Clemow, Lynn

    2012-01-01

    Posttraumatic stress disorder (PTSD) is related to acute coronary syndrome (ACS; i.e., myocardial infarction or unstable angina) recurrence and poor post-ACS adherence to medical advice. Since risk perceptions are a primary motivator of adherence behaviors, we assessed the relationship of probable PTSD to ACS risk perceptions in hospitalized ACS patients (n = 420). Participants completed a brief PTSD screen 3–7 days post-ACS, and rated their 1-year ACS recurrence risk relative to other men or women their age. Most participants exhibited optimistic bias (mean recurrence risk estimate between “average” and “below average”). Further, participants who screened positive for current PTSD (n = 15) showed significantly greater optimistic bias than those who screened negative (p < 0.05), after adjustment for demographics, ACS severity, medical comorbidities, depression, and self-confidence in their ability to control their heart disease. Clinicians should be aware that psychosocial factors, and PTSD in particular, may be associated with poor adherence to medical advice due to exaggerated optimistic bias in recurrence risk perceptions. PMID:22593749

  13. Permanent stress may be the trigger of an acute myocardial infarction on the first work-day of the week.

    PubMed

    Bodis, Jozsef; Boncz, Imre; Kriszbacher, Ildiko

    2010-10-29

    Numerous studies have reported the weekly variation of an acute myocardial infarction. The Monday peek has been connected with higher rate of physical and mental, work-related stress. We wished to study the weekly variation of an acute myocardial infarction (AMI) in the group of workers and pensioners, and to find out whether National Holidays on the first day of the week could influence the weekly rhythm of an acute myocardial infarction. We carried out the retrospective analysis of patients admitted to Hungarian hospitals with the diagnose of an AMI (n=90,187) between 2002 and 2007. According to the morbidity data of an AMI, the weekly peek was detected on the first work-day of the week, showing a gradually decreasing tendency until the end of the week. Morbidity rates on Mondays being National Holidays were similar to the number of events on Saturdays and Sundays (Z=-24,431; p<0.001). There was a significant difference between the number of events on work-days and weekends (Z=-27,321; p<0.001). No marked difference was found between workers under the age of 65 and pensioners above the age of 65, or between the two sexes. The results of our study reveal that the occurrence of an AMI shows characteristic changes throughout the days of the week, and the first work-days of the week may be related to higher incidence of an acute myocardial infarction. PMID:19345426

  14. Effects of a New Glutamic Acid Derivative on Myocardial Contractility of Stressed Animals under Conditions of Nitric Oxide Synthesis Blockade.

    PubMed

    Tyurenkov, I N; Perfilova, V N; Sadikova, N V; Berestovitskaya, V M; Vasil'eva, O S

    2015-07-01

    Glufimet (glutamic acid derivative) in a dose of 28.7 mg/kg limited the reduction of the cardiac functional reserve in animals subjected to 24-h stress under conditions of nonselective NO synthase blockade with L-NAME (10 mg/kg). Adrenoreactivity and increased afterload tests showed that the increment of myocardial contraction/relaxation rates, left-ventricular pressure, and HR were significantly higher in glufimet-treated stressed animals with NO synthesis blockade than in animals which received no glufimet. The efficiency of glufimet was higher than that of phenibut (the reference drug).

  15. Heme Oxygenase-1 Induction Improves Cardiac Function following Myocardial Ischemia by Reducing Oxidative Stress

    PubMed Central

    Issan, Yossi; Kornowski, Ran; Aravot, Dan; Shainberg, Asher; Laniado-Schwartzman, Michal; Sodhi, Komal; Abraham, Nader G.; Hochhauser, Edith

    2014-01-01

    Background Oxidative stress plays a key role in exacerbating diabetes and cardiovascular disease. Heme oxygenase-1 (HO-1), a stress response protein, is cytoprotective, but its role in post myocardial infarction (MI) and diabetes is not fully characterized. We aimed to investigate the protection and the mechanisms of HO-1 induction in cardiomyocytes subjected to hypoxia and in diabetic mice subjected to LAD ligation. Methods In vitro: cultured cardiomyocytes were treated with cobalt-protoporphyrin (CoPP) and tin protoporphyrin (SnPP) prior to hypoxic stress. In vivo: CoPP treated streptozotocin-induced diabetic mice were subjected to LAD ligation for 2/24 h. Cardiac function, histology, biochemical damage markers and signaling pathways were measured. Results HO-1 induction lowered release of lactate dehydrogenase (LDH) and creatine phospho kinase (CK), decreased propidium iodide staining, improved cell morphology and preserved mitochondrial membrane potential in cardiomyocytes. In diabetic mice, Fractional Shortening (FS) was lower than non-diabetic mice (35±1%vs.41±2, respectively p<0.05). CoPP-treated diabetic animals improved cardiac function (43±2% p<0.01), reduced CK, Troponin T levels and infarct size compared to non-treated diabetic mice (P<0.01, P<0.001, P<0.01 respectively). CoPP-enhanced HO-1 protein levels and reduced oxidative stress in diabetic animals, as indicated by the decrease in superoxide levels in cardiac tissues and plasma TNFα levels (p<0.05). The increased levels of HO-1 by CoPP treatment after LAD ligation led to a shift of the Bcl-2/bax ratio towards the antiapoptotic process (p<0.05). CoPP significantly increased the expression levels of pAKT and pGSK3β (p<0.05) in cardiomyocytes and in diabetic mice with MI. SnPP abolished CoPP's cardioprotective effects. Conclusions HO-1 induction plays a role in cardioprotection against hypoxic damage in cardiomyocytes and in reducing post ischemic cardiac damage in the diabetic heart as proved by

  16. Energetic myocardial metabolism and oxidative stress: let's make them our friends in the fight against heart failure.

    PubMed

    Scolletta, Sabino; Biagioli, Bonizella

    2010-03-01

    Heart failure (HF) is a syndrome causing a huge burden in morbidity and mortality worldwide. Current medical therapies for HF are aimed at suppressing the neurohormonal activation. However, novel therapies are needed for HF, independent of the neurohormonal axis, that can improve cardiac performance and prevent the progression of heart dysfunction. The modulation of cardiac metabolism may represent a new approach to the treatment of HF. The healthy heart converts chemical energy stored in fatty acids (FA) and glucose. Utilization of FA costs more oxygen per unit of ATP generated than glucose, and the heart gets 60-90% of its energy for oxidative phosphorylation from FA oxidation. The failing heart has been demonstrated to be metabolically abnormal, in both animal models and in patients, showing a shift toward an increased glucose uptake and utilization. The manipulation of myocardial substrate oxidation toward greater carbohydrate oxidation and less FA oxidation may improve ventricular performance and slow the progression of heart dysfunction. Impaired mitochondrial function and oxidative phosphorylation can reduce cardiac function by providing an insufficient supply of ATP to cardiomyocytes and by increasing myocardial oxidative stress. Although there are no effective stimulators of oxidative phosphorylation, several classes of drugs have been shown to open mitochondrial K(ATP) channels and, indirectly, to improve cardiac protection against oxidative stress. This article focuses on the energetic myocardial metabolism and oxidative status in the normal and failing heart, and briefly, it overviews the therapeutic potential strategies to improve cardiac energy and oxidative status in HF patients.

  17. Eplerenone attenuates cardiac dysfunction and oxidative stress in β-receptor stimulated myocardial infarcted rats

    PubMed Central

    Reddy, Navya M; Mahajan, Umesh B; Patil, Chandragouda R; Agrawal, Yogeeta O; Ojha, Shreesh; Goyal, Sameer N

    2015-01-01

    Eplerenone is a competitive antagonist of the aldosterone receptor with an additional PI3K-Akt activity. The existing cram has been intended to explore, whether eplerenone treatment attenuates the expansion of myocardial infarction in isoproterenol treated rats by restoring hemodynamic, biochemical, and histopathological changes. Isoproterenol induced cardiotoxicity was evidenced by marked ST elevation, decrease in systolic, diastolic, mean arterial pressures. Maximal positive rate of developed left ventricular pressure (+LVdP/dt max, a indicator of myocardial contraction), maximal negative rate of developed left ventricular pressure (-LVdP/dt max, a meter of myocardial relaxation) and an increase in left ventricular end-diastolic pressure (LVEDP, a marker of pre-load) were also shown. In addition, a significant reduction in activities of myocardial creatine kinase-MB isoenzyme, lactate dehydrogenase, superoxide dismutase, catalase, and reduced glutathione level along with increase in malondialdehyde content were observed. Oral pre-treatment with eplerenone (50, 100 and 150 mg/kg) daily for a period of 14 days, constructively modulated the studied parameters in isoproterenol-induced myocardial injury. The protective role of eplerenone on isoproterenolinduced myocardial damage was further confirmed by histopathological examinations. Eplerenone at doses of 100 mg/kg and 150 mg/kg produced more pronounced protective effects than 50 mg/kg body weight. Together, our study provides evidence for protective effects of eplerenone on myocardium in experimentally induced myocardial infarction. PMID:26550459

  18. Eplerenone attenuates cardiac dysfunction and oxidative stress in β-receptor stimulated myocardial infarcted rats.

    PubMed

    Reddy, Navya M; Mahajan, Umesh B; Patil, Chandragouda R; Agrawal, Yogeeta O; Ojha, Shreesh; Goyal, Sameer N

    2015-01-01

    Eplerenone is a competitive antagonist of the aldosterone receptor with an additional PI3K-Akt activity. The existing cram has been intended to explore, whether eplerenone treatment attenuates the expansion of myocardial infarction in isoproterenol treated rats by restoring hemodynamic, biochemical, and histopathological changes. Isoproterenol induced cardiotoxicity was evidenced by marked ST elevation, decrease in systolic, diastolic, mean arterial pressures. Maximal positive rate of developed left ventricular pressure (+LVdP/dt max, a indicator of myocardial contraction), maximal negative rate of developed left ventricular pressure (-LVdP/dt max, a meter of myocardial relaxation) and an increase in left ventricular end-diastolic pressure (LVEDP, a marker of pre-load) were also shown. In addition, a significant reduction in activities of myocardial creatine kinase-MB isoenzyme, lactate dehydrogenase, superoxide dismutase, catalase, and reduced glutathione level along with increase in malondialdehyde content were observed. Oral pre-treatment with eplerenone (50, 100 and 150 mg/kg) daily for a period of 14 days, constructively modulated the studied parameters in isoproterenol-induced myocardial injury. The protective role of eplerenone on isoproterenolinduced myocardial damage was further confirmed by histopathological examinations. Eplerenone at doses of 100 mg/kg and 150 mg/kg produced more pronounced protective effects than 50 mg/kg body weight. Together, our study provides evidence for protective effects of eplerenone on myocardium in experimentally induced myocardial infarction.

  19. MnSODtg Mice Control Myocardial Inflammatory and Oxidative Stress and Remodeling Responses Elicited in Chronic Chagas Disease

    PubMed Central

    Dhiman, Monisha; Wan, Xianxiu; Popov, Vsevolod L.; Vargas, Gracie; Garg, Nisha Jain

    2013-01-01

    Background We utilized genetically modified mice equipped with a variable capacity to scavenge mitochondrial and cellular reactive oxygen species to investigate the pathological significance of oxidative stress in Chagas disease. Methods and Results C57BL/6 mice (wild type, MnSODtg, MnSOD+/−, GPx1−/−) were infected with Trypanosoma cruzi and harvested during the chronic disease phase. Chronically infected mice exhibited a substantial increase in plasma levels of inflammatory markers (nitric oxide, myeloperoxidase), lactate dehydrogenase, and myocardial levels of inflammatory infiltrate and oxidative adducts (malondialdehyde, carbonyls, 3‐nitrotyrosine) in the order of wild type=MnSOD+/−>GPx1−/−>MnSODtg. Myocardial mitochondrial damage was pronounced and associated with a >50% decline in mitochondrial DNA content in chronically infected wild‐type and GPx1−/− mice. Imaging of intact heart for cardiomyocytes and collagen by the nonlinear optical microscopy techniques of multiphoton fluorescence/second harmonic generation showed a significant increase in collagen (>10‐fold) in chronically infected wild‐type mice, whereas GPx1−/− mice exhibited a basal increase in collagen that did not change during the chronic phase. Chronically infected MnSODtg mice exhibited a marginal decline in mitochondrial DNA content and no changes in collagen signal in the myocardium. P47phox−/− mice lacking phagocyte‐generated reactive oxygen species sustained a low level of myocardial oxidative stress and mitochondrial DNA damage in response to Trypanosoma cruzi infection. Yet chronically infected p47phox−/− mice exhibited increase in myocardial inflammatory and remodeling responses, similar to that noted in chronically infected wild‐type mice. Conclusions Inhibition of oxidative burst of phagocytes was not sufficient to prevent pathological cardiac remodeling in Chagas disease. Instead, enhancing the mitochondrial reactive oxygen species scavenging

  20. Periostin expression induced by oxidative stress contributes to myocardial fibrosis in a rat model of high salt-induced hypertension

    PubMed Central

    WU, HAN; CHEN, LIANG; XIE, JUN; LI, RAN; LI, GUAN-NAN; CHEN, QIN-HUA; ZHANG, XIN-LIN; KANG, LI-NA; XU, BIAO

    2016-01-01

    Periostin is an extracellular matrix protein involved in fibrosis. The present study investigated the importance of periostin in hypertension-induced myocardial fibrosis. Rats were randomly divided into either the normal group (0.4% NaCl diet; n=8) or hypertension group (8% NaCl diet; n=8). For 36 weeks, the blood pressure and heart rate of the rats were monitored. At week 36, the hearts were extracted for further analysis. Masson's staining and western blotting were performed to determine the levels of periostin protein expression, oxidative stress and fibrosis. In addition, fibroblasts were isolated from adult rats and cultured in vitro, and following treatment with angiotensin II (Ang II) and N-acetyl-L-cysteine (NAC), western blotting, immunofluorescence and 2′,7′ dichlorodihydrofluorescin staining were performed to examine reactive oxygen species production, and periostin and α-smooth muscle actin (α-SMA) expression levels. The results demonstrated that periostin expression and oxidative stress were increased in hypertensive hearts compared with normal hearts. The in vitro experiments demonstrated that Ang II upregulated the expression levels of periostin and α-SMA compared with the control, whereas, pretreatment with NAC inhibited oxidative stress, periostin and α-SMA expression in fibroblasts. In conclusion, the results of the current study suggested that oxidative stress-induced periostin is involved in myocardial fibrosis and hypertension. The present study demonstrated that periostin inhibition may be a promising approach for the inhibition of hypertension-induced cardiac remodeling. PMID:27220372

  1. 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

  2. The interactive association between heat shock factor 1 and heat shock proteins in primary myocardial cells subjected to heat stress.

    PubMed

    Tang, Shu; Chen, Hongbo; Cheng, Yanfen; Nasir, Mohammad Abdel; Kemper, Nicole; Bao, Endong

    2016-01-01

    Heat shock factor 1 (HSF1) is a heat shock transcription factor that rapidly induces heat shock gene transcription following thermal stress. In this study, we subjected primary neonatal rat myocardial cells to heat stress in vitro to create a model system for investigating the trends in expression and association between various heat shock proteins (HSPs) and HSF1 under adverse environmental conditions. After the cells were subjected to heat stress at 42˚C for different periods of time, HSP and HSF1 mRNA and protein levels were detected by qPCR and western blot analysis in the heat-stressed cells. The HSF1 expression levels significantly increased in the cells following 120 min of exposure to heat stess compared to the levels observed at the beginning of heat stress exposure. HSP90 followed a similar trend in expression to HSF1, whereas HSP70 followed an opposite trend. However, no significant changes were observed in the crystallin, alpha B (CRYAB, also known as HSP beta-5) expression levels during the 480‑min period of exposure to heat stress. The interaction between the HSPs and HSF1 was analyzed by STRING 9.1, and it was found that HSF1 interacted with HSP90 and HSP70, and that it did not play a role in regulating CRYAB expression. Based on our findings, HSP70 may suppress HSF1 in rat myocardial cells under conditions of heat stress. Furthermore, our data demonstrate that HSF1 is not the key factor for all HSPs, and this was particularly the case for CRYAB.

  3. Assessment of myocardial viability in patients with acute myocardial infarction by two-dimensional speckle tracking echocardiography combined with low-dose dobutamine stress echocardiography.

    PubMed

    Gong, Lei; Li, Dongye; Chen, Junhong; Wang, Xiaoping; Xu, Tongda; Li, Wenhua; Ren, Shaoyang; Wang, Cheng

    2013-06-01

    It is clinically important to determine the myocardial viability of regional wall motion abnormality segments in patients with acute myocardial infarction (AMI). The purpose of this study was to ascertain the ability and value of a combination of speckle tracking echocardiography (STE) and low dose dobutamine stress echocardiography (LDDSE) for the evaluation of viable myocardium in patients with AMI. Forty-two hospitalized patients with AMI and left ventricular systolic dysfunction (left ventricular ejection fraction <50%) were underwent STE in conjunction with LDDSE and dual isotope simultaneous acquisition single photon emission computed tomography (DISA-SPECT). Percutaneous coronary intervention (PCI) was performed subsequently in all patients. STE was used to measure radial, circumferential, and longitudinal end-systolic strain and peak systolic strain rate. The movement of each segment was observed by routine echocardiography 1, 3, and 6 months after PCI, and its improvement over time was the criterion of viable myocardium. The sensitivity, specificity and accuracy of DISA-SPECT for the assessment of viable myocardium were 83.6, 74.4, and 80.7%, respectively. Among the radial, circumferential, and longitudinal strain and strain rate parameters, only longitudinal strain (LS) and longitudinal strain rate (LSr) at rest and LDDSE emerged as independent predictors of viable myocardium, When combining LS and LSr at LDDSE, the sensitivity, specificity and accuracy for the assessment of viable myocardium rose to 89.8, 90.2 and 89.9%, respectively. The sensitivity of STE in conjunction with LDDSE was similar to DISA-SPECT for detecting viable myocardium in patients with AMI, but the specificity and accuracy of STE performed with LDDSE were higher than DISA-SPECT.

  4. Harnessing nature's own cardiac defense mechanism with acadesine, an adenosine regulating agent: importance of the endothelium.

    PubMed

    Engler, R L

    1994-05-01

    Although the effects of adenosine on the heart, including the clinical suppression of cardiac arrhythmias, have been recognized for more than half a century, it is only in the last decade that the therapeutic potential of adenosine has been recognized. Research related to the clinical application of adenosine has concentrated on two areas. The first came directly from early observations about the use of adenosine in treating cardiac arrhythmias, in particular supraventricular tachycardias. The second relates to the use of adenosine to protect the heart from the deleterious consequences of myocardial ischemia and reperfusion. This review will focus on the latter cardioprotective properties of adenosine, particularly those shown by a novel group of drugs termed adenosine regulating agents, the prototype of which is acadesine (Protara).

  5. 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. PMID:26830261

  6. 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

  7. 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

  8. Attenuation by creatine of myocardial metabolic stress in Brattleboro rats caused by chronic inhibition of nitric oxide synthase.

    PubMed

    Constantin-Teodosiu, D; Greenhaff, P L; Gardiner, S M; Randall, M D; March, J E; Bennett, T

    1995-12-01

    1. The present experiment was undertaken to investigate: (a) the effect of nitric oxide synthase (NOS) inhibition, mediated by oral supplementation of the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on measures of myocardial energy metabolism and function: (b) the effect of oral creatine supplementation on these variables, in the absence and presence of L-NAME. 2. In one series of experiments, 4 weeks oral administration of L-NAME (0.05 mg ml-1 day-1 in the drinking water) to Brattleboro rats caused significant reductions in myocardial ATP, creatine, and total creatine concentrations and an accumulation of tissue lactate when compared with control animals. Administration of creatine (0.63 mg ml-1 day-1 in the drinking water) for 4 weeks elevated myocardial creatine and total creatine concentrations and reduced lactate accumulation, but did not significantly affect ATP or phosphocreatine (PCr). Concurrent treatment with creatine and L-NAME prevented the reduction in creatine and total creatine concentrations, and significantly attenuated the accumulation of lactate and the reduction in ATP seen with L-NAME alone. 3. In a second series of experiments, 4 weeks treatment with L-NAME and creatine plus L-NAME increased mean arterial blood pressure in conscious Brattleboro rats. Hearts isolated from these animals showed decreased coronary flow and left ventricular developed pressure (LVDP), and total mechanical performance. Treatment with creatine alone had no measurable effect on either mean arterial blood pressure or coronary flow in isolated hearts. However, there was an increase in LVDP, but not in total mechanical performance, because there was a bradycardia. 4. These results indicate that creatine supplementation can attenuate the metabolic stress associated with L-NAME administration and that this effect occurs as a consequence of the action of creatine on myocardial energy metabolism.

  9. In vivo levels of diadenosine tetraphosphate and adenosine tetraphospho-guanosine in Physarum polycephalum during the cell cycle and oxidative stress.

    PubMed Central

    Garrison, P N; Mathis, S A; Barnes, L D

    1986-01-01

    Cellular levels of diadenosine tetraphosphate (Ap4A) and adenosine tetraphospho-guanosine (Ap4G) were specifically measured during the cell cycle of Physarum polycephalum by a high-pressure liquid chromatographic method. Ap4A was also measured indirectly by a coupled phosphodiesterase-luciferase assay. No cell cycle-specific changes in either Ap4A or Ap4G were detected in experiments involving different methods of assay, different strains of P. polycephalum, or different methods of fixation of macroplasmodia. Our results on Ap4A are in contrast with those reported previously (C. Weinmann-Dorsch, G. Pierron, R. Wick, H. Sauer, and F. Grummt, Exp. Cell Res. 155:171-177, 1984). Weinmann-Dorsch et al. reported an 8- to 30-fold increase in Ap4A in early S phase in P. polycephalum, as measured by the phosphodiesterase-luciferase assay. We also measured levels of Ap4A, Ap4G, and ATP in macroplasmodia treated with 0.1 mM dinitrophenol. Ap4A and Ap4G transiently increased three- to sevenfold after 1 h and then decreased concomitantly with an 80% decrease in the level of ATP after 2 h in the presence of dinitrophenol. These results do not support the hypothesis that Ap4A is a positive pleiotypic activator that modulates DNA replication, but they are consistent with the hypothesis proposed for procaryotes that Ap4A and Ap4G are signal nucleotides or alarmones of oxidative stress (B.R. Bochner, P.C. Lee, S.W. Wilson, C.W. Cutler, and B.N. Ames, Cell 37:225-232, 1984). PMID:3785160

  10. Low-fat diet and regular, supervised physical exercise in patients with symptomatic coronary artery disease: reduction of stress-induced myocardial ischemia

    SciTech Connect

    Schuler, G.; Schlierf, G.; Wirth, A.; Mautner, H.P.; Scheurlen, H.; Thumm, M.; Roth, H.; Schwarz, F.; Kohlmeier, M.; Mehmel, H.C.

    1988-01-01

    The effects of physical exercise and normalization of serum lipoproteins on stress-induced myocardial ischemia were studied in 18 patients with coronary artery disease, stable angina pectoris, and mild hypercholesterolemia (total serum cholesterol 242 +/- 32 mg/dl). These patients underwent a combined regimen of low-fat/low-cholesterol diet and regular, supervised physical exercise at high intensity for 12 months. At 1 year serum lipoproteins has been lowered to ideal levels (serum cholesterol 202 +/- 31 mg/dl, low-density lipoproteins 130 +/- 30 mg/dl, very low-density lipoproteins 22 +/- 15 mg/dl, serum triglycerides 105 (69 to 304) mg/dl) and physical work capacity was improved by 21% (p less than .01). No significant effect was noted on high-density lipoproteins, probably as a result of the low-fat/high-carbohydrate diet. Stress-induced myocardial ischemia, as assessed by thallium-201 scintigraphy, was decreased by 54% (p less than .05) despite higher myocardial oxygen consumption. Eighteen patients matched for age and severity of coronary artery disease served as a control group and ''usual medical care'' was rendered by their private physicians. No significant changes with respect to serum lipoproteins, physical work capacity, maximal rate-pressure product, or stress-induced myocardial ischemia were observed in this group. These data indicate that regular physical exercise at high intensity, lowered body weight, and normalization of serum lipoproteins may alleviate compromised myocardial perfusion during stress.

  11. Doxorubicin induced myocardial injury is exacerbated following ischaemic stress via opening of the mitochondrial permeability transition pore

    SciTech Connect

    Gharanei, M.; Hussain, A.; Janneh, O.; Maddock, H.L.

    2013-04-15

    Chemotherapeutic agents such as doxorubicin are known to cause or exacerbate cardiovascular cell death when an underlying heart condition is present. However, the mechanism of doxorubicin-induced cardiotoxicity is unclear. Here we assess the cardiotoxic effects of doxorubicin in conditions of myocardial ischaemia reperfusion and the mechanistic basis of protection, in particular the role of the mitochondrial permeability transition pore (mPTP) in such protection. The effects of doxorubicin (1 μM) ± cyclosporine A (CsA, 0.2 μM; inhibits mPTP) were investigated in isolated male Sprague–Dawley rats using Langendorff heart and papillary muscle contraction models subjected to simulated ischaemia and reperfusion injury. Isolated rat cardiac myocytes were used in an oxidative stress model to study the effects of drug treatment on mPTP by confocal microscopy. Western blot analysis evaluated the effects of drug treatment on p-Akt and p-Erk 1/2 levels. Langendorff and the isometric contraction models showed a detrimental effect of doxorubicin throughout reperfusion/reoxygenation as well as increased p-Akt and p-Erk levels. Interestingly, CsA not only reversed the detrimental effects of doxorubicin, but also reduced p-Akt and p-Erk levels. In the sustained oxidative stress assay to study mPTP opening, doxorubicin decreased the time taken to depolarization and hypercontracture, but these effects were delayed in the presence of CsA. Collectively, our data suggest for the first that doxorubicin exacerbates myocardial injury in an ischaemia reperfusion model. If the inhibition of mPTP ameliorates the cardiotoxic effects of doxorubicin, then more selective inhibitors of mPTP should be further investigated for their utility in patients receiving doxorubicin. - Highlights: ► Doxorubicin exacerbates myocardial ischaemia reperfusion injury. ► Co-treatment with CsA protects against doxorubicin induced myocardial injury. ► CsA delays doxorubicin induced mPTP opening in laser

  12. Sex Differences in Perceived Stress and Early Recovery in Young and Middle-Aged Patients with Acute Myocardial Infarction

    PubMed Central

    Xu, Xiao; Bao, Haikun; Strait, Kelly; Spertus, John A.; Lichtman, Judith H; D’Onofrio, Gail; Spatz, Erica; Bucholz, Emily M.; Geda, Mary; Lorenze, Nancy P.; Bueno, Héctor; Beltrame, John F.; Krumholz, Harlan M.

    2015-01-01

    Background Younger age and female sex are both associated with greater mental stress in the general population, but limited data exist on status of perceived stress in young and middle-aged patients presenting with acute myocardial infarction (AMI). Methods and Results We examined sex difference in stress, contributing factors to such difference, and whether this difference helps explain sex-based disparities in 1-month recovery using data from 3,572 AMI patients (2,397 women and 1,175 men) 18–55 years of age. The average score of 14-item Perceived Stress Scale (PSS-14) at baseline was 23.4 for men and 27.0 for women (p<0.001). Higher stress in women was largely explained by sex differences in comorbidities, physical and mental health status, intra-family conflict, care-giving demand, and financial hardship. After adjustment for demographic and clinical characteristics, women had worse recovery than men at 1-month post-AMI, with mean differences in improvement score ranging from −0.04 for Euro-Qol utility index to −3.96 for angina-related quality of life (p<0.05 for all). Further adjustment for baseline stress reduced these sex-based differences in recovery to −0.03 to −3.63, which however remained statistically significant (p<0.05 for all). High stress at baseline was associated with significantly worse recovery in angina-specific and overall quality of life, as well as mental health status. The effect of baseline stress on recovery did not vary between men and women. Conclusions Among young and middle-aged patients, higher stress at baseline is associated with worse recovery in multiple health outcomes after AMI. Women perceive greater psychological stress than men at baseline, which partially explains women’s worse recovery. PMID:25679303

  13. In adenosine A2B knockouts acute treatment with inorganic nitrate improves glucose disposal, oxidative stress, and AMPK signaling in the liver

    PubMed Central

    Peleli, Maria; Hezel, Michael; Zollbrecht, Christa; Persson, A. Erik G.; Lundberg, Jon O.; Weitzberg, Eddie; Fredholm, Bertil B.; Carlström, Mattias

    2015-01-01

    Rationale: Accumulating studies suggest that nitric oxide (NO) deficiency and oxidative stress are central pathological mechanisms in type 2 diabetes (T2D). Recent findings demonstrate therapeutic effects by boosting the nitrate-nitrite-NO pathway, which is an alternative pathway for NO formation. This study aimed at investigating the acute effects of inorganic nitrate on glucose and insulin signaling in adenosine A2B receptor knockout mice (A−/−2B), a genetic mouse model of impaired metabolic regulation. Methods: Acute effects of nitrate treatment were investigated in aged wild-type (WT) and A−/−2B mice. One hour after injection with nitrate (0.1 mmol/kg, i.p.) or placebo, metabolic regulation was evaluated by intraperitoneal glucose and insulin tolerance tests. NADPH oxidase-mediated superoxide production and AMPK phosphorylation were measured in livers obtained from non-treated or glucose-treated mice, with or without prior nitrate injection. Plasma was used to determine insulin resistance (HOMA-IR) and NO signaling. Results: A−/−2B displayed increased body weight, reduced glucose clearance, and attenuated overall insulin responses compared with age-matched WT mice. Nitrate treatment increased circulating levels of nitrate, nitrite and cGMP in the A−/−2B, and improved glucose clearance. In WT mice, however, nitrate treatment did not influence glucose clearance. HOMA-IR increased following glucose injection in the A−/−2B, but remained at basal levels in mice pretreated with nitrate. NADPH oxidase activity in livers from A−/−2B, but not WT mice, was reduced by nitrate treatment. Livers from A−/−2B displayed reduced AMPK phosphorylation compared with WT mice, and this was increased by nitrate treatment. Finally, injection with the anti-diabetic agent metformin induced similar therapeutic effects in the A−/−2B as observed with nitrate. Conclusion: The A−/−2B mouse is a genetic mouse model of metabolic syndrome. Acute treatment

  14. 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

  15. 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.

  16. 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.

  17. Evaluation of myocardial viability in old myocardial infarcted patients with CHF: delayed enhancement MRI vs. low-dose dobutamine stress speckle tracking echocardiography

    PubMed Central

    Wang, Chaofan; Han, Shuguang; Xu, Tongda; Wang, Fengli; Wang, Xiaoping; Chen, Jing; Hu, Chunfeng; Li, Dongye

    2016-01-01

    The aim of this study was to explore the significance of delayed enhancement magnetic resonance imaging (DE-MRI) combined with two-dimensional speckle tracking echocardiography (STE) and low dose dobutamine stress echocardiography (LDDSE) to assess viable myocardium (VM) in the patients with old myocardial infarction (OMI) associated with congestive heart failure (CHF). Thirty five hospitalized OMI patients with regional wall motion abnormalities and left ventricular ejection fraction (LVEF) < 50% were recruited based on routine echocardiography. The results showed that DE-MRI facilitated the detection of VM, with a sensitivity, specificity and accuracy of 92.41%, 89.19% and 91.32%, respectively. In a parallel test of the two main parameters in STE, the sensitivity, specificity, and accuracy were improved from baseline to LDDSE (71.72% vs. 91.72%, 70.27% vs. 85.14%, and 71.23% vs. 89.50%, P < 0.05). A parallel test involving STE with LDDSE showed high sensitivity for VM. However its specificity and accuracy were lower than DE-MRI, even when combined with LDDSE. Therefore, combining these two methods, improves the sensitivity, specificity and accuracy for assessment of VM. The combination approach is the best option for the evaluation of VM using serial test. It provides further treatment options and prognosis of patients with OMI. LVEF is improved significantly after PCI in OMI patients with VM and CHF. PMID:27725854

  18. Alcohol Dehydrogenase Protects against Endoplasmic Reticulum Stress-Induced Myocardial Contractile Dysfunction via Attenuation of Oxidative Stress and Autophagy: Role of PTEN-Akt-mTOR Signaling

    PubMed Central

    Pang, Jiaojiao; Fuller, Nathan D.; Hu, Nan; Barton, Linzi A.; Henion, Jeremy M.; Guo, Rui; Chen, Yuguo; Ren, Jun

    2016-01-01

    Background The endoplasmic reticulum (ER) plays an essential role in ensuring proper folding of the newly synthesized proteins. Aberrant ER homeostasis triggers ER stress and development of cardiovascular diseases. ADH is involved in catalyzing ethanol to acetaldehyde although its role in cardiovascular diseases other than ethanol metabolism still remains elusive. This study was designed to examine the impact of ADH on ER stress-induced cardiac anomalies and underlying mechanisms involved using cardiac-specific overexpression of alcohol dehydrogenase (ADH). Methods ADH and wild-type FVB mice were subjected to the ER stress inducer tunicamycin (1 mg/kg, i.p., for 48 hrs). Myocardial mechanical and intracellular Ca2+ properties, ER stress, autophagy and associated cell signaling molecules were evaluated. Results ER stress compromised cardiac contractile function (evidenced as reduced fractional shortening, peak shortening, maximal velocity of shortening/relengthening, prolonged relengthening duration and impaired intracellular Ca2+ homeostasis), oxidative stress and upregulated autophagy (increased LC3B, Atg5, Atg7 and p62), along with dephosphorylation of PTEN, Akt and mTOR, all of which were attenuated by ADH. In vitro study revealed that ER stress-induced cardiomyocyte anomaly was abrogated by ADH overexpression or autophagy inhibition using 3-MA. Interestingly, the beneficial effect of ADH was obliterated by autophagy induction, inhibition of Akt and mTOR. ER stress also promoted phosphorylation of the stress signaling ERK and JNK, the effect of which was unaffected by ADH transgene. Conclusions Taken together, these findings suggested that ADH protects against ER stress-induced cardiac anomalies possibly via attenuation of oxidative stress and PTEN/Akt/mTOR pathway-regulated autophagy. PMID:26807981

  19. Impaired Transcriptional Activity of Nrf2 in Age-Related Myocardial Oxidative Stress Is Reversible by Moderate Exercise Training

    PubMed Central

    Gounder, Sellamuthu S.; Kannan, Sankaranarayanan; Devadoss, Dinesh; Miller, Corey J.; Whitehead, Kevin S.; Odelberg, Shannon J.; Firpo, Matthew A.; Paine, Robert; Hoidal, John R.; Abel, E. Dale; Rajasekaran, Namakkal S.

    2012-01-01

    Aging promotes accumulation of reactive oxygen/nitrogen species (ROS/RNS) in cardiomyocytes, which leads to contractile dysfunction and cardiac abnormalities. These changes may contribute to increased cardiovascular disease in the elderly. Inducible antioxidant pathways are regulated by nuclear erythroid 2 p45-related factor 2 (Nrf2) through antioxidant response cis-elements (AREs) and are impaired in the aging heart. Whereas acute exercise stress (AES) activates Nrf2 signaling and promotes myocardial antioxidant function in young mice (∼2 months), aging mouse (>23 months) hearts exhibit significant oxidative stress as compared to those of the young. The purpose of this study was to investigate age-dependent regulation of Nrf2-antioxidant mechanisms and redox homeostasis in mouse hearts and the impact of exercise. Old mice were highly susceptible to oxidative stress following high endurance exercise stress (EES), but demonstrated increased adaptive redox homeostasis after moderate exercise training (MET; 10m/min, for 45 min/day) for ∼6 weeks. Following EES, transcription and protein levels for most of the ARE-antioxidants were increased in young mice but their induction was blunted in aging mice. In contrast, 6-weeks of chronic MET promoted nuclear levels of Nrf2 along with its target antioxidants in the aging heart to near normal levels as seen in young mice. These observations suggest that enhancing Nrf2 function and endogenous cytoprotective mechanisms by MET, may combat age-induced ROS/RNS and protect the myocardium from oxidative stress diseases. PMID:23029187

  20. Detection of Obstructive Coronary Artery Disease Using Regadenoson Stress and 82Rb PET/CT Myocardial Perfusion Imaging

    PubMed Central

    Hsiao, Edward; Ali, Bilal; Blankstein, Ron; Skali, Hicham; Ali, Towhid; Bruyere, John; Kwong, Raymond Y.; Di Carli, Marcelo F.; Dorbala, Sharmila

    2014-01-01

    Our objective was to study the diagnostic performance of regadenoson 82Rb myocardial perfusion PET imaging to detect obstructive coronary artery disease (CAD). Methods We studied 134 patients (mean age, 63 ± 12 y; mean body mass index, 31 ± 9 kg/m2) without known CAD (96 with coronary angiography and 38 with low pretest likelihood of CAD). Stress left ventricular ejection fraction (LVEF) minus rest LVEF defined LVEF reserve. The Duke score was used to estimate the anatomic extent of jeopardized myocardium. Results Regadenoson PET had a high sensitivity, 92% (95% confidence interval [CI], 83%–97%), in detecting obstructive CAD, with a normalcy rate of 97% (95% CI, 86%–99%), specificity of 77% (54/70 patients; 95% CI, 66%–86%), and area under the receiver-operator-characteristic curve of 0.847 (95% CI, 0.774–0.903; P < 0.001). Regadenoson PET demonstrated high sensitivity to detect CAD in patients with single-vessel CAD (89%; 95% CI, 70%–98%). The mean LVEF reserve was significantly higher in patients with normal myocardial perfusion imaging results (6.5% ± 5.4%) than in those with mild (4.3 ± 5.1, P = 0.03) and moderate to severe reversible defects (−0.2% ± 8.4%, P = 0.001). Also, mean LVEF reserve was significantly higher in patients with a low likelihood of CAD (7.2% ± 4.5%, P < 0.0001) and mild or moderate jeopardized myocardium than in those with significant jeopardized myocardium (score ≥ 6), −2.8% ± 8.3%. Conclusion Regadenoson 82Rb myocardial perfusion imaging is accurate for the detection of obstructive CAD. LVEF reserve is high in patients without significant ischemia or significant angiographic jeopardized myocardium. PMID:23940305

  1. [Development and clinical application of an expert system for supporting diagnosis of 201Tl stress myocardial SPECT].

    PubMed

    Horino, M; Hosoba, M; Wani, H; Oriuchi, N; Tateno, M; Inoue, T; Sasaki, Y; Igarashi, H; Iizuka, T

    1990-02-01

    A consultation expert system which supports our computer aided reporting system was developed. The system was used for the evaluation of the two dimensional polar (bull's eye) display of 201Tl myocardial SPECT. The system consists of patients management (PM) and consultation expert systems (ES). The former is connected to image processors coupled with scinticameras. The bull's eye display of myocardial SPECT is transferred from image processor to the data base of PM. When inference request is made, the feature extraction program extracts information on localization, extent and severity of focal defects comparing count-rates pixel by pixel with the reference obtained from seven normal controls. The inference engine is activated to determine presence of focal defects utilizing diagnostic rules in the knowledge base. The results are sent back to PM and reported with the probability of assurance. Fifty eight patients with old myocardial infarction (OMI), angina pectoris (AP) and other diseases as well as normal controls were included in the study. The decision for presence or absence of focal defects by ES agreed with that by nuclear physicians (NP) in 301 segments among 330 (91%) in stress images. The presence of redistribution in delayed images agreed in 43 segments among 67 (64%). Image interpretation by ES agreed well with that of NP in patients with OMI (19/20) and AP (9/11). Seven were interpreted as normal by both ES and NP. The system is useful, as it provides NP with complementary and supportive information applicable to decision making and reporting. Further clinical experiences can improve knowledge base for better ES function.

  2. Licorice treatment prevents oxidative stress, restores cardiac function, and salvages myocardium in rat model of myocardial injury.

    PubMed

    Ojha, Shreesh Kumar; Sharma, Charu; Golechha, Mahaveer Jain; Bhatia, Jagriti; Kumari, Santosh; Arya, Dharamvir Singh

    2015-02-01

    The present study examined the effects of licorice on antioxidant defense, functional impairment, histopathology, and ultrastructural alterations in isoproterenol (ISP)-induced myocardial injury in rats. Myocardial necrosis was induced by two subcutaneous injection of ISP (85 mg/kg) at an interval of 24 h. Licorice was administered orally for 30 days in the doses of 100, 200, 400, or 800 mg/kg. ISP-treated rats showed impaired hemodynamics, left ventricular dysfunction, and caused depletion of antioxidants and marker enzymes along with lipid peroxidation from myocardium. ISP also induced histopathological and ultrastructural alterations in myocardium. Pretreatment with licorice prevented the depletion of endogenous antioxidants and myocyte injury marker enzymes, inhibited lipid peroxidation, and showed recovery of hemodynamic and ventricular functions. Licorice treatment also reduced myonecrosis, edema, and infiltration of inflammatory cells and showed preservation of subcellular and ultrastructural components. Our results demonstrate that licorice exerts cardioprotection by reducing oxidative stress, augmenting endogenous antioxidants, and restoring functional parameters as well as maintaining structural integrity.

  3. F-18 deoxyglucose and stress N-13 ammonia positron emission tomography in anterior wall healed myocardial infarction

    SciTech Connect

    Fudo, T.; Kambara, H.; Hashimoto, T.; Hayashi, M.; Nohara, R.; Tamaki, N.; Yonekura, Y.; Senda, M.; Konishi, J.; Kawai, C.

    1988-06-01

    To evaluate myocardial blood flow and glucose utilization, N-13 ammonia (NH3) and F-18 deoxyglucose positron emission tomography scanning was performed in 22 patients with previous anterior wall myocardial infarction, using a high-resolution, multi-slice, whole-body scanner. The N-13 ammonia study was performed at rest and after exercise. The F-18 deoxyglucose study was performed at rest after fasting greater than 5 hours. The N-13 ammonia study revealed a hypoperfused area in 19 of the 22 patients (86%), that corresponded to the infarcted regions as diagnosed by electrocardiography, coronary arteriography and left ventriculography (21 patients). The hypoperfused areas expanded after exercise in 16 of 22 patients (73%). F-18 deoxyglucose uptake was observed in these hypoperfused areas, especially in patients with hypokinetic wall motion on left ventriculography and in exercise-induced hypoperfused areas. However, positron emission tomography demonstrated diffuse uptake of F-18 deoxyglucose in 3 of 8 patients with dyskinetic wall motion. Thus, metabolically active myocardium in infarcted areas or periinfarct ischemia can be visualized with F-18 deoxyglucose and stress N-13 ammonia studies.

  4. 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.

  5. 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.

  6. Myocardial stress and hypertrophy: a complex interface between biophysics and cardiac remodeling.

    PubMed

    Grossman, William; Paulus, Walter J

    2013-09-01

    Pressure and volume overload results in concentric and eccentric hypertrophy of cardiac ventricular chambers with, respectively, parallel and series replication of sarcomeres. These divergent patterns of hypertrophy were related 40 years ago to disparate wall stresses in both conditions, with systolic wall stress eliciting parallel replication of sarcomeres and diastolic wall stress, series replication. These observations are relevant to clinical practice, as they relate to the excessive hypertrophy and contractile dysfunction regularly observed in patients with aortic stenosis. Stress-sensing mechanisms in cardiomyocytes and activation of cardiomyocyte death by elevated wall stress continue to intrigue cardiovascular scientists.

  7. 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

  8. Estrogen modulation of the ethanol-evoked myocardial oxidative stress and dysfunction via DAPK3/Akt/ERK activation in male rats.

    PubMed

    El-Mas, Mahmoud M; Abdel-Rahman, Abdel A

    2015-09-15

    Evidence suggests that male rats are protected against the hypotensive and myocardial depressant effects of ethanol compared with females. We investigated whether E2 modifies the myocardial and oxidative effects of ethanol in male rats. Conscious male rats received ethanol (0.5, 1 or 1.5g/kg i.v.) 30-min after E2 (1μg/kg i.v.) or its vehicle (saline), and hearts were collected at the conclusion of hemodynamic measurements for ex vivo molecular studies. Ethanol had no effect in vehicle-treated rats, but it caused dose-related reductions in LV developed pressure (LVDP), end-diastolic pressure (LVEDP), rate of rise in LV pressure (dP/dtmax) and systolic (SBP) and diastolic (DBP) blood pressures in E2-pretreated rats. These effects were associated with elevated (i) indices of reactive oxygen species (ROS), (ii) malondialdehyde (MDA) protein adducts, and (iii) phosphorylated death-associated protein kinase-3 (DAPK3), Akt, and extracellular signal-regulated kinases (ERK1/2). Enhanced myocardial anti-oxidant enzymes (heme oxygenase-1, catalase and aldehyde dehydrogenase 2) activities were also demonstrated. In conclusion, E2 promotes ethanol-evoked myocardial oxidative stress and dysfunction in male rats. The present findings highlight the risk of developing myocardial dysfunction in men who consume alcohol while receiving E2 for specific medical conditions.

  9. Comparison of myocardial ischemia during intense mental stress using flight simulation in airline pilots with coronary artery disease to that produced with conventional mental and treadmill exercise stress testing.

    PubMed

    Doorey, Andrew; Denenberg, Barry; Sagar, Vidya; Hanna, Tracy; Newman, Jack; Stone, Peter H

    2011-09-01

    Mental stress increases cardiovascular morbidity and mortality. Although laboratory mental stress often causes less myocardial ischemia than exercise stress (ES), it is unclear whether mental stress is intrinsically different or differences are due to less hemodynamic stress with mental stress. We sought to evaluate the hemodynamic and ischemic response to intense realistic mental stress created by modern flight simulators and compare this response to that of exercise treadmill testing and conventional laboratory mental stress (CMS) testing in pilots with coronary disease. Sixteen airline pilots with angiographically documented coronary disease and documented myocardial ischemia during ES were studied using maximal treadmill ES, CMS, and aviation mental stress (AMS) testing. AMS testing was done in a sophisticated simulator using multiple system failures as stressors. Treadmill ES testing resulted in the highest heart rate, but AMS caused a higher blood pressure response than CMS. Maximal rate-pressure product was not significantly different between ES and AMS (25,646 vs 23,347, p = 0.08), although these were higher than CMS (16,336, p <0.0001). Despite similar hemodynamic stress induced by ES and AMS, AMS resulted in significantly less ST-segment depression and nuclear ischemia than ES. Differences in induction of ischemia by mental stress compared to ES do not appear to be due to the creation of less hemodynamic stress. In conclusion, even with equivalent hemodynamic stress, intense realistic mental stress induced by flight simulators results in significantly less myocardial ischemia than ES as measured by ST-segment depression and nuclear ischemia.

  10. Selection of patients for preoperative coronary angiography: use of dipyridamole-stress--thallium myocardial imaging

    SciTech Connect

    Brewster, D.C.; Okada, R.D.; Strauss, H.W.; Abbott, W.M.; Darling, R.C.; Boucher, C.A.

    1985-05-01

    To identify patients likely to benefit from preoperative coronary angiography, a method utilizing pharmacologically induced coronary vasodilatation in conjunction with serial thallium 201 myocardial perfusion imaging was investigated. Fifty-four patients admitted for elective aortic or femoropopliteal procedures were studied. There were no cardiac ischemic complications in 32 patients with normal scans or persistent defects (scar). In contrast, 7 of 15 patients with thallium redistribution (ischemia) on pre-operative scanning had perioperative ischemic events, including one death and two acute infarcts. An additional seven patients with positive scans (redistribution) underwent coronary angiography prior to vascular surgery; surgically important two- or three-vessel disease was confirmed in all. Dipyridamole-thallium imaging facilitates selection of the subset of truly high-risk patients in whom preoperative coronary angiography may be warranted.

  11. Prevalence of and variables associated with silent myocardial ischemia on exercise thallium-201 stress testing

    SciTech Connect

    Gasperetti, C.M.; Burwell, L.R.; Beller, G.A. )

    1990-07-01

    The prevalence of silent myocardial ischemia was prospectively assessed in a group of 103 consecutive patients (mean age 59 +/- 10 years, 79% male) undergoing symptom-limited exercise thallium-201 scintigraphy. Variables that best correlated with the occurrence of painless ischemia by quantitative scintigraphic criteria were examined. Fifty-nine patients (57%) had no angina on exercise testing. A significantly greater percent of patients with silent ischemia than of patients with angina had a recent myocardial infarction (31% versus 7%, p less than 0.01), had no prior angina (91% versus 64%, p less than 0.01), had dyspnea as an exercise test end point (56% versus 35%, p less than 0.05) and exhibited redistribution defects in the supply regions of the right and circumflex coronary arteries (50% versus 35%, p less than 0.05). The group with exercise angina had more ST depression (64% versus 41%, p less than 0.05) and more patients with four or more redistribution defects. However, there was no difference between the two groups with respect to mean total thallium-201 perfusion score, number of redistribution defects per patient, multi-vessel thallium redistribution pattern or extent of angiographic coronary artery disease. There was also no difference between the silent ischemia and angina groups with respect to antianginal drug usage, prevalence of diabetes mellitus, exercise duration, peak exercise heart rate, peak work load, peak double (rate-pressure) product and percent of patients achieving greater than or equal to 85% of maximal predicted heart rate for age. Thus, in this study group, there was a rather high prevalence rate of silent ischemia (57%) by exercise thallium-201 criteria.

  12. Ventricular Ectopy: Impact of Self-reported Stress following Myocardial Infarction

    PubMed Central

    Smith, Patrick J.; Blumenthal, James A.; Babyak, Michael A.; Georgiades, Anastasia; Sherwood, Andrew; Sketch, Michael H.; Watkins, Lana L.

    2007-01-01

    Background Although psychological stress has been implicated in the pathogenesis of ventricular arrhythmias, the relationship between self-reported stress and ventricular ectopy has not been evaluated under naturalistic conditions in acute post-MI patients, a group at elevated risk for arrhythmias. Methods Diary-reported stress was measured during 24-hour Holter monitoring in 80 patients (52 men, 28 women) approximately 12 weeks following MI. In addition, state and trait anxiety were measured using the Spielberger State and Trait anxiety inventory (STAI), administered at the beginning of the 24-hour holter monitoring session. The relationship between diary reported stress, anxiety, and ventricular ectopy was evaluated. Results Mean diary-reported stress (β= .29, p = .01) was associated with total ventricular ectopy. State anxiety was also associated with 24-hour ectopy (β= .24, p = .04); however, trait anxiety was not significantly associated with ectopy. Temporal analyses of the relationship between stress and ectopy showed that diary-reported stress was associated with an increase in the number of VPBs occurring in the following hour (B = 0.74, p < .0001). Conclusions These findings extend existing evidence linking psychological factors to ventricular arrhythmias by demonstrating that psychological stress predicts increased arrhythmic activity during routine daily activities in post-MI patients. PMID:17174651

  13. Effect of Diltiazem on Coronary Artery Flow and Myocardial Perfusion in Patients With Isolated Coronary Artery Ectasia and Either Stable Angina Pectoris or Positive Myocardial Ischemic Stress Test.

    PubMed

    Ozcan, Ozgur Ulas; Atmaca, Yusuf; Goksuluk, Huseyin; Akbulut, Irem Muge; Ozyuncu, Nil; Ersoy, Nedret; Erol, Cetin

    2015-10-15

    Isolated coronary artery ectasia (CAE) may be associated with stable or unstable coronary events despite the absence of epicardial coronary stenosis. Impaired coronary flow dynamics and myocardial perfusion have been demonstrated in stable patients with ectatic coronary arteries. We aimed to assess whether epicardial flow and tissue-level perfusion would be improved by diltiazem in myocardial regions subtended by the ectatic coronary arteries in patients with isolated CAE. A total of 60 patients with isolated CAE were identified of 9,780 patients who underwent elective coronary angiography. Patients were randomized to 5 mg of intracoronary diltiazem or saline. Coronary blood flow of the microvascular network was assessed using myocardial blush grade (MBG) technique. The thrombolysis in myocardial infarction (TIMI) flow grade and TIMI frame count (TFC) were used to assess epicardial coronary flow. MBG (from 2.4 to 2.6, p = 0.02), TIMI flow grades (from 2.4 to 2.8, p <0.001), and TFC (from 35 to 26, p <0.001) were significantly improved after diltiazem, whereas no significant change was noticed after saline (from 2.4 to 2.4, p = 0.86 for MBG; from 2.3 to 2.3, p = 0.71 for TIMI flow grade; and from 35 to 33, p = 0.43 for TFC). Diltiazem provided amelioration of the altered coronary flow dynamics, which was suggested as the pathophysiological influence of CAE. In conclusion, the favorable effects of the diltiazem on myocardial perfusion were observed at both epicardial and tissue levels.

  14. Technetium-99m sestamibi myocardial imaging: Same-day rest-stress studies and dipyridamole

    SciTech Connect

    Taillefer, R. )

    1990-10-16

    Unlike thallium-201, technetium-99m (Tc-99m) sestamibi does not redistribute in the myocardium after injection. Thus, 2 separate injections, 1 at rest and the other at stress (or after dipyridamole), are required to differentiate ischemia from scar. From a physical viewpoint, a 24-hour interval between the 2 injections is preferable for detection of coronary artery disease (CAD) with Tc-99m sestamibi imaging. However, same-day studies are more convenient in clinical practice. Results of studies using different Tc-99m sestamibi injection protocols are presented with emphasis on the advantages of a rest-stress injection sequence with a low dose at rest (7 mCi) followed 2 hours later by a higher dose at stress (25 mCi). A prospective study was conducted in a patient population with proven CAD using same-day studies to compare a rest-stress (7 and 25 mCi, respectively) to a stress-rest (7 and 25 mCi) Tc-99m sestamibi injection sequence. There was an agreement in 87.3% of the analyzed segments between the 2 protocols. However, the largest discordance for type of defect applied to 7.4% of the segments judged ischemic in the rest-stress protocol, which were called scars on stress-rest. This study showed that a rest-stress sequence is preferable when using a same-day protocol with a short time interval (less than 2 hours) between the 2 Tc-99m sestamibi injections because the rest image performed initially represents a true rest study, which is not necessarily the case with the stress-rest sequence. Preliminary studies were performed to evaluate dipyridamole with Tc-99m sestamibi imaging in normal subjects and in patients with CAD. These studies showed that treadmill and dipyridamole Tc-99m sestamibi imaging are comparable and the results are similar to those obtained with thallium-201.

  15. A single CT for attenuation correction of both rest and stress SPECT myocardial perfusion imaging: a retrospective feasibility study

    PubMed Central

    Ahlman, Mark A; Nietert, Paul J; Wahlquist, Amy E; Serguson, Jill M; Berry, Max W; Suranyi, Pal; Liu, Songtao; Spicer, Kenneth M

    2014-01-01

    Purpose: In the effort to reduce radiation exposure to patients undergoing myocardial perfusion imaging (MPI) with SPECT/CT, we evaluate the feasibility of a single CT for attenuation correction (AC) of single-day rest (R)/stress (S) perfusion. Methods: Processing of 20 single isotope and 20 dual isotope MPI with perfusion defects were retrospectively repeated in three steps: (1) the standard method using a concurrent R-CT for AC of R-SPECT and S-CT for S-SPECT; (2) the standard method repeated; and (3) with the R-CT used for AC of S-SPECT, and the S-CT used for AC of R-SPECT. Intra-Class Correlation Coefficients (ICC) and Choen’s kappa were used to measure intra-operator variability in sum scoring. Results: The highest level of intra-operator reliability was seen with the reproduction of the sum rest score (SRS) and sum stress score (SSS) (ICC > 95%). ICCs were > 85% for SRS and SSS when alternate CTs were used for AC, but when sum difference scores were calculated, ICC values were much lower (~22% to 27%), which may imply that neither CT substitution resulted in a reproducible difference score. Similar results were seen when evaluating dichotomous outcomes (sum scores difference of ≥ 4) when comparing different processing techniques (kappas ~0.32 to 0.43). Conclusions: When a single CT is used for AC of both rest and stress SPECT, there is disproportionately high variability in sum scoring that is independent of user error. This information can be used to direct further investigation in radiation reduction for common imaging exams in nuclear medicine. PMID:24482701

  16. Comparison of the usefulness of heart rate variability versus exercise stress testing for the detection of myocardial ischemia in patients without known coronary artery disease.

    PubMed

    Goldkorn, Ronen; Naimushin, Alexey; Shlomo, Nir; Dan, Ariella; Oieru, Dan; Moalem, Israel; Rozen, Eli; Gur, Ilan; Levitan, Jacob; Rosenmann, David; Mogilewsky, Yakov; Klempfner, Robert; Goldenberg, Ilan

    2015-06-01

    Heart rate variability (HRV) has been shown to be attenuated in patients with coronary artery disease (CAD) and may, therefore, be possibly used for the early detection of myocardial ischemia. We aimed to evaluate the diagnostic yield of a novel short-term HRV algorithm for the detection of myocardial ischemia in subjects without known CAD. We prospectively enrolled 450 subjects without known CAD who were referred to tertiary medical centers for exercise stress testing (EST) with single-photon emission computed tomography myocardial perfusion imaging (MPI). All subjects underwent 1-hour Holter testing with subsequent HRV analysis before EST with MPI. The diagnostic yield of HRV analysis was compared with EST, using MPI as the gold standard for the noninvasive detection of myocardial ischemia. All subjects had intermediate pretest probability for CAD. Mean age was 62 years, 38% were women, 51% had hypertension, and 25% diabetes mellitus. HRV analysis showed superior sensitivity (77%) compared with standard EST (27%). After multivariate adjustment, HRV was independently associated with an 8.4-fold (p <0.001) increased likelihood for the detection of myocardial ischemia by MPI, whereas EST did not show a statistically significant association with a positive MPI (odds ratio 2.1; p = 0.12). Of subjects who were referred for subsequent coronary angiography, the respective sensitivities of HRV and EST for the detection of significant CAD were 73% versus 26%. Our data suggest that HRV can be used as an important noninvasive technique for the detection of myocardial ischemia in subjects without known CAD, providing superior sensitivity to conventional EST in this population.

  17. Estrogen modulation of the ethanol-evoked myocardial oxidative stress and dysfunction via DAPK3/Akt/ERK activation in male rats

    SciTech Connect

    El-Mas, Mahmoud M. Abdel-Rahman, Abdel A.

    2015-09-15

    Evidence suggests that male rats are protected against the hypotensive and myocardial depressant effects of ethanol compared with females. We investigated whether E{sub 2} modifies the myocardial and oxidative effects of ethanol in male rats. Conscious male rats received ethanol (0.5, 1 or 1.5 g/kg i.v.) 30-min after E{sub 2} (1 μg/kg i.v.) or its vehicle (saline), and hearts were collected at the conclusion of hemodynamic measurements for ex vivo molecular studies. Ethanol had no effect in vehicle-treated rats, but it caused dose-related reductions in LV developed pressure (LVDP), end-diastolic pressure (LVEDP), rate of rise in LV pressure (dP/dt{sub max}) and systolic (SBP) and diastolic (DBP) blood pressures in E{sub 2}-pretreated rats. These effects were associated with elevated (i) indices of reactive oxygen species (ROS), (ii) malondialdehyde (MDA) protein adducts, and (iii) phosphorylated death-associated protein kinase-3 (DAPK3), Akt, and extracellular signal-regulated kinases (ERK1/2). Enhanced myocardial anti-oxidant enzymes (heme oxygenase-1, catalase and aldehyde dehydrogenase 2) activities were also demonstrated. In conclusion, E{sub 2} promotes ethanol-evoked myocardial oxidative stress and dysfunction in male rats. The present findings highlight the risk of developing myocardial dysfunction in men who consume alcohol while receiving E{sub 2} for specific medical conditions. - Highlights: • Ethanol lowers blood pressure and causes LV dysfunction in E{sub 2}-treated rats. • E{sub 2}/ethanol aggravates cardiac oxidative state via of DAPK3/Akt/ERK activation. • E{sub 2}/ethanol causes a feedback increase in cardiac HO-1, catalase and ALDH2. • Alcohol might increase risk of myocardial dysfunction in men treated with E{sub 2}.

  18. High-fat, low-carbohydrate diet alters myocardial oxidative stress and impairs recovery of cardiac function after ischemia and reperfusion in obese rats.

    PubMed

    Liu, Jian; Lloyd, Steven G

    2013-04-01

    Obesity is associated with elevated risk of heart disease. A solid understanding of the safety and potential adverse effects of high-fat, low-carbohydrate diet (HFLCD) similar to that used by humans for weight loss on the heart is crucial. High fat intake is known to promote increases in reactive oxygen species and mitochondrial damage. We hypothesized that there would be adverse effects of HFLCD on myocardial ischemia/reperfusion injury through enhancing oxidative stress injury and impairing mitochondrial biogenesis in a nongenetic, diet-induced rat model of obesity. To test the hypothesis, 250-g male Sprague-Dawley rats were fed an obesity-promoting diet for 7 weeks to induce obesity, then switched to HFLCD or a low-fat control diet for 2 weeks. Isolated hearts underwent global low flow ischemia for 60 minutes and reperfusion for 60 minutes. High-fat, low-carbohydrate diet resulted in greater weight gain and lower myocardial glycogen, plasma adiponectin, and insulin. Myocardial antioxidant gene transcript and protein expression of superoxide dismutase and catalase were reduced in HFLCD, along with increased oxidative gene NADPH oxidase-4 transcript and xanthine oxidase activity, and a 37% increase in nitrated protein (nitrotyrosine) in HFLCD hearts. The cardiac expression of key mitochondrial regulatory factors such as nuclear respiratory factor-1 and transcription factor A-mitochondrial were inhibited and myocardial mitochondrial DNA copy number decreased. The cardiac expression of adiponectin and its receptors was down-regulated in HFLCD. High-fat, low-carbohydrate diet impaired recovery of left ventricular rate-pressure product after ischemia/reperfusion and led to 3.5-fold increased injury as measured by lactate dehydrogenase release. In conclusion, HFLCD leads to increased ischemic myocardial injury and impaired recovery of function after reperfusion and was associated with attenuation of mitochondrial biogenesis and enhanced oxidative stress in obese rats

  19. Role of TFEB Mediated Autophagy, Oxidative Stress, Inflammation, and Cell Death in Endotoxin Induced Myocardial Toxicity of Young and Aged Mice

    PubMed Central

    Li, Fang; Lang, Fangfang; Zhang, Huilin; Xu, Liangdong; Wang, Yidan; Hao, Enkui

    2016-01-01

    Elderly patients are susceptible to sepsis. LPS induced myocardial injury is a widely used animal model to assess sepsis induced cardiac dysfunction. The age dependent mechanisms behind sepsis susceptibility were not studied. We analyzed age associated changes to cardiac function, cell death, inflammation, oxidative stress, and autophagy in LPS induced myocardial injury. Both young and aged C57BL/6 mice were used for LPS administration. The results demonstrated that LPS induced more cardiac injury (creatine kinase, lactate dehydrogenase, troponin I, and cardiac myosin-light chains 1), cardiac dysfunction (left ventricular inner dimension, LVID, and ejection fraction (EF)), cell death, inflammation, and oxidative stress in aged mice compared to young mice. However, a significant age dependent decline in autophagy was observed. Translocation of Transcription Factor EB (TFEB) to nucleus and formation of LC3-II were significantly reduced in LPS administered aged mice compared to young ones. In addition to that, downstream effector of TFEB, LAMP-1, was induced in response to LPS challenge in young mice. The present study newly demonstrates that TFEB mediated autophagy is crucial for protection against LPS induced myocardial injury particularly in aging senescent heart. Targeting this autophagy-oxidative stress-inflammation-cell death axis may provide a novel therapeutic strategy for cardioprotection in the elderly. PMID:27200146

  20. Oxidative Stress-Related Biomarkers in Essential Hypertension and Ischemia-Reperfusion Myocardial Damage

    PubMed Central

    Rodrigo, Ramón; Feliú, Felipe; Hasson, Daniel

    2013-01-01

    Cardiovascular diseases are a leading cause of mortality and morbidity worldwide, with hypertension being a major risk factor. Numerous studies support the contribution of reactive oxygen and nitrogen species in the pathogenesis of hypertension, as well as other pathologies associated with ischemia/reperfusion. However, the validation of oxidative stress-related biomarkers in these settings is still lacking and novel association of these biomarkers and other biomarkers such as endothelial progenitor cells, endothelial microparticles, and ischemia modified albumin, is just emerging. Oxidative stress has been suggested as a pathogenic factor and therapeutic target in early stages of essential hypertension. Systolic and diastolic blood pressure correlated positively with plasma F2-isoprostane levels and negatively with total antioxidant capacity of plasma in hypertensive and normotensive patients. Cardiac surgery with extracorporeal circulation causes an ischemia/reperfusion event associated with increased lipid peroxidation and protein carbonylation, two biomarkers associated with oxidative damage of cardiac tissue. An enhancement of the antioxidant defense system should contribute to ameliorating functional and structural abnormalities derived from this metabolic impairment. However, data have to be validated with the analysis of the appropriate oxidative stress and/or nitrosative stress biomarkers. PMID:24347798

  1. Dobutamine stress-redistribution-reinjection versus rest-redistribution thallium-201 SPECT in the assessment of myocardial viability.

    PubMed

    Cornel, J H; Bax, J J; Elhendy, A; Reijs, A E; Fioretti, P M

    1997-02-01

    The aim of this study was to evaluate the value of thallium-201 chloride (201Tl) reinjection imaging following dobutamine stress (DRi) to identify viable myocardium in comparison with a rest-redistribution 201Tl protocol (RR). The identification of viable myocardium bears important consequences for adequate selection of patients with poor left ventricular function, often unable to exercise, who are considered for revascularization. Twenty-six patients with chronic coronary artery disease and depressed left ventricular function (ejection fraction 36 +/- 10%) were studied by both DRi and RR single photon emission computed tomography (SPECT). Semi-quantitative analysis of regional 201Tl activity (5-point score) and wall motion by echocardiography using a 16-segment model was performed. Regions were classified as viable (normal/reversible/fixed moderate defects) or non-viable (fixed severe defects) and related to regional wall motion. Target heart rate was reached in 25 patients. Myocardial viability was demonstrated in 353/416 (85%) by DRi SPECT and in 346/416 (83%) by RR SPECT. The agreement between the 2 protocols was 98% with a K-value of 0.94; similar results were obtained when the analysis was limited to dyscontractile segments. In conclusion, this study demonstrates the feasibility and diagnostic value of DRi SPECT to identify viable myocardium.

  2. Paeonol and danshensu combination attenuates apoptosis in myocardial infarcted rats by inhibiting oxidative stress: Roles of Nrf2/HO-1 and PI3K/Akt pathway

    PubMed Central

    Li, Hua; Song, Fan; Duan, Lin-Rui; Sheng, Juan-Juan; Xie, Yan-Hua; Yang, Qian; Chen, Ying; Dong, Qian-Qian; Zhang, Bang-Le; Wang, Si-Wang

    2016-01-01

    Paeonol and danshensu is the representative active ingredient of traditional Chinese medicinal herbs Cortex Moutan and Radix Salviae Milthiorrhizae, respectively. Paeonol and danshensu combination (PDSS) has putative cardioprotective effects in treating ischemic heart disease (IHD). However, the evidence for the protective effect is scarce and the pharmacological mechanisms of the combination remain unclear. The present study was designed to investigate the protective effect of PDSS on isoproterenol (ISO)-induced myocardial infarction in rats and to elucidate the potential mechanism. Assays of creatine kinase-MB, cardiac troponin I and T and histopathological analysis revealed PDSS significantly prevented myocardial injury induced by ISO. The ISO-induced profound elevation of oxidative stress was also suppressed by PDSS. TUNEL and caspase-3 activity assay showed that PDSS significantly inhibited apoptosis in myocardia. In exploring the underlying mechanisms of PDSS, we found PDSS enhanced the nuclear translocation of Nrf2 in myocardial injured rats. Furthermore, PDSS increased phosphorylated PI3K and Akt, which may in turn activate antioxidative and antiapoptotic signaling events in rat. These present findings demonstrated that PDSS exerts significant cardioprotective effects against ISO-induced myocardial infarction in rats. The protective effect is, at least partly, via activation of Nrf2/HO-1 signaling and involvement of the PI3K/Akt cell survival signaling pathway. PMID:27021411

  3. Middle age aggravates myocardial ischemia through surprising upholding of complex II activity, oxidative stress, and reduced coronary perfusion.

    PubMed

    Mourmoura, Evangelia; Leguen, Marie; Dubouchaud, Hervé; Couturier, Karine; Vitiello, Damien; Lafond, Jean-Luc; Richardson, Melanie; Leverve, Xavier; Demaison, Luc

    2011-09-01

    Aging compromises restoration of the cardiac mechanical function during reperfusion. We hypothesized that this was due to an ampler release of mitochondrial reactive oxygen species (ROS). This study aimed at characterising ex vivo the mitochondrial ROS release during reperfusion in isolated perfused hearts of middle-aged rats. Causes and consequences on myocardial function of the observed changes were then evaluated. The hearts of rats aged 10- or 52-week old were subjected to global ischemia followed by reperfusion. Mechanical function was monitored throughout the entire procedure. Activities of the respiratory chain complexes and the ratio of aconitase to fumarase activities were determined before ischemia and at the end of reperfusion. H(2)O(2) release was also evaluated in isolated mitochondria. During ischemia, middle-aged hearts displayed a delayed contracture, suggesting a maintained ATP production but also an increased metabolic proton production. Restoration of the mechanical function during reperfusion was however reduced in the middle-aged hearts, due to lower recovery of the coronary flow associated with higher mitochondrial oxidative stress indicated by the aconitase to fumarase ratio in the cardiac tissues. Surprisingly, activity of the respiratory chain complex II was better maintained in the hearts of middle-aged animals, probably because of an enhanced preservation of its membrane lipid environment. This can explain the higher mitochondrial oxidative stress observed in these conditions, since cardiac mitochondria produce much more H(2)O(2) when they oxidize FADH(2)-linked substrates than when they use NADH-linked substrates. In conclusion, the lower restoration of the cardiac mechanical activity during reperfusion in the middle-aged hearts was due to an impaired recovery of the coronary flow and an insufficient oxygen supply. The deterioration of the coronary perfusion was explained by an increased mitochondrial ROS release related to the

  4. Adenosine and Sleep

    PubMed Central

    Bjorness, Theresa E; Greene, Robert W

    2009-01-01

    Over the last several decades the idea that adenosine (Ado) plays a role in sleep control was postulated due in large part to pharmacological studies that showed the ability of Ado agonists to induce sleep and Ado antagonists to decrease sleep. A second wave of research involving in vitro cellular analytic approaches and subsequently, the use of neurochemical tools such as microdialysis, identified a population of cells within the brainstem and basal forebrain arousal centers, with activity that is both tightly coupled to thalamocortical activation and under tonic inhibitory control by Ado. Most recently, genetic tools have been used to show that Ado receptors regulate a key aspect of sleep, the slow wave activity expressed during slow wave sleep. This review will briefly introduce some of the phenomenology of sleep and then summarize the effect of Ado levels on sleep, the effect of sleep on Ado levels, and recent experiments using mutant mouse models to characterize the role for Ado in sleep control and end with a discussion of which Ado receptors are involved in such control. When taken together, these various experiments suggest that while Ado does play a role in sleep control, it is a specific role with specific functional implications and it is one of many neurotransmitters and neuromodulators affecting the complex behavior of sleep. Finally, since the majority of adenosine-related experiments in the sleep field have focused on SWS, this review will focus largely on SWS; however, the role of adenosine in REM sleep behavior will be addressed. PMID:20190965

  5. Assesment of Myocardial Ischemia by Combination of Tissue Synchronisation Imaging and Dobutamine Stress Echocardiography

    PubMed Central

    Aksakal, Enbiya; Gurlertop, Yekta; Simsek, Ziya; Gundogdu, Fuat; Sevimli, Serdar; Bakirci, Eftal Murat; Karakelleoglu, Sule

    2013-01-01

    Background and Objectives Dobutamine stress echocardiography (DSE) is an important non-invasive imaging method for evaluating ischemia. However, wall motion interpretation can be impaired by the experience level of the interpreter and the subjectivity of the visual assessment. In our study we aimed to combine DSE and tissue syncronisation imaging to increase sensitivity for detecting ischemia. Subjects and Methods 50 patients with indications for DSE were included in the study. In 25 patients we found DSE positive for ischemia and in the other 25 patients we found it to be negative. The negative group was accepted as the control group. There was no significant difference in terms of risk factors and echocardiographic parameters between the two groups, except for wall motion scores. In both groups, left ventricular dyssychrony was accepted as the difference between time to peak systolic velocity (Ts) in the reciprocal four couple of non-apical segments at rest and during peak stress. Timings were corrected for heart rate. We compared the differences of the dyssynchronisation value at rest and during peak stress to determine the distinctions within the groups and between the groups of DSE positive and negative patients. Results We found that stress and ischemia did not create any significant difference over the left intraventricular dyssynchrony with DSE, although at the segmenter level it prolonged the time to peak systolic velocity (p<0.05). These alterations did not show any significant difference between positive and negative DSE groups. Conclusion As a result, this segmenter dyssynchrony and the time to peak systolic velocity, which is corrected for heart rate, did not enhance any new value over DSE for detecting ischemia. PMID:23882287

  6. Soy Isoflavone Protects Myocardial Ischemia/Reperfusion Injury through Increasing Endothelial Nitric Oxide Synthase and Decreasing Oxidative Stress in Ovariectomized Rats

    PubMed Central

    Tang, Yan; Li, Shuangyue; Zhang, Ping; Zhu, Jinbiao; Meng, Guoliang; Xie, Liping; Yu, Ying; Ji, Yong; Han, Yi

    2016-01-01

    There is a special role for estrogens in preventing and curing cardiovascular disease in women. Soy isoflavone (SI), a soy-derived phytoestrogen, has similar chemical structure to endogenous estrogen-estradiol. We investigate to elucidate the protective mechanism of SI on myocardial ischemia/reperfusion (MI/R) injury. Female SD rats underwent bilateral ovariectomy. One week later, rats were randomly divided into several groups, sham ovariectomy (control group), ovariectomy with MI/R, or ovariectomy with sham MI/R. Other ovariectomy rats were given different doses of SI or 17β-estradiol (E2). Four weeks later, they were exposed to 30 minutes of left coronary artery occlusion followed by 6 or 24 hours of reperfusion. SI administration significantly reduced myocardial infarct size and improved left ventricle function and restored endothelium-dependent relaxation function of thoracic aortas after MI/R in ovariectomized rats. SI also decreased serum creatine kinase and lactate dehydrogenase activity, reduced plasma malonaldehyde, and attenuated oxidative stress in the myocardium. Meanwhile, SI increased phosphatidylinositol 3 kinase (PI3K)/Akt/endothelial nitric oxide synthase (eNOS) signal pathway. SI failed to decrease infarct size of hearts with I/R in ovariectomized rats if PI3K was inhibited. Overall, these results indicated that SI protects myocardial ischemia/reperfusion injury in ovariectomized rats through increasing PI3K/Akt/eNOS signal pathway and decreasing oxidative stress. PMID:27057277

  7. Adenosine decreases post-ischaemic cardiac TNF-alpha production: anti-inflammatory implications for preconditioning and transplantation.

    PubMed Central

    Meldrum, D R; Cain, B S; Cleveland, J C; Meng, X; Ayala, A; Banerjee, A; Harken, A H

    1997-01-01

    Tumour necrosis factor-alpha (TNF-alpha) is an autocrine contributor to myocardial dysfunction and cardiomyocyte death in ischaemia-reperfusion injury (I/R), sepsis, chronic heart failure and cardiac allograft rejection. Cardiac resident macrophages, infiltrating leucocytes, and cardiomyocytes themselves produce TNF-alpha. Although adenosine reduces macrophage TNF-alpha production and protects myocardium against I/R, it remains unknown whether I/R induces an increase in cardiac TNF-alpha in a crystalloid-perfused model (in the absence of blood), and, whether adenosine decreases cardiac TNF-alpha and protects function after I/R. To study this, isolated rat hearts were crystalloid-perfused using the Langendorff method and subjected to I/R, with or without adenosine pretreatment. Post-ischaemic cardiac TNF-alpha (enzyme-linked immunosorbent assay and bioassay) and function were determined (Langendorff). I/R increased cardiac TNF-alpha and impaired myocardial function. Adenosine decreased cardiac TNF-alpha and improved post-ischaemic functional recovery. This study demonstrates that: first, I/R induces an increase in cardiac tissue TNF-alpha in a crystalloid-perfused model: second, adenosine decreases cardiac TNF-alpha and improves post-ischaemic myocardial function; third, decreased cardiac TNF-alpha may represent a mechanism by which adenosine protects myocardium; and fourth, adenosine-induced suppression of cardiac TNF-alpha may provide an anti-inflammatory link to preconditioning and have implications for cardiac allograft preservation. PMID:9497488

  8. Phosphorylation at Connexin43 Serine-368 Is Necessary for Myocardial Conduction During Metabolic Stress.

    PubMed

    Nassal, Michelle M J; Werdich, Andreas A; Wan, Xiaoping; Hoshi, Malcolm; Deschênes, Isabelle; Rosenbaum, David S; Donahue, J Kevin

    2016-01-01

    Connexin43 (Cx43) phosphorylation alters gap junction localization and function. In particular, phosphorylation at serine-368 (S368) has been suggested to alter gap junctional conductance, but previous reports have shown inconsistent results for both timing and functional effects of S368 phosphorylation. The objective of this study was to determine the functional effects of isolated S368 phosphorylation. We evaluated wild-type Cx43 (AdCx43) and mutations simulating permanent phosphorylation (Ad368E) or preventing phosphorylation (Ad368A) at S368. Function was assessed by optical mapping of electrical conduction in patterned cultures of neonatal rat ventricular myocytes, under baseline and metabolic stress (MS) conditions. Baseline conduction velocity (CV) was similar for all groups. In the AdCx43 and Ad368E groups, MS moderately decreased CV. Ad368A caused complete conduction block during MS. Triton-X solubility assessment showed no change in Cx43 location during conduction impairment. Western blot analysis showed that Cx43-S368 phosphorylation was present at baseline, and that it decreased during MS. Our data indicate that phosphorylation at S368 does not affect CV under baseline conditions, and that preventing S368 phosphorylation makes Cx43 hypersensitive to MS. These results show the critical role of S368 phosphorylation during stress conditions.

  9. Loss of NHE1 activity leads to reduced oxidative stress in heart and mitigates high-fat diet-induced myocardial stress.

    PubMed

    Prasad, Vikram; Lorenz, John N; Miller, Marian L; Vairamani, Kanimozhi; Nieman, Michelle L; Wang, Yigang; Shull, Gary E

    2013-12-01

    Acute inhibition of the NHE1 Na(+)/H(+) exchanger protects against ischemia-reperfusion injury and chronic inhibition attenuates development of cardiac hypertrophy and failure. To determine the cardiac effects of chronic inhibition of NHE1 under non-pathological conditions we used NHE1-null mice as a model of long-term NHE1 inhibition. Cardiovascular performance was relatively normal in Nhe1(-/-) mice although cardiac contractility and relaxation were slightly improved in mutant mice of the FVB/N background. GSH levels and GSH:GSSG ratios were elevated in Nhe1(-/-) hearts indicating an enhanced redox potential. Consistent with a reduced need for antioxidant protection, expression of heat shock proteins Hsp60 and Hsp25 was lower in Nhe1(-/-) hearts. Similarly, expression of mitochondrial superoxide dismutase 2 was reduced, with no increase in expression of other ROS scavenging enzymes. GLUT1 levels were increased in Nhe1(-/-) hearts, the number of lipid droplets in myocytes was reduced, and PDK4 expression was refractory to high-fat diet-induced upregulation observed in wild-type hearts. High-fat diet-induced stress was attenuated in Nhe1(-/-) hearts, as indicated by smaller increases in phosphorylation of Hsp25 and α-B crystallin, and there was better preservation of insulin sensitivity, as evidenced by PKB/Akt phosphorylation. Plasma glucose and insulin levels were lower and high-fat diet-induced hepatic lipid accumulation was reduced in Nhe1(-/-) mice, demonstrating extracardiac effects of NHE1 ablation. These data indicate that long-term ablation of NHE1 activity increases the redox potential, mitigates high-fat diet-induced myocardial stress and fatty liver disease, leads to better preservation of insulin sensitivity, and may alter both cardiac and systemic metabolic substrate handling in mice. PMID:24080184

  10. Eleven-year prognostic value of dobutamine stress (99m)Tc-sestamibi myocardial perfusion imaging in patients with limited exercise capacity.

    PubMed

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

    2015-04-01

    Myocardial perfusion single-photon emission computed tomography is a routine technique for the evaluation of coronary artery disease. However, information on the very long term prognostic value of dobutamine stress single-photon emission computed tomographic myocardial perfusion imaging (MPI) in patients with limited exercise capacity is scarce. The aim of this study was to assess the long-term prognostic value of dobutamine stress technetium-99m ((99m)Tc)-sestamibi MPI in these patients. The study population consisted of a high-risk cohort of 531 consecutive patients with limited exercise capacity who underwent dobutamine stress (99m)Tc-sestamibi MPI for the assessment of known or suspected coronary artery disease. Follow-up was successful in 528 patients. Because of early revascularization, 55 patients were excluded. The present data are based on 473 patients. The end points were all-cause mortality, cardiac death, nonfatal myocardial infarction, and late (>60 days) coronary revascularization. Kaplan-Meier survival curves were performed and univariate and multivariate analyses were performed to identify predictors of very long term outcome. The mean age of the patients was 61 ± 12 years, and 58% were men. Abnormal results (defined as the presence of reversible or fixed defects) were observed in 312 patients (66%). During a mean follow-up period of 11.3 ± 6.7 years, 287 patients (61%) died (all-cause mortality), of whom 125 (26%) died due to cardiac causes. Nonfatal myocardial infarction occurred in 59 patients (12%). Late coronary revascularization was performed in 61 patients (13%). Univariate predictors of major cardiac events included age, male gender, previous infarction, diabetes mellitus, history of angina, heart failure, ST-segment changes, abnormal results on (99m)Tc-sestamibi scan, reversible defect, fixed defect, summed rest score, and summed stress score. Multivariate analysis identified abnormal results on MPI as a strong independent predictor of

  11. Ticagrelor Does Not Inhibit Adenosine Transport at Relevant Concentrations: A Randomized Cross-Over Study in Healthy Subjects In Vivo

    PubMed Central

    Rongen, G. A.; van den Broek, P. H. H.; Bilos, A.; Donders, A. R. T.; Gomes, M. E.; Riksen, N. P.

    2015-01-01

    Background and Purpose In patients with myocardial infarction, ticagrelor reduces cardiovascular and sepsis-related mortality, and can cause dyspnea. It is suggested that this is caused by adenosine receptor stimulation, because in preclinical studies, ticagrelor blocks the nucleoside transporter and increases cellular ATP release. We now investigated the effects of ticagrelor on the adenosine system in humans in vivo. Experimental Approach In a double-blinded, placebo-controlled cross-over trial in 14 healthy subjects, we have tested whether ticagrelor (180 mg) affects adenosine- and dipyridamole-induced forearm vasodilation, as surrogates of nucleoside uptake inhibition and adenosine formation, respectively. Also, ex vivo uptake of adenosine and uridine in isolated red blood cells was measured. Primary endpoint was adenosine-induced vasodilation. Key Results Ticagrelor did not affect adenosine- or dipyridamole-induced forearm vasodilation. Also, ex vivo uptake of adenosine and uridine in isolated red blood cells was not affected by ticagrelor. In vitro, ticagrelor dose-dependently inhibited nucleoside uptake, but only at supra-physiological concentrations. Conclusion and Implications In conclusion, at relevant plasma concentration, ticagrelor does not affect adenosine transport, nor adenosine formation in healthy subjects. Therefore, it is unlikely that this mechanism is a relevant pleiotropic effect of ticagrelor. Trial Registration ClinicalTrials.gov NCT01996735 PMID:26509673

  12. Adenosine Receptors: Expression, Function and Regulation

    PubMed Central

    Sheth, Sandeep; Brito, Rafael; Mukherjea, Debashree; Rybak, Leonard P.; Ramkumar, Vickram

    2014-01-01

    Adenosine receptors (ARs) comprise a group of G protein-coupled receptors (GPCR) which mediate the physiological actions of adenosine. To date, four AR subtypes have been cloned and identified in different tissues. These receptors have distinct localization, signal transduction pathways and different means of regulation upon exposure to agonists. This review will describe the biochemical characteristics and signaling cascade associated with each receptor and provide insight into how these receptors are regulated in response to agonists. A key property of some of these receptors is their ability to serve as sensors of cellular oxidative stress, which is transmitted by transcription factors, such as nuclear factor (NF)-κB, to regulate the expression of ARs. Recent observations of oligomerization of these receptors into homo- and heterodimers will be discussed. In addition, the importance of these receptors in the regulation of normal and pathological processes such as sleep, the development of cancers and in protection against hearing loss will be examined. PMID:24477263

  13. The response of the heart to stress: a biological view of myocardial adaptation and failure.

    PubMed

    Alpert, N R; Mulieri, L A

    1987-01-01

    The response of the myocardium to persistent stress involves an increase in mass and a restructuring of the cellular and subcellular elements. The experiments described in this article are designed to test the hypothesis that the restructuring of the various systems (contractile, excitation-contraction coupling, recovery, etc.) that occurs in adaptive hypertrophy is a coordinated (matched) process. When the restructuring of the systems in response to stress occurs in an uncoordinated fashion, congestive heart failure results. In addition to controls, three heart models with normal pump performance are used (control, C; pressure overload, P; thyrotoxic, T; and pressure overload plus thyrotoxic, PT4) and one with inadequate pump performance (pressure overload plus thyrotoxic, PT2). In this analysis the contractile and excitation-contraction coupling systems are evaluated. The former is assessed by sensitive myothermal measurement of tension dependent heat (TDH) normalized for the isometric tension time integral (integral of Pdt). The latter is assessed from measurement of the time to peak isometric tension (TPT). The TDH/integral of Pdt (mu cal/g.cm.s) and TPT (ms) for the C, P, T, PT4, and PT2 hearts are 2.4, 1.8, 5.2, 5.1, and 0.1, mu cal/g.cm.s and 627, 816, 352, 484, and 465 ms, respectively. According to the coordination or matching hypothesis, if TDH/integral of Pdt is low, then TPT should be increased, or if TDH/integral of Pdt is high, then TPT should be decreased. Relative to control hearts, matched restructuring of the contractile and excitation-contraction coupling systems occurred for the P, T, and PT4 preparations. In these animals the hypertrophy has been adaptive and the pump performance is adequate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2485028

  14. Uric acid induces oxidative stress and growth inhibition by activating adenosine monophosphate-activated protein kinase and extracellular signal-regulated kinase signal pathways in pancreatic β cells.

    PubMed

    Zhang, Yongneng; Yamamoto, Tetsuya; Hisatome, Ichiro; Li, Youfeng; Cheng, Weijie; Sun, Ning; Cai, Bozhi; Huang, Tianliang; Zhu, Yuzhang; Li, Zhi; Jing, Xubin; Zhou, Rui; Cheng, Jidong

    2013-08-15

    Hyperuricaemia is a disorder of purine metabolism, and is strongly associated with insulin resistance and abnormal glucose metabolism. As the producer of insulin, pancreatic β cells might be affected by elevated serum uric acid levels and contribute to the disregulated glucose metabolism. In this study, we investigated the effect of high uric acid on rat pancreatic β cell function. Under high uric acid condition, proliferation of pancreatic β cells was inhibited, production of reactive oxygen species increased, and glucose stimulated insulin secretion was also compromised. Further examination on signal transduction pathways revealed that uric acid-induced ROS is involved in the activation of adenosine monophosphate-activated protein kinase (AMPK), and extracellular signal-regulated kinase (ERK). Pharmacological inhibition of ERK activation rescued β cells from growth inhibition. More importantly, activation of ERK induced by uric acid is significantly diminished by AMPK inhibitor, indicating ERK as a downstream target of AMPK in response to high uric acid condition. We also investigated the transportation channel for uric acid into pancreatic β cells. While major urate transporter URAT1 is not expressed in β cells, organic anion transporter (OAT) inhibitor successfully blocked the activation of ERK by uric acid. Our data indicate that high uric acid levels induce oxidative damage and inhibit growth of rat pancreatic β cells by activating the AMPK and ERK signal pathways. Hyperuricemia may contribute to abnormal glucose metabolism by causing oxidative damage and function inhibition of pancreatic β cells.

  15. Genetics Home Reference: adenosine deaminase 2 deficiency

    MedlinePlus

    ... Health Conditions adenosine deaminase 2 deficiency adenosine deaminase 2 deficiency Enable Javascript to view the expand/collapse ... PDF Open All Close All Description Adenosine deaminase 2 (ADA2) deficiency is a disorder characterized by abnormal ...

  16. No Evidence of Myocardial Oxygen Deprivation in Nonischemic Heart Failure

    PubMed Central

    Dass, Sairia; Holloway, Cameron J.; Cochlin, Lowri E.; Rider, Oliver J.; Mahmod, Masliza; Robson, Matthew; Sever, Emily; Clarke, Kieran; Watkins, Hugh; Ashrafian, Houman; Karamitsos, Theodoros D.

    2015-01-01

    Background— Whether the myocardium in nonischemic heart failure experiences oxygen limitation remains a long-standing controversy. We addressed this question in patients with dilated cardiomyopathy (DCM) using a dual approach. First, we tested the changes in myocardial oxygenation between rest and stress states, using oxygenation-sensitive cardiovascular magnetic resonance. Second, we sought to assess the functional consequences of oxygen limitation at rest by measuring myocardial energetics before and after short-term oxygen supplementation. Methods and Results— Twenty-six subjects (14 DCM and 12 normal) underwent cardiac magnetic resonance imaging at 3 Tesla to assess cardiac volumes, function, oxygenation, and first-pass perfusion (0.03 mmol/kg Gd-DTPA bolus) at stress and rest (4–6 minutes IV adenosine, 140 μg/kg per minute). Signal intensity change (SIΔ) and myocardial perfusion reserve index (MPRI) were measured from oxygenation and perfusion images, respectively. Furthermore, the effect of oxygen supplementation on resting myocardial energy metabolism was tested using 31P MR spectroscopy, measuring PCr/ATP ratios in both groups at baseline and after 4 hours of oxygen via facemask in the DCM group. During stress, there were equivalent rises in rate pressure product in both groups (DCM, 76±15% and normal, 79±9%; P=0.84). MPRI was significantly reduced in DCM (1.51±0.11 versus normal 1.86±0.10; P=0.03). However, there was no difference in oxygenation between groups: SIΔ in DCM 17±3% versus normal 20±2% (P=0.38). Furthermore, at a left ventricular segmental level, there was no correlation between oxygenation-sensitive SIΔ and MPRI (R=0.06; P=0.43). Resting PCr/ATP was reduced in DCM (1.66±0.07 versus normal 2.12±0.06; P=0.002). With oxygen supplementation, there was no change in PCr/ATP (1.61±0.08; P=0.58; Δ=0.04±0.05). There was also no effect of oxygen on systolic function (ejection fraction pre oxygen, 34±1%; post oxygen, 36±2%; P=0

  17. Imaging Adenosine Triphosphate (ATP).

    PubMed

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

    2016-08-01

    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 provide 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 the organismal levels in live specimens. Over the last several decades, a number of molecular probes that are specific to 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 available for visualizing ATP in living cells, and identify areas where new tools and approaches are needed to expand our capabilities. PMID:27638696

  18. Imaging Adenosine Triphosphate (ATP).

    PubMed

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

    2016-08-01

    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 provide 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 the organismal levels in live specimens. Over the last several decades, a number of molecular probes that are specific to 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 available for visualizing ATP in living cells, and identify areas where new tools and approaches are needed to expand our capabilities.

  19. 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.

  20. The Munich Triathlon Heart Study: ventricular function, myocardial velocities, and two-dimensional strain in healthy children before and after endurance stress.

    PubMed

    Hauser, Michael; Petzuch, Kurt; Kühn, Andreas; Schön, Patrick; Elmenhorst, Julia; Schönfelder, Martin; Oberhoffer, Renate; Vogt, Manfred O

    2013-03-01

    Intense exercise has been shown to have negative effects on systolic and diastolic ventricular function in adults. Very little is known about the normal reaction of the growing heart to endurance stress. For this study, 26 healthy children (18 males) with a mean age of 12.61 years (range, 7.92-16.42 years) took part in an age-adapted triathlon circuit. The athletes were investigated by two-dimensional (2D) echocardiographic/speckle tracking, M-mode, pulse-wave Doppler, color Doppler, and color-coded tissue Doppler at 2-4 weeks before and immediately after the race. After the competition, cardiac output increased, mediated by an increase in heart rate and not by an elevated preload, according the Frank-Starling mechanism. Two-dimensional speckle tracking showed a reduced longitudinal strain in the right and left ventricles and additionally reduced circumferential strain in the left ventricle. The late diastolic inflow velocities were increased in both ventricles, indicating reduced diastolic function due to an impairment of myocardial relaxation. Immediately after endurance exercise, systolic and diastolic functions were attenuated in children and adolescents. In contrast to adult studies, this study could show a heart rate-mediated increase in cardiac output. The sequelae of these alterations are unclear, and the growing heart especially may be more susceptible to myocardial damage caused by intense endurance stress.

  1. Expression profiles of heat shock protein 27 and αB-crystallin and their effects on heat-stressed rat myocardial cells in vitro and in vivo.

    PubMed

    Tang, Shu; Chen, Hongbo; Cheng, Yanfen; Nasir, Mohammad Abdel; Kemper, Nicole; Bao, Endong

    2016-02-01

    The present study established a heat-stressed rat heart model, and used an H9c2 myocardial cell line to investigate the expression profiles of heat shock protein (Hsp)27 and αB-crystallin, both in vivo and in vitro. Rats and myocardial cells were subjected to 42 ˚C for 0, 20, 40, 60, 80 or 100 min, following which the mRNA and protein expression levels of Hsp27 and αB-crystallin were measured. Following heat shock, the protein expression levels of Hsp27 and αB-crystallin were significantly decreased in the rat heart cells in vivo, whereas their mRNA levels were significantly increased. The opposing association between the protein and mRNA expression levels of Hsp27 and αB-crystallin suggests that the progression from mRNA into proteins via translation may delayed, or proteins may exist as either oligomers or in the phosphorylated form under heat stress. In vitro, Hsp27 and αB-crystallin exhibited similar reductions in the protein levels at 40 and 60 min, then increased to normal values following 80 min of heat stress. However, the mRNA levels were not consistent with the protein levels. The mRNA levels of Hsp27 and αB-crystallin did however exhibit similar tendencies following 60 min of heat stress. The present study investigated these apparently conflicting results between the in vitro cell line and the in vivo body system. The results demonstrated that the protein and mRNA expression levels of Hsp27 and αB-crystallin exhibited similar trends in vivo and in vitro, respectively. These results were confirmed by analysis with STRING 9.1 software, which indicated that Hsp27 and αB-crystallin are co-expressed in rat myocardial cells. However, the individual cell lines and whole body system exhibited different trends in Hsp27 and αB-crystallin levels prior to and following heat stress, thus require further investigation.

  2. 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

  3. [Mechanisms of gross saponins of Tribulus terrestris via activating PKCepsilon against myocardial apoptosis induced by oxidative stress].

    PubMed

    Wang, Si-Si; Ji, Ying-Shi; Li, Hong; Yang, Shi-Jie

    2009-02-01

    This study is to observe the effect of gross saponins of Tribulus terrestris (GSTT) on protein kinase Cepsilon (PKCepsilon) and apoptosis-associated protein in the apoptosis of cultured cardiocyte apoptosis induced by hydrogen peroxide (H2O2), and to explore the mechanisms of GSTT against myocardial apoptosis. Primary cardiocytes were isolated and cultured. Myocardial apoptosis was induced by H2O2 and analyzed with flow cytometry. Protein content of phospho-PKCepsilon, Bcl-2, and Bax were detected with Western blotting analysis. Cleaved caspase-3 protein content was determined with immunocytochemical technique. After the pretreatment of 100 mg x L(-1) GSTT, compared with H2O2 group, GSTT could not only decrease the apoptotic percentage in cardiocytes damaged by H2O2 (P < 0.01), but also reduce protein contents of Bax and cleaved caspase-3 (P < 0.01), and increase protein content of phospho-PKCepsilon and Bcl-2 significantly (P < 0.01). PKC inhibitor chelerythrine (Che) could prevent partly the effect of GSTT against myocardial apoptosis (P < 0.05 and P < 0.01). Mechanisms of GSTT against myocardial apoptosis might be associated with inhibition of mitochondrial apoptosis pathway after PKCepsilon activation.

  4. 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

  5. Chrysin, a PPAR-γ agonist improves myocardial injury in diabetic rats through inhibiting AGE-RAGE mediated oxidative stress and inflammation.

    PubMed

    Rani, Neha; Bharti, Saurabh; Bhatia, Jagriti; Nag, T C; Ray, Ruma; Arya, Dharamvir Singh

    2016-04-25

    AGE-RAGE interaction mediated oxidative stress and inflammation is the key mechanism involved in the pathogenesis of cardiovascular disease in diabetes. Inhibition of AGE-RAGE axis by several PPAR-γ agonists has shown positive results in ameliorating cardio-metabolic disease conditions. Chrysin, a natural flavonoid has shown to possess PPAR-γ agonist activity along with antioxidant and anti-inflammatory effect. Therefore, the present study was designed to evaluate the effect of chrysin in isoproterenol-induced myocardial injury in diabetic rats. In male albino Wistar rats, diabetes was induced by single injection of streptozotocin (70 mg/kg, i.p.). After confirmation of the diabetes, rats were treated with vehicle (1.5 mL/kg, p.o.), chrysin (60 mg/kg, p.o.) or PPAR-γ antagonist GW9662 (1 mg/kg, i.p.) for 28 days. Simultaneously, on 27th and 28th day myocardial injury was induced by isoproterenol (85 mg/kg, s.c.). Chrysin significantly ameliorated cardiac dysfunction as reflected by improved MAP, ±LVdP/dtmax and LVEDP in diabetic rats. This improvement was associated with increased PPAR-γ expression and reduced RAGE expression in diabetic rats. Chrysin significantly decreased inflammation through inhibiting NF-κBp65/IKK-β expression and TNF-α level. Additionally, chrysin significantly reduced apoptosis as indicated by augmented Bcl-2 expression and decreased Bax and caspase-3 expressions. Furthermore, chrysin inhibited nitro-oxidative stress by normalizing the alteration in 8-OHdG, GSH, TBARS, NO and CAT levels and Nox4, MnSOD, eNOS and NT expressions. Co-administration of GW9662 significantly blunted the chrysin mediated cardioprotective effect as there was increase in oxidative stress, inflammation and apoptosis markers. Chrysin significantly ameliorated isoproterenol-induced myocardial injury in diabetic rats via PPAR-γ activation and inhibition of AGE-RAGE mediated oxidative stress and inflammation. PMID:26972669

  6. Myocardial Bridging

    PubMed Central

    Yuan, Shi-Min

    2016-01-01

    Myocardial bridging is rare. Myocardial bridges are most commonly localized in the middle segment of the left anterior descending coronary artery. The anatomic features of the bridges vary significantly. Alterations of the endothelial morphology and the vasoactive agents impact on the progression of atherosclerosis of myocardial bridging. Patients may present with chest pain, myocardial infarction, arrhythmia and even sudden death. Patients who respond poorly to the medical treatment with β-blockers warrant a surgical intervention. Myotomy is a preferred surgical procedure for the symptomatic patients. Coronary stent deployment has been in limited use due to the unsatisfactory long-term results. PMID:27074276

  7. Immediate response of Ca2+ concentration in myocardial cells against oxidation stress by extracellular photosensitization reaction using Talaporfin sodium for the arrhythmia treatment application

    NASA Astrophysics Data System (ADS)

    Ogawa, Emiyu; Takahashi, Mei; Ito, Arisa; Arai, Tsunenori

    2014-02-01

    We studied the immediate response of myocardial cells by continuous observation using confocal microscope against oxidation stress by extracellular photosensitization reaction using Talaporfin sodium for tachyarrhythmia treatment application. Immediate response in order from several seconds to several minutes is required for the arrhythmia treatment since operators should judge the therapeutic effect during the tachyarrhythmia ablation procedure. To understand the immediate response of myocardial cells, we measured the intracellular Ca2+ concentration using fluo-4 AM during and after the extracellular photosensitization reaction. Talaporfin sodium concentration was varied 10-30 μg/ml. A red diode laser of 663 nm in wavelength was irradiated under the microscope with the radiant exposure of 40 J/cm2 and irradiance of 0.29 W/cm2. We observed the fluorescence image of fluo-4 AM each 400 ms during until 10 min after the photosensitization reaction. The myocardial cell beatings were stopped about 2 s after the beginning of the laser irradiation. The blebs were formed with the Ca2+ inflow. The intracellular Ca2+ was re-decreased after the bleb formation and then the cell necrosis was induced. The cell lethality 10 min after the laser irradiation was less than bleb formation ratio. The time response of the cell necrosis was shortened with the photosensitizer concentration increasing and the minimum average value was 209 s in the case of the 30 μg/ml in photosensitizer concentration and 40 J/cm2 in the radiant exposure. We think this extracellular photosensitization reaction may be applicable to tachyarrhythmia treatment in terms of its immediate response.

  8. Nongenomic effects of estrogen mediate the dose-related myocardial oxidative stress and dysfunction caused by acute ethanol in female rats

    PubMed Central

    El-Mas, Mahmoud M.

    2013-01-01

    Acute ethanol lowers blood pressure (BP) and cardiac output in proestrus and after chronic estrogen (E2) replacement in ovariectomized (OVX) female rats. However, whether rapid nongenomic effects of estrogen mediate these hemodynamic effects of ethanol remains unanswered. To test this hypothesis, we investigated the effect of ethanol (0.5 or 1.5 g/kg iv) on left ventricular (LV) function and oxidative markers in OVX rats pretreated 30 min earlier with 1 μg/kg E2 (OVXE2) or vehicle (OVX) and in proestrus sham-operated (SO) rats. In SO rats, ethanol caused significant and dose-related reductions in BP, rate of rise in LV pressure (LV dP/dtmax), and LV developed pressure (LVDP). These effects of ethanol disappeared in OVX rats and were restored in OVXE2 rats, suggesting rapid estrogen receptor signaling mediates the detrimental effects of ethanol on LV function. Ex vivo studies revealed that the estrogen-dependent myocardial dysfunction caused by ethanol was coupled with higher LV 1) generation of reactive oxygen species (ROS), 2) expression of malondialdehyde and 4-hydroxynonenal protein adducts, 3) phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinases (ERK1/2), and 4) catalase activity. ERK1/2 inhibition by PD-98059 (1 mg/kg iv) abrogated the myocardial dysfunction, hypotension, and the elevation in myocardial ROS generation caused by ethanol. We conclude that rapid estrogen receptor signaling is implicated in cellular events that lead to the generation of aldehyde protein adducts and Akt/ERK1/2 phosphorylation, which ultimately mediate the estrogen-dependent LV oxidative stress and dysfunction caused by ethanol in female rats. PMID:24368668

  9. 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

  10. Coconut Haustorium Maintains Cardiac Integrity and Alleviates Oxidative Stress in Rats Subjected to Isoproterenol-induced Myocardial Infarction

    PubMed Central

    Chikku, A. M.; Rajamohan, T.

    2012-01-01

    The present study evaluates the effect of aqueous extract of coconut haustorium on isoproterenol-induced myocardial infarction in Sprague Dawley rats. Rats were pretreated with aqueous extract of coconut haustorium (40 mg/100 g) orally for 45 days. After pretreatment, myocardial infarction was induced by injecting isoproterenol subcutaneously (20 mg/100 g body weight) twice at an interval of 24 h. Activity of marker enzymes like lactate dehydrogenase, creatinine kinase-MB, aspartate transaminase and alanine transaminase were increased in the serum and decreased in the heart of isoproterenol treated rats indicating cardiac damage. These changes were significantly reduced in haustorium pretreated rats. Moreover, an increase in the activities of antioxidant enzymes and decrease in the levels of peroxidation products were observed in the myocardium of coconut haustorium pretreated rats. Histopathology of the heart of these rats showed almost normal tissue morphology. From these results, it is clear that aqueous extract of coconut haustorium possess significant cardioprotective and antioxidant properties during isoproterenol-induced myocardial infarction in rats. PMID:23716867

  11. Endoplasmic Reticulum Is Involved in Myocardial Injury in a Miniature Swine Model of Coronary Artery Stenosis Exposed to Acceleration-Associated Stress

    PubMed Central

    Zhang, Haitao; Chai, Meng; Liu, Chaozhong; Sun, Jinjin; Huang, Congchun; Yu, Xinya; Tian, Yi; Luo, Huilan

    2015-01-01

    This study aimed to investigate the effects of myocardial injury in a minimally-invasive miniature swine model with different levels of coronary artery stenosis (CAS) and exposed to maximal tolerated +Gz. Proximal left anterior descending branch was ligated in 20 swine. Five swine underwent a sham operation. A trapezoid acceleration curve was used for +Gz stress. Pathological changes of myocardial tissue were detected by H&E staining. Apoptotic cardiomyocytes were detected by TUNEL. GRP78 and CHOP were investigated by immunohistochemistry and western blot. CAS models were successful in 18 animals.Compared with the sham-operated group (+8.00±0.71 Gz), the maximal tolerated +Gz values of the moderate stenosis (+6.00±0.89 Gz, P<0.05) and severe stenosis groups (+5.20±0.84 Gz, P<0.05) were decreased.Compared with sham animals (12.16±1.25%), after exposure to maximum +Gz, apoptotic cells of the moderate (43.53±8.42%, P<0.05) and severe stenosis group (60.50±9.35%, P<0.05) were increased, MDA content was increased (1.89 and 4.91 folds, respectively, P<0.05), and SOD activity was reduced (-13.66% and -21.71%, respectively). After exposure to maximum +Gz, GRP78 protein expression was low in the sham-operated (0.29±0.05) and mild stenosis groups (0.35±0.04), while expression was high in the moderate (0.72±0.04, P<0.05) and severe stenosis groups (0.65±0.07, P<0.05). CHOP protein expression was not observed in the sham-operated group, while expression was high in the moderate and severe stenosis groups. These results indicated that Under maximum exposure to +Gz stress, different levels of CAS led to different levels of myocardial injury. Endoplasmic reticulum response is involved in the apoptosis of cardiomyocytes after +Gz stress. PMID:26167928

  12. 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

  13. 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

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

    PubMed Central

    Davidson, Jesse A.; Urban, Tracy; Tong, Suhong; Twite, Mark; Woodruff, Alan

    2016-01-01

    Rationale 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. Objectives 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. Methods and Research 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). Conclusions Alkaline phosphatase represents the primary serum ectonucleotidase after infant cardiac surgery and low post

  15. Comparative study of single-injection, single-acquisition 99mTc-MIBI gated SPET and stress-rest perfusion SPET for the evaluation of myocardial viability after bypass surgery in coronary artery disease.

    PubMed

    Yoon, S N; Lee, D S; Chung, J K; Lee, M C

    2000-12-01

    In patients without previous myocardial infarction, the single-injection stress perfusion/rest function (SISPRF) approach using stress technetium-99m methoxyisobutylisonitrile (MIBI) gated single-photon emission tomography (SPET) can substitute for conventional stress-rest myocardial perfusion imaging for the assessment of myocardial viability. This study compared pre-operative single-injection, single-acquisition 99mTc-MIBI gated SPET and conventional stress-rest imaging for the prediction of myocardial viability in patients who underwent coronary artery bypass surgery (CABG). Rest thallium-201 SPET followed by stress 99mTc-MIBI gated SPET was performed in 20 patients [nine with previous myocardial infarction (MI) and 11 without previous MI). The study was performed before and 3 months after CABG, and viability assessment was validated by wall motion improvement after CABG. A four-point scoring system (0-3 for normal to absent tracer uptake) for 17 segments of the left ventricular myocardium was used for the assessment of stress and rest uptake. Wall motion, wall thickening and perfusion status were analysed by semi-quantitative visual assessment. On gated SPET, perfusion defect reversibility was considered present when a definite perfusion defect was observed and wall motion or thickening was normal or showed only a mild decrease. In patients with a previous MI, the left ventricular ejection fraction improved significantly after CABG (46% +/- 7% vs 42% +/- 11% before CABG, P < 0.05). In patients without previous MI, the ejection fraction improved significantly after CABG (50 +/- 12% vs 44% +/- 16% before CABG, P<0.05). In patients with previous MI, positive predictive values using the stress-rest reversibility and SISPRF approaches were 91% and 90%, respectively, and corresponding negative predictive values were 25% and 18%. In patients without previous MI, positive predictive values using the stress-rest and SISPRF approaches were 70% and 61%, respectively, and

  16. Introduction to Adenosine Receptors as Therapeutic Targets

    PubMed Central

    Jacobson, Kenneth A.

    2012-01-01

    Adenosine acts as a cytoprotective modulator in response to stress to an organ or tissue. Although short-lived in the circulation, it can activate four sub-types of G protein-coupled adenosine receptors (ARs): A1, A2A, A2B, and A3. The alkylxanthines caffeine and theophylline are the prototypical antagonists of ARs, and their stimulant actions occur primarily through this mechanism. For each of the four AR subtypes, selective agonists and antagonists have been introduced and used to develop new therapeutic drug concepts. ARs are notable among the GPCR family in the number and variety of agonist therapeutic candidates that have been proposed. The selective and potent synthetic AR agonists, which are typically much longer lasting in the body than adenosine, have potential therapeutic applications based on their anti-inflammatory (A2A and A3), cardioprotective (preconditioning by A1 and A3 and postconditioning by A2B), cerebroprotective (A1 and A3), and antinociceptive (A1) properties. Potent and selective AR antagonists display therapeutic potential as kidney protective (A1), antifibrotic (A2A), neuroprotective (A2A), and antiglaucoma (A3) agents. AR agonists for cardiac imaging and positron-emitting AR antagonists are in development for diagnostic applications. Allosteric modulators of A1 and A3 ARs have been described. In addition to the use of selective agonists/antagonists as pharmacological tools, mouse strains in which an AR has been genetically deleted have aided in developing novel drug concepts based on the modulation of ARs. PMID:19639277

  17. 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.

  18. Stress testing predischarge and six weeks after myocardial infarction to compare submaximal and maximal exercise predischarge and to assess the reproducibility of induced abnormalities.

    PubMed

    Handler, C E; Sowton, E

    1985-10-01

    Submaximal and maximal treadmill exercise tests were performed predischarge in 64 patients after acute myocardial infarction to assess the relative yield of residual ischaemic abnormalities. The reproducibility of individual abnormalities resulting from maximal stress tests performed predischarge and 6 weeks after infarction was also assessed in 55 of these patients. Compared with predischarge submaximal exercise testing, a maximal exercise test identified a significantly greater number of patients with residual myocardial ischaemia (26 vs. 15, P less than 0.05) and this was associated with a significantly longer average maximal exercise duration (P less than 0.001), and a higher rate-pressure product (P less than 0.001). Among the 55 patients who had maximal stress tests both predischarge and 6 weeks after infarction, there was a significant lack of reproducibility in the occurrence of exercise induced angina (P less than 0.01) and an abnormal blood pressure response (P less than 0.02). In contrast, exercise induced ST segment depression and elevation and ventricular arrhythmias were relatively reproducible. More patients had an ischaemic test result (ST depression or angina) at the later test compared to the predischarge test (33 vs. 25 patients) but this increase was not statistically significant. There were, however, significant increases at the later test in mean maximal exercise duration (P less than 0.001). mean maximal heart rate (P less than 0.001) and heart rate-systolic blood pressure double product (P less than 0.001). The majority of patients who had a cardiac event in the period between the two tests had a predischarge test abnormality. We conclude that a significantly greater number of patients with residual reversible myocardial ischaemia after infarction will be identified by symptom limited exercise testing compared with a submaximal predischarge test. Because ST depression and elevation appear reproducible, patients who develop these

  19. Genetics Home Reference: adenosine monophosphate deaminase deficiency

    MedlinePlus

    Skip to main content Your Guide to Understanding Genetic Conditions Enable Javascript for addthis links to activate. ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Home Health Conditions adenosine monophosphate deaminase deficiency adenosine ...

  20. Treatment with bone morphogenetic protein 2 limits infarct size after myocardial infarction in mice.

    PubMed

    Ebelt, Henning; Hillebrand, Ina; Arlt, Stephan; Zhang, Ying; Kostin, Sawa; Neuhaus, Herbert; Müller-Werdan, Ursula; Schwarz, Elisabeth; Werdan, Karl; Braun, Thomas

    2013-04-01

    Various strategies have been devised to reduce the clinical consequences of myocardial infarction, including acute medical care, revascularization, stem cell transplantations, and more recently, prevention of cardiomyocyte cell death. Activation of embryonic signaling pathways is a particularly interesting option to complement these strategies and to improve the functional performance and survival rate of cardiomyocytes. Here, we have concentrated on bone morphogenetic protein 2 (BMP-2), which induces ectopic formation of beating cardiomyocytes during development in the mesoderm and protects neonatal cardiomyocytes from ischemia-reperfusion injury. In a mouse model of acute myocardial infarction, an i.v. injection of BMP-2 reduced infarct size in mice when given after left anterior descending artery ligation. Mice treated with BMP-2 are characterized by a reduced rate of apoptotic cardiomyocytes both in the border zone of the infarcts and in the remote myocardium. In vitro, BMP-2 increases the frequency of spontaneously beating neonatal cardiomyocytes and the contractile performance under electrical pacing at 2 Hz, preserves cellular adenosine triphosphate stores, and decreases the rate of apoptosis despite the increased workload. In addition, BMP-2 specifically induced phosphorylation of Smad1/5/8 proteins and protected adult cardiomyocytes from long-lasting hypoxia-induced cellular damage and oxidative stress without activation of the cardiodepressant transforming growth factor-β pathway. Our data suggest that BMP-2 treatment may have considerable therapeutic potential in individuals with acute and chronic myocardial ischemia by improving the contractility of cardiomyocytes and preventing cardiomyocyte cell death.

  1. TAK1 Regulates Myocardial Response to Pathological Stress via NFAT, NFκB, and Bnip3 Pathways.

    PubMed

    Li, Lei; Chen, Yi; Li, Jing; Yin, Haifeng; Guo, Xiaoyun; Doan, Jessica; Molkentin, Jeffery D; Liu, Qinghang

    2015-11-13

    TAK1 (TGFβ-activated kinase-1) signaling is essential in regulating a number of important biological functions, including innate immunity, inflammatory response, cell growth and differentiation, and myocardial homeostasis. The precise role of TAK1 in the adult heart under pathological conditions remains largely unknown. Importantly, we observed that TAK1 is upregulated during compensatory hypertrophy but downregulated in end-stage heart failure. Here we generated transgenic mice with inducible expression of an active TAK1 mutant (TAK1ΔN) in the adult heart. TAK1ΔN transgenic mice developed greater cardiac hypertrophy compared with control mice after transverse aortic constriction (TAC), which was largely blocked by ablation of calcineurin Aβ. Expression of TAK1ΔN also promoted NFAT (nuclear factor of activated T-cells) transcriptional activity in luciferase reporter mice at baseline, which was further enhanced after TAC. Our results revealed that activation of TAK1 promoted adaptive cardiac hypertrophy through a cross-talk between calcineurin-NFAT and IKK-NFκB pathways. More significantly, adult-onset inducible expression of TAK1ΔN protected the myocardium from adverse remodeling and heart failure after myocardial infarction or long-term pressure overload, by preventing cardiac cell death and fibrosis. Mechanistically, TAK1 exerts its cardioprotective effect through activation of NFAT/NFκB, downregulation of Bnip3, and inhibition of cardiac cell death.

  2. Detection of coronary artery stenosis in children with Kawasaki disease. Usefulness of pharmacologic stress sup 201 Tl myocardial tomography

    SciTech Connect

    Kondo, C.; Hiroe, M.; Nakanishi, T.; Takao, A. )

    1989-09-01

    This study determined the feasibility and accuracy of quantitative 201Tl myocardial single-photon emission computed tomography (SPECT) after dipyridamole infusion to detect coronary obstructive lesions in children with Kawasaki disease. 201Tl distribution after dipyridamole infusion was measured in 23 normal children, and with these normal values, quantitative analysis of SPECT was performed in 49 patients. Thirty-four patients had coronary stenosis 90% or greater on angiograms. Side effects resulting from systemic vasodilation were observed in about 70%. Angina pectoris and ischemic ST changes were observed only in patients with coronary stenosis. These symptoms disappeared after aminophylline infusion. Results of visual and quantitative analysis of SPECT were compared. SPECT data were shown on two-dimensional polar maps, and the extent and severity scores were calculated. The sensitivity of SPECT for detection of overall coronary stenosis was 91% (visual analysis) and 88% (quantitative analysis). The specificity of SPECT was 60% visually and 93% quantitatively. The sensitivity of quantitative analysis to detect individual coronary stenosis was similar to that of visual analysis. However, the specificity of visual analysis to detect individual coronary artery stenosis was significantly less than that of quantitative analysis. From these data, we conclude that quantitative analysis of myocardial SPECT after dipyridamole infusion is a safe and accurate diagnostic method for identifying coronary stenosis in children with Kawasaki disease.

  3. Brain vasopressin V(1) receptors contribute to enhanced cardiovascular responses to acute stress in chronically stressed rats and rats with myocardial infarcton.

    PubMed

    Cudnoch-Jedrzejewska, Agnieszka; Szczepanska-Sadowska, Ewa; Dobruch, Jakub; Gomolka, Ryszard; Puchalska, Liana

    2010-03-01

    The present study was designed to determine the role of central vasopressin 1 receptors (V(1)R) in the regulation of cardiovascular parameters in chronically stressed infarcted rats and sham-operated rats under resting conditions and during exposure to acute alarming stress. The experiments were performed on four groups of conscious sham-operated and four groups of infarcted rats subjected to intraventricular infusion of either vehicle or a V(1)R antagonist (V(1)RANT). Two groups of infarcted and two groups of sham-operated rats were subjected to mild chronic stressing. Mean arterial blood pressure (MABP) and heart rate (HR) were determined under resting conditions and after exposure to acute stress (air jet). During vehicle infusion, MABP and HR increases in response to acute stress in the infarcted rats not subjected to chronic stress, and in the infarcted and sham-operated chronically stressed rats, were significantly greater than in the sham-operated rats not exposed to chronic stress. However, MABP and HR responses to acute stress in the chronically stressed infarcted rats and chronically stressed sham-operated rats did not differ. V(1)RANT abolished differences in cardiovascular responses to acute stress between the experimental groups. Resting cardiovascular parameters were not affected by any of the experimental treatments. It is concluded that chronic stressing enhances the pressor and tachycardic responses to acute stress in the sham-operated rats but does not further intensify these responses in infarcted rats.The results provide evidence that central V(1)Rs are involved in potentiation of cardiovascular responses to acute stress in chronically stressed rats, infarcted rats, and chronically stressed infarcted rats.

  4. Myocardial Bridge

    MedlinePlus

    ... artery. See also on this site: Ask a Texas Heart Institute Doctor: Search "myocardial bridge" Updated August ... comments. Terms of Use and Privacy Policy © Copyright Texas Heart Institute All rights reserved.

  5. Normal Myocardial Flow Reserve in HIV-Infected Patients on Stable Antiretroviral Therapy

    PubMed Central

    Knudsen, Andreas; Christensen, Thomas E.; Ghotbi, Adam Ali; Hasbak, Philip; Lebech, Anne-Mette; Kjær, Andreas; Ripa, Rasmus Sejersten

    2015-01-01

    Abstract Studies have found HIV-infected patients to be at increased risk of myocardial infarction, which may be caused by coronary microvascular dysfunction. For the first time among HIV-infected patients, we assessed the myocardial flow reserve (MFR) by Rubidium-82 (82Rb) positron emission tomography (PET), which can quantify the coronary microvascular function. MFR has proved highly predictive of future coronary artery disease and cardiovascular events in the general population. In a prospective cross-sectional study, HIV-infected patients all receiving antiretroviral therapy (ART) with full viral suppression and HIV-uninfected controls were scanned using 82Rb PET/computed tomography at rest and adenosine-induced stress, thereby obtaining the MFR (stress flow/rest flow), stratified into low ≤1.5, borderline >1.5 to 2.0, or normal >2.0. Fifty-six HIV-infected patients and 25 controls were included. The HIV-infected patients had a mean age of 53 years (range 37–68 years) with 23% active smokers. The controls had a mean age of 52 years (range 36–68 years) and 26% active smokers. In the HIV-infected group 73% had a normal MFR, 17% borderline, and 10% low values of MFR. Among controls these values were 71%, 19%, and 10%, respectively (P = 0.99). However, the HIV-infected group had lower values of stress myocardial blood flow (MBF) (2.63 ± 0.09 mL/g/min vs 2.99 ± 0.14 mL/g/min; P = 0.03). We found no evidence of decreased MFR as assessed by 82Rb PET among HIV-infected patients on stable ART with full viral suppression compared with HIV-uninfected controls. We did notice a decreased MBF during stress. PMID:26512605

  6. Usefulness of MRI to demonstrate the mechanisms of myocardial ischemia in hypertrophic cardiomyopathy with myocardial bridge.

    PubMed

    Thomson, Vivien; Botnar, Rene; Croisille, Pierre

    2007-01-01

    We present a case of symptomatic primary hypertrophic cardiomyopathy (HCM) associated with myocardial bridging of the left anterior descending (LAD) artery and suspected ischemia that could be related either to LAD artery compression or to microvascular perfusion abnormalities. MRI demonstrated the morphological appearance of myocardial hypertrophy, and coronary MR angiography evidenced the myocardial bridge and its functional consequences with stress MR perfusion. In conclusion, as a non-invasive comprehensive imaging technique, MRI should be considered in identifying the mechanisms of myocardial ischemia in HCM with myocardial bridge. PMID:16888385

  7. 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. PMID:27063086

  8. Baicalin ameliorates isoproterenol-induced acute myocardial infarction through iNOS, inflammation, oxidative stress and P38MAPK pathway in rat

    PubMed Central

    Sun, Shen-Jie; Wu, Xiao-Peng; Song, Heng-Liang; Li, Gui-Qi

    2015-01-01

    Baicalin is one of the active ingredients in the skullcap, with a variety of pharmacological effects, such as blood pressure reduction, sedation, liver-protection, gallbladder-protection, anti-bacteria, anti-inflammation, etc. The aim of this study was to investigate the potential cardioprotective effects of baicalin ameliorates isoproterenol-induced acute myocardial infarction (AMI) through inducible nitric oxide synthase (iNOS), inflammation, oxidative stress and P38MAPK passageway in rat. Rat model of AMI was induced by isoproterenol (100 mg/kg) and then treated baicalin (various does of baicalin: 1 mg/kg, 10 mg/kg and 100 mg/kg, respectively) for 24 h. Infarct size, the heart weight to body weight ratio and creatine kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT) of rats with AMI induced by isoproterenol were used to evaluate curative effect of baicalin on AMI. Meanwhile, iNOS and phosphorylation-p38 MAPK (p-p38) protein expressions, inflammatory factor and oxidative stress were inspected using western blot and commercial kits, respectively. In the present study, pre-treatment with baicalin (10 or 100 mg/kg) significantly ameliorated infarct size, the heart weight to body weight ratio and CK, CK-MB, LDH and cTnT levels in rats with AMI induced by isoproterenol. iNOS protein expression, the serum TNF-α, IL-6, MDA and SOD levels and p-38 protein expressions were significantly suppressed by treatment with baicalin (10 or 100 mg/kg). These results suggest that acute treatment with baicalin ameliorates AMI, iNOS, inflammation, oxidative stress and P38MAPK pathway in rat with AMI induced by isoproterenol. PMID:26885181

  9. Myocardial infarction worsens glomerular injury and microalbuminuria in rats with pre-existing renal impairment accompanied by the activation of ER stress and inflammation.

    PubMed

    Dong, Zhifeng; Wu, Penglong; Li, Yongguang; Shen, Yuan; Xin, Ping; Li, Shuai; Wang, Zhihua; Dai, Xiaoyan; Zhu, Wei; Wei, Meng

    2014-12-01

    Deterioration of renal function occurs after chronic heart failure in approximately one-third of patients, particularly in those with pre-existing renal impairment such as diabetic nephropathy. Impaired renal function in these patients is always associated with a worse prognosis. However, the mechanisms underlying such deterioration of renal function are still largely unknown. In three separate protocols, we compared 1) sham operation (Ctr, n = 10) with surgically induced myocardial infarction (MI, n = 10); 2) unilateral nephrectomy (UNX, n = 10) with UNX + MI (n = 10); and 3) STZ-induced type 1 diabetes (DB, n = 10) with DB + MI (n = 10). The differences between combined injury models (UNX + MI, DB + MI) and simple MI were also examined. Renal remodeling, function, ER stress (CHOP and GRP78) and inflammation (infiltration of inflammatory cells, NF-κB p65) were evaluated 12 weeks after MI. In common SD rats, MI activated less glomerular ER stress and inflammation, resulting in a minor change of glomerular remodeling and microalbuminuria. However, MI significantly increased the glomerular expression of GRP78 and CHOP in UNX and DB rats. In addition, it also promoted the infiltration of CD4+ T cells, particularly inflammatory cytokine (IFN-γ, IL-17, IL-4)-producing CD4+ T cells, and the expression of NF-κB p65 in the glomeruli. By contrast, significant glomerular fibrosis, glomerulosclerosis, podocyte injury and microalbuminuria were found in rats with UNX + MI and DB + MI. MI significantly increased chronic glomerular injury and microalbuminuria at 12 weeks in rats with pre-existing renal impairment, i.e., UNX and DB, but not common SD rats. These changes were accompanied by increased glomerular ER stress and immune-associated inflammation.

  10. The Rickettsia prowazekii invasion gene homolog (invA) encodes a Nudix hydrolase active on adenosine (5')-pentaphospho-(5')-adenosine.

    PubMed

    Gaywee, Jariyanart; Xu, WenLian; Radulovic, Suzana; Bessman, Maurice J; Azad, Abdu F

    2002-03-01

    The genomic sequence of Rickettsia prowazekii, the obligate intracellular bacterium responsible for epidemic typhus, reveals an uncharacterized invasion gene homolog (invA). The deduced protein of 18,752 Da contains a Nudix signature, the specific motif found in the Nudix hydrolase family. To characterize the function of InvA, the gene was cloned and overexpressed in Escherichia coli. The expressed protein was purified to near homogeneity and subsequently tested for its enzymatic activity against a series of nucleoside diphosphate derivatives. The purified InvA exhibits hydrolytic activity toward dinucleoside oligophosphates (Np(n)N; n > or = 5), a group of cellular signaling molecules. At optimal pH 8.5, the enzyme actively degrades adenosine (5')-pentaphospho-(5')-adenosine into ATP and ADP with a K(m) of 0.1 mM and k(cat) of 1.9 s(-1). Guanosine (5')-pentaphospho-(5')-guanosine and adenosine-(5')-hexaphospho (5')-adenosine are also substrates. Similar to other Nudix hydrolases, InvA requires a divalent metal cation, Mg(2+) or Zn(2+), for optimal activity. These data suggest that the rickettsial invasion protein likely plays a role in controlling the concentration of stress-induced dinucleoside oligophosphates following bacterial invasion.

  11. Fluorescent ligands for adenosine receptors.

    PubMed

    Kozma, Eszter; Jayasekara, P Suresh; Squarcialupi, Lucia; Paoletta, Silvia; Moro, Stefano; Federico, Stephanie; Spalluto, Giampiero; Jacobson, Kenneth A

    2013-01-01

    Interest is increasing in developing fluorescent ligands for characterization of adenosine receptors (ARs), which hold a promise of usefulness in the drug discovery process. The size of a strategically labeled AR ligand can be greatly increased after the attachment of a fluorophore. The choice of dye moiety (e.g. Alexa Fluor 488), attachment point and linker length can alter the selectivity and potency of the parent molecule. Fluorescent derivatives of adenosine agonists and antagonists (e.g. XAC and other heterocyclic antagonist scaffolds) have been synthesized and characterized pharmacologically. Some are useful AR probes for flow cytometry, fluorescence correlation spectroscopy, fluorescence microscopy, fluorescence polarization, fluorescence resonance energy transfer, and scanning confocal microscopy. Thus, the approach of fluorescent labeled GPCR ligands, including those for ARs, is a growing dynamic research field.

  12. Berberine Attenuates Myocardial Ischemia/Reperfusion Injury by Reducing Oxidative Stress and Inflammation Response: Role of Silent Information Regulator 1

    PubMed Central

    Yu, Liming; Li, Qing; Yu, Bo; Yang, Yang; Jin, Zhenxiao; Duan, Weixun; Zhao, Guolong; Zhai, Mengen; Liu, Lijun; Yi, Dinghua; Chen, Min; Yu, Shiqiang

    2016-01-01

    Berberine (BBR) exerts potential protective effect against myocardial ischemia/reperfusion (MI/R) injury. Activation of silent information regulator 1 (SIRT1) signaling attenuates MI/R injury by reducing oxidative damage and inflammation response. This study investigated the antioxidative and anti-inflammatory effects of BBR treatment in MI/R condition and elucidated its potential mechanisms. Sprague-Dawley rats were treated with BBR in the absence or presence of the SIRT1 inhibitor sirtinol (Stnl) and then subjected to MI/R injury. BBR conferred cardioprotective effects by improving postischemic cardiac function, decreasing infarct size, reducing apoptotic index, diminishing serum creatine kinase and lactate dehydrogenase levels, upregulating SIRT1, Bcl-2 expressions, and downregulating Bax and caspase-3 expressions. Stnl attenuated these effects by inhibiting SIRT1 signaling. BBR treatment also reduced myocardium superoxide generation, gp91phox expression, malondialdehyde (MDA) level, and cardiac inflammatory markers and increased myocardium superoxide dismutase (SOD) level. However, these effects were also inhibited by Stnl. Consistently, BBR conferred similar antioxidative and anti-inflammatory effects against simulated ischemia reperfusion injury in cultured H9C2 cardiomyocytes. SIRT1 siRNA administration also abolished these effects. In summary, our results demonstrate that BBR significantly improves post-MI/R cardiac function recovery and reduces infarct size against MI/R injury possibly due to its strong antioxidative and anti-inflammatory activity. Additionally, SIRT1 signaling plays a key role in this process. PMID:26788242

  13. 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

  14. Nonnucleoside inhibitors of adenosine kinase.

    PubMed

    Gomtsyan, Arthur; Lee, Chih-Hung

    2004-01-01

    Adenosine (ADO) is an endogenous inhibitory neuromodulator that increases nociceptive thresholds in response to tissue trauma and inflammation. Adenosine kinase (AK) is a key intracellular enzyme regulating intra- and extracellular concentrations of ADO. AK inhibition selectively amplifies extracellular ADO levels at cell and tissue sites where accelerated release of ADO occurs. AK inhibitors have been shown to provide effective antinociceptive, antiinflammatory and anticonvulsant activity in animal models, thus suggesting their potential therapeutic utility for pain, inflammation, epilepsy and possibly other central and peripheral nervous system diseases associated with cellular trauma and inflammation. This beneficial outcome may potentially lack nonspecific effects associated with the systemic administration of ADO receptor agonists. Until recently all of the reported AK inhibitors contained adenosine-like structural motif. The present review will discuss design, synthesis and analgesic and antiinflammatory properties of the novel nonnucleoside AK inhibitors that do not have close structural resemblance with the natural substrate ADO. Two classes of the nonnucleoside AK inhibitors are built on pyridopyrimidine and alkynylpyrimidine cores.

  15. [Ischemia-reperfusion myocardial injury].

    PubMed

    de Micheli, Alfredo; Chávez, Edmundo

    2003-01-01

    In this article, we present some considerations on the myocardial damage due to a deficit of oxygen supply. In fact, this damage properly constitutes a partial diastolic depolarization or injury, i.e., a moderate reduction of the rest transmembrane potential. This phenomenon is characteristic of the acute phase of the myocardial infarction syndrome and is responsible for the main electrical manifestations appearing in this phase: disorders of rhythm and conduction, as well as a reduced contractility of the involved myocardial fibers. All the mentioned phenomena are due to a defect of the myocardial energetic mechanisms, owing to the mitochondrial alterations in myocytes: early reduction of the nicotinamide adenine nucleotides, accumulation of calcium ("calcium overload") into mitochondria, and a drop in oxidative phosphorylation. These changes can present again, more exaggerated, in a following phase of evolution of the myocardial infarction due to myocardial reperfusion. Its severity is related to the duration of the initial ischemia period. Moreover, consequences of the oxidative stress can add producing cellular damage by liberation of reactive oxygen species. Oxidant stress causes also alterations in the mitochondrial DNA, i.e., mutations due to oxidation of nitrogenous bases. During the initial ischemia phase, as well as during reperfusion, metabolic therapy can be very useful as, for example, glucose-insulin-potassium solutions (G-I-K). These could act as scavengers of the free radicals derived from oxygen and avoid or reduce the myocardial damage due to reperfused myocytes. Metabolic drugs, as for example trimetazidine, antioxidants, etc, can also be used in the myocardial reperfusion phase.

  16. Incidence of acute myocardial infarction in patients with exercise-induced silent myocardial ischemia

    SciTech Connect

    Assey, M.E.; Walters, G.L.; Hendrix, G.H.; Carabello, B.A.; Usher, B.W.; Spann, J.F. Jr.

    1987-03-01

    Fifty-five patients with angiographically proved coronary artery disease (CAD) underwent Bruce protocol exercise stress testing with thallium-201 imaging. Twenty-seven patients (group I) showed myocardial hypoperfusion without angina pectoris during stress, which normalized at rest, and 28 patients (group II) had a similar pattern of reversible myocardial hypoperfusion but also had angina during stress. Patients were followed for at least 30 months. Six patients in group I had an acute myocardial infarction (AMI), 3 of whom died, and only 1 patient in group II had an AMI (p = 0.05), and did not die. Silent myocardial ischemia uncovered during exercise stress thallium testing may predispose to subsequent AMI. The presence of silent myocardial ischemia identified in this manner is of prognostic value, independent of angiographic variables such as extent of CAD and left ventricular ejection fraction.

  17. Omega-3-fatty acid adds to the protective effect of flax lignan concentrate in pressure overload-induced myocardial hypertrophy in rats via modulation of oxidative stress and apoptosis.

    PubMed

    Ghule, Arvindkumar E; Kandhare, Amit D; Jadhav, Suresh S; Zanwar, Anand A; Bodhankar, Subhash L

    2015-09-01

    Objective of the present investigation was to study the effect of the flax lignan concentrate (FLC) and Omega-3-fatty acid (O-3-FA) on myocardial apoptosis, left ventricular (LV) contractile dysfunction and electrocardiographic abnormalities in pressure overload-induced cardiac hypertrophy. The rats were divided into five groups such as sham, aortic stenosis (AS), AS+FLC, AS+O-3-FA and AS+FLC+O-3-FA. Cardiac hypertrophy was produced in rats by abdominal aortic constriction. The rats were treated with FLC (400mg/kg, p.o.), O-3-FA (400mg/kg, p.o.) and FLC+O-3-FA orally per day for four weeks. The LV function, myocardial apoptosis, and oxidative stress were quantified. FLC+O-3-FA treatment significantly reduced hemodynamic changes, improved LV contractile dysfunction, reduced cardiomyocyte apoptosis and cellular oxidative stress. Moreover, it significantly up-regulated the VEGF expression and decreased TNF-alpha level in serum. The histological analysis also revealed that FLC+O-3-FA treatment markedly preserved the cardiac structure and inhibited interstitial fibrosis. In conclusion, FLC+O-3-FA treatment improved LV dysfunction, inhibited cardiomyocyte apoptosis, improved myocardial angiogenesis, conserved activities of membrane-bound phosphatase enzymes and suppressed inflammation through reduced oxidative stress in an additive manner than FLC alone and O-3-FA alone treatment in pressure overload-induced cardiac hypertrophy.

  18. Noninvasive identification of left main and triple vessel coronary artery disease: improved accuracy using quantitative analysis of regional myocardial stress distribution and washout of thallium-201

    SciTech Connect

    Maddahi, J.; Abdulla, A.; Garcia, E.V.; Swan, H.J.; Berman, D.S.

    1986-01-01

    The capabilities of visual and quantitative analysis of stress redistribution thallium-201 scintigrams, exercise electrocardiography and exercise blood pressure response were compared for correct identification of extensive coronary disease, defined as left main or triple vessel coronary artery disease, or both (50% or more luminal diameter coronary narrowing), in 105 consecutive patients with suspected coronary artery disease. Extensive disease was present in 56 patients and the remaining 49 had either less extensive coronary artery disease (n = 34) or normal coronary arteriograms (n = 15). Although exercise blood pressure response, exercise electrocardiography and visual thallium-201 analysis were highly specific (98, 88 and 96%, respectively), they were insensitive for identification of patients with extensive disease (14, 45 and 16%, respectively). Quantitative thallium-201 analysis significantly improved the sensitivity of visual thallium-201 analysis for identification of patients with extensive disease (from 16 to 63%, p less than 0.001) without a significant loss of specificity (96 versus 86%, p = NS). Eighteen (64%) of the 28 patients who were misclassified by visual analysis as having less extensive disease were correctly classified as having extensive disease by virtue of quantitative analysis of regional myocardial thallium-201 washout. When the results of quantitative thallium-201 analysis were combined with those of blood pressure and electrocardiographic response to exercise, the sensitivity and specificity for identification of patients with extensive disease was 86 and 76%, respectively, and the highest overall accuracy (0.82) was obtained.

  19. Silent myocardial ischemia.

    PubMed

    Gutterman, David D

    2009-05-01

    Although much progress has been made in reducing mortality from ischemic cardiovascular disease, this condition remains the leading cause of death throughout the world. This might in part be due to the fact that over half of patients have a catastrophic event (heart attack or sudden death) as their initial manifestation of coronary disease. Contributing to this statistic is the observation that the majority of myocardial ischemic episodes are silent, indicating an inability or failure to sense ischemic damage or stress on the heart. This review examines the clinical characteristics of silent myocardial ischemia, and explores mechanisms involved in the generation of angina pectoris. Possible mechanisms for the more common manifestation of injurious reductions in coronary flow; namely, silent ischemia, are also explored. A new theory for the mechanism of silent ischemia is proposed. Finally, the prognostic importance of silent ischemia and potential future directions for research are discussed.

  20. Vasodilator effects of adenosine on retinal arterioles in streptozotocin-induced diabetic rats.

    PubMed

    Nakazawa, Taisuke; Mori, Asami; Saito, Maki; Sakamoto, Kenji; Nakahara, Tsutomu; Ishii, Kunio

    2008-02-01

    Adenosine is a potent vasodilator of retinal blood vessels and is implicated to be a major regulator of retinal blood flow during metabolic stress, but little is known about the impact of diabetes on the role of adenosine in regulation of retinal hemodynamics. Therefore, we examined how diabetes affects adenosine-induced vasodilation of retinal arterioles. Male Wistar rats were treated with streptozotocin (80 mg/kg, intraperitoneally), and experiments were performed 6-8 weeks later. Rats were treated with tetrodotoxin (50 microg/kg, intravenously [i.v.]) to eliminate any nerve activity and prevent movement of the eye and infused with methoxamine continuously to maintain adequate systemic circulation. Fundus images were captured with a digital camera that was equipped with a special objective lens, and diameters of retinal arterioles were measured. Adenosine increased diameters of retinal arterioles and decreased systemic blood pressure. These responses were significantly attenuated by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (30 mg/kg, i.v.) and the adenosine triphosphate-dependent K+ (K(ATP)) channel blocker glibenclamide (20 mg/kg, i.v.). The depressor responses to adenosine were reduced in diabetic rats, whereas diabetes did not alter vasodilation of retinal arterioles to adenosine. In contrast, both depressor response and vasodilation of retinal arteriole to acetylcholine were reduced in diabetic rats. The retinal vasodilator responses to adenosine and acetylcholine observed in diabetic rats were diminished by N(G)-nitro-L-arginine methyl ester. There were no differences in the responses to pinacidil, a K(ATP) channel opener, between the diabetic and nondiabetic rats. These results suggest that both the activation of nitric oxide synthase and opening of K(ATP) channels contribute to the vasodilator effects of adenosine in rats in vivo. However, diabetes has no significant impact on the vasodilation mediated by these mechanisms in

  1. Effects of oral testosterone treatment on myocardial perfusion and vascular function in men with low plasma testosterone and coronary heart disease.

    PubMed

    Webb, Carolyn M; Elkington, Andrew G; Kraidly, Mustafa M; Keenan, Niall; Pennell, Dudley J; Collins, Peter

    2008-03-01

    Intracoronary testosterone infusions induce coronary vasodilatation and increase coronary blood flow. Longer term testosterone supplementation favorably affected signs of myocardial ischemia in men with low plasma testosterone and coronary heart disease. However, the effects on myocardial perfusion are unknown. Effects of longer term testosterone treatment on myocardial perfusion and vascular function were investigated in men with CHD and low plasma testosterone. Twenty-two men (mean age 57 +/- 9 [SD] years) were randomly assigned to oral testosterone undecanoate (TU; 80 mg twice daily) or placebo in a crossover study design. After each 8-week period, subjects underwent at rest and adenosine-stress first-pass myocardial perfusion cardiovascular magnetic resonance, pulse-wave analysis, and endothelial function measurements using radial artery tonometry, blood sampling, anthropomorphic measurements, and quality-of-life assessment. Although no difference was found in global myocardial perfusion after TU compared with placebo, myocardium supplied by unobstructed coronary arteries showed increased perfusion (1.83 +/- 0.9 vs 1.52 +/- 0.65; p = 0.037). TU decreased basal radial and aortic augmentation indexes (p = 0.03 and p = 0.02, respectively), indicating decreased arterial stiffness, but there was no effect on endothelial function. TU significantly decreased high-density lipoprotein cholesterol and increased hip circumference, but had no effect on hemostatic factors, quality of life, and angina symptoms. In conclusion, oral TU had selective and modest enhancing effects on perfusion in myocardium supplied by unobstructed coronary arteries, in line with previous intracoronary findings. The TU-related decrease in basal arterial stiffness may partly explain previously shown effects of exogenous testosterone on signs of exercise-induced myocardial ischemia. PMID:18308009

  2. Effects of adenosine on polymorphonuclear leucocyte function, cyclic 3': 5'-adenosine monophosphate, and intracellular calcium.

    PubMed Central

    Nielson, C. P.; Vestal, R. E.

    1989-01-01

    1. Inhibition of human polymorphonuclear leucocyte (PMN) function by adenosine was studied with respect to effects of adenosine on intracellular cyclic AMP and calcium during the PMN respiratory burst. 2. The adenosine analogue 5'-N-ethylcarboxamide-adenosine (NECA) and L-N6-phenyl-isopropyl-adenosine (L-PIA) inhibited PMN oxygen metabolite generation with relative potencies (NECA greater than adenosine greater than L-PIA) characteristic of an A2 receptor. 3. The respiratory burst was inhibited by adenosine when PMN were activated by calcium ionophore or chemotactic peptide but not when cells where activated by oleoyl-acetyl-glycerol (OAG). 4. Adenosine increased intracellular cyclic AMP during the PMN respiratory burst regardless of whether cells were stimulated by ionophore, chemotactic peptide or OAG. 5. To determine whether the differences in cell inhibition by adenosine were related to differences in intracellular calcium mobilization by each activating agent, calcium was evaluated with the fluorescent probe, indo-1. Adenosine suppressed the increase in intracellular calcium following PMN activation by calcium ionophore or chemotactic peptide. In contrast, calcium did not increase in PMN activated by OAG and adenosine did not affect intracellular calcium changes following this stimulus. 6. These results demonstrate that physiological concentrations of adenosine inhibit the PMN respiratory burst in association with an increase in intracellular cyclic AMP and reduction of intracellular calcium. PMID:2547490

  3. 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.

  4. Caffeine reduces dipyridamole-induced myocardial ischemia

    SciTech Connect

    Smits, P.; Aengevaeren, W.R.; Corstens, F.H.; Thien, T. )

    1989-10-01

    The mechanism of action of coronary vasodilation after dipyridamole may be based on inhibition of cellular uptake of circulating endogenous adenosine. Since caffeine has been reported to be a competitive antagonist of adenosine we studied the effect of caffeine on the outcome of dipiridamole-{sup 201}Tl cardiac imaging in one patient. During caffeine abstinence dipyridamole induced myocardial ischemia with down-slope ST depressions on the ECG, and reversible perfusion defects on the scintigrams. When the test was repeated 1 wk later on similar conditions, but now shortly after infusion of caffeine (4 mg/kg), the ECG showed nodepressions, and the scintigrams only slight signs of ischemia. We conclude that when caffeine abstinence is not sufficient, the widespread use of coffee and related products may be responsible for false-negative findings in dipyridamole-201Tl cardiac imaging.

  5. Spousal Adjustment to Myocardial Infarction.

    ERIC Educational Resources Information Center

    Ziglar, Elisa J.

    This paper reviews the literature on the stresses and coping strategies of spouses of patients with myocardial infarction (MI). It attempts to identify specific problem areas of adjustment for the spouse and to explore the effects of spousal adjustment on patient recovery. Chapter one provides an overview of the importance in examining the…

  6. Mass spectrometry-based quantification of myocardial protein adducts with acrolein in an in vivo model of oxidative stress

    PubMed Central

    Wu, Jianyong; Stevens, Jan F.; Maier, Claudia S.

    2012-01-01

    Acrolein exposure leads to the formation of protein-acrolein adducts. Protein modification by acrolein has been associated with various chronic diseases including cardiovascular and neurodegenerative diseases. Here we report an analytical strategy that enables the quantification of Michael-type protein adducts of acrolein in mitochondrial proteome samples using liquid chromatography in combination with tandem mass spectrometry and selected ion monitoring (LC-MS/MS SRM) analysis. Our approach combines site-specific identification and relative quantification at the peptide level of protein–acrolein adducts in relation to the unmodified protein thiol pool. Treatment of 3-month old rats with CCl4, an established in vivo model of acute oxidative stress, resulted in significant increases in the ratios of distinct acrolein-adducted peptides to the corresponding unmodified thiol-peptides obtained from proteins that were isolated from cardiac mitochondria. The mitochondrial proteins that were found adducted by acrolein were malate dehydrogenase, NADH dehydrogenase [ubiquinone] flavoprotein 1, cytochrome c oxidase subunit VIb isoform 1, ATP synthase d chain, and ADP/ATP translocase 1. The findings indicate that protein modification by acrolein has potential value as an index of mitochondrial oxidative stress. PMID:21809440

  7. Pyridopyrimidine analogues as novel adenosine kinase inhibitors.

    PubMed

    Zheng, G Z; Lee, C; Pratt, J K; Perner, R J; Jiang, M Q; Gomtsyan, A; Matulenko, M A; Mao, Y; Koenig, J R; Kim, K H; Muchmore, S; Yu, H; Kohlhaas, K; Alexander, K M; McGaraughty, S; Chu, K L; Wismer, C T; Mikusa, J; Jarvis, M F; Marsh, K; Kowaluk, E A; Bhagwat, S S; Stewart, A O

    2001-08-20

    A novel series of pyridopyrimidine analogues 9 was identified as potent adenosine kinase inhibitors based on the SAR and computational studies. Substitution of the C7 position of the pyridopyrimidino core with C2' substituted pyridino moiety increased the in vivo potency and enhanced oral bioavailability of these adenosine kinase inhibitors.

  8. 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.

  9. 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.

  10. 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.

  11. Myocardial perfusion imaging for detection of silent myocardial ischemia

    SciTech Connect

    Beller, G.A.

    1988-04-21

    Despite the widespread use of the exercise stress test in diagnosing asymptomatic myocardial ischemia, exercise radionuclide imaging remains useful for detecting silent ischemia in numerous patient populations, including those who are totally asymptomatic, those who have chronic stable angina, those who have recovered from an episode of unstable angina or an uncomplicated myocardial infarction, and those who have undergone angioplasty or received thrombolytic therapy. Studies show that thallium scintigraphy is more sensitive than exercise electrocardiography in detecting ischemia, i.e., in part, because perfusion defects occur more frequently than ST depression and before angina in the ischemic cascade. Thallium-201 scintigraphy can be performed to differentiate a true- from a false-positive exercise electrocardiographic test in patients with exercise-induced ST depression and no angina. The development of technetium-labeled isonitriles may improve the accuracy of myocardial perfusion imaging. 11 references.

  12. 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

  13. 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

  14. 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. PMID:25175974

  15. MYOCARDIAL AKT: THE OMNIPRESENT NEXUS

    PubMed Central

    Sussman, Mark A.; Völkers, Mirko; Fischer, Kimberlee; Bailey, Brandi; Cottage, Christopher T.; Din, Shabana; Gude, Natalie; Avitabile, Daniele; Alvarez, Roberto; Sundararaman, Balaji; Quijada, Pearl; Mason, Matt; Konstandin, Mathias H.; Malhowski, Amy; Cheng, Zhaokang; Khan, Mohsin; McGregor, Michael

    2013-01-01

    One of the greatest examples of integrated signal transduction is revealed by examination of effects mediated by AKT kinase in myocardial biology. Positioned at the intersection of multiple afferent and efferent signals, AKT exemplifies a molecular sensing node that coordinates dynamic responses of the cell in literally every aspect of biological responses. The balanced and nuanced nature of homeostatic signaling is particularly essential within the myocardial context, where regulation of survival, energy production, contractility, and response to pathological stress all flow through the nexus of AKT activation or repression. Equally important, the loss of regulated AKT activity is primarily the cause or consequence of pathological conditions leading to remodeling of the heart and eventual decompensation. This review presents an overview compendium of the complex world of myocardial AKT biology gleaned from more than a decade of research. Summarization of the widespread influence that AKT exerts upon myocardial responses leaves no doubt that the participation of AKT in molecular signaling will need to be reckoned with as a seemingly omnipresent regulator of myocardial molecular biological responses. PMID:21742795

  16. Salutary effect of adjunctive intracoronary nicorandil administration on restoration of myocardial blood flow and functional improvement in patients with acute myocardial infarction.

    PubMed

    Sakata, Y; Kodama, K; Komamura, K; Lim, Y J; Ishikura, F; Hirayama, A; Kitakaze, M; Masuyama, T; Hori, M

    1997-06-01

    Salutary effect of nicorandil, a K+ adenosine triphosphate channel opener, on restoration of myocardial blood flow and functional improvement after coronary revascularization was investigated in 20 patients with first anterior acute myocardial infarction. Ten patients received intracoronary administration of nicorandil (2 mg) after coronary revascularization; the other 10 patients received coronary revascularization only and served as control subjects. Myocardial contrast echocardiography and two-dimensional echocardiography were performed to assess microvascular integrity and regional function in the infarcted area. Nicorandil improved peak contrast intensity ratio (p < 0.001), calculated as the ratio of peak contrast intensity in the infarcted and noninfarcted areas, indicating the restoration of myocardial blood flow to the infarcted myocardium. Regional wall motion improved more significantly in 1 month in patients who received nicorandil (p < 0.01). Thus our results suggested the usefulness of intracoronary nicorandil administration after coronary revascularization for restoring blood flow and functional improvement in patients with acute myocardial infarction. PMID:9200388

  17. Clinical utility of digital dobutamine stress echocardiography in the noninvasive evaluation of coronary artery disease.

    PubMed

    Madu, E C; Ahmar, W; Arthur, J; Fraker, T D

    1994-05-23

    Exercise electrocardiography is an established mode of evaluation for patients with suspected coronary artery disease. It also provides prognostic information and guides therapeutic management in patients with established disease. However, some patients are unable to exercise because of orthopedic problems, neurologic diseases, peripheral vascular disease, or deconditioning. In the past, these patients have been referred for angiography to help assess their disease. Recently, however, new techniques to assess myocardial perfusion and/or function, including stress echocardiography, have been used in the noninvasive assessment of coronary artery disease in this group of patients. Echocardiography has been used in combination with different drugs, including dobutamine, dipyridamole, and adenosine. Dobutamine is probably the single most studied drug for stress echocardiography. Dobutamine stress echocardiography is a safe, feasible, and valuable technique for evaluating coronary artery disease.

  18. Myocardial abscess complicating healed myocardial infarction.

    PubMed Central

    Weisz, S.; Young, D. G.

    1977-01-01

    An isolated myocardial abscess due to Bacteroides fragilis developed in the scar of a myocardial infarction. Fever, chills and signs of pericarditis were the main clinical features. Mild enteritis 1 week prior to the onset of symptoms related to the abscess was the most likely cause of the bacteremia. The diagnosis was established at thoracotomy, performed because of cardiac tamponade. Thirteen other cases of isolated bacterial myocardial abscess accompanying myocardial infarction have been reported, but all the infarctions were recent. Surgical resection for a suspected myocardial abscess should be considered in view of the high mortality, largely from cardiac rupture. Images FIG. 1 PMID:861868

  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. Effect of temperature on myocardial infarction in swine.

    PubMed

    Duncker, D J; Klassen, C L; Ishibashi, Y; Herrlinger, S H; Pavek, T J; Bache, R J

    1996-04-01

    Body core temperature in the normothermic range alters infarct size in rabbits. Moreover, temperature may modulate the protection by adenosine during a coronary artery occlusion. We investigated the effect of core temperature within the normothermic range (35-39 degrees C) on myocardial infarct size produced by a 45-min coronary occlusion in open-chest swine (n = 10), and we determined whether adenosine blockade with 8-phenyltheophylline and adenosine deaminase increased infarct size in the normothermic range (n = 9). After 4 h of reperfusion the area at risk and infarct size were determined with Evans blue dye and triphenyltetrazolium chloride. Infarct size strongly correlated with temperature (r2 = 0.71, P = 0.0001) so that at 35 degrees C no infarction occurred and with each 1 degree C increase in temperature 20% of the area at risk became infarcted. In contrast, neither the low levels of collateral flow (0.03 +/- 0.01 ml.min-1.g-1) nor the rate-pressure product correlated with infarct size. In the normothermic range, adenosine blockade had no effect on infarct size. The data demonstrate that temperature can exert a profound effect on infarct size but fail to demonstrate a protective effect on endogenous adenosine at normothermic temperatures. Our findings emphasize the need for stringent control of core temperature during investigation of interventions aimed at reducing infarct size.

  1. Mast Cell Adenosine Receptors Function: A Focus on the A3 Adenosine Receptor and Inflammation

    PubMed Central

    Rudich, Noam; Ravid, Katya; Sagi-Eisenberg, Ronit

    2012-01-01

    Adenosine is a metabolite, which has long been implicated in a variety of inflammatory processes. Inhaled adenosine provokes bronchoconstriction in asthmatics or chronic obstructive pulmonary disease patients, but not in non-asthmatics. This hyper responsiveness to adenosine appears to be mediated by mast cell activation. These observations have marked the receptor that mediates the bronchoconstrictor effect of adenosine on mast cells (MCs), as an attractive drug candidate. Four subtypes (A1, A2a, A2b, and A3) of adenosine receptors have been cloned and shown to display distinct tissue distributions and functions. Animal models have firmly established the ultimate role of the A3 adenosine receptor (A3R) in mediating hyper responsiveness to adenosine in MCs, although the influence of the A2b adenosine receptor was confirmed as well. In contrast, studies of the A3R in humans have been controversial. In this review, we summarize data on the role of different adenosine receptors in mast cell regulation of inflammation and pathology, with a focus on the common and distinct functions of the A3R in rodent and human MCs. The relevance of mouse studies to the human is discussed. PMID:22675325

  2. Reproducibility of ratings of perceived exertion soon after myocardial infarction: responses in the stress-testing clinic and the rehabilitation gymnasium.

    PubMed

    Buckley, John P; Sim, Julius; Eston, Roger G

    2009-04-01

    The purpose of this study was to compare ratings of perceived exertion (RPE; Borg's 6-20 scale) at the same exercise intensity, between a standard exercise electrocardiogram (ECG) treadmill stress test (exECG) and two subsequent bouts of treadmill exercise in a cardiac rehabilitation gymnasium. Eleven patients (mean +/- s) 60.8 +/- 6.1 years performed an exECG within 12.1 +/- 7.5 d after myocardial infarction (MI) and commenced their first exercise-based rehabilitation session (gym-1), which included the use of a motorised treadmill, within 5.0 +/- 1.3 d after the exECG. A second gym session (gym-2) was performed within 4.2 +/- 1.3 d of gym-1. Gym-1 and gym-2 treadmill exercise was performed at an intensity that equated to the penultimate testing stage of exECG, and RPE and heart rate were compared at this level between the three sessions of testing. The mean work rate at the penultimate testing stage of the exECG was 6.0 +/- 1.0 metabolic equivalents; approximately 67% of peak work rate. The RPE at this work rate during exECG, gym-1 and gym-2 were 15.8 +/- 2.7, 13.3 +/- 3.4 and 13.0 +/- 3.6, respectively. A repeated measures ANOVA revealed these RPE responses to be significantly different (F (2, 20) = 9.8; p = 0.001). Post-hoc Bonferroni-corrected pairwise t-tests showed significant differences (p < or = 0.008) between exECG and gym-1 and exECG and gym-2 but not between gym-1 and gym-2. There was no significant difference in heart rate between the three testing sessions (p = 0.076) but it showed signs of a similar trend to RPE. The intra-participant agreement in RPE between gym-1 and gym-2 was substantial; intraclass correlation coefficient (ICC(2,1)) = 0.85 (p < 0.001) and in all but one participant, RPE differed by < or =2 scale points. The RPE responses during standardised exECG treadmill testing, in patients soon after MI, are inflated compared to responses at the same treadmill work rate during subsequent cardiac rehabilitation exercise sessions. Caution is

  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. 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.

  5. 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.

  6. The Effect of Eplerenone on Adenosine Formation in Humans In Vivo: A Double-Blinded Randomised Controlled Study

    PubMed Central

    van den Berg, T. N. A.; Deinum, Jaap; Bilos, Albert; Donders, A. Rogier T.; Rongen, Gerard A.; Riksen, Niels P.

    2014-01-01

    Background It has been suggested that mineralocorticoid receptor antagonists have direct cardioprotective properties, because these drugs reduce mortality in patients with heart failure. In murine models of myocardial infarction, mineralocorticoid receptor antagonists reduce infarct size. Using gene deletion and pharmacological approaches, it has been shown that extracellular formation of the endogenous nucleoside adenosine is crucial for this protective effect. We now aim to translate this finding to humans, by investigating the effects of the selective mineralocorticoid receptor antagonist eplerenone on the vasodilator effect of the adenosine uptake inhibitor dipyridamole, which is a well-validated surrogate marker for extracellular adenosine formation. Methods and Results In a randomised, double-blinded, placebo-controlled, cross-over study we measured the forearm blood flow response to the intrabrachial administration of dipyridamole in 14 healthy male subjects before and after treatment with placebo or eplerenone (50 mg bid for 8 days). The forearm blood flow during administration of dipyridamole (10, 30 and 100 µg·min−1·dl−1) was 1.63 (0.60), 2.13 (1.51) and 2.71 (1.32) ml·dl−1·min−1 during placebo use, versus 2.00 (1.45), 2.68 (1.87) and 3.22 (1.94) ml·dl−1·min−1 during eplerenone treatment (median (interquartile range); P = 0.51). Concomitant administration of the adenosine receptor antagonist caffeine attenuated dipyridamole-induced vasodilation to a similar extent in both groups. The forearm blood flow response to forearm ischemia, as a stimulus for increased formation of adenosine, was similar during both conditions. Conclusion In a dosage of 50 mg bid, eplerenone does not augment extracellular adenosine formation in healthy human subjects. Therefore, it is unlikely that an increased extracellular adenosine formation contributes to the cardioprotective effect of mineralocorticoid receptor antagonists. Trial Registration Clinical

  7. The effect of cannabidiol on ischemia/reperfusion-induced ventricular arrhythmias: the role of adenosine A1 receptors.

    PubMed

    Gonca, Ersöz; Darıcı, Faruk

    2015-01-01

    Cannabidiol (CBD) is a nonpsychoactive phytocannabinoid with anti-inflammatory activity mediated by enhancing adenosine signaling. As the adenosine A1 receptor activation confers protection against ischemia/reperfusion (I/R)-induced ventricular arrhythmias, we hypothesized that CBD may have antiarrhythmic effect through the activation of adenosine A1 receptor. Cannabidiol has recently been shown to suppress ischemia-induced ventricular arrhythmias. We aimed to research the effect of CBD on the incidence and the duration of I/R-induced ventricular arrhythmias and to investigate the role of adenosine A1 receptor activation in the possible antiarrhythmic effect of CBD. Myocardial ischemia and reperfusion was induced in anesthetized male rats by ligating the left anterior descending coronary artery for 6 minutes and by loosening the bond at the coronary artery, respectively. Cannabidiol alone was given in a dose of 50 µg/kg, 10 minutes prior to coronary artery occlusion and coadministrated with adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) in a dose of 100 µg/kg, 15 minutes prior to coronary artery occlusion to investigate whether the antiarrhythmic effect of CBD is modified by the activation of adenosine A1 receptors. The experimental groups were as follows: (1) vehicle control (n = 10), (2) CBD (n = 9), (3) DPCPX (n = 7), and (4) CBD + DPCPX group (n = 7). Cannabidiol treatment significantly decreased the incidence and the duration of ventricular tachycardia, total length of arrhythmias, and the arrhythmia scores compared to control during the reperfusion period. The DPCPX treatment alone did not affect the incidence and the duration of any type of arrhythmias. However, DPCPX aborted the antiarrhythmic effect of CBD when it was combined with it. The present results demonstrated that CBD has an antiarrhythmic effect against I/R-induced arrhythmias, and the antiarrhythmic effect of CBD may be mediated through the activation of adenosine

  8. Adenosine inhibits glutamatergic input to basal forebrain cholinergic neurons

    PubMed Central

    Hawryluk, J. M.; Ferrari, L. L.; Keating, S. A.

    2012-01-01

    Adenosine has been proposed as an endogenous homeostatic sleep factor that accumulates during waking and inhibits wake-active neurons to promote sleep. It has been specifically hypothesized that adenosine decreases wakefulness and promotes sleep recovery by directly inhibiting wake-active neurons of the basal forebrain (BF), particularly BF cholinergic neurons. We previously showed that adenosine directly inhibits BF cholinergic neurons. Here, we investigated 1) how adenosine modulates glutamatergic input to BF cholinergic neurons and 2) how adenosine uptake and adenosine metabolism are involved in regulating extracellular levels of adenosine. Our experiments were conducted using whole cell patch-clamp recordings in mouse brain slices. We found that in BF cholinergic neurons, adenosine reduced the amplitude of AMPA-mediated evoked glutamatergic excitatory postsynaptic currents (EPSCs) and decreased the frequency of spontaneous and miniature EPSCs through presynaptic A1 receptors. Thus we have demonstrated that in addition to directly inhibiting BF cholinergic neurons, adenosine depresses excitatory inputs to these neurons. It is therefore possible that both direct and indirect inhibition may synergistically contribute to the sleep-promoting effects of adenosine in the BF. We also found that blocking the influx of adenosine through the equilibrative nucleoside transporters or inhibiting adenosine kinase and adenosine deaminase increased endogenous adenosine inhibitory tone, suggesting a possible mechanism through which adenosine extracellular levels in the basal forebrain are regulated. PMID:22357797

  9. The resurgence of A2B adenosine receptor signaling

    PubMed Central

    Aherne, Carol M.; Kewley, Emily M.; Eltzschig, Holger K.

    2010-01-01

    Since its discovery as a low-affinity adenosine receptor (AR), the A2B receptor (A2BAR), has proven enigmatic in its function. The previous discovery of the A2AAR, which shares many similarities with the A2BAR but demonstrates significantly greater affinity for its endogenous ligand, led to the original perception that the A2BAR was not of substantial physiologic relevance. In addition, lack of specific pharmacological agents targeting the A2BAR made its initial characterization challenging. However, the importance of this receptor was reconsidered when it was observed that the A2BAR is highly transcriptionally regulated by factors implicated in inflammatory hypoxia. Moreover, the notion that during ischemia or inflammation extracellular adenosine is dramatically elevated to levels sufficient for A2BAR activation, indicated that A2BAR signaling may be important to dampen inflammation particularly during tissue hypoxia. In addition, the recent advent of techniques for murine genetic manipulation along with development of pharmacological agents with enhanced A2BAR specificity has provided invaluable tools for focused studies on the explicit role of A2BAR signaling in different disease models. Currently, studies performed with combined genetic and pharmacological approaches have demonstrated that A2BAR signaling plays a tissue protective role in many models of acute diseases e.g. myocardial ischemia, or acute lung injury. These studies indicate that the A2BAR is expressed on a wide variety of cell types and exerts tissue/cell specific effects. This is an important consideration for future studies where tissue or cell type specific targeting of the A2BAR may be used as therapeutic approach. PMID:20546702

  10. Normal Myocardial Flow Reserve in HIV-Infected Patients on Stable Antiretroviral Therapy: A Cross-Sectional Study Using Rubidium-82 PET/CT.

    PubMed

    Knudsen, Andreas; Christensen, Thomas E; Ghotbi, Adam Ali; Hasbak, Philip; Lebech, Anne-Mette; Kjær, Andreas; Ripa, Rasmus Sejersten

    2015-10-01

    Studies have found HIV-infected patients to be at increased risk of myocardial infarction, which may be caused by coronary microvascular dysfunction. For the first time among HIV-infected patients, we assessed the myocardial flow reserve (MFR) by Rubidium-82 (82Rb) positron emission tomography (PET), which can quantify the coronary microvascular function. MFR has proved highly predictive of future coronary artery disease and cardiovascular events in the general population.In a prospective cross-sectional study, HIV-infected patients all receiving antiretroviral therapy (ART) with full viral suppression and HIV-uninfected controls were scanned using 82Rb PET/computed tomography at rest and adenosine-induced stress, thereby obtaining the MFR (stress flow/rest flow), stratified into low ≤1.5, borderline >1.5 to 2.0, or normal >2.0.Fifty-six HIV-infected patients and 25 controls were included. The HIV-infected patients had a mean age of 53 years (range 37-68 years) with 23% active smokers. The controls had a mean age of 52 years (range 36-68 years) and 26% active smokers. In the HIV-infected group 73% had a normal MFR, 17% borderline, and 10% low values of MFR. Among controls these values were 71%, 19%, and 10%, respectively (P = 0.99). However, the HIV-infected group had lower values of stress myocardial blood flow (MBF) (2.63 ± 0.09 mL/g/min vs 2.99 ± 0.14 mL/g/min; P = 0.03). We found no evidence of decreased MFR as assessed by 82Rb PET among HIV-infected patients on stable ART with full viral suppression compared with HIV-uninfected controls. We did notice a decreased MBF during stress. PMID:26512605

  11. Panic attack triggering myocardial ischemia documented by myocardial perfusion imaging study. A case report

    PubMed Central

    2012-01-01

    Background Chest pain, a key element in the investigation of coronary artery disease is often regarded as a benign prognosis when present in panic attacks. However, panic disorder has been suggested as an independent risk factor for long-term prognosis of cardiovascular diseases and a trigger of acute myocardial infarction. Objective Faced with the extreme importance in differentiate from ischemic to non-ischemic chest pain, we report a case of panic attack induced by inhalation of 35% carbon dioxide triggering myocardial ischemia, documented by myocardial perfusion imaging study. Discussion Panic attack is undoubtedly a strong component of mental stress. Patients with coronary artery disease may present myocardial ischemia in mental stress response by two ways: an increase in coronary vasomotor tone or a sympathetic hyperactivity leading to a rise in myocardial oxygen consumption. Coronary artery spasm was presumed to be present in cases of cardiac ischemia linked to panic disorder. Possibly the carbon dioxide challenge test could trigger myocardial ischemia by the same mechanisms. Conclusion The use of mental stress has been suggested as an alternative method for myocardial ischemia investigation. Based on translational medicine objectives the use of CO2 challenge followed by Sestamibi SPECT could be a useful method to allow improved application of research-based knowledge to the medical field, specifically at the interface of PD and cardiovascular disease. PMID:22999016

  12. Spontaneous changes in /sup 201/Tl myocardial perfusion imaging after myocardial infarction

    SciTech Connect

    Buda, A.J.; Dubbin, J.D.; MacDonald, I.L.; Strauss, H.D.; Orr, S.A.; Meindok, H.

    1982-12-01

    To examine regional myocardial perfusion after myocardial infarction, 26 patients underwent exercise electrocardiographic testing with /sup 201/Tl myocardial perfusion imaging 3 weeks and 3 months after infarction. At 3 weeks, 9 of 26 patients (35%) had myocardial ischemia by exercise electrocardiographic testing, whereas 18 of 26 (69%) had ischemia by /sup 201/Tl imaging. The /sup 201/Tl scintigrams were scored by dividing each image, in 3 views, into 5 segments, using a 5-point scoring scheme. The exercise /sup 201/Tl score was 44.3 +/- 1.2 and increased to 47.3 +/- 1.2 in the redistribution study (p less than 0.001). Three months after infarction, although there was a significantly greater rate-pressure product which would predict a larger ischemic defect and a decrease in the stress /sup 201/Tl score, the stress score was improved (48.3 +/- 1.1, p less than 0.001). The redistribution score was similar, that is, 48.9 +/- 1.0. The improvement in /sup 201/Tl myocardial perfusion was associated with a loss of stress-induced ischemia in 8 patients (30%). These results indicate that spontaneous improvements in /sup 201/Tl myocardial perfusion imaging may occur after myocardial infarction.

  13. Adenosine modulation of [Ca2+]i in cerebellar granular cells: multiple adenosine receptors involved.

    PubMed

    Vacas, Javier; Fernández, Mercedes; Ros, Manuel; Blanco, Pablo

    2003-12-01

    Elimination of adenosine by addition of adenosine deaminase (ADA) to the media leads to alterations in intracellular free calcium concentration ([Ca(2+)](i)) in cerebellar granular cells. Adenosine deaminase brings about increases or decreases in [Ca(2+)](i) depending on the previous activation state of the cell. These effects are dependent on the catalytic activity of adenosine deaminase, since its previous catalytic inactivation with Hg(2+) prevents the above-mentioned changes in intracellular calcium. Extracellular calcium is required for the increase in [Ca(2+)](i) promoted by ADA. This rise is insensitive to thapsigargin, but sensitive to micromolar concentrations of Ni(2+). Toxins specific for L, N and P/Q calcium channels do not overtly reduce this effect. N(6)-Cyclopentyl adenosine (CPA), an A(1) receptor agonist, produces a partial reversion of ADA effects, while CGS21680, A(2A)/A(2B) receptor agonist, slightly enhances them. Expression of A(1), A(2A), A(2B) and A(3) adenosine receptor mRNAs was detected in cerebellar granular cell cultures. These results suggest that adenosine modulate [Ca(2+)](i) in cerebellar granule cells through different adenosine receptor subtypes which, at least in part, seem to act through R-type calcium channels.

  14. 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.

  15. Role of A2B Adenosine Receptors in Regulation of Paracrine Functions of Stem Cell Antigen 1-Positive Cardiac Stromal Cells

    PubMed Central

    Ryzhov, Sergey; Goldstein, Anna E.; Novitskiy, Sergey V.; Blackburn, Michael R.; Biaggioni, Italo

    2012-01-01

    The existence of multipotent cardiac stromal cells expressing stem cell antigen (Sca)-1 has been reported, and their proangiogenic properties have been demonstrated in myocardial infarction models. In this study, we tested the hypothesis that stimulation of adenosine receptors on cardiac Sca-1+ cells up-regulates their secretion of proangiogenic factors. We found that Sca-1 is expressed in subsets of mouse cardiac stromal CD31− and endothelial CD31+ cells. The population of Sca-1+CD31+ endothelial cells was significantly reduced, whereas the population of Sca-1+CD31− stromal cells was increased 1 week after myocardial infarction, indicating their relative functional importance in this pathophysiological process. An increase in adenosine levels in adenosine deaminase-deficient mice in vivo significantly augmented vascular endothelial growth factor (VEGF) production in cardiac Sca-1+CD31− stromal cells but not in Sca-1+CD31+ endothelial cells. We found that mouse cardiac Sca-1+CD31− stromal cells predominantly express mRNA encoding A2B adenosine receptors. Stimulation of adenosine receptors significantly increased interleukin (IL)-6, CXCL1 (a mouse ortholog of human IL-8), and VEGF release from these cells. Using conditionally immortalized Sca-1+CD31− stromal cells obtained from wild-type and A2B receptor knockout mouse hearts, we demonstrated that A2B receptors are essential for adenosine-dependent up-regulation of their paracrine functions. We found that the human heart also harbors a population of stromal cells similar to the mouse cardiac Sca-1+CD31− stromal cells that increase release of IL-6, IL-8, and VEGF in response to A2B receptor stimulation. Thus, our study identified A2B adenosine receptors on cardiac stromal cells as potential targets for up-regulation of proangiogenic factors in the ischemic heart. PMID:22431204

  16. Cardioprotection against experimental myocardial ischemic injury using cornin

    PubMed Central

    Xu, Y.; Xu, Y.; Luan, H.; Jiang, Y.; Tian, X.; Zhang, S.

    2016-01-01

    Phosphorylated-cyclic adenosine monophosphate response element-binding protein (Phospho-CREB) has an important role in the pathogenesis of myocardial ischemia. We isolated the iridoid glycoside cornin from the fruit of Verbena officinalis L, investigated its effects against myocardial ischemia and reperfusion (I/R) injury in vivo, and elucidated its potential mechanism in vitro. Effects of cornin on cell viability, as well as expression of phospho-CREB and phospho-Akt in hypoxic H9c2 cells in vitro, and myocardial I/R injury in vivo, were investigated. Cornin attenuated hypoxia-induced cytotoxicity significantly in H9c2 cells in a concentration-dependent manner. Treatment of H9c2 cells with cornin (10 µM) blocked the reduction of expression of phospho-CREB and phospho-Akt in a hypoxic condition. Treatment of rats with cornin (30 mg/kg, iv) protected them from myocardial I/R injury as indicated by a decrease in infarct volume, improvement in hemodynamics, and reduction of severity of myocardial damage. Cornin treatment also attenuated the reduction of expression of phospho-CREB and phospho-Akt in ischemic myocardial tissue. These data suggest that cornin exerts protective effects due to an increase in expression of phospho-CREB and phospho-Akt. PMID:26871971

  17. Cardioprotection against experimental myocardial ischemic injury using cornin.

    PubMed

    Xu, Y; Xu, Y; Luan, H; Jiang, Y; Tian, X; Zhang, S

    2016-02-01

    Phosphorylated-cyclic adenosine monophosphate response element-binding protein (Phospho-CREB) has an important role in the pathogenesis of myocardial ischemia. We isolated the iridoid glycoside cornin from the fruit of Verbena officinalis L, investigated its effects against myocardial ischemia and reperfusion (I/R) injury in vivo, and elucidated its potential mechanism in vitro. Effects of cornin on cell viability, as well as expression of phospho-CREB and phospho-Akt in hypoxic H9c2 cells in vitro, and myocardial I/R injury in vivo, were investigated. Cornin attenuated hypoxia-induced cytotoxicity significantly in H9c2 cells in a concentration-dependent manner. Treatment of H9c2 cells with cornin (10 µM) blocked the reduction of expression of phospho-CREB and phospho-Akt in a hypoxic condition. Treatment of rats with cornin (30 mg/kg, iv) protected them from myocardial I/R injury as indicated by a decrease in infarct volume, improvement in hemodynamics, and reduction of severity of myocardial damage. Cornin treatment also attenuated the reduction of expression of phospho-CREB and phospho-Akt in ischemic myocardial tissue. These data suggest that cornin exerts protective effects due to an increase in expression of phospho-CREB and phospho-Akt.

  18. Grade III ischemia on presentation with acute myocardial infarction predicts rapid progression of necrosis and less myocardial salvage with thrombolysis.

    PubMed

    Birnbaum, Yochai; Mahaffey, Kenneth W; Criger, Douglas A; Gates, Kathy B; Barbash, Gabriel I; Barbagelata, Alejandro; Clemmensen, Peter; Sgarbossa, Elena B; Gibbons, Raymond J; Rahman, M Atiar; Califf, Robert M; Granger, Chistopher B; Wagner, Galen S

    2002-01-01

    We assessed the relation between baseline electrocardiographic ischemia grades and initial myocardial area at risk (AR) and final infarct size (IS) in 49 patients who had undergone (99m)Tc sestamibi single-photon emission computed tomography before and 6 +/- 1 days after thrombolysis. Patients were classed as having grade III ischemia (ST segment elevation with terminal QRS distortion, n = 19) or grade II ischemia (ST elevation but no terminal QRS distortion, n = 30). We compared AR and IS by baseline ischemia grade and treatment (adenosine vs. placebo) and assessed relations of infarction index (IS/AR ratio x100) to time to thrombolysis, baseline ischemia grade, and adenosine therapy. Time to thrombolysis was similar for grade II and grade III. For placebo- treated patients, the median AR did not differ significantly between grade II (38%) and grade III patients (46%, p = 0.47), nor did median IS (16 vs. 40%, p = 0.096), but the median infarction index was 66 vs. 90% (p = 0.006). For adenosine-treated patients, median AR (21 vs. 26%, p = 0.44), median IS (5 vs. 17%, p = 0.15), and their ratio (31 vs. 67%, p = 0.23) did not differ significantly between grade II and grade III patients. The infarction index independently related to grade III ischemia (p = 0.0121) and adenosine therapy (p = 0.045). Infarct size related to baseline ischemia grade and was reduced by adenosine treatment. Necrosis progressed slowlier with baseline grade II versus III ischemia, which could offer more time for myocardial salvage with reperfusion. PMID:12077570

  19. Acute myocardial infarction in rats.

    PubMed

    Wu, Yewen; Yin, Xing; Wijaya, Cori; Huang, Ming-He; McConnell, Bradley K

    2011-01-01

    With heart failure leading the cause of death in the USA (Hunt), biomedical research is fundamental to advance medical treatments for cardiovascular diseases. Animal models that mimic human cardiac disease, such as myocardial infarction (MI) and ischemia-reperfusion (IR) that induces heart failure as well as pressure-overload (transverse aortic constriction) that induces cardiac hypertrophy and heart failure (Goldman and Tarnavski), are useful models to study cardiovascular disease. In particular, myocardial ischemia (MI) is a leading cause for cardiovascular morbidity and mortality despite controlling certain risk factors such as arteriosclerosis and treatments via surgical intervention (Thygesen). Furthermore, an acute loss of the myocardium following myocardial ischemia (MI) results in increased loading conditions that induces ventricular remodeling of the infarcted border zone and the remote non-infarcted myocardium. Myocyte apoptosis, necrosis and the resultant increased hemodynamic load activate multiple biochemical intracellular signaling that initiates LV dilatation, hypertrophy, ventricular shape distortion, and collagen scar formation. This pathological remodeling and failure to normalize the increased wall stresses results in progressive dilatation, recruitment of the border zone myocardium into the scar, and eventually deterioration in myocardial contractile function (i.e. heart failure). The progression of LV dysfunction and heart failure in rats is similar to that observed in patients who sustain a large myocardial infarction, survive and subsequently develops heart failure (Goldman). The acute myocardial infarction (AMI) model in rats has been used to mimic human cardiovascular disease; specifically used to study cardiac signaling mechanisms associated with heart failure as well as to assess the contribution of therapeutic strategies for the treatment of heart failure. The method described in this report is the rat model of acute myocardial

  20. 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

  1. The role and modulation of autophagy in experimental models of myocardial ischemia-reperfusion injury.

    PubMed

    Chen-Scarabelli, Carol; Agrawal, Pratik R; Saravolatz, Louis; Abuniat, Cadigia; Scarabelli, Gabriele; Stephanou, Anastasis; Loomba, Leena; Narula, Jagat; Scarabelli, Tiziano M; Knight, Richard

    2014-12-01

    A physiological sequence called autophagy qualitatively determines cellular viability by removing protein aggregates and damaged cytoplasmic constituents, and contributes significantly to the degree of myocardial ischemia-reperfusion (I/R) injury. This tightly orchestrated catabolic cellular 'housekeeping' process provides cells with a new source of energy to adapt to stressful conditions. This process was first described as a pro-survival mechanism, but increasing evidence suggests that it can also lead to the demise of the cell. Autophagy has been implicated in the pathogenesis of multiple cardiac conditions including myocardial I/R injury. However, a debate persists as to whether autophagy acts as a protective mechanism or contributes to the injurious effects of I/R injury in the heart. This controversy may stem from several factors including the variability in the experimental models and species, and the methodology used to assess autophagy. This review provides updated knowledge on the modulation and role of autophagy in isolated cardiac cells subjected to I/R, and the growing interest towards manipulating autophagy to increase the survival of cardiac myocytes under conditions of stress-most notably being I/R injury. Perturbation of this evolutionarily conserved intracellular cleansing autophagy mechanism, by targeted modulation through, among others, mammalian target of rapamycin (mTOR) inhibitors, adenosine monophosphate-activated protein kinase (AMPK) modulators, calcium lowering agents, resveratrol, longevinex, sirtuin activators, the proapoptotic gene Bnip3, IP3 and lysosome inhibitors, may confer resistance to heart cells against I/R induced cell death. Thus, therapeutic manipulation of autophagy in the challenged myocardium may benefit post-infarction cardiac healing and remodeling. PMID:25593583

  2. Determination of adenosine effects and adenosine receptors in murine corpus cavernosum.

    PubMed

    Tostes, Rita C; Giachini, Fernanda R C; Carneiro, Fernando S; Leite, Romulo; Inscho, Edward W; Webb, R Clinton

    2007-08-01

    This study tested the hypothesis that adenosine, in murine corpora cavernosa, produces direct relaxation of smooth muscle cells and inhibition of contractile responses mediated by sympathetic nerve stimulation. Penes were excised from anesthetized male C57BL/6 mice, dissected, and cavernosal strips were mounted to record isometric force. Adenosine, 2-chloroadenosine (stable analog of adenosine), and 2-phenylaminoadenosine (CV1808) (A2(A)/A2(B) agonist) produced concentration-dependent relaxations of phenylephrine-contracted tissues. Relaxation to 2-chloroadenosine was inhibited, in a concentration-dependent manner, by 2-(2-furanyl)-7-(2-phenylethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine (SCH58261; A2(A) antagonist; 10(-9)-10(-6) M) and N-(4-acetylphenyl)-2-[4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)phenoxy]acetamida (MRS1706; A2(B) antagonist; 10(-8)-10(-6) M). The combination of both antagonists abrogated 2-chloroadenosine-induced relaxation. Electrical field stimulation (EFS; 1-32 Hz) of adrenergic nerves produced frequency-dependent contractions that were inhibited by compounds that increase adenosine levels, such as 5'-iodotubercidin (adenosine kinase inhibitor), erythro-9-(2-hydroxy-3-nonyl)adenine (adenosine deaminase inhibitor), and dipyridamole (inhibitor of adenosine transport). The adenosine A1 receptor agonist N(6)-cyclopentyladenosine (C8031) right-shifted contractile responses to EFS, with a significant inhibitory effect at 10(-6) M. Blockade of adenosine A1 receptors with 8-cyclopentyl-1,3-dipropylxanthine (C101) (10(-7) M) enhanced contractile responses to EFS and eliminated the inhibitory effects of 5'-iodotubercidin. Dipyridamole and 5'-iodotubercidin had no effect on adenosine-mediated relaxation. In summary, adenosine directly relaxes cavernosal smooth muscle cells, by the activation of A2(A)/A2(B) receptor subtypes. In addition, adenosine negatively modulates sympathetic neurotransmission, by A1 receptor

  3. Recent developments in adenosine receptor ligands and their potential as novel drugs☆

    PubMed Central

    Müller, Christa E.; Jacobson, Kenneth A.

    2012-01-01

    Medicinal chemical approaches have been applied to all four of the adenosine receptor (AR) subtypes (A1, A2A, A2B, and A3) to create selective agonists and antagonists for each. The most recent class of selective AR ligands to be reported is the class of A2BAR agonists. The availability of these selective ligands has facilitated research on therapeutic applications of modulating the ARs and in some cases has provided clinical candidates. Prodrug approaches have been developed which improve the bioavailability of the drugs, reduce side-effects, and/or may lead to site-selective effects. The A2A agonist regadenoson (Lexiscan®), a diagnostic drug for myocardial perfusion imaging, is the first selective AR agonist to be approved. Other selective agonists and antagonists are or were undergoing clinical trials for a broad range of indications, including capadenoson and tecadenoson (A1 agonists) for atrial fibrillation, or paroxysmal supraventricular tachycardia, respectively, apadenoson and binodenoson (A2A agonists) for myocardial perfusion imaging, preladenant (A2A antagonist) for the treatment of Parkinson’s disease, and CF101 and CF102 (A3 agonists) for inflammatory diseases and cancer, respectively. This article is part of a Special Issue entitled: “Adenosine Receptors”. PMID:21185259

  4. Working memory and the homeostatic control of brain adenosine by adenosine kinase.

    PubMed

    Singer, P; McGarrity, S; Shen, H-Y; Boison, D; Yee, B K

    2012-06-28

    The neuromodulator adenosine maintains brain homeostasis and regulates complex behaviour via activation of inhibitory and excitatory adenosine receptors (ARs) in a brain region-specific manner. AR antagonists such as caffeine have been shown to ameliorate cognitive impairments in animal disease models but their effects on learning and memory in normal animals are equivocal. An alternative approach to reduce AR activation is to lower the extracellular tone of adenosine, which can be achieved by up-regulating adenosine kinase (ADK), the key enzyme of metabolic adenosine clearance. However, mice that globally over-express an Adk transgene ('Adk-tg' mice) were devoid of a caffeine-like pro-cognitive profile; they instead exhibited severe spatial memory deficits. This may be mechanistically linked to cortical/hippocampal N-methyl-d-aspartate receptor (NMDAR) hypofunction because the motor response to acute MK-801 was also potentiated in Adk-tg mice. Here, we evaluated the extent to which the behavioural phenotypes of Adk-tg mice might be modifiable by up-regulating adenosine levels in the cortex/hippocampus. To this end, we investigated mutant 'fb-Adk-def' mice in which ADK expression was specifically reduced in the telencephalon leading to a selective increase in cortical/hippocampal adenosine, while the rest of the brain remained as adenosine-deficient as in Adk-tg mice. The fb-Adk-def mice showed an even greater impairment in spatial working memory and a more pronounced motor response to NMDAR blockade than Adk-tg mice. These outcomes suggest that maintenance of cortical/hippocampal adenosine homeostasis is essential for effective spatial memory and deviation in either direction is detrimental with increased expression seemingly more disruptive than decreased expression.

  5. 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

  6. Myocardial imaging. Coxsackie myocarditis

    SciTech Connect

    Wells, R.G.; Ruskin, J.A.; Sty, J.R.

    1986-09-01

    A 3-week-old male neonate with heart failure associated with Coxsackie virus infection was imaged with Tc-99m PYP and TI-201. The abnormal imaging pattern suggested myocardial infarction. Autopsy findings indicated that the cause was myocardial necrosis secondary to an acute inflammatory process. Causes of abnormal myocardial uptake of Tc-99m PYP in pediatrics include infarction, myocarditis, cardiomyopathy, bacterial endocarditis, and trauma. Myocardial imaging cannot provide a specific cause diagnosis. Causes of myocardial infarction in pediatrics are listed in Table 1.

  7. Tolerance and safety of pharmacologic coronary vasodilation with adenosine in association with thallium-201 scintigraphy in patients with suspected coronary artery disease

    SciTech Connect

    Abreu, A.; Mahmarian, J.J.; Nishimura, S.; Boyce, T.M.; Verani, M.S. )

    1991-09-01

    Adenosine thallium-201 myocardial scintigraphy is a promising test for coronary artery disease detection, but its safety has not been reported in large patient cohorts. Accordingly, the tolerance and safety profile of adenosine infusion were analyzed in 607 patients (351 men, 256 women, mean age 63 {plus minus} 11 years) undergoing this test either because of suspected coronary artery disease (Group I, n = 482) or for risk stratification early (5.2 {plus minus} 2.8 days) after myocardial infarction (Group II, n = 125). Adenosine increased the heart rate from 74.5 {plus minus} 14.0 to 91.8 {plus minus} 15.9 beats/min (p less than 0.001) and decreased systolic blood pressure from 137.8 {plus minus} 26.8 to 120.7 {plus minus} 26.1 mm Hg (p less than 0.001). Side effects were frequent and similar in both groups. Flushing occurred in 35%, chest pain in 34%, headache in 21% and dyspnea in 19% of patients. Only 35.6% of Group I patients with chest pain during adenosine infusion had concomitant transient perfusion abnormalities, compared with 60.7% of Group II patients (p less than 0.05). First- and second-degree AV block occurred in 9.6% and 3.6% of patients, respectively, and ischemic ST changes in 12.5% of cases. Concomitance of chest pain and ischemic ST depression was uncommon (6%) but, when present, predicted perfusion abnormalities in 73% of patients. Most side effects ceased rapidly after stopping the adenosine infusion. The side effects were severe in only 1.6% of patients and in only six patients (1%) was it necessary to discontinue the infusion. No serious adverse reactions such as acute myocardial infarction or death occurred.

  8. Activation of NTS A(1) adenosine receptors inhibits regional sympathetic responses evoked by activation of cardiopulmonary chemoreflex.

    PubMed

    Ichinose, Tomoko K; Minic, Zeljka; Li, Cailian; O'Leary, Donal S; Scislo, Tadeusz J

    2012-09-01

    Previously we have shown that adenosine operating via the A(1) receptor subtype may inhibit glutamatergic transmission in the baroreflex arc within the nucleus of the solitary tract (NTS) and differentially increase renal (RSNA), preganglionic adrenal (pre-ASNA), and lumbar (LSNA) sympathetic nerve activity (ASNA>RSNA≥LSNA). Since the cardiopulmonary chemoreflex and the arterial baroreflex are mediated via similar medullary pathways, and glutamate is a primary transmitter in both pathways, it is likely that adenosine operating via A(1) receptors in the NTS may differentially inhibit regional sympathetic responses evoked by activation of cardiopulmonary chemoreceptors. Therefore, in urethane-chloralose-anesthetized rats (n = 37) we compared regional sympathoinhibition evoked by the cardiopulmonary chemoreflex (activated with right atrial injections of serotonin 5HT(3) receptor agonist phenylbiguanide, PBG, 1-8 μg/kg) before and after selective stimulation of NTS A(1) adenosine receptors [microinjections of N(6)-cyclopentyl adenosine (CPA), 0.033-330 pmol/50 nl]. Activation of cardiopulmonary chemoreceptors evoked differential, dose-dependent sympathoinhibition (RSNA>ASNA>LSNA), and decreases in arterial pressure and heart rate. These differential sympathetic responses were uniformly attenuated in dose-dependent manner by microinjections of CPA into the NTS. Volume control (n = 11) and blockade of adenosine receptor subtypes in the NTS via 8-(p-sulfophenyl)theophylline (8-SPT, 1 nmol in 100 nl) (n = 9) did not affect the reflex responses. We conclude that activation of NTS A(1) adenosine receptors uniformly inhibits neural and cardiovascular cardiopulmonary chemoreflex responses. A(1) adenosine receptors have no tonic modulatory effect on this reflex under normal conditions. However, when adenosine is released into the NTS (i.e., during stress or severe hypotension/ischemia), it may serve as negative feedback regulator for depressor and sympathoinhibitory reflexes

  9. Caffeine reduces myocardial blood flow during exercise.

    PubMed

    Higgins, John P; Babu, Kavita M

    2013-08-01

    Caffeine consumption has been receiving increased interest from both the medical and lay press, especially given the increased amounts now available in energy products. Acute ingestion of caffeine usually increases cardiac work; however, caffeine impairs the expected proportional increase in myocardial blood flow to match this increased work of the heart, most notably during exercise. This appears to be mainly due to caffeine's effect on blocking adenosine-induced vasodilatation in the coronary arteries in normal healthy subjects. This review summarizes the available medical literature specifically relating to pure caffeine tablet ingestion and reduced exercise coronary blood flow, and suggests possible mechanisms. Further studies are needed to evaluate this effect for other common caffeine-delivery systems, including coffee, energy beverages, and energy gels, which are often used for exercise performance enhancement, especially in teenagers and young athletes.

  10. Caffeine reduces myocardial blood flow during exercise.

    PubMed

    Higgins, John P; Babu, Kavita M

    2013-08-01

    Caffeine consumption has been receiving increased interest from both the medical and lay press, especially given the increased amounts now available in energy products. Acute ingestion of caffeine usually increases cardiac work; however, caffeine impairs the expected proportional increase in myocardial blood flow to match this increased work of the heart, most notably during exercise. This appears to be mainly due to caffeine's effect on blocking adenosine-induced vasodilatation in the coronary arteries in normal healthy subjects. This review summarizes the available medical literature specifically relating to pure caffeine tablet ingestion and reduced exercise coronary blood flow, and suggests possible mechanisms. Further studies are needed to evaluate this effect for other common caffeine-delivery systems, including coffee, energy beverages, and energy gels, which are often used for exercise performance enhancement, especially in teenagers and young athletes. PMID:23764265

  11. 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 Central

    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. PMID:26894686

  12. Effects of adenosine infusion into renal interstitium on renal hemodynamics

    SciTech Connect

    Pawlowska, D.; Granger, J.P.; Knox, F.G.

    1987-04-01

    This study was designed to investigate the hemodynamic effects of exogenous adenosine in the interstitium of the rat kidney. Adenosine or its analogues were infused into the renal interstitium by means of chronically implanted capsules. In fusion of adenosine decreased glomerular filtration rate (GFR) from 0.81 +/- 0.06 to 0.37 +/- 0.06 ml/min while having no effect on renal blood flow (RBF). The metabolically stable analogue, 2-chloradenosine (2-ClAdo), decreased GFR from 0.73 +/- 0.07 to 021 +/- 0.06 ml/min. Interstitial infusion of theophylline, an adenosine receptor antagonist, completely abolished the effects of adenosine and 2-ClAdo on GFR. The distribution of adenosine, when infused into the renal interstitium, was determined using radiolabeled 5'-(N-ethyl)-carboxamidoadenosine (NECA), a metabolically stable adenosine agonist. After continuous infusion, (/sup 3/H)NECA was distributed throughout the kidney. The effects of NECA to reduce GFR were similar to those of adenosine and 2-ClAdo. They conclude that increased levels of adenosine in the renal interstitium markedly decrease GFR without affecting RBF in steady-state conditions. The marked effects of adenosine agonists during their infusion into the renal interstitium and the complete blockade of these effects by theophylline suggest an extracellular action of adenosine.

  13. ATP sensitive K(+) channels are critical for maintaining myocardial perfusion and high energy phosphates in the failing heart.

    PubMed

    Jameel, Mohammad N; Xiong, Qiang; Mansoor, Abdul; Bache, Robert J; Zhang, Jianyi

    2016-03-01

    Congestive heart failure (CHF) is associated with intrinsic alterations of mitochondrial oxidative phosphorylation which lead to increased myocardial cytosolic free ADP. ATP sensitive K(+) channels (KATP) act as metabolic sensors that are important for maintaining coronary blood flow (MBF) and in mediating the response of the myocardium to stress. Coronary adenosine receptors (AdR) are not normally active but cause vasodilation during myocardial ischemia. This study examined the myocardial energetic response to inhibition of KATP and AdR in CHF. CHF (as evidenced by LVEDP>20mmHg) was produced in adult mongrel dogs (n=12) by rapid ventricular pacing for 4weeks. MBF was measured with radiolabeled microspheres during baseline (BL), AdR blockade with 8-phenyltheophylline (8-PT; 5mg/kg iv), and KATP blockade with glibenclamide (GLB; 20μg/kg/min ic). High energy phosphates were examined with (31)P magnetic resonance spectroscopy (MRS) while myocardial oxygenation was assessed from the deoxymyoglobin signal (Mb-δ) using (1)H MRS. During basal conditions the phosphocreatine (PCr)/ATP ratio (1.73±0.15) was significantly lower than in previously studied normal dogs (2.42±0.11) although Mb-δ was undetectable. 8-PT caused ≈21% increase in MBF with no change in PCr/ATP. GLB caused a 33±0.1% decrease in MBF with a decrease in PCr/ATP from 1.65±0.17 to 1.11±0.11 (p<0.0001). GLB did not change the pseudo-first-order rate constant of ATP production via CK (kf), but the ATP production rate via CK was reduced by 35±0.08%; this was accompanied by an increase in Pi/PCr and appearance of a Mb-δ signal indicating tissue hypoxia. Thus, in the failing heart the balance between myocardial ATP demands and oxygen delivery is critically dependent on functioning KATP channels.

  14. Reproducibility of measurements of regional resting and hyperemic myocardial blood flow assessed with PET

    SciTech Connect

    Nagamachi, S.; Czernin, J.; Kim, A.S.

    1996-10-01

    PET with {sup 13}N-ammonia permits the noninvasive quantification of myocardial blood flow (MBF) in humans. The present study was done to assess the reproducibility of quantitative blood flow measurements at rest and during pharmacologically induced hyperemia in healthy individuals. Thirty healthy volunteers (26 men, 4 women) were studied. Paired measurements of MBF at rest (n = 21), during adenosine (n = 15) and during dipyridamole (n = 7) were performed using a two-compartment model for {sup 13}N-ammonia PET. The mean difference between baseline and follow-up blood flow (% difference) was calculated to assess reproducibility. No significant difference was observed between resting blood flow at baseline or follow-up (15.8% {plus_minus} 15.8%; p = ns). Baseline and follow-up resting blood flow were linearly correlated (r = 0.63, p < 0.005). Normalization of resting blood flow to the rate pressure product improved the reproducibility significantly (15.8% {plus_minus} 15.8% versus 10.1% {plus_minus} 10.5%, p < 0.05). Baseline and follow-up hyperemic myocardial blood flow did not differ (11.8% {plus_minus} 9.4%; p = ns) and were linearly correlated (r = 0.69, p < 0.0005). MBF at rest can be measured reproducibly with {sup 13}N-ammonia PET. The individual response to pharmacologic stress appears to be relatively consistent. Thus, serial blood flow measurements with {sup 13}N-ammonia PET can be used to quantify the effect of various interventions on MBF and vasodilatory reserve. 41 refs., 3 figs., 4 tabs.

  15. Theophylline increases coronary vascular tone in humans: evidence for a role of endogenous adenosine in flow regulation.

    PubMed

    Edlund, A; Sollevi, A

    1995-11-01

    To elucidate the role of adenosine in coronary vasoregulation, we studied the effects of adenosine antagonism (by theophylline) on coronary blood flow at different levels of adenosine formation (stimulated by hypoxia and exercise). Six healthy subjects were studied. Coronary sinus (CS) blood flow (thermodilution) and cardiac oxygen extraction [(A-CS)O2D] were determined while breathing room air at rest, and 12% oxygen, both at rest and during light exercise, on two occasions. One of the experiments was performed during infusion of theophylline. The basal CS flow was 118 (67-168) mL min-1 (mean and 95% confidence interval), and the (A-CS)O2D was 125 (111-142) mL L-1. Inhalation of 12% O2 decreased the arterial haemoglobin oxygen saturation to 83 (80-86)% at rest and to 77 (73-81)% during exercise. CS flow increased to 167 (93-214) and 261 (179-343) mL min-1, respectively, and (A-CS)O2D decreased to 102 (85-119) and 94 (77-111) mL L-1, respectively. Theophylline, at a dose lacking effects on myocardial work, markedly attenuated the coronary flow response to exogenous adenosine, and decreased CS flow to 89 (58-119), 120 (79-161) and 190 (162-218) mL min-1 at normoxic rest, hypoxic rest and hypoxic exercise, respectively. The overall decrease amounted to 23% (P < 0.05). The calculated coronary vascular conductance also decreased by 23% (P < 0.05) and (A-CS)O2D increased by 15% (P < 0.001). In conclusion, the data support the hypothesis that endogenous adenosine is involved in regulation of human coronary tone.

  16. Adenosine-induced worsening of supraventricular tachycardia

    PubMed Central

    Kunnumpuram, Georgey Koshy; Patel, Ashfaq

    2012-01-01

    An approximately 20-year-old to 30-year-old patient presented with a haemodynamically stable supraventricular tachycardia . The patient was managed with intravenous adenosine primarily, with two bolus doses of 6 and 12 mg. This, however, caused a rare paradoxical surge of tachycardia with mild haemodynamic compromise. The patient further required a combination of Metoprolol and Verapamil administration to slow down and reverse the arrhythmia. Following this the patient remained stable with no further episodes till discharge. PMID:23230260

  17. Chemoelectrical energy conversion of adenosine triphosphate

    NASA Astrophysics Data System (ADS)

    Sundaresan, Vishnu Baba; Sarles, Stephen Andrew; Leo, Donald J.

    2007-04-01

    Plant and animal cell membranes transport charged species, neutral molecules and water through ion pumps and channels. The energy required for moving species against established concentration and charge gradients is provided by the biological fuel - adenosine triphosphate (ATP) -synthesized within the cell. The adenosine triphosphatase (ATPases) in a plant cell membrane hydrolyze ATP in the cell cytoplasm to pump protons across the cell membrane. This establishes a proton gradient across the membrane from the cell exterior into the cell cytoplasm. This proton motive force stimulates ion channels that transport nutrients and other species into the cell. This article discusses a device that converts the chemical energy stored in adenosine triphosphate into electrical power using a transporter protein, ATPase. The V-type ATPase proteins used in our prototype are extracted from red beet(Beta vulgaris) tonoplast membranes and reconstituted in a bilayer lipid membrane or BLM formed from POPC and POPS lipids. A pH7 medium that can support ATP hydrolysis is provided on both sides of the membrane and ATP is dissolved in the pH7 buffer on one side of the membrane. Hydrolysis of ATP results in the formation of a phosphate ion and adenosine diphosphate. The energy from the reaction activates ATPase in the BLM and moves a proton across the membrane. The charge gradient established across the BLM due to the reaction and ion transport is converted into electrical current by half-cell reference electrodes. The prototype ATPase cell with an effective BLM area of 4.15 mm2 carrying 15 μl of ATPase proteins was observed to develop a steady state peak power output of 70 nW, which corresponds to a specific power of 1.69 μW/cm2 and a current density of 43.4 μA/cm2 of membrane area.

  18. Myocardial mechanics in cardiomyopathies.

    PubMed

    Modesto, Karen; Sengupta, Partho P

    2014-01-01

    Cardiomyopathies are a heterogeneous group of diseases that can be phenotypically recognized by specific patterns of ventricular morphology and function. The authors summarize recent clinical observations that mechanistically link the multidirectional components of left ventricular (LV) deformation with morphological phenotypes of cardiomyopathies for offering key insights into the transmural heterogeneity of myocardial function. Subendocardial dysfunction predominantly alters LV longitudinal shortening, lengthening and suction performance and contributes to the phenotypic patterns of heart failure (HF) with preserved ejection fraction (EF) seen with hypertrophic and restrictive patterns of cardiomyopathy. On the other hand, a more progressive transmural disease results in reduction of LV circumferential and twist mechanics leading to the phenotypic pattern of dilated cardiomyopathy and the clinical syndrome of HF with reduced (EF). A proper characterization of LV transmural mechanics, energetics, and space-time distributions of pressure and shear stress may allow recognition of early functional changes that can forecast progression or reversal of LV remodeling. Furthermore, the interactions between LV muscle and fluid mechanics hold the promise for offering newer mechanistic insights and tracking impact of novel therapies.

  19. Effect of adenosine and adenosine analogs on ( sup 14 C)aminopyrine accumulation by rabbit parietal cells

    SciTech Connect

    Ota, S.; Hiraishi, H.; Terano, A.; Mutoh, H.; Kurachi, Y.; Shimada, T.; Ivey, K.J.; Sugimoto, T. )

    1989-12-01

    Adenosine receptors that modulate adenylate cyclase activity have been identified recently in a number of tissues. Adenosine A2 receptor is stimulatory to adenylate cyclase, whereas adenosine A1 receptor is inhibitory to adenylate cyclase. We investigated the effect of adenosine and its analogs on (14C)aminopyrine accumulation by rabbit parietal cells. Rabbit gastric mucosal cells were isolated by enzyme digestion. Parietal cells were enriched by nonlinear percoll gradients. (14C)Aminopyrine accumulation was used as an indicator of acid secretion. The effect of 2-chloroadenosine on histamine-stimulated (14C)aminopyrine accumulation was studied. The effects of N-ethylcarboxamideadenosine, 2-chloroadenosine, stable analogs of adenosine, and adenosine on (14C)aminopyrine accumulation were assessed. Cyclic AMP content of parietal cells was determined by radioimmunoassay. Histamine and carbachol, known secretagogues, stimulated (14C)aminopyrine accumulation. 2-Chloroadenosine did not suppress histamine-stimulated (14C)aminopyrine accumulation. 2-Chloroadenosine, N-ethylcarboxamideadenosine, and adenosine dose dependently increased (14C)aminopyrine accumulation. The order of potency was N-ethylcarboxamideadenosine greater than 2-chloroadenosine greater than adenosine. 8-Phenyltheophylline and theophylline, adenosine-receptor antagonists, or cimetidine did not have significant effects on the increase of AP uptake induced by 2-chloroadenosine. Coadministration of dipyridamole, and adenosine uptake inhibitor, augmented the effect of adenosine on (14C)aminopyrine accumulation. 2-Chloroadenosine, N-ethylcarboxamideadenosine, and adenosine each induced a significant increase in cellular cyclic AMP. We conclude that there may be adenosine A2 receptors on rabbit parietal cells which modulate gastric acid secretion.

  20. N6-(2-Hydroxyethyl)-Adenosine Exhibits Insecticidal Activity against Plutella xylostella via Adenosine Receptors

    PubMed Central

    Fang, Ming; Chai, Yiqiu; Chen, Guanjv; Wang, Huidong; Huang, Bo

    2016-01-01

    The diamondback moth, Plutella xylostella, is one of the most important pests of cruciferous crops. We have earlier shown that N6-(2-hydroxyethyl)-adenosine (HEA) exhibits insecticidal activity against P. xylostella. In the present study we investigated the possible mechanism of insecticidal action of HEA on P. xylostella. HEA is a derivative of adenosine, therefore, we speculated whether it acts via P. xylostella adenosine receptor (PxAdoR). We used RNAi approach to silence PxAdoR gene and used antagonist of denosine receptor (AdoR) to study the insecticidal effect of HEA. We cloned the whole sequence of PxAdoR gene. A BLAST search using NCBI protein database showed a 61% identity with the Drosophila adenosine receptor (DmAdoR) and a 32–35% identity with human AdoR. Though the amino acids sequence of PxAdoR was different compared to other adenosine receptors, most of the amino acids that are known to be important for adenosine receptor ligand binding and signaling were present. However, only 30% binding sites key residues was similar between PxAdoR and A1R. HEA, at a dose of 1 mg/mL, was found to be lethal to the second-instar larvae of P. xylostella, and a significant reduction of mortality and growth inhibition ratio were obtained when HEA was administered to the larvae along with PxAdoR-dsRNA or antagonist of AdoR (SCH58261) for 36, 48, or 60 h. Especially at 48 h, the rate of growth inhibition of the PxAdoR knockdown group was 3.5-fold less than that of the HEA group, and the corrected mortality of SCH58261 group was reduced almost 2-fold compared with the HEA group. Our findings show that HEA may exert its insecticidal activity against P. xylostella larvae via acting on PxAdoR. PMID:27668428

  1. [Risk assessment and measuring the need for revascularization on the basis of residual ischemia by means of dobutamine stress echocardiography in the early phase of the first myocardial infarction].

    PubMed

    Nyúzó, B; Pálinkás, A; Szabó, E; Ungi, I; Szécsi, J

    1999-08-29

    The aim of this study is to present a modern method which can be used in the early phase of myocardial infarction. Its results show that with the detection of residual ischaemia, valuable information can be gained concerning the progression of the disease and the claim to revascularisation. During the first week (2-7 days), the authors performed risk assessing dobutamine stress echocardiography in 52 nonselected acute patients with first myocardial infarction. Patients with negative results were regarded as low risk cases 35/52 (67.3%), while those with positive results were regarded as high risk cases 17/52 (32.7%). The number of the serious postinfarction hard events was 22/52 (42.3%) during the one-year following period. In the case of the positive group, during mainly the first three months the occurrence of such events was found to be extremely high: 16/17 (94.1%), while in the case of the negative group it was only 6/35 (17.1%). On the basis of the test results it can be stated that coronarography was performed in 14/17 (82.4%) vs. 3/35 (8.6%) of the cases, and revascularisation in 10/17 (58.8%) vs. 1/35 (2.9%) of the cases. In 2/17 (11.8%) vs. 3/35 (8.6%) of the cases, the patients suffered from acute coronary syndrome and the mortality rate was 2/17 (11.8%) vs. 1/35 (2.9%). The sensitivity value was 79.1%, the specificity value 90.6%, and the positive and negative predictive values 86.3% and 85.3%. There was no such significant complication detected which could be attributable to the examination. On the basis of the results and corresponding to the data in special literature, the authors found the dobutamine stress test a good and safe prognostical method even some days after the infarction. With the help of this method the high and low risk groups of patients can be separated early, and at the same time the claim to revascularisation in the first three months can be measured too.

  2. Measurement of plasma adenosine concentration: methodological and physiological considerations

    SciTech Connect

    Gewirtz, H.; Brown, P.; Most, A.S.

    1987-05-01

    This study tested the hypothesis that measurements of plasma adenosine concentration made on samples of blood obtained in dipyridamole and EHNA (i.e., stopping solution) may be falsely elevated as a result of ongoing in vitro production and accumulation of adenosine during sample processing. Studies were performed with samples of anticoagulated blood obtained from anesthesized domestic swine. Adenosine concentration of ultra filtrated plasma was determined by HPLC. The following parameters were evaluated: (i) rate of clearance of (/sup 3/H)adenosine added to plasma, (ii) endogenous adenosine concentration of matched blood samples obtained in stopping solution alone, stopping solution plus EDTA, and perchloric acid (PCA), (iii) plasma and erythrocyte endogenous adenosine concentration in nonhemolyzed samples, and (iv) plasma adenosine concentration of samples hemolyzed in the presence of stopping solution alone or stopping solution plus EDTA. We observed that (i) greater than or equal to 95% of (/sup 3/H)adenosine added to plasma is removed from it by formed elements of the blood in less than 20 s, (ii) plasma adenosine concentration of samples obtained in stopping solution alone is generally 10-fold greater than that of matched samples obtained in stopping solution plus EDTA, (iii) deliberate mechanical hemolysis of blood samples obtained in stopping solution alone resulted in substantial augmentation of plasma adenosine levels in comparison with matched nonhemolyzed specimens--addition of EDTA to stopping solution prevented this, and (iv) adenosine content of blood samples obtained in PCA agreed closely with the sum of plasma and erythrocyte adenosine content of samples obtained in stopping solution plus EDTA.

  3. Role of adenosine receptor subtypes in methamphetamine reward and reinforcement.

    PubMed

    Kavanagh, Kevin A; Schreiner, Drew C; Levis, Sophia C; O'Neill, Casey E; Bachtell, Ryan K

    2015-02-01

    The neurobiology of methamphetamine (MA) remains largely unknown despite its high abuse liability. The present series of studies explored the role of adenosine receptors on MA reward and reinforcement and identified alterations in the expression of adenosine receptors in dopamine terminal areas following MA administration in rats. We tested whether stimulating adenosine A1 or A2A receptor subtypes would influence MA-induced place preference or MA self-administration on fixed and progressive ratio schedules in male Sprague-Dawley rats. Stimulation of either adenosine A1 or A2A receptors significantly reduced the development of MA-induced place preference. Stimulating adenosine A1, but not A2A, receptors reduced MA self-administration responding. We next tested whether repeated experimenter-delivered MA administration would alter the expression of adenosine receptors in the striatal areas using immunoblotting. We observed no change in the expression of adenosine receptors. Lastly, rats were trained to self-administer MA or saline for 14 days and we detected changes in adenosine A1 and A2A receptor expression using immunoblotting. MA self-administration significantly increased adenosine A1 in the nucleus accumbens shell, caudate-putamen and prefrontal cortex. MA self-administration significantly decreased adenosine A2A receptor expression in the nucleus accumbens shell, but increased A2A receptor expression in the amygdala. These findings demonstrate that MA self-administration produces selective alterations in adenosine receptor expression in the nucleus accumbens shell and that stimulation of adenosine receptors reduces several behavioral indices of MA addiction. Together, these studies shed light onto the neurobiological alterations incurred through chronic MA use that may aid in the development of treatments for MA addiction.

  4. Caffeine intensifies taste of certain sweeteners: role of adenosine receptor.

    PubMed

    Schiffman, S S; Diaz, C; Beeker, T G

    1986-03-01

    Caffeine, a potent antagonist of adenosine receptors, potentiates the taste of some but not all sweeteners. It significantly enhances the taste of acesulfam-K, neohesperidin dihydrochalcone, d-tryptophan, thaumatin, stevioside, and sodium saccharin. Adenosine reverses the enhancement. Caffeine has no effect on aspartame, sucrose, fructose, and calcium cyclamate. These results suggest that the inhibitory A1 adenosine receptor plays an important local role in modulating the taste intensity of certain sweeteners and that several transduction mechanisms mediate sweet taste.

  5. 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

  6. Myocardial perfusion imaging with dual energy CT.

    PubMed

    Jin, Kwang Nam; De Cecco, Carlo N; Caruso, Damiano; Tesche, Christian; Spandorfer, Adam; Varga-Szemes, Akos; Schoepf, U Joseph

    2016-10-01

    Dual-energy CT (DECT) enables simultaneous use of two different tube voltages, thus different x-ray absorption characteristics are acquired in the same anatomic location with two different X-ray spectra. The various DECT techniques allow material decomposition and mapping of the iodine distribution within the myocardium. Static dual-energy myocardial perfusion imaging (sCTMPI) using pharmacological stress agents demonstrate myocardial ischemia by single snapshot images of myocardial iodine distribution. sCTMPI gives incremental values to coronary artery stenosis detected on coronary CT angiography (CCTA) by showing consequent reversible or fixed myocardial perfusion defects. The comprehensive acquisition of CCTA and sCTMPI offers extensive morphological and functional evaluation of coronary artery disease. Recent studies have revealed that dual-energy sCTMPI shows promising diagnostic accuracy for the detection of hemodynamically significant coronary artery disease compared to single-photon emission computed tomography, invasive coronary angiography, and cardiac MRI. The aim of this review is to present currently available DECT techniques for static myocardial perfusion imaging and recent clinical applications and ongoing investigations.

  7. Effect of astragaloside IV against rat myocardial cell apoptosis induced by oxidative stress via mitochondrial ATP-sensitive potassium channels.

    PubMed

    Guan, Feng-Ying; Yang, Shi-Jie; Liu, Jinxiang; Yang, Si-Rui

    2015-07-01

    Astragaloside is one of the most common traditional Chinese medicines and is derived from Astragalus membranaceus. Astragaloside IV (AsIV) is a monomer located in an extract of astragaloside. The current study investigated the protective effects of AsIV against hydrogen peroxide (H2O2)-induced injury in cardiocytes and elucidated the mechanisms responsible for this protective effect. Cultured neonatal rat cardiocytes were divided into five experimental groups as follows: i) Dimethyl sulfoxide; ii) H2O2; iii) AsIV+H2O2; iv) AsIV+H2O2+5-hydroxydecanoate (5-HD); and v) nicorandil+H2O2. Cardiocyte survival was analyzed using an MTT assay. Lactate dehydrogenase (LDH) release was also assessed to evaluate the viability of the cells. Intracellular reactive oxygen species (ROS) were measured by 2,7-dichlorodihydrofluorescein diacetate staining. The apoptotic rate was measured by flow cytometry. Mitochondrial membrane potential (ΔΨm) and intracellular calcium were observed using a laser confocal microscopy system. The results indicated that AsIV promoted the survival of cardiocytes (P<0.05), attenuated LDH release (P<0.05), ROS production (P<0.01) and apoptosis (P<0.01), stabilized the ΔΨm and reduced intracellular calcium overload (P<0.01) compared with the H2O2 group. The mitochondrial adenosine triphosphate-sensitive potassium channel (mitoKATP) inhibitor 5-HD was observed to partially reverse the protective effect of AsIV. Following treatment with 5-HD, the survival of cardiocytes was reduced (P<0.05), LDH release (P<0.01) and ROS production (P<0.05) were stimulated, ΔΨm and intracellular calcium change were increased (P<0.01) and apoptosis was increased (P<0.01) compared with the AsIV+H2O2 group. Thus, AsIV has potential for use in the suppression of apoptosis resulting from H2O2 exposure, and mitoKATP activation may underlie this protective mechanism. PMID:25739067

  8. A Metabolic Immune Checkpoint: Adenosine in Tumor Microenvironment.

    PubMed

    Ohta, Akio

    2016-01-01

    Within tumors, some areas are less oxygenated than others. Since their home ground is under chronic hypoxia, tumor cells adapt to this condition by activating aerobic glycolysis; however, this hypoxic environment is very harsh for incoming immune cells. Deprivation of oxygen limits availability of energy sources and induces accumulation of extracellular adenosine in tumors. Extracellular adenosine, upon binding with adenosine receptors on the surface of various immune cells, suppresses pro-inflammatory activities. In addition, signaling through adenosine receptors upregulates a number of anti-inflammatory molecules and immunoregulatory cells, leading to the establishment of a long-lasting immunosuppressive environment. Thus, due to hypoxia and adenosine, tumors can discourage antitumor immune responses no matter how the response was induced, whether it was spontaneous or artificially introduced with a therapeutic intention. Preclinical studies have shown the significance of adenosine in tumor survival strategy by demonstrating tumor regression after inactivation of adenosine receptors, inhibition of adenosine-producing enzymes, or reversal of tissue hypoxia. These promising results indicate a potential use of the inhibitors of the hypoxia-adenosine pathway for cancer immunotherapy. PMID:27066002

  9. Adenosine analogs inhibit fighting in isolated male mice

    SciTech Connect

    Palmour, R.M.; Lipowski, C.J.; Simon, C.K.; Ervin, F.R.

    1989-01-01

    The potent adenosine analogs N-ethylcarboxamide adenosine (NECA) and phenylisopropyladenosine (PIA) inhibit fighting and associated agonistic behaviors in isolated male mice. These effects are reversed by methylxanthines; moderate doses of NECA which inhibit fighting have minimal effects on spontaneous locomotor activity. At very low doses, both NECA and PIA increase fighting in parallel with previously reported increases of motor activity. Brain levels of (/sup 3/H)-NECA and (/sup 3/H)-PIA achieved at behaviorally effective doses suggest an involvement of adenosine receptors. The biochemical mechanism of adenosine receptor action with respect to fighting is unknown, but may include neuromodulatory effects on the release of other, more classical neurotransmitters.

  10. Adenosine signaling: good or bad in erectile function?

    PubMed

    Wen, Jiaming; Xia, Yang

    2012-04-01

    The erectile status of penile tissue is governed largely by the tone of cavernosal smooth muscle cells, which is determined by the balance of vascular relaxants and constrictors. Vascular relaxants play a key role in regulating the tone of cavernosal smooth muscle and thus the initiation and maintenance of penile erection. Early studies drew attention to the potential role of adenosine signaling in this process. However, the serendipitous discovery of the effect of sildenafil on erectile physiology drew more attention toward nitric oxide (NO) as a vasodilator in the process of penile erection, and a recently discovered, unexpected erectile phenotype of adenosine deaminase-deficient mice reemphasizes the importance of adenosine as a key regulatory of erectile status. Adenosine, like NO, is a potent and short-lived vasorelaxant that functions via cyclic nucleotide second messenger signaling to promote smooth muscle relaxation. Recent studies reviewed here show that adenosine functions to relax the corpus cavernosum and promote penile erection. Excess adenosine in penile tissue contributes to the disorder called priapism, and impaired adenosine signaling is associated with erectile dysfunction. More recent research summarized in this review reveals that adenosine functions as a key endogenous vasodilator in the initiation and maintenance of normal penile erection. This new insight highlights adenosine signaling pathways operating in penile tissue as significant therapeutic targets for the treatment of erectile disorders.

  11. 21 CFR 864.7040 - Adenosine triphosphate release assay.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... device that measures the release of adenosine triphosphate (ATP) from platelets following aggregation.... Simultaneous measurements of platelet aggregation and ATP release are used to evaluate platelet...

  12. Unstable Angina Pectoris and the Progression to Acute Myocardial Infarction

    PubMed Central

    Willerson, James T.; Yao, Sheng-Kun; Ferguson, James J.; Anderson, H. Vernon; Golino, Paolo; Buja, L. Maximilian

    1991-01-01

    The conversion from stable to unstable angina and the further progression to myocardial infarction are usually associated with atherosclerotic plaque fissuring or ulceration at sites of coronary artery stenosis and subsequent development of a thrombus. This thrombus formation is initiated by platelet adhesion and aggregation; these, in turn, are promoted by the local release and accumulation of thromboxane A2 and serotonin. This accumulation and the resulting platelet aggregation at sites of endothelial injury cause dynamic vasoconstriction. With time, the platelet-initiated thrombus expands to include white and red blood cells in a fibrin mesh. Thus, a fully occlusive coronary thrombus may develop and cause the progression from unstable angina to acute myocardial infarction, often Q-wave myocardial infarction. We believe that the connection between unstable angina and acute myocardial infarction is a continuum relative to the processes of coronary artery thrombosis and vasoconstriction. When the period of platelet aggregation or dynamic vasoconstriction at sites of endothelial injury and coronary stenosis lasts only a few minutes and is repetitive, unstable angina or non-Q wave myocardial infarction occurs. However, when complete coronary artery occlusion lasts for longer than 4 hours, a transmural or Q-wave myocardial infarction results. Recently, in experimental animal models with mechanically induced coronary artery stenoses and endothelial injury, we have found that other mediators, including adenosine diphosphate and thrombin, also contribute to coronary artery thrombosis. Moreover, in humans with limiting angina, we have identified spontaneous coronary blood flow variations in a pattern similar to the variations caused by alternating platelet attachment and dislodgement in experimental canine modes. In this review, we add information to our previous observations in order to present the possible mechanisms of conversion from chronic to acute coronary heart

  13. Regional wall motion abnormality in apical ballooning syndrome (Takotsubo/stress cardiomyopathy): importance of biplane left ventriculography for differentiating from spontaneously aborted anterior myocardial infarction.

    PubMed

    Patel, Sandeep M; Lennon, Ryan J; Prasad, Abhiram

    2012-04-01

    Understanding the precise distribution of the regional wall motion abnormality (RWMA) in apical ballooning syndrome (ABS) is important because the cardiomyopathy can mimic an acute anterior ST-elevation myocardial infarction (STEMI). The aim of the study was to quantify the severity and distribution of RWMA in ABS, compare it to anterior STEMI, and correlate with clinical features. RWMA (normal = 1, hypokinetic = 2, akinetic = 3) was quantified from the biplane left ventriculogram using a nine-segment model in 95 ABS and 17 anterior STEMI patients at the time of their presentation. Regional wall motion score index (RWMSI) was higher in ABS [2.1 (1.9, 2.1)] compared to anterior STEMI [2.0 (1.8, 2.0)], P = 0.024]. The region that most clearly differentiated ABS from anterior STEMI was the posterolateral segment (sensitivity 81% and specificity 100%) which was hypocontractile in 81% of ABS, but none of the STEMI patients (P < 0.001). RWMSI in ABS had a modest positive correlation with the troponin T levels (r = 0.23, P = 0.029). Patients with ABS with ST-segment elevation had the highest RWMSI [2.1(2.0, 2.2)], while those with non specific changes had the lowest [1.9 (1.8, 2.1)] (P = 0.007). In conclusion, patients with ABS have greater and more diffuse RWMA compared to anterior STEMI. The presence of systolic dysfunction in the posterolateral segment in the left anterior oblique projection of the left ventriculogram most accurately distinguishes ABS from an anterior STEMI highlighting the utility of biplane angiography for this purpose. The severity of RWMA correlates with the extent of troponin release and ECG abnormality.

  14. Myocardial ischemic protection in natural mammalian hibernation.

    PubMed

    Yan, Lin; Kudej, Raymond K; Vatner, Dorothy E; Vatner, Stephen F

    2015-03-01

    Hibernating myocardium is an important clinical syndrome protecting the heart with chronic myocardial ischemia, named for its assumed resemblance to hibernating mammals in winter. However, the effects of myocardial ischemic protection have never been studied in true mammalian hibernation, which is a unique strategy for surviving extreme winter environmental stress. The goal of this investigation was to test the hypothesis that ischemic stress may also be protected in woodchucks as they hibernate in winter. Myocardial infarction was induced by coronary occlusion followed by reperfusion in naturally hibernating woodchucks in winter with and without hibernation and in summer, when not hibernating. The ischemic area at risk was similar among groups. Myocardial infarction was significantly less in woodchucks in winter, whether hibernating or not, compared with summer, and was similar to that resulting after ischemic preconditioning. Whereas several genes were up or downregulated in both hibernating woodchuck and with ischemic preconditioning, one mechanism was unique to hibernation, i.e., activation of cAMP-response element binding protein (CREB). When CREB was upregulated in summer, it induced protection similar to that observed in the woodchuck heart in winter. The cardioprotection in hibernation was also mediated by endothelial nitric oxide synthase, rather than inducible nitric oxide synthase. Thus, the hibernating woodchuck heart is a novel model to study cardioprotection for two major reasons: (1) powerful cardioprotection occurs naturally in winter months in the absence of any preconditioning stimuli, and (2) it resembles ischemic preconditioning, but with novel mechanisms, making this model potentially useful for clinical translation.

  15. Myocardial ischemic protection in natural mammalian hibernation.

    PubMed

    Yan, Lin; Kudej, Raymond K; Vatner, Dorothy E; Vatner, Stephen F

    2015-03-01

    Hibernating myocardium is an important clinical syndrome protecting the heart with chronic myocardial ischemia, named for its assumed resemblance to hibernating mammals in winter. However, the effects of myocardial ischemic protection have never been studied in true mammalian hibernation, which is a unique strategy for surviving extreme winter environmental stress. The goal of this investigation was to test the hypothesis that ischemic stress may also be protected in woodchucks as they hibernate in winter. Myocardial infarction was induced by coronary occlusion followed by reperfusion in naturally hibernating woodchucks in winter with and without hibernation and in summer, when not hibernating. The ischemic area at risk was similar among groups. Myocardial infarction was significantly less in woodchucks in winter, whether hibernating or not, compared with summer, and was similar to that resulting after ischemic preconditioning. Whereas several genes were up or downregulated in both hibernating woodchuck and with ischemic preconditioning, one mechanism was unique to hibernation, i.e., activation of cAMP-response element binding protein (CREB). When CREB was upregulated in summer, it induced protection similar to that observed in the woodchuck heart in winter. The cardioprotection in hibernation was also mediated by endothelial nitric oxide synthase, rather than inducible nitric oxide synthase. Thus, the hibernating woodchuck heart is a novel model to study cardioprotection for two major reasons: (1) powerful cardioprotection occurs naturally in winter months in the absence of any preconditioning stimuli, and (2) it resembles ischemic preconditioning, but with novel mechanisms, making this model potentially useful for clinical translation. PMID:25613166

  16. Oxidative stress does not play a primary role in the toxicity induced with clinical doses of doxorubicin in myocardial H9c2 cells.

    PubMed

    Rharass, Tareck; Gbankoto, Adam; Canal, Christophe; Kurşunluoğlu, Gizem; Bijoux, Amandine; Panáková, Daniela; Ribou, Anne-Cécile

    2016-02-01

    The implication of oxidative stress as primary mechanism inducing doxorubicin (DOX) cardiotoxicity is still questionable as many in vitro studies implied supra-clinical drug doses or unreliable methodologies for reactive oxygen species (ROS) detection. The aim of this study was to clarify whether oxidative stress is involved in compliance with the conditions of clinical use of DOX, and using reliable tools for ROS detection. We examined the cytotoxic mechanisms of 2 μM DOX 1 day after the beginning of the treatment in differentiated H9c2 rat embryonic cardiac cells. Cells were exposed for 2 or 24 h with DOX to mimic a single chronic dosage or to favor accumulation, respectively. We found that apoptosis was prevalent in cells exposed for a short period with DOX: cells showed typical hallmarks as loss of anchorage ability, mitochondrial hyperpolarization followed by the collapse of mitochondrial activity, and nuclear condensation. Increasing the exposure period favored a shift to necrosis as the cells preferentially exhibited early DNA impairment and nuclear swelling. In either case, measuring the fluorescence lifetime of 1-pyrenebutyric acid or the intensities of dihydroethidium or amplex red showed a consistent pattern in ROS production which was a slight increased level far from representative of an oxidative stress. Moreover, pre-treatment with dexrazoxane provided a cytoprotective effect although it failed to detoxify ROS. Our data support that oxidative stress is unlikely to be the primary mechanism of DOX cardiac toxicity in vitro.

  17. Adenosine signaling in normal and sickle erythrocytes and beyond

    PubMed Central

    Zhang, Yujin; Xia, Yang

    2012-01-01

    Sickle cell disease (SCD) is a debilitating hemolytic genetic disorder with high morbidity and mortality affecting millions of individuals worldwide. Although SCD was discovered more than a century ago, no effective mechanism-based prevention and treatment are available due to poorly understood molecular basis of sickling, the fundamental pathogenic process of the disease. SCD patients constantly face hypoxia. One of the best-known signaling molecules to be induced under hypoxic conditions is adenosine. Recent studies demonstrate that hypoxia-mediated elevated adenosine signaling plays an important role in normal erythrocyte physiology. In contrast, elevated adenosine signaling contributes to sickling and multiple life threatening complications including tissue damage, pulmonary dysfunction and priapism. Here, we summarize recent research on the role of adenosine signaling in normal and sickle erythrocytes, progression of the disease and therapeutic implications. In normal erythrocytes, both genetic and pharmacological studies demonstrate that adenosine can enhance 2,3-bisphosphoglycerate (2,3-BPG) production via A2B receptor (ADORA2B) activation, suggesting that elevated adenosine has an unrecognized role in normal erythrocytes to promote O2 release and prevent acute ischemic tissue injury. However, in sickle erythrocytes, the beneficial role of excessive adenosine-mediated 2,3-BPG induction becomes detrimental by promoting deoxygenation, polymerization of sickle hemoglobin and subsequent sickling. Additionally, adenosine signaling via the A2A receptor (ADORA2A) on invariant natural killer T (iNKT) cells inhibits iNKT cell activation and attenuates pulmonary dysfunction in SCD mice. Finally, elevated adenosine coupled with ADORA2BR activation is responsible for priapism, a dangerous complication seen in SCD. Overall, the research reviewed here reveals a differential role of elevated adenosine in normal erythrocytes, sickle erythrocytes, iNK cells and progression

  18. Characterization of adenosine binding proteins in human placental membranes

    SciTech Connect

    Hutchison, K.A.

    1989-01-01

    We have characterized two adenosine binding proteins in human placenta. In membranes, one site is detected with ({sup 3}H) -N-ethylcarboxamidoadenosine (({sup 3}H)NECA). This site is similar to the adenosine A{sub 2} receptor. We call this site the adenosine A{sub 2}-like binding site. In detergent extracts, the second site is detected and has the characteristics of an adenosine A{sub 1} receptor. The soluble adenosine A{sub 2}-like binding site cannot be detected without a rapid assay. Binding to the adenosine A{sub 1} receptor with ({sup 3}H)-2-chloroadenosine and ({sup 3}H)NECA is time dependent, saturable, and reversible. Equilibrium displacement analysis with adenosine agonists reveals an A{sub 1} specificity: 2-chloroadenosine > R-phenylisopropyladenosine > 5{prime}-N-ethylcarboxamidoadenosine. The antagonist potency order is 1,3-diethyl-8-phenylxanthine > isobutylmethylxanthine > theophylline. Competition analysis of membranes with the A,-selective ligands ({sup 3}H)-cyclohexyladenosine ({sup 3}H) cylopentylxanthine revealed adenosine A{sub 1} agonist and antagonist potency orders. We have purified the adenosine A{sub 2}-like binding site. The adenosine A{sub 2}-like binding site is an ubiquitous major cellular protein. It is glycosylated, highly asymmetric, and acidic. The native protein is an homodimer with a subunit molecular mass of 98 kDa. The sedimentation coefficient and partial specific volume of the binding complex are 6.9 s and 0.698 ml/g, respectively. The Stokes' radius is 70 {Angstrom}. The native molecular mass of the detergent-protein complex is 230 kDa. The adenosine A{sub 2}-like binding site has an agonist potency order of 5'-N-ethylcarboxamidoadenosine > 2-chloroadenosine >> R-phenylisopropyladenosine and an antagonist potency order of isobutylmethylxanthine > theophylline >> 1,3-diethyl-8-phenylxanthine.

  19. PARP inhibition and postinfarction myocardial remodeling.

    PubMed

    Halmosi, Robert; Deres, Laszlo; Gal, Roland; Eros, Krisztian; Sumegi, Balazs; Toth, Kalman

    2016-08-01

    Coronary artery disease accounts for the greatest proportion of cardiovascular diseases therefore it is the major cause of death worldwide. Its therapeutic importance is indicated by still high mortality of myocardial infarction, which is one of the most severe forms of CVDs. Moreover, the risk of developing heart failure is very high among survivors. Heart failure is accompanied by high morbidity and mortality rate, therefore this topic is in the focus of researchers' interest. After a myocardial infarct, at first ventricular hypertrophy develops as a compensatory mechanism to decrease wall stress but finally leads to left ventricular dilation. This phenomenon is termed as myocardial remodeling. The main characteristics of underlying mechanisms involve cardiomyocyte growth, vessel changes and increased collagen production, in all of which several mechanical stress induced neurohumoral agents, oxidative stress and signal transduction pathways are involved. The long term activation of these processes ultimately leads to left ventricular dilation and heart failure with decreased systolic function. Oxidative stress causes DNA breaks producing the activation of nuclear poly(ADP-ribose) polymerase-1 (PARP-1) enzyme that leads to energy depletion and unfavorable modulation of different kinase cascades (Akt-1/GSK-3β, MAPKs, various PKC isoforms) and thus it promotes the development of heart failure. Therefore inhibition of PARP enzyme could offer a promising new therapeutical approach to prevent the onset of heart failure among postinfarction patients. The purpose of this review is to give a comprehensive summary about the most significant experimental results and mechanisms in postinfarction remodeling. PMID:27392900

  20. cAMP-independent dilation of coronary arterioles to adenosine : role of nitric oxide, G proteins, and K(ATP) channels.

    PubMed

    Hein, T W; Kuo, L

    1999-10-01

    Adenosine is known to play an important role in the regulation of coronary blood flow during metabolic stress. However, there is sparse information on the mechanism of adenosine-induced dilation at the microcirculatory levels. In the present study, we examined the role of endothelial nitric oxide (NO), G proteins, cyclic nucleotides, and potassium channels in coronary arteriolar dilation to adenosine. Pig subepicardial coronary arterioles (50 to 100 microm in diameter) were isolated, cannulated, and pressurized to 60 cm H(2)O without flow for in vitro study. The arterioles developed basal tone and dilated dose dependently to adenosine. Disruption of endothelium, blocking of endothelial ATP-sensitive potassium (K(ATP)) channels by glibenclamide, and inhibition of NO synthase by N(G)-nitro-L-arginine methyl ester and of soluble guanylyl cyclase by 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one produced identical attenuation of vasodilation to adenosine. Combined administration of these inhibitors did not further attenuate the vasodilatory response. Production of NO from coronary arterioles was significantly increased by adenosine. Pertussis toxin, but not cholera toxin, significantly inhibited vasodilation to adenosine, and this inhibitory effect was only evident in vessels with an intact endothelium. Tetraethylammonium, glibenclamide, and a high concentration of extraluminal KCl abolished vasodilation of denuded vessels to adenosine; however, inhibition of calcium-activated potassium channels by iberiotoxin had no effect on this dilation. Rp-8-Br-cAMPS, a cAMP antagonist, inhibited vasodilation to cAMP analog 8-Br-cAMP but failed to block adenosine-induced dilation. Furthermore, vasodilations to 8-Br-cAMP and sodium nitroprusside were not inhibited by glibenclamide, indicating that cAMP- and cGMP-induced dilations are not mediated by the activation of K(ATP) channels. These results suggest that adenosine activates both endothelial and smooth muscle pathways to exert

  1. Norepinephrines effect on adenosine transport in the proximal straight tubule

    SciTech Connect

    Barfuss, D.W.; McCann, W.P.; Katholi, R.E.

    1986-03-01

    The effect of norepinephrine on C/sup 14/-adenosine transport in the rabbit proximal tubule (S/sub 2/) was studied. The transepithelial transport of adenosine (0.02 mM0 from lumin to bathing solution was measured by its rate of appearance (J/sub A/) in the bathing solution and by its disappearances (J/sub D/) from the luminal fluid. Norepinephrine (0.24 ..mu..M) was added to the bathing solution after a control flux period. After three samples from the experiment period the tubules were quickly harvested and the cellular concentration of C/sup 14/-adenosine was determined. The high cellular adenosine concentration and th marked difference in adenosine appearance rate in the bathing solution compared to the luminal disappearance rate indicates the absorbed adenosine is trapped in the cells. This trapping may be due to adenosine metabolism or difficulty of crossing the basolateral membrane. Whichever is the case, norepinephrine appears to stimulate movement of adenosine or its metabolites into the bathing solution across the basolateral membrane.

  2. Comorbidities in Neurology: Is Adenosine the Common Link?

    PubMed Central

    Boison, Detlev; Aronica, Eleonora

    2015-01-01

    Comorbidities in Neurology represent a major conceptual and therapeutic challenge. For example, temporal lobe epilepsy (TLE) is a syndrome comprised of epileptic seizures and comorbid symptoms including memory and psychiatric impairment, depression, and sleep dysfunction. Similarly, Alzheimer’s disease (AD), Parkinson’s disease (PD), and Amyotrophic Lateral Sclerosis (ALS) are accompanied by various degrees of memory dysfunction. Patients with AD have an increased likelihood for seizures, whereas all four conditions share certain aspects of psychosis, depression, and sleep dysfunction. This remarkable overlap suggests common pathophysiological mechanisms, which include synaptic dysfunction and synaptotoxicity, as well as glial activation and astrogliosis. Astrogliosis is linked to synapse function via the tripartite synapse, but astrocytes also control the availability of gliotransmitters and adenosine. Here we will specifically focus on the ‘adenosine hypothesis of comorbidities’ implying that astrocyte activation, via overexpression of adenosine kinase (ADK), induces a deficiency in the homeostatic tone of adenosine. We present evidence from patient-derived samples showing astrogliosis and overexpression of ADK as common pathological hallmark of epilepsy, AD, PD, and ALS. We discuss a transgenic ‘comorbidity model’, in which brain-wide overexpression of ADK and resulting adenosine deficiency produces a comorbid spectrum of seizures, altered dopaminergic function, attentional impairment, and deficits in cognitive domains and sleep regulation. We conclude that dysfunction of adenosine signaling is common in neurological conditions, that adenosine dysfunction can explain comorbid phenotypes, and that therapeutic adenosine augmentation might be effective for the treatment of comorbid symptoms in multiple neurological conditions. PMID:25979489

  3. Myocardial protection after whole body heat stress in the rabbit is dependent on metabolic substrate and is related to the amount of the inducible 70-kD heat stress protein.

    PubMed Central

    Marber, M S; Walker, J M; Latchman, D S; Yellon, D M

    1994-01-01

    The aims of this study were to examine the effects of whole body heat stress and subsequent stress protein induction on glycolytic metabolism, mitochondrial metabolism, and calcium handling within the heart. The effect of heat stress on glycolytic and mitochondrial pathways was examined by measuring contractile performance in the presence of glucose and pyruvate, respectively. Calcium handling was assessed using force-interval relationships. Right ventricular papillary muscles taken from heat-stressed and control rabbit hearts were superfused with Kreb's solution containing either glucose or pyruvate and rendered hypoxic for 30 min. After reoxygenation, the greatest recovery of contractile function occurred in the heat-stressed muscles with pyruvate as substrate; there was, however, no difference in the force-interval relationship between the groups. The degree of contractile recovery was related to the content of the inducible 70-kD but not the 65-kD, heat stress protein. This study suggests that heat stress enhances the ability of rabbit papillary muscle to use pyruvate, but not glucose, after reoxygenation, and that the differences seen in contractility may be secondary to induction of the 72-kD stress protein. Images PMID:8132747

  4. A2B adenosine receptor contributes to penile erection via PI3K/AKT signaling cascade-mediated eNOS activation

    PubMed Central

    Wen, Jiaming; Grenz, Almut; Zhang, Yujin; Dai, Yingbo; Kellems, Rodney E.; Blackburn, Michael R.; Eltzschig, Holger K.; Xia, Yang

    2011-01-01

    Normal penile erection is under the control of multiple factors and signaling pathways. Although adenosine signaling is implicated in normal and abnormal penile erection, the exact role and the underlying mechanism for adenosine signaling in penile physiology remain elusive. Here we report that shear stress leads to increased adenosine release from endothelial cells. Subsequently, we determined that ecto-5′-nucleotidase (CD73) is a key enzyme required for the production of elevated adenosine from ATP released by shear-stressed endothelial cells. Mechanistically, we demonstrate that shear stress-mediated elevated adenosine functions through the adenosine A2B receptor (A2BR) to activate the PI3K/AKT signaling cascade and subsequent increased endothelial nitric oxide synthase (eNOS) phosphorylation. These in vitro studies led us to discover further that adenosine was induced during sustained penile erection and contributes to PI3K/AKT activation and subsequent eNOS phosphorylation via A2BR signaling in intact animal. Finally, we demonstrate that lowering adenosine in wild-type mice or genetic deletion of A2BR in mutant mice significantly attenuated PI3K/AKT activation, eNOS phosphorylation, and subsequent impaired penile erection featured with the reduction of ratio of maximal intracavernosal pressure to systemic arterial pressure from 0.49 ± 0.03 to 0.41 ± 0.05 and 0.38 ± 0.04, respectively (both P<0.05). Overall, using biochemical, cellular, genetic, and physiological approaches, our findings reveal that adenosine is a novel molecule signaling via A2BR activation, contributing to penile erection via PI3K/AKT-dependent eNOS activation. These studies suggest that this signaling pathway may be a novel therapeutic target for erectile disorders.—Wen, J., Grenz, A., Zhang, Y., Dai, Y., Kellems, R. E., Blackburn, M. R., Eltzschig, H. K., Xia, Y. A2B adenosine receptor contributes to penile erection via PI3K/AKT signaling cascade-mediated eNOS activation. PMID

  5. Fractal regional myocardial blood flows pattern according to metabolism, not vascular anatomy.

    PubMed

    Yipintsoi, Tada; Kroll, Keith; Bassingthwaighte, James B

    2016-02-01

    Regional myocardial blood flows are markedly heterogeneous. Fractal analysis shows strong near-neighbor correlation. In experiments to distinguish control by vascular anatomy vs. local vasomotion, coronary flows were increased in open-chest dogs by stimulating myocardial metabolism (catecholamines + atropine) with and without adenosine. During control states mean left ventricular (LV) myocardial blood flows (microspheres) were 0.5-1 ml·g(-1)·min(-1) and increased to 2-3 ml·g(-1)·min(-1) with catecholamine infusion and to ∼4 ml·g(-1)·min(-1) with adenosine (Ado). Flow heterogeneity was similar in all states: relative dispersion (RD = SD/mean) was ∼25%, using LV pieces 0.1-0.2% of total. During catecholamine infusion local flows increased in proportion to the mean flows in 45% of the LV, "tracking" closely (increased proportionately to mean flow), while ∼40% trended toward the mean. Near-neighbor regional flows remained strongly spatially correlated, with fractal dimension D near 1.2 (Hurst coefficient 0.8). The spatial patterns remain similar at varied levels of metabolic stimulation inferring metabolic dominance. In contrast, adenosine vasodilation increased flows eightfold times control while destroying correlation with the control state. The Ado-induced spatial patterns differed from control but were self-consistent, inferring that with full vasodilation the relaxed arterial anatomy dominates the distribution. We conclude that vascular anatomy governs flow distributions during adenosine vasodilation but that metabolic vasoregulation dominates in normal physiological states. PMID:26589329

  6. Fractal regional myocardial blood flows pattern according to metabolism, not vascular anatomy.

    PubMed

    Yipintsoi, Tada; Kroll, Keith; Bassingthwaighte, James B

    2016-02-01

    Regional myocardial blood flows are markedly heterogeneous. Fractal analysis shows strong near-neighbor correlation. In experiments to distinguish control by vascular anatomy vs. local vasomotion, coronary flows were increased in open-chest dogs by stimulating myocardial metabolism (catecholamines + atropine) with and without adenosine. During control states mean left ventricular (LV) myocardial blood flows (microspheres) were 0.5-1 ml·g(-1)·min(-1) and increased to 2-3 ml·g(-1)·min(-1) with catecholamine infusion and to ∼4 ml·g(-1)·min(-1) with adenosine (Ado). Flow heterogeneity was similar in all states: relative dispersion (RD = SD/mean) was ∼25%, using LV pieces 0.1-0.2% of total. During catecholamine infusion local flows increased in proportion to the mean flows in 45% of the LV, "tracking" closely (increased proportionately to mean flow), while ∼40% trended toward the mean. Near-neighbor regional flows remained strongly spatially correlated, with fractal dimension D near 1.2 (Hurst coefficient 0.8). The spatial patterns remain similar at varied levels of metabolic stimulation inferring metabolic dominance. In contrast, adenosine vasodilation increased flows eightfold times control while destroying correlation with the control state. The Ado-induced spatial patterns differed from control but were self-consistent, inferring that with full vasodilation the relaxed arterial anatomy dominates the distribution. We conclude that vascular anatomy governs flow distributions during adenosine vasodilation but that metabolic vasoregulation dominates in normal physiological states.

  7. Transcriptomic Analysis of Myocardial Ischemia Using the Blood of Rat.

    PubMed

    Hou, Jincai; Fu, Jianhua; Li, Dan; Han, Xiao; Li, Lei; Song, Wenting; Yao, Mingjiang; Liu, Jianxun

    2015-01-01

    Myocardial ischemia is a pathological state of heart with reduced blood flow to heart and abnormal myocardial energy metabolism. This disease occurs commonly in middle aged and elderly people. Several studies have indicated that the rat was an appropriate animal model used to study myocardial ischemia. In this study, in order to gain insights into the pathogenesis of myocardial ischemia, we sequenced the transcriptomes of three normal rats as control and the same number of myocardial ischemia rats. We sequenced the genomes of 6 rats, including 3 cases (myocardial ischemia) and 3 controls using Illumina HiSeq 2000. Then we calculated the gene expression values and identified differentially expressed genes based on reads per kilobase transcriptome per million (RPKM). Meanwhile we performed a GO enrichment analysis and predicted novel transcripts. In our study, we found that 707 genes were up-regulated and 21 genes were down-regulated in myocardial ischemia rats by at least 2-fold compared with controls. By the distribution of reads and the annotation of reference genes, we found 1,703 and 1,552 novel transcripts in cases and controls, respectively. At the same time, we refined the structure of 9,587 genes in controls and 10,301 in cases. According to the results of GO term and pathway analysis of differentially expressed genes, we found that the immune response, stimulus response, response to stress and some diseases may be associated with myocardial ischemia. Since many diseases, especially immune diseases, are associated with myocardial ischemia, we should pay more attention to the complications which might result from myocardial ischemia.

  8. A High-Affinity Adenosine Kinase from Anopheles Gambiae

    SciTech Connect

    M Cassera; M Ho; E Merino; E Burgos; A Rinaldo-Matthis; S Almo; V Schramm

    2011-12-31

    Genome analysis revealed a mosquito orthologue of adenosine kinase in Anopheles gambiae (AgAK; the most important vector for the transmission of Plasmodium falciparum in Africa). P. falciparum are purine auxotrophs and do not express an adenosine kinase but rely on their hosts for purines. AgAK was kinetically characterized and found to have the highest affinity for adenosine (K{sub m} = 8.1 nM) of any known adenosine kinase. AgAK is specific for adenosine at the nucleoside site, but several nucleotide triphosphate phosphoryl donors are tolerated. The AgAK crystal structure with a bound bisubstrate analogue Ap{sub 4}A (2.0 {angstrom} resolution) reveals interactions for adenosine and ATP and the geometry for phosphoryl transfer. The polyphosphate charge is partly neutralized by a bound Mg{sup 2+} ion and an ion pair to a catalytic site Arg. The AgAK structure consists of a large catalytic core in a three-layer {alpha}/{beta}/{alpha} sandwich, and a small cap domain in contact with adenosine. The specificity and tight binding for adenosine arise from hydrogen bond interactions of Asn14, Leu16, Leu40, Leu133, Leu168, Phe168, and Thr171 and the backbone of Ile39 and Phe168 with the adenine ring as well as through hydrogen bond interactions between Asp18, Gly64, and Asn68 and the ribosyl 2'- and 3'-hydroxyl groups. The structure is more similar to that of human adenosine kinase (48% identical) than to that of AK from Toxoplasma gondii (31% identical). With this extraordinary affinity for AgAK, adenosine is efficiently captured and converted to AMP at near the diffusion limit, suggesting an important role for this enzyme in the maintenance of the adenine nucleotide pool. mRNA analysis verifies that AgAK transcripts are produced in the adult insects.

  9. Myocardial contractile function and intradialytic hypotension.

    PubMed

    Owen, Paul J; Priestman, William S; Sigrist, Mhairi K; Lambie, Stewart H; John, Stephen G; Chesterton, Lindsay J; McIntyre, Christopher W

    2009-07-01

    Dialysis-induced hypotension remains a significant problem in hemodialysis (HD) patients. Numerous factors result in dysregulation of blood pressure control and impaired myocardial reserve in response to HD-induced cardiovascular stress. Episodic intradialytic hypotension may be involved in the pathogenesis of evolving myocardial injury. We performed an initial pilot investigation of cardiovascular functional response to pharmacological cardiovascular stress in hypotension-resistant (HR) and hypotension-prone (HP) HD patients. We studied 10 matched chronic HD patients (5 HP, 5 HR). Dobutamine-atropine stress (DAS) was performed on a nondialysis short interval day, with noninvasive pulse-wave analysis using the Finometer to continuously measure hemodynamic variables. Baroreflex sensitivity was assessed at rest and during DAS. Baseline hemodynamic variables were not significantly different. The groups had differing hemodynamic responses to DAS. The Mean arterial pressure was unchanged in the HR group but decreased in HP patients (-13.6 +/- 3.5 mmHg; P<0.001). This was associated with failure to significantly increase cardiac output in the HP group (cf. increase in cardiac output in the HR group of +33.4 +/- 6%; P<0.05), and a reduced response in total peripheral resistance (HP -10.3 +/- 6.8%, HR -22.7 +/- 2.9%, P=NS). Baroreflex sensitivity was not significantly different between groups at baseline or within groups with increasing levels of DAS; however, the mean baroreflex sensitivity was higher in HR cf. HP subjects throughout pharmacological stress (P<0.05). Hypotension-prone patients appear to have an impaired cardiovascular response to DAS. The most significant abnormality is an impaired myocardial contractile reserve. Early identification of these patients would allow utilization of therapeutic strategies to improve intradialytic tolerability, potentially abrogating aggravation of myocardial injury.

  10. Cardioprotection and pharmacological therapies in acute myocardial infarction: Challenges in the current era

    PubMed Central

    Dominguez-Rodriguez, Alberto; Abreu-Gonzalez, Pedro; Reiter, Russel J

    2014-01-01

    In patients with an acute ST-segment elevation myocardial infarction, timely myocardial reperfusion using primary percutaneous coronary intervention is the most effective therapy for limiting myocardial infarct size, preserving left-ventricular systolic function and reducing the onset of heart failure. Within minutes after the restoration of blood flow, however, reperfusion itself results in additional damage, also known as myocardial ischemia-reperfusion injury. An improved understanding of the pathophysiological mechanisms underlying reperfusion injury has resulted in the identification of several promising pharmacological (cyclosporin-A, exenatide, glucose-insulin-potassium, atrial natriuretic peptide, adenosine, abciximab, erythropoietin, metoprolol and melatonin) therapeutic strategies for reducing the severity of myocardial reperfusion injury. Many of these agents have shown promise in initial proof-of-principle clinical studies. In this article, we review the pathophysiology underlying myocardial reperfusion injury and highlight the potential pharmacological interventions which could be used in the future to prevent reperfusion injury and improve clinical outcomes in patients with coronary heart disease. PMID:24669291

  11. Compartmental analysis of technetium-99m-teboroxime kinetics employing fast dynamic SPECT at rest and stress

    SciTech Connect

    Chiao, P.C.; Ficaro, E.P.; Dayaniki, F.

    1994-08-01

    The authors have examined the feasibility of compartmental analysis of {sup 99m}Tc-teboroxime kinetics in measuring physiological changes in response to adenosine-induced coronary vasodilation. To evaluate the effect of tracer recirculation on {sup 99m}Tc-teboroxime kinetics in the myocardium, they also compared compartmental analysis with washout analysis (monoexponertial fitting), which does not account for this effect. Eight healthy male volunteers were imaged using fast dynamic SPECT protocols (5 sec per tomographic image) at rest and during adenosine infusion. A two-compartment model was used and compartmental parameters K1 and k2 (characterizing the diffusion of {sup 99m}Tc-teboroxime from the blood to the myocardium and from the myocardium to the blood, respectively) were fitted from myocardial time-activity curves and left ventricular input functions. Both K1 and washout estimates for the whole left ventricular myocardium changed significantly in response to coronary vasodilation. Mean stress-to-rest (S/R) ratios were almost two times higher for K1 (S/R = 2.7 {plus_minus} 1.1) than for washout estimates (S/R = 1.5 {plus_minus} 0.3). Estimation of K1 for all local regions, except the septal wall, is feasible because variations in K1 estimates for all local regions, except the septum during stress, are comparable with those for the global region. The authors conclude that quantitative compartmental analysis of {sup 99m}Tc-teboroxime kinetics provides a sensitive indicator for changes in response to adenosine-induced coronary vasodilation. 39 refs., 7 figs., 1 tab.

  12. Stress

    MedlinePlus

    ... hurt or killed. Examples include a major accident, war, assault, or a natural disaster. This type of ... stress, so you can avoid more serious health effects. NIH: National Institute of Mental Health

  13. Comparison of endocardial electromechanical mapping with radionuclide perfusion imaging to assess myocardial viability and severity of myocardial ischemia in angina pectoris.

    PubMed

    Fuchs, S; Hendel, R C; Baim, D S; Moses, J W; Pierre, A; Laham, R J; Hong, M K; Kuntz, R E; Pietrusewicz, M; Bonow, R O; Mintz, G S; Leon, M B; Kornowski, R

    2001-04-01

    The assessment of left ventricular electromechanical activity using a novel, nonfluoroscopic 3-dimensional mapping system demonstrates considerable differences in electrical and mechanical activities within regions of myocardial infarction or ischemia. We sought to determine whether these changes correlate with indexes of myocardial perfusion, viability, or ischemia. A 12-segment comparative analysis was performed in 61 patients (45 men, 61 +/- 12 years old) with class III to IV angina, having reversible and/or fixed myocardial perfusion defects on single-photon emission computed tomographic perfusion imaging. A dual-isotope protocol was used, consisting of rest and 4-hour redistribution thallium images followed by adenosine technetium-99m sestamibi imaging. Average rest endocardial unipolar voltage (UpV) and local shortening (LS) mapping values were compared with visually derived perfusion scores. There was gradual and proportional reduction in regional UpV and LS in relation to thallium-201 uptake score at rest (p = 0.0001 and p = 0.0002, respectively) and redistribution studies (p = 0.0001 and p = 0.003, respectively). UpV > or = 7.4 mV and LS > or = 5.0% had a sensitivity of 78% and 65%, respectively, with a specificity of 68% and 67% for detecting viable myocardium. UpV values of 12.3 and 5.4 mV had 90% specificity and sensitivity, respectively, to predict viable tissue. UpV, but not LS, values differentiated between normal segments and those with adenosine-induced severe perfusion defects (11.8 +/- 5.3 vs 8.8 +/- 4.1 mV, p = 0.005). Catheter-based left ventricular assessment of electromechanical activity correlates with the degree of single-photon emission computed tomographic perfusion abnormality and can identify myocardial viability with a greater accuracy than myocardial ischemia.

  14. Identification of the heart as the critical site of adenosine mediated embryo protection

    PubMed Central

    2010-01-01

    Background Our understanding of the mechanisms that protect the developing embryo from intrauterine stress is limited. Recently, adenosine has been demonstrated to play a critical role in protecting the embryo against hypoxia via adenosine A1 receptors (A1ARs), which are expressed in the heart, nervous system, and other sites during development. However, the sites of A1AR action that mediate embryo protection are not known. To determine if the heart is a key site of adenosine-mediated embryo protection, A1ARs were selectively deleted in the embryonic heart using a Cre-LoxP system in which the alpha-myosin heavy chain promoter drives Cre-recombinase expression and excision of the A1AR gene from cardiomyocytes. Results With increasing exposure of maternal hypoxia (10% O2) from 48-96 hours beginning at embryonic day (E) 8.5, embryo viability decreased in the cardiac-A1AR deleted embryos. 48 hours of hypoxia reduced embryonic viability by 49% in embryos exposed from E10.5-12.5 but no effect on viability was observed in younger embryos exposed to hypoxia from E8.5-10.5. After 72 hours of hypoxia, 57.8% of the cardiac-A1AR deleted embryos were either dead or re-absorbed compared to 13.7% of control littermates and after 96 hours 81.6% of cardiac-A1AR deleted embryos were dead or re-absorbed. After 72 hours of hypoxia, cardiac size was reduced significantly more in the cardiac-A1AR deleted hearts compared to controls. Gene expression analysis revealed clusters of genes that are regulated by both hypoxia and A1AR expression. Conclusions These data identify the embryonic heart as the critical site where adenosine acts to protect the embryo against hypoxia. As such these studies identify a previously unrecognized mechanism of embryo protection. PMID:20509906

  15. Dobutamine 99Tcm-MIBI SPET myocardial perfusion scintigraphy in the prediction of restenosis after percutaneous transluminal coronary angioplasty in patients unable to perform an exercise stress test.

    PubMed

    Elhendy, A; Geleijnse, M L; Roelandt, J R; van Domburg, R T; Nierop, P R; Bax, J J; Kasprzak, J D; el-Said, G M; Ibrahim, M M; Fioretti, P M

    1997-02-01

    After successful percutaneous transluminal coronary angioplasty (PTCA), restenosis occurs in a relatively high proportion of patients. Exercise thallium scintigraphy is a useful method for the detection of restenosis. In patients unable to exercise, dobutamine perfusion scintigraphy may represent a feasible alternative. However, its diagnostic accuracy in this clinical setting has not been evaluated. We studied 40 patients (29 males, 11 females) aged 57 +/- 9 years, at a mean of 185 +/- 80 days after successful PTCA with a high-dose dobutamine (up to 40 micrograms kg-1 min-1) stress test, in conjunction with 99Tcm-methoxyisobutyl isonitrile (99Tcm-MIBI) single photon emission tomography (SPET). Significant restenosis was defined as > or = 50% luminal diameter stenosis of a coronary segment with previous PTCA and was predicted on the basis of the occurrence of reversible perfusion defects in the corresponding territories. Reversible perfusion defects occurred in 20 of 29 arteries with and in 4 of 17 arteries without restenosis. The sensitivity of dobutamine MIBI for the detection of restenosis in arteries with previous PTCA was 69% (CI = 56-82), the specificity 76% (CI = 64-89), the positive predictive value 83% (CI = 73-94), the negative predictive value 59% (CI = 45-73) and accuracy 72% (CI = 59-85). The overall sensitivity of 99Tcm-MIBI SPET for the diagnosis of significant coronary stenosis (including arteries without previous PTCA) on a patient basis was 79% (CI = 67-92), the specificity 82% (CI = 70-94) and accuracy 80% (CI = 68-92). The sensitivity of 99Tcm-MIBI SPET was significantly higher than that of electrocardiography (79 vs 38%, P < 0.005). It is concluded that dobutamine 99Tcm-MIBI SPET is a useful method for the detection of restenosis after PTCA in patients unable to perform an exercise stress test.

  16. Impaired mitochondrial energy supply coupled to increased H2O2 emission under energy/redox stress leads to myocardial dysfunction during Type I diabetes.

    PubMed

    Tocchetti, Carlo G; Stanley, Brian A; Sivakumaran, Vidhya; Bedja, Djahida; O'Rourke, Brian; Paolocci, Nazareno; Cortassa, Sonia; Aon, Miguel A

    2015-10-01

    In Type I diabetic (T1DM) patients, both peaks of hyperglycaemia and increased sympathetic tone probably contribute to impair systolic and diastolic function. However, how these stressors eventually alter cardiac function during T1DM is not fully understood. In the present study, we hypothesized that impaired mitochondrial energy supply and excess reactive oxygen species (ROS) emission is centrally involved in T1DM cardiac dysfunction due to metabolic/redox stress and aimed to determine the mitochondrial sites implicated in these alterations. To this end, we used isolated myocytes and mitochondria from Sham and streptozotocin (STZ)-induced T1DM guinea pigs (GPs), untreated or treated with insulin. Relative to controls, T1DM myocytes exhibited higher oxidative stress when challenged with high glucose (HG) combined with β-adrenergic stimulation [via isoprenaline (isoproterenol) (ISO)], leading to contraction/relaxation deficits. T1DM mitochondria had decreased respiration with complex II and IV substrates and markedly lower ADP phosphorylation rates and higher H2O2 emission when challenged with oxidants to mimic the more oxidized redox milieu present in HG + ISO-treated cardiomyocytes. Since in T1DM hearts insulin-sensitivity is preserved and a glucose-to-fatty acid (FA) shift occurs, we next tested whether insulin therapy or acute palmitate (Palm) infusion prevents HG + ISO-induced cardiac dysfunction. We found that insulin rescued proper cardiac redox balance, but not mitochondrial respiration or contractile performance. Conversely, Palm restored redox balance and preserved myocyte function. Thus, stressors such as peaks of HG and adrenergic hyperactivity impair mitochondrial respiration, hampering energy supply while exacerbating ROS emission. Our study suggests that an ideal therapeutic measure to treat metabolically/redox-challenged T1DM hearts should concomitantly correct energetic and redox abnormalities to fully maintain cardiac function. PMID:26186741

  17. Impaired mitochondrial energy supply coupled to increased H2O2 emission under energy/redox stress leads to myocardial dysfunction during Type I diabetes.

    PubMed

    Tocchetti, Carlo G; Stanley, Brian A; Sivakumaran, Vidhya; Bedja, Djahida; O'Rourke, Brian; Paolocci, Nazareno; Cortassa, Sonia; Aon, Miguel A

    2015-10-01

    In Type I diabetic (T1DM) patients, both peaks of hyperglycaemia and increased sympathetic tone probably contribute to impair systolic and diastolic function. However, how these stressors eventually alter cardiac function during T1DM is not fully understood. In the present study, we hypothesized that impaired mitochondrial energy supply and excess reactive oxygen species (ROS) emission is centrally involved in T1DM cardiac dysfunction due to metabolic/redox stress and aimed to determine the mitochondrial sites implicated in these alterations. To this end, we used isolated myocytes and mitochondria from Sham and streptozotocin (STZ)-induced T1DM guinea pigs (GPs), untreated or treated with insulin. Relative to controls, T1DM myocytes exhibited higher oxidative stress when challenged with high glucose (HG) combined with β-adrenergic stimulation [via isoprenaline (isoproterenol) (ISO)], leading to contraction/relaxation deficits. T1DM mitochondria had decreased respiration with complex II and IV substrates and markedly lower ADP phosphorylation rates and higher H2O2 emission when challenged with oxidants to mimic the more oxidized redox milieu present in HG + ISO-treated cardiomyocytes. Since in T1DM hearts insulin-sensitivity is preserved and a glucose-to-fatty acid (FA) shift occurs, we next tested whether insulin therapy or acute palmitate (Palm) infusion prevents HG + ISO-induced cardiac dysfunction. We found that insulin rescued proper cardiac redox balance, but not mitochondrial respiration or contractile performance. Conversely, Palm restored redox balance and preserved myocyte function. Thus, stressors such as peaks of HG and adrenergic hyperactivity impair mitochondrial respiration, hampering energy supply while exacerbating ROS emission. Our study suggests that an ideal therapeutic measure to treat metabolically/redox-challenged T1DM hearts should concomitantly correct energetic and redox abnormalities to fully maintain cardiac function.

  18. Decreased selenium levels in acute myocardial infarction

    SciTech Connect

    Kok, F.J.; Hofman, A.; Witteman, J.C.M.; de Bruijn, A.M.; Kruyssen, D.H.C.M.; de Bruin, M.; Valkenburg, H.A. )

    1989-02-24

    To study the association between selenium status and the risk of myocardial infarction, the authors compared plasma, erythrocyte, and toenail selenium levels and the activity of erythrocyte glutathione peroxidase among 84 patients with acute myocardial infarction and 84 population controls. Mean concentrations of all selenium measurements were lower in cases than controls. The differences were statistically significant, except for the plasma selenium level. A positive trend in the risk of acute myocardial infarction from high to low toenail selenium levels was observed, which persisted after adjustment for other risk factors for myocardial infarction. In contrast, erythrocyte glutathione peroxidase activity was significantly higher in cases than controls. Because toenail selenium level reflects blood levels up to one year before sampling, these findings suggest that a low selenium status was present before the infarction and, thus, may be of etiologic relevance. The higher glutathione peroxidase activity in the cases may be interpreted as a defense against increased oxidant stress either preceding or following the acute event.

  19. Serum adenosine deaminase activity in cutaneous anthrax

    PubMed Central

    Sunnetcioglu, Mahmut; Karadas, Sevdegul; Aslan, Mehmet; Ceylan, Mehmet Resat; Demir, Halit; Oncu, Mehmet Resit; Karahocagil, Mustafa Kasım; Sunnetcioglu, Aysel; Aypak, Cenk

    2014-01-01

    Background Adenosine deaminase (ADA) activity has been discovered in several inflammatory conditions; however, there are no data associated with cutaneous anthrax. The aim of this study was to investigate serum ADA activity in patients with cutaneous anthrax. Material/Methods Sixteen patients with cutaneous anthrax and 17 healthy controls were enrolled. We measured ADA activity; peripheral blood leukocyte, lymphocyte, neutrophil, and monocyte counts; erythrocyte sedimentation rate; and C reactive protein levels. Results Serum ADA activity was significantly higher in patients with cutaneous anthrax than in the controls (p<0.001). A positive correlation was observed between ADA activity and lymphocyte counts (r=0.589, p=0.021) in the patient group. Conclusions This study suggests that serum ADA could be used as a biochemical marker in cutaneous anthrax. PMID:24997584

  20. Ethanol Tolerance Affects Endogenous Adenosine Signaling in Mouse Hippocampus.

    PubMed

    Zhang, Dali; Xiong, Wei; Jackson, Michael F; Parkinson, Fiona E

    2016-07-01

    Ethanol has many pharmacological effects, including increases in endogenous adenosine levels and adenosine receptor activity in brain. Ethanol consumption is associated with both positive and negative health outcomes, but tolerance to the behavioral effects of ethanol can lead to increased consumption, which increases the risk of negative health outcomes. The present study was performed to test whether a 7-day treatment with ethanol is linked to reduced adenosine signaling and whether this is a consequence of reduced ecto-5'-nucleotidase activity. Wild-type (CD73(+/+)) and ecto-5'-nucleotidase-deficient (CD73(-/-)) mice were treated with ethanol (2 g/kg) or saline for 7 days. In CD73(+/+) mice, repeated ethanol treatment reduced the hypothermic and ataxic effects of acute ethanol, indicating the development of tolerance to the acute effects of ethanol. In CD73(+/+) mice, this 7-day ethanol treatment led to increased hippocampal synaptic activity and reduced adenosine A1 receptor activity under both basal and low Mg(2+) conditions. These effects of ethanol tolerance were associated with an 18% decrease in activity of ecto-5'-nucleotidase activity in hippocampal cell membranes. In contrast, ethanol treatment was not associated with changes in synaptic activity or adenosine signaling in hippocampus from CD73(-/-) mice. These data indicate that ethanol treatment is associated with a reduction in adenosine signaling through adenosine A1 receptors in hippocampus, mediated, at least in part, via reduced ecto-5'-nucleotidase activity. PMID:27189965

  1. Ethanol Tolerance Affects Endogenous Adenosine Signaling in Mouse Hippocampus

    PubMed Central

    Zhang, Dali; Xiong, Wei; Jackson, Michael F.

    2016-01-01

    Ethanol has many pharmacological effects, including increases in endogenous adenosine levels and adenosine receptor activity in brain. Ethanol consumption is associated with both positive and negative health outcomes, but tolerance to the behavioral effects of ethanol can lead to increased consumption, which increases the risk of negative health outcomes. The present study was performed to test whether a 7-day treatment with ethanol is linked to reduced adenosine signaling and whether this is a consequence of reduced ecto-5′-nucleotidase activity. Wild-type (CD73+/+) and ecto-5′-nucleotidase-deficient (CD73−/−) mice were treated with ethanol (2 g/kg) or saline for 7 days. In CD73+/+ mice, repeated ethanol treatment reduced the hypothermic and ataxic effects of acute ethanol, indicating the development of tolerance to the acute effects of ethanol. In CD73+/+ mice, this 7-day ethanol treatment led to increased hippocampal synaptic activity and reduced adenosine A1 receptor activity under both basal and low Mg2+ conditions. These effects of ethanol tolerance were associated with an 18% decrease in activity of ecto-5′-nucleotidase activity in hippocampal cell membranes. In contrast, ethanol treatment was not associated with changes in synaptic activity or adenosine signaling in hippocampus from CD73−/− mice. These data indicate that ethanol treatment is associated with a reduction in adenosine signaling through adenosine A1 receptors in hippocampus, mediated, at least in part, via reduced ecto-5′-nucleotidase activity. PMID:27189965

  2. Identification of possible adenosine receptors in vascular smooth muscle

    SciTech Connect

    Doctrow, S.R.

    1985-01-01

    Adenosine is a vasodilator and has been implicated in increased blood flow in tissues that undergo energy deficiency. During conditions such as hypoxia and ischemia, adenosine is produced and is said to increase blood flow by relaxing the vascular smooth muscle (VSM) lining the resistance vessels. The goal of this research was to identify receptors that might be responsible for adenosine-mediated VSM relaxation. When an insoluble fraction from calf aortic VSM was incubated with /sup 32/P-ATP, two components were phosphorylated. One was identified as myosin light chain by MW, pl, and immunoprecipitation. The other product was identified as phosphatidylinositol-4-phosphate (DPI) by tic. Both phosphorylations were inhibited by adenosine and by 5'-chloro-5'-deoxyadenosine (Cl-Ado). DPI production was much more sensitive to the nucleosides than was myosin phosphorylation. Neither inhibition involved change in cAMP production. Phosphatidylinositol (Pl) kinase in the VSM membranes required magnesium, was activated and solubilized by Triton X-100, and phosphorylated both endogenous and exogenous Pl. Cl-Ado inhibited Pl kinase in a manner competitive with respect to ATP and noncompetitive with respect to Pl. Adenosine and adenosine analogs modified in the ribose ring were inhibitors with potencies comparable to that of Cl-Ado. Adenine nucleotides and purine-modified adenosine analogs were weaker inhibitors than Cl-Ado.

  3. No effect of nutritional adenosine receptor antagonists on exercise performance in the heat.

    PubMed

    Cheuvront, Samuel N; Ely, Brett R; Kenefick, Robert W; Michniak-Kohn, Bozena B; Rood, Jennifer C; Sawka, Michael N

    2009-02-01

    Nutritional adenosine receptor antagonists can enhance endurance exercise performance in temperate environments, but their efficacy during heat stress is not well understood. This double-blinded, placebo-controlled study compared the effects of an acute dose of caffeine or quercetin on endurance exercise performance during compensable heat stress (40 degrees C, 20-30% rh). On each of three occasions, 10 healthy men each performed 30-min of cycle ergometry at 50% Vo2peak followed by a 15-min performance time trial after receiving either placebo (Group P), caffeine (Group C; 9 mg/kg), or quercetin (Group Q; 2,000 mg). Serial blood samples, physiological (heart rate, rectal, and mean skin body temperatures), perceptual (ratings of perceived exertion, pain, thermal comfort, motivation), and exercise performance measures (total work and pacing strategy) were made. Supplementation with caffeine and quercetin increased preexercise blood concentrations of caffeine (55.62 +/- 4.77 microM) and quercetin (4.76 +/- 2.56 microM) above their in vitro inhibition constants for adenosine receptors. No treatment effects were observed for any physiological or perceptual measures, with the exception of elevated rectal body temperatures (0.20-0.30 degrees C; P < 0.05) for Group C vs. Groups Q and P. Supplementation did not affect total work performed (Groups P: 153.5 +/- 28.3, C: 157.3 +/- 28.9, and Q: 151.1 +/- 31.6 kJ; P > 0.05) or the self-selected pacing strategy employed. These findings indicate that the nutritional adenosine receptor antagonists caffeine and quercetin do not enhance endurance exercise performance during compensable heat stress.

  4. [Myocardial infarction related to the association of physical exertion and the ingestion of cold drinks].

    PubMed

    Marcuschamer Miller, J; Pérez de Juan Romero, M A; Castellano Reyes, C; Murrieta Gutiérrez, T; Fernández Domínguez, L

    1987-01-01

    We describe 3 young individuals with acute myocardial infarction that developed after extenous stress followed by the intake of cold fluids. The patients had retrosternal chest pain and EKG changes suggestive of posterior-inferior myocardial infarction. Coronartiography demonstrated 40% and 50% narrowing of the right coronary artery. The remaining case had normal coronary arteries.

  5. Assessment of coronary artery disease using single-photon emission computed tomography with thallium-201 during adenosine-induced coronary hyperemia

    SciTech Connect

    Iskandrian, A.S.; Heo, J.; Nguyen, T.; Beer, S.G.; Cave, V.; Ogilby, J.D.; Untereker, W.; Segal, B.L. )

    1991-06-01

    Thallium-201 myocardial imaging during dipyridamole-induced coronary hyperemia has been an accepted method for diagnosing coronary artery disease (CAD) and risk stratification. Adenosine is a powerful short-acting coronary vasodilator. Initial results of thallium imaging during adenosine infusion have been encouraging. In 132 patients with CAD and in 16 patients with normal coronary angiograms, adenosine was given intravenously at a dose of 0.14 mg/kg/min for 6 minutes and thallium-201 was injected at 3 minutes. The thallium images using single-photon emission computed tomography were abnormal in 47 of the 54 patients (87%) with 1-vessel, in 34 of 37 patients (92%) with 2-vessel and in 40 of 41 patients (98%) with 3-vessel CAD. The sensitivity was 92% in the 132 patients with CAD (95% confidence intervals, 86 to 96%). In patients with normal coronary angiograms, 14 of 16 patients had normal thallium images (specificity, 88%; 95% confidence intervals, 59 to 100%). The results were very similar when subgroups of patients were analyzed: those without prior myocardial infarction, elderly patients and women. The nature of the perfusion defects (fixed or reversible) was assessed in relation to whether the 4-hour delayed images were obtained with or without the reinjection technique. In patients who underwent conventional delayed imaging, there were more fixed perfusion defects than in patients with reinjection delayed imaging (16 vs 0%, p less than 0.0001). The adverse effects were mild, transient and well tolerated. Thus, adenosine thallium tomographic imaging provides a high degree of accuracy in the diagnosis of CAD. The use of the reinjection technique enhances the ability to detect reversible defects.

  6. Altered phosphate metabolism in myocardial infarction: P-31 MR spectroscopy

    SciTech Connect

    Bottomley, P.A.; Herfkens, R.J.; Smith, L.S.; Bashore, T.M.

    1987-12-01

    The high-energy myocardial phosphate metabolism of four patients with acute anterior myocardial infarction after coronary angioplasty and drug therapy was evaluated with cardiac-gated phosphorus magnetic resonance (MR) depth-resolved surface coil spectroscopy (DRESS) 5-9 days after the onset of symptoms. Significant reductions (about threefold) in the phosphocreatine (PCr) to inorganic phosphate (Pi) ratio and elevations in the Pi to adenosine triphosphate (ATP) ratio were observed in endocardially or transmurally derived MR spectra when compared with values from epicardially displaced spectra and values from seven healthy volunteers (P less than .05). High-energy phosphate metabolites and Pi ratios did not vary significantly during the cardiac cycle in healthy volunteers. However, contamination of Pi resonances by phosphomonoester components, including blood 2,3-diphosphoglycerate, precluded accurate spectral quantification of Pi and pH. The results indicate that localized P-31 MR spectroscopy may be used to directly assess cellular energy reserve in clinical myocardial infarction and to evaluate metabolic response to interventions.

  7. Adenosine deaminase in disorders of purine metabolism and in immune deficiency

    SciTech Connect

    Tritsch, G.L.

    1985-01-01

    This book consists of five parts and a section of poster papers. Some of the selection titles are: Adenosine Deaminase Impairment and Ribonucleotide Reductase in Human Cells; Adenosine Deaminase and Malignant Cells; Inhibition of Adenosine Deaminase to Increase the Antitumor Activity of Adenine Nucleoside Analogues; and Molecular Biology of the Adenosine Deaminase Gene and Messenger RNA.

  8. Adenosine through the A2A adenosine receptor increases IL-1β in the brain contributing to anxiety

    PubMed Central

    Chiu, Gabriel S.; Darmody, Patrick T.; Walsh, John P.; Moon, Morgan L.; Kwakwa, Kristin A.; Bray, Julie K.; McCusker, Robert H.; Freund, Gregory G.

    2014-01-01

    Anxiety is one of the most commonly reported psychiatric conditions, but its pathogenesis is poorly understood. Ailments associated with activation of the innate immune system, however, are increasingly linked to anxiety disorders. In adult male mice, we found that adenosine doubled caspase-1 activity in brain by a pathway reliant on ATP-sensitive potassium (KATP) channels, protein kinase A (PKA) and the A2A adenosine receptor (AR). In addition, adenosine-dependent activation of caspase-1 increased interleukin (IL)-1β in the brain by two-fold. Peripheral administration of adenosine in wild-type (WT) mice led to a 2.3-fold increase in caspase-1 activity in the amygdala and to a 33% and 42% reduction in spontaneous locomotor activity and food intake, respectively, that were not observed in caspase-1 knockout (KO), IL-1 receptor type 1 (IL-1R1) KO and A2A AR KO mice or in mice administered a caspase-1 inhibitor centrally. Finally, adenosine administration increased anxiety-like behaviors in WT mice by 28% in the open field test and by 55% in the elevated zero-maze. Caspase-1 KO mice, IL-1R1 KO mice, A2A AR KO mice and WT mice treated with the KATP channel blocker, glyburide, were resistant to adenosine-induced anxiety-like behaviors. Thus, our results indicate that adenosine can act as an anxiogenic by activating caspase-1 and increasing IL-1β in the brain. PMID:24907587

  9. Myocardial bioenergetic abnormalities in experimental uremia

    PubMed Central

    Chesser, Alistair MS; Harwood, Steven M; Raftery, Martin J; Yaqoob, Muhammad M

    2016-01-01

    Purpose Cardiac bioenergetics are known to be abnormal in experimental uremia as exemplified by a reduced phosphocreatine (PCr)/adenosine triphosphate (ATP) ratio. However, the progression of these bioenergetic changes during the development of uremia still requires further study and was therefore investigated at baseline, 4 weeks and 8 weeks after partial nephrectomy (PNx). Methods A two-stage PNx uremia model in male Wistar rats was used to explore in vivo cardiac and skeletal muscles’ bioenergetic changes over time. High-energy phosphate nucleotides were determined by phosphorus-31 nuclear magnetic resonance (31P-NMR) and capillary zone electrophoresis. Results 31P-NMR spectroscopy revealed lower PCr/ATP ratios in PNx hearts compared to sham (SH)-operated animals 4 weeks after PNx (median values given ± SD, 0.64±0.16 PNx, 1.13±0.31 SH, P<0.02). However, 8 weeks after PNx, the same ratio was more comparable between the two groups (0.84±0.15 PNx, 1.04±0.44 SH, P= not significant), suggestive of an adaptive mechanism. When 8-week hearts were prestressed with dobutamine, the PCr/ATP ratio was again lower in the PNx group (1.08±0.36 PNx, 1.55±0.38 SH, P<0.02), indicating a reduced energy reserve during the progression of uremic heart disease. 31P-NMR data were confirmed by capillary zone electrophoresis, and the changes in myocardial bioenergetics were replicated in the skeletal muscle. Conclusion This study provides evidence of the changes that occur in myocardial energetics in experimental uremia and highlights how skeletal muscle bioenergetics mirror those found in the cardiac tissue and so might potentially serve as a practical surrogate tissue during clinical cardiac NMR investigations. PMID:27307758

  10. Prediction of Flow-Limiting Fractional Flow Reserve in Patients With Stable Coronary Artery Disease Based on Quantitative Myocardial Perfusion Imaging.

    PubMed

    Tanaka, Haruki; Takahashi, Teruyuki; Kozono, Nami; Tanakamaru, Yoshiki; Ohashi, Norihiko; Yasunobu, Yuji; Tanaka, Koichi; Okada, Takenori; Kaseda, Shunichi; Nakanishi, Toshio; Kihara, Yasuki

    2016-05-01

    Although fractional flow reserve (FFR) and myocardial perfusion imaging (MPI) findings fundamentally differ, several cohort studies have revealed that these findings correlate. Here, we investigated whether flow-limiting FFR could be predicted from adenosine stress thallium-201 MPI with single-photon emission computed tomography (SPECT) findings derived from 84 consecutive, prospectively identified patients with stable coronary artery disease and 212 diseased vessels. Among them, FFR was measured in 136 diseased vessels (64%). The findings were compared with regional perfusion abnormalities including stress total perfusion defect (TPD) - rest TPD determined using quantitative perfusion single-photon emission computed tomography software. The FFR inversely correlated the most accurately with stress TPD - rest TPD (r = -0.552, p <0.001). Predictors of major vessels of interest comprising FFR <0.80, included stress TPD - rest TPD, the transient ischemic dilation ratio, left ventricular ejection fraction at rest and beta blockers for left anterior descending artery (LAD) regions, and stress TPD - rest TPD, left ventricular mass, left ventricular ejection fraction at rest, right coronary artery lesions, the transient ischemic dilation ratio, and age for non-LAD regions. The diagnostic accuracy of formulas to predict major vessels of interest with FFR <0.80 was high (sensitivity, specificity and accuracy for LAD and non-LAD: 84%, 87% and 86%, and 75%, 93% and 87%, respectively). In conclusion, although somewhat limited by a sample size and a single-center design, flow-limiting FFR could be predicted from MPI findings with a defined probability. A cohort study might validate our results and provide a novel adjunctive tool with which to diagnose functionally significant coronary artery disease from MPI findings. PMID:26970815

  11. Adenosine receptor ligands: differences with acute versus chronic treatment

    PubMed Central

    Jacobson, Kenneth A.; von Lubitz, Dag K. J. E.; Daly, John W.; Fredholm, Bertil B.

    2012-01-01

    Adenosine receptors have been the target of intense research with respect to potential use of selective ligands in a variety of therapeutic areas. Caffeine and theophylline are adenosine receptor antagonists, and over the past three decades a wide range of selective agonists and antagonists for adenosine receptor subtypes have been developed. A complication to the therapeutic use of adenosine receptor ligands is the observation that the effects of acute administration of a particular ligand can be diametrically opposite to the chronic effects of the same ligand. This ‘effect inversion’ is discussed here by Ken Jecobson and colleagues, and has been observed for effects on cognitive processes, seizures and ischaemic damage. PMID:8936347

  12. Extracellular Adenosine Mediates a Systemic Metabolic Switch during Immune Response

    PubMed Central

    Bajgar, Adam; Kucerova, Katerina; Jonatova, Lucie; Tomcala, Ales; Schneedorferova, Ivana; Okrouhlik, Jan; Dolezal, Tomas

    2015-01-01

    Immune defense is energetically costly, and thus an effective response requires metabolic adaptation of the organism to reallocate energy from storage, growth, and development towards the immune system. We employ the natural infection of Drosophila with a parasitoid wasp to study energy regulation during immune response. To combat the invasion, the host must produce specialized immune cells (lamellocytes) that destroy the parasitoid egg. We show that a significant portion of nutrients are allocated to differentiating lamellocytes when they would otherwise be used for development. This systemic metabolic switch is mediated by extracellular adenosine released from immune cells. The switch is crucial for an effective immune response. Preventing adenosine transport from immune cells or blocking adenosine receptor precludes the metabolic switch and the deceleration of development, dramatically reducing host resistance. Adenosine thus serves as a signal that the “selfish” immune cells send during infection to secure more energy at the expense of other tissues. PMID:25915062

  13. Myocardial diseases of animals.

    PubMed Central

    Van Vleet, J. F.; Ferrans, V. J.

    1986-01-01

    In this review we have attempted a comprehensive compilation of the cardiac morphologic changes that occur in spontaneous and experimental myocardial diseases of animals. Our coverage addresses diseases of mammals and birds and includes these diseases found in both domesticated and wild animals. A similar review of the myocardial diseases in this broad range of animal species has not been attempted previously. We have summarized and illustrated the gross, microscopic, and ultrastructural alterations for these myocardial diseases; and, whenever possible, we have reviewed their biochemical pathogenesis. We have arranged the myocardial diseases for presentation and discussion according to an etiologic classification with seven categories. These include a group of idiopathic or primary cardiomyopathies recognized in man (hypertrophic, dilated, and restrictive types) and a large group of secondary cardiomyopathies with known causes, such as inherited tendency; nutritional deficiency; toxicity; physical injury and shock; endocrine disorders, and myocarditides of viral, bacterial, and protozoal causation. Considerable overlap exists between each of the etiologic groups in the spectrum of pathologic alterations seen in the myocardium. These include various degenerative changes, myocyte necrosis, and inflammatory lesions. However, some diseases show rather characteristic myocardial alterations such as vacuolar degeneration in anthracycline cardiotoxicity, myofibrillar lysis in furazolidone cardiotoxicity, calcification in calcinosis of mice, glycogen accumulation in the glycogenoses, lipofuscinosis in cattle, fatty degeneration in erucic acid cardiotoxicity, myofiber disarray in hypertrophic cardiomyopathy, and lymphocytic inflammation with inclusion bodies in canine parvoviral myocarditis. The myocardial diseases represent the largest group in the spectrum of spontaneous cardiac diseases of animals. Pericardial and endocardial diseases and congential cardiac diseases are

  14. Energy-related metabolites during and after induced myocardial infarction with special emphasis on the reperfusion injury after extracorporeal circulation.

    PubMed

    Zemgulis, V; Ronquist, G; Bjerner, T; Henze, A; Waldenström, A; Thelin, S; Wikström, G

    2001-02-01

    In the clinical setting great efforts have been made with contradictory results to operate upon acutely myocardial ischaemic patients. The reasons for the absence of clear-cut results are not well understood nor are they scientifically explored. To resolve this problem further, we attempted to design an experimental in vivo model to mimic acute myocardial ischaemia followed by extracorporeal circulation (ECC) and reperfusion. One of the main targets of our protocol was monitoring of myocardial energy metabolism by microdialysis (MCD) during the periods of coronary occlusion (60 min), hypothermic (30 degrees C) ECC and cardioplegia (45 min), followed by reperfusion with (30 min) and without (60 min) ECC. In eight anaesthetized, open-chest pigs, myocardial lactate, pyruvate, adenosine, taurine, inosine, hypoxanthine and guanosine were sampled with MCD in both ischaemic and non-ischaemic areas. Myocardial area at risk and infarct size were quantified with the modified topographical evaluation methods. The principal finding with this experimental setup was a biphasic release pattern of lactate, adenosine, taurine, inosine, hypoxanthine and guanosine from ischaemic myocardium. Lactate levels were equally high in reperfused ischaemic and non-ischaemic myocardial tissue. Pyruvate demonstrated consistently higher values in non-ischaemic myocardium throughout the experiment. A pattern was discernible, lactate being a marker of compromised cell energy metabolism, and taurine being a marker of disturbed cell integrity. Of special interest was the increased level of pyruvate in microdialysates of non-ischaemic myocardium as compared with its ischaemic counterpart. In conclusion, we found disturbances in energy metabolism and cell integrity not only in ischaemic but also in non-ischaemic tissue during reperfusion implying that non-ischaemic myocardium demonstrated an unexpected accumulation of lactate and pyruvate. These new findings could at least partly be explicatory to the

  15. Early experimental hypertension preserves the myocardial microvasculature but aggravates cardiac injury distal to chronic coronary artery obstruction.

    PubMed

    Urbieta Caceres, Victor Hugo; Lin, Jing; Zhu, Xiang-Yang; Favreau, Frederic D; Gibson, Matthew E; Crane, John A; Lerman, Amir; Lerman, Lilach O

    2011-02-01

    Coronary artery disease is a leading cause of death. Hypertension (HT) increases the incidence of cardiac events, but its effect on cardiac adaptation to coexisting coronary artery stenosis (CAS) is unclear. We hypothesized that concurrent HT modulates microvascular function in chronic CAS and aggravates microvascular remodeling and myocardial injury. Four groups of pigs (n=6 each) were studied: normal, CAS, HT, and CAS+HT. CAS and HT were induced by placing local irritant coils in the left circumflex coronary artery and renal artery, respectively. Six weeks later multidetector computerized tomography (CT) was used to assess systolic and diastolic function, microvascular permeability, myocardial perfusion, and responses to adenosine in the "area at risk." Microvascular architecture, inflammation, and fibrosis were then explored in cardiac tissue. Basal myocardial perfusion was similarly decreased in CAS and CAS+HT, but its response to adenosine was significantly more attenuated in CAS. Microvascular permeability in CAS+HT was greater than in CAS and was accompanied by amplified myocardial inflammation, fibrosis, and microvascular remodeling, as well as cardiac systolic and diastolic dysfunction. On the other hand, compared with normal, micro-CT-derived microvascular (20-200 μm) transmural density decreased in CAS but not in HT or CAS+HT. We conclude that the coexistence of early renovascular HT exacerbated myocardial fibrosis and vascular remodeling distal to CAS. These changes were not mediated by loss of myocardial microvessels, which were relatively preserved, but possibly by exacerbated myocardial inflammation and fibrosis. HT modulates cardiac adaptive responses to CAS and bears cardiac functional consequences. PMID:21131477

  16. A label-free fluorescent molecular beacon based on DNA-templated silver nanoclusters for detection of adenosine and adenosine deaminase.

    PubMed

    Zhang, Min; Guo, Su-Miao; Li, Ying-Ru; Zuo, Peng; Ye, Bang-Ce

    2012-06-01

    A simple and reliable fluorescent molecular beacon is developed utilizing DNA-templated silver nanoclusters as a signal indicator and adenosine triphosphate (ATP) and adenosine deaminase as mechanical activators.

  17. Myocardial effects of flavonoids from Crataegus species.

    PubMed

    Schüssler, M; Hölzl, J; Fricke, U

    1995-08-01

    The influence of the main flavonoids from Crataegus species (hawthorn, Rosaceae) on coronary flow, heart rate and left ventricular pressure as well as on the velocity of contraction and relaxation was investigated in Langendorff perfused isolated guinea pig hearts at a constant pressure of 70 cmH2O. Drug action was evaluated in a concentration range of 10(-7) to 5 x 10(-4) mol/l. An increase of coronary flow caused by the O-glycosides luteolin-7-glucoside (186%), hyperoside (66%) and rutin (66%) as well as an increase of the relaxation velocity (positive lusitropism) by luteolin-7-glucoside (104%), hyperoside (62%) and rutin (73%) were the major effects observed at a maximum concentration of 0.5 mmol/l. Furthermore, slight positive inotropic effects and a rise in heart rate were seen. Similar but less intensive actions were found with the C-glycosides vitexin, vitexin-rhamnoside and monoacetyl-vitexin-rhamnoside. Possible beta-adrenergic activities of the flavonoids could be excluded by the addition of propranolol in fixed concentrations of 10(-8) to 10(-5) mol/l. Moreover, pretreatment of the animals with reserpine (7 mg/kg) did not influence myocardial activity of hyperoside (10(-4) mol/l). As previous experiments showed an inhibition of the 3',5'-cyclic adenosine monophosphate phosphodiesterase, the results suggest an inhibition of this enzyme as the possible underlying mechanism of cardiac action of flavonoids from Crataegus species.

  18. 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.

  19. Myocardial effects of flavonoids from Crataegus species.

    PubMed

    Schüssler, M; Hölzl, J; Fricke, U

    1995-08-01

    The influence of the main flavonoids from Crataegus species (hawthorn, Rosaceae) on coronary flow, heart rate and left ventricular pressure as well as on the velocity of contraction and relaxation was investigated in Langendorff perfused isolated guinea pig hearts at a constant pressure of 70 cmH2O. Drug action was evaluated in a concentration range of 10(-7) to 5 x 10(-4) mol/l. An increase of coronary flow caused by the O-glycosides luteolin-7-glucoside (186%), hyperoside (66%) and rutin (66%) as well as an increase of the relaxation velocity (positive lusitropism) by luteolin-7-glucoside (104%), hyperoside (62%) and rutin (73%) were the major effects observed at a maximum concentration of 0.5 mmol/l. Furthermore, slight positive inotropic effects and a rise in heart rate were seen. Similar but less intensive actions were found with the C-glycosides vitexin, vitexin-rhamnoside and monoacetyl-vitexin-rhamnoside. Possible beta-adrenergic activities of the flavonoids could be excluded by the addition of propranolol in fixed concentrations of 10(-8) to 10(-5) mol/l. Moreover, pretreatment of the animals with reserpine (7 mg/kg) did not influence myocardial activity of hyperoside (10(-4) mol/l). As previous experiments showed an inhibition of the 3',5'-cyclic adenosine monophosphate phosphodiesterase, the results suggest an inhibition of this enzyme as the possible underlying mechanism of cardiac action of flavonoids from Crataegus species. PMID:7575743

  20. A selective adenosine sensor derived from a triplex DNA aptamer.

    PubMed

    Patel, Mayurbhai; Dutta, Avishek; Huang, Haidong

    2011-07-01

    The aim of this study is to develop a selective adenosine aptamer sensor using a rational approach. Unlike traditional RNA aptamers developed from SELEX, duplex DNA containing an abasic site can function as a general scaffold to rationally design aptamers for small aromatic molecules. We discovered that abasic site-containing triplex DNA can also function as an aptamer and provide better affinity than duplex DNA aptamers. A novel adenosine aptamer sensor was designed using such a triplex. The aptamer is modified with furano-dU in the binding site to sense the binding. The sensor bound adenosine has a dissociation constant of 400 nM, more than tenfold stronger than the adenosine aptamer developed from SELEX. The binding quenched furano-dU fluorescence by 40%. It was also demonstrated in this study that this sensor is selective for adenosine over uridine, cytidine, guanosine, ATP, and AMP. The detection limit of this sensor is about 50 nM. The sensor can be used to quantify adenosine concentrations between 50 nM and 2 μM. PMID:21547431

  1. Intrarenal blood flow distribution during adenosine-mediated vasoconstriction.

    PubMed

    Macias, J F; Fiksen-Olsen, M; Romero, J C; Knox, F G

    1983-01-01

    Intrarenal infusion of adenosine induces an initial vasoconstriction followed by a subsequent vasodilation. The intrarenal distribution of blood flow in the vasoconstriction phase is unknown. The present study was undertaken to assess the effect of intrarenal infusion of adenosine on intracortical distribution of renal blood flow during both the vasoconstriction and vasodilation phases. Renal blood flow distribution was measured with radiolabeled microspheres in anesthetized sodium-depleted dogs before and during the early vasoconstriction phase and the late vasodilation phase of intrarenal infusion of adenosine. During the vasoconstriction phase, there was a uniform decrease in blood flow in each renal cortical zone. In the late phase of adenosine infusion, there was a significant increase in deep cortical flow without significant changes in superficial cortical flow compared with control. The effects of adenosine were also compared with those exerted by norepinephrine in which decreased blood flow was demonstrated in all zones. We conclude that the vasoconstrictor phase of adenosine infusion is characterized by a uniform reduction of renal blood flow to all cortical zones, whereas the vasodilator phase is characterized by a selective deep cortical vasodilation.

  2. Detrimental effects of adenosine signaling in sickle cell disease

    PubMed Central

    Zhang, Yujin; Dai, Yingbo; Wen, Jiaming; Zhang, Weiru; Grenz, Almut; Sun, Hong; Tao, Lijian; Lu, Guangxiu; Alexander, Danny C; Milburn, Michael V; Carter-Dawson, Louvenia; Lewis, Dorothy E; Zhang, Wenzheng; Eltzschig, Holger K; Kellems, Rodney E; Blackburn, Michael R; Juneja, Harinder S; Xia, Yang

    2016-01-01

    Hypoxia can act as an initial trigger to induce erythrocyte sickling and eventual end organ damage in sickle cell disease (SCD). Many factors and metabolites are altered in response to hypoxia and may contribute to the pathogenesis of the disease. Using metabolomic profiling, we found that the steady-state concentration of adenosine in the blood was elevated in a transgenic mouse model of SCD. Adenosine concentrations were similarly elevated in the blood of humans with SCD. Increased adenosine levels promoted sickling, hemolysis and damage to multiple tissues in SCD transgenic mice and promoted sickling of human erythrocytes. Using biochemical, genetic and pharmacological approaches, we showed that adenosine A2B receptor (A2BR)-mediated induction of 2,3-diphosphoglycerate, an erythrocyte-specific metabolite that decreases the oxygen binding affinity of hemoglobin, underlies the induction of erythrocyte sickling by excess adenosine both in cultured human red blood cells and in SCD transgenic mice. Thus, excessive adenosine signaling through the A2BR has a pathological role in SCD. These findings may provide new therapeutic possibilities for this disease. PMID:21170046

  3. Adenosine 5'-tetraphosphate and adenosine 5'-pentaphosphate are synthesized by yeast acetyl coenzyme A synthetase.

    PubMed Central

    Guranowski, A; Günther Sillero, M A; Sillero, A

    1994-01-01

    Yeast (Saccharomyces cerevisiae) acetyl coenzyme A (CoA) synthetase (EC 6.2.1.1) catalyzes the synthesis of adenosine 5'-tetraphosphate (P4A) and adenosine 5'-pentaphosphate (p5A) from ATP and tri- or tetrapolyphosphate (P3 or P4), with relative velocities of 7:1, respectively. Of 12 nucleotides tested as potential donors of nucleotidyl moiety, only ATP, adenosine-5'-O-[3-thiotriphosphate], and acetyl-AMP were substrates, with relative velocities of 100, 62, and 80, respectively. The Km values for ATP, P3, and acetyl-AMP were 0.16, 4.7, and 1.8 mM, respectively. The synthesis of p4A could proceed in the absence of exogenous acetate but was stimulated twofold by acetate, with an apparent Km value of 0.065 mM. CoA did not participate in the synthesis of p4A (p5A) and inhibited the reaction (50% inhibitory concentration of 0.015 mM). At pH 6.3, which was optimum for formation of p4A (p5A), the rate of acetyl-CoA synthesis (1.84 mumol mg-1 min-1) was 245 times faster than the rate of synthesis of p4A measured in the presence of acetate. The known formation of p4A (p5A) in yeast sporulation and the role of acetate may therefore be related to acetyl-CoA synthetase. Images PMID:7910605

  4. Depression after myocardial infarction.

    PubMed

    Ziegelstein, R C

    2001-01-01

    Depression is an independent risk factor for increased postmyocardial infarction morbidity and mortality, even after controlling for the extent of coronary artery disease, infarct size, and the severity of left ventricular dysfunction. This risk factor takes on added significance when one considers that almost half of patients recovering from a myocardial infarction have major or minor depression and that major depression alone occurs in about one in five of these individuals. Despite the well-documented risk of depression, questions remain about the mechanism of the relationship between mood disturbance and adverse outcome. The link may be explained by an association with lower levels of social support, poor adherence to recommended medical therapy and lifestyle changes intended to reduce the risk of subsequent cardiac events, disturbances in autonomic tone, enhanced platelet activation and aggregation, and systemic immune activation. Unfortunately, questions about the pathophysiologic mechanism of depression in this setting are paralleled by uncertainties about the optimal treatment of depression for patients recovering from a myocardial infarction and by a lack of knowledge about whether treating depression lowers the associated increased mortality risk. Ongoing research studies will help to determine the benefits of psychosocial interventions and of antidepressant therapy for patients soon after myocardial infarction. Although the identification of depression as a risk factor may by itself be a reason to incorporate a comprehensive psychological evaluation into the routine care of patients with myocardial infarction, this practice should certainly become standard if studies show that treating depression reduces the increased mortality risk of these patients.

  5. 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.

  6. Adaptations in adenosine signaling in drug dependence: therapeutic implications.

    PubMed

    Hack, Stephen P; Christie, Macdonald J

    2003-01-01

    Adenosine is an important endogenous purine neuromodulator in the central nervous system that modulates many important cellular processes in neurons. The physiological effects of adenosine are transduced through four pharmacologically classified receptor types i.e., A1, A2A, A2B and A3. All adenosine receptors are G-protein coupled receptors (GPCR) of the type 1 variety. Adaptations in adenosine signaling have been implicated in a wide range of pathophysiological processes, such as epilepsies, sleep disorders, pain, and drug addictions. Knowledge relating to the etiology of addictive processes is far from complete, and as a result the therapeutic options to deal with drug dependence issues are limited. Drugs of abuse mediate their effects through many distinct cellular effectors, such as neurotransmitter transporters, ion channels, and receptor proteins. However, a unifying feature of the major drugs of abuse-i.e., opiates, cocaine, and alcohol-is that they all directly or indirectly modulate adenosine signaling in neurons. Agents targeting adenosine receptors may therefore offer novel avenues for the development of therapies to manage or treat addictions. A consistent cellular adaptation to long-term drug use is the up- or down-regulation of signaling pathways driven by adenylyl cyclase/cyclic AMP (cAMP) in several brain regions linked to addiction. Withdrawal from mu-opioids or cocaine following their chronic administration leads to an upregulation of adenylyl cyclase-mediated signaling, resulting in high levels of cAMP. Cyclic AMP produced in this way acts as a substrate for the endogenous production of adenosine. Increased levels of endogenous adenosine interact with presynaptic A1 receptors to inhibit the excessive neuronal excitation often seen during morphine/cocaine withdrawal. These pre-clinical findings fit well with other data indicating that drugs which boost endogenous adenosine levels or directly interact with inhibitory A1 receptors can alleviate

  7. Interstitial adenosine concentration is increased by dipyridamole

    SciTech Connect

    Gorman, M.W.; Wangler, R.D.; DeWitt, D.F.; Wang, C.Y.; Bassingthwaighte, J.B.; Sparks, H.V.

    1986-03-01

    The authors used the multiple indicator dilution technique to observe the capillary transport of adenosine (ADO) in isolated guinea pig hearts. Radiolabelled albumin, sucrose and ADO were injected on the arterial side and measured in venous samples collected during the following 20 seconds. Transport parameters calculated from these data include permeability-surface area products (PS) for transendothelial diffusion, endothelial cell (EC) uptake at the lumenal and ablumenal membranes, and EC metabolism. With simultaneous measurements of arterial and venous ADO concentrations and flow, the authors calculated the steady-state interstitial fluid (ISF) ADO concentration. Under control conditions the venous ADO concentration was 7.1 +/- 2.8 nM. The calculated ISF concentration depends on whether they assume the venous ADO comes from the ISF, or directly from ECs. These ISF concentrations are 25 +/- 12 nM and 9.8 +/- 4.0 nM, respectively. During dipyridamole infusion (10 uM) the EC transport parameters became nearly zero. Venous and ISF ADO concentrations increased to 33 +/- 8.9 nM and 169 +/- 42 nM, respectively. The authors conclude that the ISF ADO concentration is 1.5-4 fold higher than the venous concentration at rest, and the ISF concentration increases greatly with dipyridamole.

  8. Bovine myocardial epithelial inclusions.

    PubMed

    Baker, D C; Schmidt, S P; Langheinrich, K A; Cannon, L; Smart, R A

    1993-01-01

    Light microscopic, histochemical, immunohistochemical, and ultrastructural methods were used to examine myocardial epithelial masses in the hearts of ten cattle. The tissues consisted of paraffin-embedded or formalin-fixed samples from eight hearts that were being inspected in slaughter houses and from two hearts from calves that died of septicemia. The ages of the cattle ranged from 4 days to 12 years; the breeds were unspecified for all but one Hereford female and the two Holstein calves; and there were three males, four females, and three steers. The masses in these cases were compared with similar appearing lesions found in other animal species. The lesions in the bovine hearts were single to multiple, well circumscribed, found in the left ventricle wall, and composed of squamous to cuboidal epithelial cells that formed tubular, ductular, and acinar structures with lumens that were void or filled with amorphous protein globules. Electron microscopic examination revealed epithelial cells that had sparse apical microvilli, tight apical intercellular junctions, perinuclear bundles of filaments, and rare cilia. Almost half of the bovine epithelial masses (4/9) had occasional diastase-resistant periodic acid-Schiff-positive granules in their cytoplasm, and few had hyaluronidase-resistant alcian blue-positive granules (2/9) or colloidal iron-positive granules (1/9). All myocardial masses had abundant collagen surrounding the tubular and acinar structures, and 2/9 had elastin fibers as well. None of the myocardial masses had Churukian-Schenk or Fontana Masson's silver staining granules in epithelial cells. Immunohistochemically, all bovine myocardial tumors stained positively for cytokeratin (8/8), and occasional masses stained positively for vimentin (3/8) or carcinoembryonic antigen (3/8). None of the masses stained positively for desmin. The myocardial epithelial tumors most likely represent endodermal rests of tissue misplaced during organogenesis.

  9. Postsynaptic Adenosine A2A Receptors Modulate Intrinsic Excitability of Pyramidal Cells in the Rat Basolateral Amygdala

    PubMed Central

    Rau, Andrew R.; Ariwodola, Olusegun J.

    2015-01-01

    Background: The basolateral amygdala plays a critical role in the etiology of anxiety disorders and addiction. Pyramidal neurons, the primary output cells of this region, display increased firing following exposure to stressors, and it is thought that this increase in excitability contributes to stress responsivity and the expression of anxiety-like behaviors. However, much remains unknown about the underlying mechanisms that regulate the intrinsic excitability of basolateral amygdala pyramidal neurons. Methods: Ex vivo gramicidin perforated patch recordings were conducted in current clamp mode where hyper- and depolarizing current steps were applied to basolateral amygdala pyramidal neurons to assess the effects of adenosine A2A receptor modulation on intrinsic excitability. Results: Activation of adenosine A2A receptors with the selective A2A receptor agonist CGS-21680 significantly increased the firing rate of basolateral amygdala pyramidal neurons in rat amygdala brain slices, likely via inhibition of the slow afterhyperpolarization potential. Both of these A2A receptor-mediated effects were blocked by preapplication of a selective A2A receptor antagonist (ZM-241385) or by intra-pipette infusion of a protein kinase A inhibitor, suggesting a postsynaptic locus of A2A receptors on basolateral amygdala pyramidal neurons. Interestingly, bath application of the A2A receptor antagonist alone significantly attenuated basolateral amygdala pyramidal cell firing, consistent with a role for tonic adenosine in the regulation of the intrinsic excitability of these neurons. Conclusions: Collectively, these data suggest that adenosine, via activation of A2A receptors, may directly facilitate basolateral amygdala pyramidal cell output, providing a possible balance for the recently described inhibitory effects of adenosine A1 receptor activation on glutamatergic excitation of basolateral amygdala pyramidal cells. PMID:25716780

  10. [Cyclic adenosine monophosphate and atherogenic factors].

    PubMed

    Gerasimova, E N

    1977-01-01

    Hypercholesterolemia caused a decrease in the activity of adenylcyclase in rabbit liver tissue and in thrombocytes; hypertriglyceridemia, which developed after administration of hydrocortisone, led to an increase in the activity of adenylcyclase and in the content of 3,5-AMP in adipose tissue. Activities of adenylcyclase, phosphodiesterase and content of prostaglandines E1 and F2alpha were measured in thrombocytes of 39 healthy men without any symptoms of of ischemic heart impairment, in 52 patients with coronary atherosclerosis of the III degree (by Myasnikov's classification) as well as in 12 patients during the period of rehabilitation after myocardial infarction. The activity of adenylate cyclase system was impaired in atherosclerosis. This phenomenon might be caused by alteration in concentration of glucocorticoids in the organism.

  11. Perioperative Assessment of Myocardial Deformation

    PubMed Central

    Duncan, Andra E.; Alfirevic, Andrej; Sessler, Daniel I.; Popovic, Zoran B.; Thomas, James D.

    2014-01-01

    Evaluation of left ventricular performance improves risk assessment and guides anesthetic decisions. However, the most common echocardiographic measure of myocardial function, the left ventricular ejection fraction (LVEF), has important limitations. LVEF is limited by subjective interpretation which reduces accuracy and reproducibility, and LVEF assesses global function without characterizing regional myocardial abnormalities. An alternative objective echocardiographic measure of myocardial function is thus needed. Myocardial deformation analysis, which performs quantitative assessment of global and regional myocardial function, may be useful for perioperative care of surgical patients. Myocardial deformation analysis evaluates left ventricular mechanics by quantifying strain and strain rate. Strain describes percent change in myocardial length in the longitudinal (from base to apex) and circumferential (encircling the short-axis of the ventricle) direction and change in thickness in the radial direction. Segmental strain describes regional myocardial function. Strain is a negative number when the ventricle shortens longitudinally or circumferentially and is positive with radial thickening. Reference values for normal longitudinal strain from a recent meta-analysis using transthoracic echocardiography are (mean ± SD) −19.7 ± 0.4%, while radial and circumferential strain are 47.3 ± 1.9 and −23.3 ± 0.7%, respectively. The speed of myocardial deformation is also important and is characterized by strain rate. Longitudinal systolic strain rate in healthy subjects averages −1.10 ± 0.16 sec−1. Assessment of myocardial deformation requires consideration of both strain (change in deformation), which correlates with LVEF, and strain rate (speed of deformation), which correlates with rate of rise of left ventricular pressure (dP/dt). Myocardial deformation analysis also evaluates ventricular relaxation, twist, and untwist, providing new and noninvasive methods to

  12. Adenosine deaminase from Streptomyces coelicolor: recombinant expression, purification and characterization.

    PubMed

    Pornbanlualap, Somchai; Chalopagorn, Pornchanok

    2011-08-01

    The sequencing of the genome of Streptomyces coelicolor A3(2) identified seven putative adenine/adenosine deaminases and adenosine deaminase-like proteins, none of which have been biochemically characterized. This report describes recombinant expression, purification and characterization of SCO4901 which had been annotated in data bases as a putative adenosine deaminase. The purified putative adenosine deaminase gives a subunit Mr=48,400 on denaturing gel electrophoresis and an oligomer molecular weight of approximately 182,000 by comparative gel filtration. These values are consistent with the active enzyme being composed of four subunits with identical molecular weights. The turnover rate of adenosine is 11.5 s⁻¹ at 30 °C. Since adenine is deaminated ∼10³ slower by the enzyme when compared to that of adenosine, these data strongly show that the purified enzyme is an adenosine deaminase (ADA) and not an adenine deaminase (ADE). Other adenine nucleosides/nucleotides, including 9-β-D-arabinofuranosyl-adenine (ara-A), 5'-AMP, 5'-ADP and 5'-ATP, are not substrates for the enzyme. Coformycin and 2'-deoxycoformycin are potent competitive inhibitors of the enzyme with inhibition constants of 0.25 and 3.4 nM, respectively. Amino acid sequence alignment of ScADA with ADAs from other organisms reveals that eight of the nine highly conserved catalytic site residues in other ADAs are also conserved in ScADA. The only non-conserved residue is Asn317, which replaces Asp296 in the murine enzyme. Based on these data, it is suggested here that ADA and ADE proteins are divergently related enzymes that have evolved from a common α/β barrel scaffold to catalyze the deamination of different substrates, using a similar catalytic mechanism. PMID:21511036

  13. Role of A3 adenosine receptor in diabetic neuropathy.

    PubMed

    Yan, Heng; Zhang, Enshui; Feng, Chang; Zhao, Xin

    2016-10-01

    Neuropathy is the most common diabetic complication. Although the A1 and A2A adenosine receptors are important pharmacological targets in alleviating diabetic neuropathy, the role of the A3 adenosine receptor remains unknown. Because the A3 adenosine receptor regulates pain induced by chronic constriction injury or chemotherapy, its stimulation might also attenuate diabetic neuropathy. This study examines the effects of systemic treatment with the A3 adenosine receptor agonist 1-deoxy-1-[6-[[(3-iodophenyl)methyl]amino]-9H-purin-9-yl]-N-methyl-β-d-ribofuranuronamide (IB-MECA) on diabetic neuropathy and explores the putative mechanisms underlying its pharmacological effects. We show that IB-MECA alleviated mechanical hyperalgesia and thermal hypoalgesia in mice 2 weeks but not 4 weeks after streptozocin (STZ) treatment. Furthermore, IB-MECA prevented the reduction in sciatic motor nerve conduction velocity and sensory nerve conduction velocity in diabetic mice 2 weeks but not 4 weeks after STZ treatment. Similarly, IB-MECA inhibited the activation of nuclear factor-κB and decreased the generation of tumor necrosis factor-α in the spinal cord of mice 2 weeks but not 4 weeks after STZ treatment. These phenomena were associated with reduction of A3 adenosine receptor expression in the spinal cord after long-term diabetes. Our results suggest that the A3 adenosine receptor plays a critical role in regulating diabetic neuropathy and that reduction in A3 adenosine receptor expression/function might contribute to the progression of diabetic neuropathy. © 2016 Wiley Periodicals, Inc.

  14. Myocardial perfusion imaging study of CO(2)-induced panic attack.

    PubMed

    Soares-Filho, Gastão L F; Machado, Sergio; Arias-Carrión, Oscar; Santulli, Gaetano; Mesquita, Claudio T; Cosci, Fiammetta; Silva, Adriana C; Nardi, Antonio E

    2014-01-15

    Chest pain is often seen alongside with panic attacks. Moreover, panic disorder has been suggested as a risk factor for cardiovascular disease and even a trigger for acute coronary syndrome. Patients with coronary artery disease may have myocardial ischemia in response to mental stress, in which panic attack is a strong component, by an increase in coronary vasomotor tone or sympathetic hyperactivity setting off an increase in myocardial oxygen consumption. Indeed, coronary artery spasm was presumed to be present in cases of cardiac ischemia linked to panic disorder. These findings correlating panic disorder with coronary artery disease lead us to raise questions about the favorable prognosis of chest pain in panic attack. To investigate whether myocardial ischemia is the genesis of chest pain in panic attacks, we developed a myocardial perfusion study through research by myocardial scintigraphy in patients with panic attacks induced in the laboratory by inhalation of 35% carbon dioxide. In conclusion, from the data obtained, some hypotheses are discussed from the viewpoint of endothelial dysfunction and microvascular disease present in mental stress response. PMID:24188891

  15. Increased adenosine contributes to penile fibrosis, a dangerous feature of priapism, via A2B adenosine receptor signaling

    PubMed Central

    Wen, Jiaming; Jiang, Xianzhen; Dai, Yingbo; Zhang, Yujin; Tang, Yuxin; Sun, Hong; Mi, Tiejuan; Phatarpekar, Prasad V.; Kellems, Rodney E.; Blackburn, Michael R.; Xia, Yang

    2010-01-01

    Priapism is a condition of persistent penile erection in the absence of sexual excitation. Of men with sickle cell disease (SCD), 40% display priapism. The disorder is a dangerous and urgent condition, given its association with penile fibrosis and eventual erectile dysfunction. Current strategies to prevent its progression are poor because of a lack of fundamental understanding of the molecular mechanisms for penile fibrosis in priapism. Here we demonstrate that increased adenosine is a novel causative factor contributing to penile fibrosis in two independent animal models of priapism, adenosine deaminase (ADA)-deficient mice and SCD transgenic mice. An important finding is that chronic reduction of adenosine by ADA enzyme therapy successfully attenuated penile fibrosis in both mouse models, indicating an essential role of increased adenosine in penile fibrosis and a novel therapeutic possibility for this serious complication. Subsequently, we identified that both mice models share a similar fibrotic gene expression profile in penile tissue (including procollagen I, TGF-β1, and plasminogen activator inhibitor-1 mRNA), suggesting that they share similar signaling pathways for progression to penile fibrosis. Thus, in an effort to decipher specific cell types and underlying mechanism responsible for adenosine-mediated penile fibrosis, we purified corpus cavernosal fibroblast cells (CCFCs), the major cell type involved in this process, from wild-type mice. Quantitative RT-PCR showed that the major receptor expressed in these cells is the adenosine receptor A2BR. Based on this fact, we further purified CCFCs from A2BR-deficient mice and demonstrated that A2BR is essential for excess adenosine-mediated penile fibrosis. Finally, we revealed that TGF-β functions downstream of the A2BR to increase CCFC collagen secretion and proliferation. Overall, our studies identify an essential role of increased adenosine in the pathogenesis of penile fibrosis via A2BR signaling and

  16. [Vascular effects of adenosine-triphosphate].

    PubMed

    Colson, P; Saussine, M; Gaba, S; Sequin, J; Chaptal, P A; Roquefeuil, B

    1991-01-01

    This study assessed the effects of adenosine triphosphate (ATP) on systemic vascular resistances during the hypothermic cardiopulmonary bypass phase of cardiac surgery. Twenty patients scheduled for cardiac surgery were randomly divided into an ATP group (n = 10), and a placebo group (n = 10). Anaesthesia was similar for all the patients (diazepam, fentanyl and pancuronium). During the heart arrest phase, and as soon as the arterial pressure, the level in the venous return reservoir, and the pump flow rate had all been in steady state for 5 min, ATP or placebo was injected into the venous line of the oxygenator. Injection speed was doubled every three minutes, twice. The following ATP doses were administered: 0.012, 0.025 and 0.05 mg.kg-1.min-1. The level in the venous return reservoir was kept constant. Mean arterial pressure (MAP) and pump flow rate (DP) were assessed every half minute. Systemic vascular resistances were calculated with the relationship MAP/DP. Changes in vascular capacitance were directly proportional to changes in DP as the heart had been excluded, and all the blood returned to the pump, the blood volume being kept constant. MAP and DP remained unchanged in the placebo group. In the opposite ATP induced a dose-related systemic vasodilation: MAP decreased from 82.8 +/- 12.5 mmHg (control) to 66.0 +/- 14.8 mmHg, 59.8 +/- 10.6 mmHg, and 49.0 +/- 4.7 mmHg with 0.012, 0.025 and 0.05 mg.kg-1.min-1 ATP respectively. The MAP returned to preinfusion control levels when the ATP infusion was discontinued (90.0 +/- 17.8 mmHg). The DP, and therefore venous return, did not change, neither during ATP infusion, nor after its discontinuation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1854051

  17. Effect of adenosine on the growth of human T-lymphocyte leukemia cell line MOLT-4.

    PubMed

    Streitová, Denisa; Weiterová, Lenka; Hofer, Michal; Holá, Jirina; Horváth, Viktor; Kozubík, Alois; Znojil, Vladimír

    2007-09-01

    Adenosine has been observed to suppress the growth of MOLT-4 human leukemia cells in vitro. Changes in the cell cycle, especially increased percentage of cells in S phase, prolonged generation time, and induction of apoptosis at higher adenosine concentrations have been found to be responsible for the growth suppression. Dipyridamole, a drug inhibiting the cellular uptake of adenosine, reversed partially but significantly the adenosine-induced growth suppression. It follows from these results that the action of adenosine on the MOLT-4 cells comprises its cellular uptake and intracellular operation. These findings present new data on anticancer efficacy of adenosine.

  18. Myocardial apoptosis and SIDS.

    PubMed

    Grasmeyer, Sarah; Madea, Burkhard

    2015-01-01

    Apoptosis mediates cardiac damage in severe forms of myocarditis. In fatal myocarditis, large amounts of cardiomyocytes show apoptotic DNA fragmentation, while in human controls, few apoptotic cardiomyocytes are found. In the present study the frequency of apoptosis in 88 SIDS cases (category 1b according to the San Diego Classification) and 15 control cases was investigated. In every case myocardial samples from 8 standard locations were collected. Detection of apoptotic cardiomyocytes was performed by TUNEL method. Furthermore the myocardial tissue was stained with HE and immunohistochemical methods (LCA, CD68, CD45-R0). More than 90% of the slides did not contain apoptotic cardiomyocytes at all. The detection rate of apoptotic cardiomyocytes was almost equal in control group (26.7%) and SIDS group (23.86%). A quantification of apoptotic cardiomyocytes per mm(2) revealed no significant difference between both groups either. Altogether there is no evidence for a higher rate of apoptosis in SIDS.

  19. [Effect of complications in the acute period of myocardial infarction on physical exertion tolerance at the hospital stage of rehabilitation].

    PubMed

    Al'khimovich, V M; Golubev, V G; Rudina, M D; Rusetskaia, V G

    1988-11-01

    Physical stress tolerance and its hemodynamic support were examined in 95 patients with early myocardial infarction, 50 normal subjects and 25 coronary patients. It is suggested that the stress tolerance test is advisable at an early stage of complicated macrofocal myocardial infarction. The safety of the test improves considerably where it is performed under continuous electrocardiographic and chest-rheographic control. An abnormal diastolic impedance wave, emerging during exercise, may serve an additional diagnostic indicator of stress intolerance.

  20. Myocardial gene therapy

    NASA Astrophysics Data System (ADS)

    Isner, Jeffrey M.

    2002-01-01

    Gene therapy is proving likely to be a viable alternative to conventional therapies in coronary artery disease and heart failure. Phase 1 clinical trials indicate high levels of safety and clinical benefits with gene therapy using angiogenic growth factors in myocardial ischaemia. Although gene therapy for heart failure is still at the pre-clinical stage, experimental data indicate that therapeutic angiogenesis using short-term gene expression may elicit functional improvement in affected individuals.

  1. Tomoscintigraphic assessment of myocardial metabolic heterogenity

    SciTech Connect

    Roesler, H.; Hess, T.; Weiss, M.; Noelpp, U.; Mueller, G.; Hoeflin, F.; Kinser, J.

    1983-04-01

    I-123-omega-heptadecanoic acid (HDA) was evaluated for myocardial scanning in 59 healthy volunteers and 133 patients, using a 7-pinhole collimator. Early (uptake) and late (retention) images were compared visually. Regional HDA elimination was also followed semiquantitatively based on the calculation of a retention-over-uptake ratio, R(phi), derived from the maximal counts/pixel in 60 midventricular slice sectors. The healthy heart concentrated HDA homogeneously in all segments with no difference between early and late images. The minimal R(phi), taken as representative of that myocardium with the best function, was unchanged after maximal ergometer stress and with dipyramidole-induced hyperperfusion. A circumscribed decreased HDA uptake is the clear-cut criterion for an abnormal finding. HDA tomography of the myocardium had an 86% sensitivity for myocardial infarcts (MIs) up to 4 wk old, and 83% for myocardial scars (MSs). Comparing early and late tomograms, we find a cool-warm sequence more often with acute and subacute MIs. A cool-cool or a cold-cold sequence dominated with MSs. HDA tomoscintigraphy cannot replace TI-201 for the evaluation of regional coronary reserve in coronary heart disease.

  2. Myocardial infarction: management of the subacute period.

    PubMed

    Mercado, Michael G; Smith, Dustin K; McConnon, Michael L

    2013-11-01

    Optimal management of myocardial infarction in the subacute period focuses on improving the discharge planning process, implementing therapies early to prevent recurrent myocardial infarction, and avoiding hospital readmission. Evidence-based guidelines for the care of patients with acute coronary syndrome are not followed up to 25% of the time. Antiplatelet therapy, renin-angiotensin-aldosterone system inhibitors, beta blockers, and statins constitute the foundation of medical therapy. Early noninvasive stress testing is an important risk assessment tool, especially in patients who do not undergo revascularization. Discharge preparation should include a review of medications, referral for exercise-based cardiac rehabilitation, activity recommendations, education about lifestyle modification and recognition of cardiac symptoms, and a clear follow-up plan. Because nonadherence to medications is common in patients after a myocardial infarction and is associated with increased mortality risk, modifiable factors associated with medication self-discontinuation should be addressed before discharge. Structured discharge processes should be used to enhance communication and facilitate the transition from the hospital to the family physician's care.

  3. Dicinnamoylquinides in roasted coffee inhibit the human adenosine transporter.

    PubMed

    de Paulis, Tomas; Schmidt, Dennis E; Bruchey, Aleksandra K; Kirby, Michael T; McDonald, Michael P; Commers, Patricia; Lovinger, David M; Martin, Peter R

    2002-05-10

    Preliminary screening of a minor, non-xanthine constituent of roasted coffee, 3,4-diferuloyl-1,5-quinolactone (DIFEQ), showed inhibition of the adenosine transporter at low micromolar concentration. DIFEQ is a neutral derivative of the chlorogenic acids, i.e. isomeric mono- and di-substituted coumaroyl-, caffeoyl-, and feruloyl-esters of quinic acid, formed in the roasting process of coffee. Displacement of the adenosine transporter antagonist [(3)H](S)-(nitrobenzyl)-6-thioinosine binding by DIFEQ in cultured U-937 cell preparations, expressing the human adenosine transporter protein (hENT1), showed a K(i) of 0.96+/-0.13 microM. Extracts of regular and decaffeinated coffee showed binding activities equivalent to 30-40 mg DIFEQ per three cups of coffee. Acute administration of a high dose of DIFEQ (100 mg/kg i.p.) reduced open field locomotion in mice for 20 min in correlation with brain levels of DIFEQ. Both 3,4-dicaffeoyl-1,5-quinide and 3,4-dicoumaroyl-1,5-quinide, two close structural analogs of DIFEQ also present in roasted coffee, showed similar affinities for the adenosine transporter, while the corresponding 3- and 4-mono caffeoyl- and feruloyl-quinides were one to two orders of magnitudes less active. This suggests that 3,4-dicinnamoyl-1,5-quinides in coffee could have the potential to raise extra-cellular adenosine levels, thereby counteracting the stimulant effect of caffeine.

  4. Dicinnamoylquinides in roasted coffee inhibit the human adenosine transporter.

    PubMed

    de Paulis, Tomas; Schmidt, Dennis E; Bruchey, Aleksandra K; Kirby, Michael T; McDonald, Michael P; Commers, Patricia; Lovinger, David M; Martin, Peter R

    2002-05-10

    Preliminary screening of a minor, non-xanthine constituent of roasted coffee, 3,4-diferuloyl-1,5-quinolactone (DIFEQ), showed inhibition of the adenosine transporter at low micromolar concentration. DIFEQ is a neutral derivative of the chlorogenic acids, i.e. isomeric mono- and di-substituted coumaroyl-, caffeoyl-, and feruloyl-esters of quinic acid, formed in the roasting process of coffee. Displacement of the adenosine transporter antagonist [(3)H](S)-(nitrobenzyl)-6-thioinosine binding by DIFEQ in cultured U-937 cell preparations, expressing the human adenosine transporter protein (hENT1), showed a K(i) of 0.96+/-0.13 microM. Extracts of regular and decaffeinated coffee showed binding activities equivalent to 30-40 mg DIFEQ per three cups of coffee. Acute administration of a high dose of DIFEQ (100 mg/kg i.p.) reduced open field locomotion in mice for 20 min in correlation with brain levels of DIFEQ. Both 3,4-dicaffeoyl-1,5-quinide and 3,4-dicoumaroyl-1,5-quinide, two close structural analogs of DIFEQ also present in roasted coffee, showed similar affinities for the adenosine transporter, while the corresponding 3- and 4-mono caffeoyl- and feruloyl-quinides were one to two orders of magnitudes less active. This suggests that 3,4-dicinnamoyl-1,5-quinides in coffee could have the potential to raise extra-cellular adenosine levels, thereby counteracting the stimulant effect of caffeine. PMID:12065074

  5. Antagonism by theophylline of respiratory inhibition induced by adenosine.

    PubMed

    Eldridge, F L; Millhorn, D E; Kiley, J P

    1985-11-01

    The effects on respiration of an analogue of adenosine, L-2-N6-(phenylisopropyl)adenosine (PIA), and of the methylxanthine, theophylline, were determined in 19 vagotomized glomectomized cats whose end-tidal PCO2 was kept constant by means of a servo-controlled ventilator. Integrated phrenic nerve activity was used to represent respiratory output. Our results show that PIA, whether given systemically or into the third cerebral ventricle, depressed respiration. Systemically administered theophylline stimulated respiration. Theophylline given intravenously, or into the third ventricle not only reversed the depressive effects of previously administered PIA but caused further increases of respiration above the control level. Prior systemic administration of theophylline blocked both respiratory and hypotensive effects of subsequently administered PIA. Effects of either agent on medullary extracellular fluid pH did not explain the results. We conclude that the adenosine analogue PIA, acts to inhibit neurons in the brain that are involved in the control of respiration and that its effects are blocked by theophylline. We suggest that adenosine acts as a tonic modulator of respiration and that theophylline stimulates breathing by competitive antagonism of adenosine at neuronal receptor sites. PMID:4066573

  6. Adenosine signaling and the regulation of chronic lung disease

    PubMed Central

    Zhou, Yang; Schneider, Daniel J.; Blackburn, Michael R.

    2009-01-01

    Chronic lung diseases such as asthma, chronic obstructive pulmonary disease and interstitial lung disease are characterized by inflammation and tissue remodeling processes that compromise pulmonary function. Adenosine is produced in the inflamed and damaged lung where it plays numerous roles in the regulation of inflammation and tissue remodeling. Extracellular adenosine serves as an autocrine and paracrine signaling molecule by engaging cell surface adenosine receptors. Preclinical and cellular studies suggest that adenosine plays an anti-inflammatory role in processes associated with acute lung disease, where activation of the A2AR and A2BR have promising implications for the treatment of these disorders. In contrast, there is growing evidence that adenosine signaling through the A1R, A2BR and A3R may serve pro-inflammatory and tissue remodeling functions in chronic lung diseases. This review discusses the current progress of research efforts and clinical trials aimed at understanding the complexities of this signaling pathway as they pertain to the development of treatment strategies for chronic lung diseases. PMID:19426761

  7. Myocardial Tagging With SSFP

    PubMed Central

    Herzka, Daniel A.; Guttman, Michael A.; McVeigh, Elliot R.

    2007-01-01

    This work presents the first implementation of myocardial tagging with refocused steady-state free precession (SSFP) and magnetization preparation. The combination of myocardial tagging (a noninvasive method for quantitative measurement of regional and global cardiac function) with the high tissue signal-to-noise ratio (SNR) obtained with SSFP is shown to yield improvements in terms of the myocardium–tag contrast-to-noise ratio (CNR) and tag persistence when compared to the current standard fast gradient-echo (FGRE) tagging protocol. Myocardium–tag CNR and tag persistence were studied using numerical simulations as well as phantom and human experiments. Both quantities were found to decrease with increasing imaging flip angle (α) due to an increased tag decay rate and a decrease in myocardial steady-state signal. However, higher α yielded better blood–myocardium contrast, indicating that optimal α is dependent on the application: higher α for better blood–myocardium boundary visualization, and lower α for better tag persistence. SSFP tagging provided the same myocardium–tag CNR as FGRE tagging when acquired at four times the bandwidth and better tag– and blood–myocardium CNRs than FGRE tagging when acquired at equal or twice the receiver bandwidth (RBW). The increased acquisition efficiency of SSFP allowed decreases in breath-hold duration, or increases in temporal resolution, as compared to FGRE. PMID:12541254

  8. Multiplane Transesophageal Echocardiography with Dobutamine in Patients with Biventricular Inferior Myocardial Infarction.

    PubMed

    Espinola-Zavaleta, Nilda; Vargas-Barrón, Jesús; Romero-Cárdenas, Angel; Bialostozky, David; Alexanderson, Erick; Martinez-Sanchez, Carlos; Peña-Duque, Marco; Keirns, Candace; Rijlaarsdam, María; Lupi-Herrera, Eulo

    1998-02-01

    The purpose of this study was to evaluate the alterations of ventricular wall movement in patients with acute posteroinferior myocardial infarction with extension to right cavities with multiplane transesophageal echocardiography (TEE), as well as the utility of dobutamine with this technique to analyze myocardial viability. Nine men with a mean age of 51 years fulfilled the inclusion criteria. Myocardial TEE was performed in all the men 72 hours after the acute event with long- and short-axis transgastric images of both ventricles under basal conditions and with dobutamine infusions of 5 and 10 µg/kg per minute. Results were compared with myocardial perfusion findings obtained with Tc-99m Sestamibi SPECT. Left ventricular myocardial viability was demonstrated in 28 of 45 altered segments with dobutamine stress myocardial TEE and Tc-99m Sestamibi SPECT. Right ventricular myocardial viability was identified in 27 of 30 altered segments with dobutamine stress myocardial TEE in transgastric short and long axes, and with Tc-99m Sestamibi SPECT in 23 of 25 segments only in short-axis images. Multiplane TEE provided excellent image resolution and better definition of endocardial and epicardial borders, which facilitated detailed evaluation of ventricular segmental wall movement. Infusion of low doses of dobutamine made it possible to identify viable tissue in both ventricles, and results were comparable to those of nuclear medicine.

  9. Effect of adenosine and inosine on ureagenesis in hepatocytes.

    PubMed Central

    Guinzberg, R; Laguna, I; Zentella, A; Guzman, R; Piña, E

    1987-01-01

    Adenosine and inosine produced a dose-dependent stimulation of ureagenesis in isolated rat hepatocytes. Hypoxanthine, xanthine and uric acid were without effect. Half-maximally effective concentrations were 0.08 microM for adenosine and 5 microM for inosine. Activation of ureagenesis by both nucleosides had the following characteristics: (a) it was observed with either glutamine or (NH4)2CO3, provided that glucose was present; (b) it was not detected when glucose was replaced by lactate plus oleate; (c) it was mutually antagonized by glucagon, but not by adrenaline; and (d) it was dependent on Ca2+. We suggest that the action of adenosine and inosine on ureagenesis might be of physiological significance. PMID:3663162

  10. Adenosine receptor agonists for promotion of dermal wound healing

    PubMed Central

    Valls, María D.; Cronstein, Bruce N.; Montesinos, M. Carmen

    2009-01-01

    Wound healing is a dynamic and complex process that involves a well coordinated, highly regulated series of events including inflammation, tissue formation, revascularization and tissue remodeling. However, this orderly sequence is impaired in certain pathophysiological conditions such as diabetes mellitus, venous insufficiency, chronic glucocorticoid use, aging and malnutrition. Together with proper wound care, promotion of the healing process is the primary objective in the management of chronic poorly healing wounds. Recent studies have demonstrated that A2A adenosine receptor agonists promote wound healing in normal and diabetic animals and one such agonist, Sonedenoson, is currently being evaluated as a prospective new therapy of diabetic foot ulcers. We will review the mechanisms by which adenosine receptor activation affects the function of the cells and tissues that participate in wound healing, emphasizing the potential beneficial impact of adenosine receptor agonists in diabetic impaired healing. PMID:19041853

  11. Perioperative myocardial infarction in patients undergoing myocardial revascularization surgery

    PubMed Central

    Pretto, Pericles; Martins, Gerez Fernandes; Biscaro, Andressa; Kruczan, Dany David; Jessen, Barbara

    2015-01-01

    Introduction Perioperative myocardial infarction adversely affects the prognosis of patients undergoing coronary artery bypass graft and its diagnosis was hampered by numerous difficulties, because the pathophysiology is different from the traditional instability atherosclerotic and the clinical difficulty to be characterized. Objective To identify the frequency of perioperative myocardial infarction and its outcome in patients undergoing coronary artery bypass graft. Methods Retrospective cohort study performed in a tertiary hospital specialized in cardiology, from May 01, 2011 to April 30, 2012, which included all records containing coronary artery bypass graft records. To confirm the diagnosis of perioperative myocardial infarction criteria, the Third Universal Definition of Myocardial Infarction was used. Results We analyzed 116 cases. Perioperative myocardial infarction was diagnosed in 28 patients (24.1%). Number of grafts and use and cardiopulmonary bypass time were associated with this diagnosis and the mean age was significantly higher in this group. The diagnostic criteria elevated troponin I, which was positive in 99.1% of cases regardless of diagnosis of perioperative myocardial infarction. No significant difference was found between length of hospital stay and intensive care unit in patients with and without this complication, however patients with perioperative myocardial infarction progressed with worse left ventricular function and more death cases. Conclusion The frequency of perioperative myocardial infarction found in this study was considered high and as a consequence the same observed average higher troponin I, more cases of worsening left ventricular function and death. PMID:25859867

  12. Phosphorylation of adenosine with trimetaphosphate under simulated prebiotic conditions.

    PubMed

    Cheng, Changmei; Fan, Chang; Wan, Rong; Tong, Chunyuan; Miao, Zhiwei; Chen, Jing; Zhao, Yufen

    2002-06-01

    The phosphorylation of adenosine with trimetaphosphate in solution, in solid phase and using wet-dry cycles was carried out and it was found that wet-dry cycles were the most efficient. The catalytic effects of some metal ions on the phosphorylation were also studied and it was discovered that Ni(II) is the most effective. The combination of wet-dry cycles (4 cycles) and catalysis by Ni(II) led to an unprecedented high conversion of adenosine to phosphorylated products (30%) near neutral pH. The main phosphorylated products were 2',3'-cyclic AMP (10.4%) and 5'-ATP (13.0%). PMID:12227426

  13. S-Adenosylhomocysteine toxicity in normal and adenosine kinase-deficient lymphoblasts of human origin

    PubMed Central

    Kredich, Nicholas M.; Hershfield, Michael S.

    1979-01-01

    The human lymphoblast line WI-L2 is subject to growth inhibition by a combination of the adenosine deaminase (ADA; adenosine aminohydrolase, EC 3.5.4.4.) inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and adenosine. Although adenosine-induced pyrimidine starvation appears to contribute to this effect, uridine only partially reverses adenosine toxicity in WI-L2 and not at all in strain 107, an adenosine kinase-(ATP:adenosine 5′-phosphotransferase, EC 2.7.1.20) deficient derivative of WI-L2. Treatment of both cell lines with EHNA and adenosine leads to striking elevations in intracellular S-adenosyl-L-homocysteine (AdoHcy), a potent inhibitor of S-adenosyl-L-methionine (AdoMet)-dependent methylation reactions. The methylation in vivo of both DNA and RNA is inhibited by concentrations of EHNA and adenosine that elevate intracellular AdoHcy. Addition of 100 μM L-homocysteine thiolactone to cells treated with EHNA and adenosine enhances adenosine toxicity and further elevates AdoHcy to levels approximately 60-fold higher than those obtained in the absence of this amino acid, presumably by combining with adenosine to form AdoHcy in a reaction catalyzed by S-adenosylhomocysteine hydrolase (EC 3.3.1.1). In the adenosine kinase-deficient strain 107, a combination of ADA inhibition and L-homocysteine thiolactone markedly increases intracellular AdoHcy and inhibits growth even in the absence of exogenous adenosine. These results demonstrate a form of toxicity from endogenously produced adenosine and support the view that AdoHcy, by inhibiting methylation, is a mediator of uridine-resistant adenosine toxicity in these human lymphoblast lines. Furthermore, they suggest that AdoHcy may play a role in the pathogenesis of the severe combined immunodeficiency disease found in most children with heritable ADA deficiency. PMID:221926

  14. Effect of eating on thallium-201 myocardial redistribution after myocardial ischemia

    SciTech Connect

    Angello, D.A.; Wilson, R.A.; Palac, R.T.

    1987-09-01

    To determine whether eating a high-carbohydrate meal between initial and delayed postexercise thallium-201 (Tl-201) imaging affects detection of Tl-201 redistribution during exercise stress testing, 16 patients with stable angina performed 2 Tl-201 treadmill exercise stress tests within a 14-day interval. Immediately after initial postexercise imaging, patients either drank a commercially available instant breakfast preparation for the intervention test or drank an equivalent volume of water for the control test. Comparable exercise workloads were achieved by exercising patients to the same heart rate for both tests. The order of the 2 (intervention and control) tests were randomized. All patients had at least 1 region of Tl-201 myocardial redistribution on either their eating or control test scans, although only 7 of the 16 had positive treadmill exercise test responses. Forty-six regions showing Tl-201 myocardial redistribution were identified in all 144 regions examined. Significantly more of these regions were identified on control test scans than on eating test scans: 11 of 46 on both test scans, 6 of 46 only on eating test scans and 29 of 46 only on control scans (p less than 0.001). Consistent with results of the quantitative regional analysis, the percentage of Tl-201 clearance over 4 hours in the 46 Tl-201 myocardial redistribution regions was 39 +/- 8% for the eating tests and 29 +/- 8% for control tests (mean +/- standard deviation, p less than 0.003). In 4 patients diagnosis of transient ischemia would have been missed because their 14 Tl-201 myocardial redistribution regions were detected only on the control test scans.

  15. The Second Extracellular Loop of the Adenosine A1 Receptor Mediates Activity of Allosteric Enhancers

    PubMed Central

    Kennedy, Dylan P.; McRobb, Fiona M.; Leonhardt, Susan A.; Purdy, Michael; Figler, Heidi; Marshall, Melissa A.; Chordia, Mahendra; Figler, Robert; Linden, Joel

    2014-01-01

    Allosteric enhancers of the adenosine A1 receptor amplify signaling by orthosteric agonists. Allosteric enhancers are appealing drug candidates because their activity requires that the orthosteric site be occupied by an agonist, thereby conferring specificity to stressed or injured tissues that produce adenosine. To explore the mechanism of allosteric enhancer activity, we examined their action on several A1 receptor constructs, including (1) species variants, (2) species chimeras, (3) alanine scanning mutants, and (4) site-specific mutants. These findings were combined with homology modeling of the A1 receptor and in silico screening of an allosteric enhancer library. The binding modes of known docked allosteric enhancers correlated with the known structure-activity relationship, suggesting that these allosteric enhancers bind to a pocket formed by the second extracellular loop, flanked by residues S150 and M162. We propose a model in which this vestibule controls the entry and efflux of agonists from the orthosteric site and agonist binding elicits a conformational change that enables allosteric enhancer binding. This model provides a mechanism for the observations that allosteric enhancers slow the dissociation of orthosteric agonists but not antagonists. PMID:24217444

  16. Nuclear cardiac imaging for the assessment of myocardial viability

    PubMed Central

    Slart, R.H.J.A.; Bax, J.J.; van der Wall, E.E.; van Veldhuisen, D.J.; Jager, P.L.; Dierckx, R.A.

    2005-01-01

    An important aspect of the diagnostic and prognostic work-up of patients with ischaemic cardiomyopathy is the assessment of myocardial viability. Patients with left ventricular dysfunction who have viable myocardium are the patients at highest risk because of the potential for ischaemia but at the same time benefit most from revascularisation. It is important to identify viable myocardium in these patients, and radionuclide myocardial scintigraphy is an excellent tool for this. Single-photon emission computed tomography perfusion scintigraphy (SPECT), whether using 201thallium, 99mTc-sestamibi, or 99mTc- tetrofosmin, in stress and/or rest protocols, has consistently been shown to be an effective modality for identifying myocardial viability and guiding appropriate management. Metabolic and perfusion imaging with positron emission tomography radiotracers frequently adds additional information and is a powerful tool for predicting which patients will have an improved outcome from revascularisation. New techniques in the nuclear cardiology field, such as attenuation corrected SPECT, dual isotope simultaneous acquisition (DISA) SPECT and gated FDG PET are promising and will further improve the detection of myocardial viability. Also the combination of multislice computed tomography scanners with PET opens possibilities of adding coronary calcium scoring and noninvasive coronary angiography to myocardial perfusion imaging and quantification. ImagesFigure 1Figure 2Figure 3 PMID:25696432

  17. Case of angina pectoris at rest and during effort due to coronary spasm and myocardial bridging

    PubMed Central

    Teragawa, Hiroki; Fujii, Yuichi; Ueda, Tomohiro; Murata, Daiki; Nomura, Shuichi

    2015-01-01

    We present a case of a 71-year-old male who had chest symptoms at rest and during effort. He had felt chest oppression during effort for 1 year, and his chest symptoms had recently worsened. One month before admission he felt chest squeezing at rest in the early morning. He presented at our institution to evaluate his chest symptoms. Electrocardiography and echocardiography failed to show any specific changes. Because of the possibility that his chest symptoms were due to myocardial ischemia, he was admitted to our institution for coronary angiography (CAG). An initial CAG showed mild atherosclerotic changes in the proximal segment of the left anterior descending coronary artery (LAD) and mid-segment of the left circumflex coronary artery. Subsequent spasm provocation testing using acetylcholine revealed a bilateral coronary vasospasm, which was relieved after the intracoronary infusion of nitroglycerin. Finally, a CAG showed myocardial bridging (MB) of the mid-distal segments of the LAD. Fractional flow reserve using the intravenous administration of adenosine triphosphate was positive at 0.77, which jumped up to 0.90 through the myocardial bridging segments when the pressure wire was pulled back. Thus, coronary vasospasm and MB might have contributed to his chest symptoms at rest and during effort. Interventional cardiologists should consider the presence of MB as a potential cause of myocardial ischemia. PMID:26131343

  18. Pacing-induced regional differences in adenosine receptors mRNA expression in a swine model of dilated cardiomyopathy.

    PubMed

    Del Ry, Silvia; Cabiati, Manuela; Lionetti, Vincenzo; Aquaro, Giovanni D; Martino, Alessandro; Mattii, Letizia; Morales, Maria-Aurora

    2012-01-01

    The adenosinergic system is essential in the mediation of intrinsic protection and myocardial resistance to insult; it may be considered a cardioprotective molecule and adenosine receptors (ARs) represent potential therapeutic targets in the setting of heart failure (HF). The aim of the study was to test whether differences exist between mRNA expression of ARs in the anterior left ventricle (LV) wall (pacing site: PS) compared to the infero septal wall (opposite region: OS) in an experimental model of dilated cardiomyopathy. Cardiac tissue was collected from LV PS and OS of adult male minipigs with pacing-induced HF (n = 10) and from a control group (C, n = 4). ARs and TNF-α mRNA expression was measured by Real Time-PCR and the results were normalized with the three most stably expressed genes (GAPDH, HPRT1, TBP). Immunohistochemistry analysis was also performed. After 3 weeks of pacing higher levels of expression for each analyzed AR were observed in PS except for A(1)R (A(1)R: C = 0.6±0.2, PS = 0.1±0.04, OS = 0.04±0.01, p<0.0001 C vs. PS and OS respectively; A(2A)R: C = 1.04±0.59, PS = 2.62±0.79, OS = 2.99±0.79; A(2B)R: C = 1.2±0.1, PS = 5.59±2.3, OS = 1.59±0.46; A(3)R: C = 0.76±0.18, PS = 8.40±3.38, OS = 4.40±0.83). Significant contractile impairment and myocardial hypoperfusion were observed at PS after three weeks of pacing as compared to OS. TNF-α mRNA expression resulted similar in PS (6.3±2.4) and in OS (5.9±2.7) although higher than in control group (3.4±1.5). ARs expression was mainly detected in cardiomyocytes. This study provided new information on ARs local changes in the setting of LV dysfunction and on the role of these receptors in relation to pacing-induced abnormalities of myocardial perfusion and contraction. These results suggest a possible therapeutic role of adenosine in patients with HF and dyssynchronous LV contraction.

  19. Intracellular adenosine 5'-triphosphate, adenosine 5'-diphosphate, and adenosine 5'-monophosphate detection by short-end injection capillary electrophoresis using methylcellulose as the effective electroosmostic flow suppressor.

    PubMed

    Zinellu, Angelo; Sotgia, Salvatore; Pasciu, Valeria; Madeddu, Manuela; Leoni, Giovanni Giuseppe; Naitana, Salvatore; Deiana, Luca; Carru, Ciriaco

    2008-07-01

    We present a new rapid CE method to measure adenine nucleotides adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP), and adenosine 5'-monophosphate (AMP) in cells. The short-end injection mode allows a decrease in the analysis time by injecting samples at the outlet end of a silica capillary closest to the detection window, reducing the migration distance. Moreover, the use of methylcellulose (MC) as run buffer additive to suppress EOF permits to further reduce the migration times of analytes. Thus, when a capillary with an effective length of 10.2 cm was used with a 60 mmol/L sodium acetate buffer pH 3.80 in the presence of 0.01% of MC, the migration time of analytes were 1.35 min for ATP, 1.85 min for ADP, and 4.64 min for AMP. These conditions gave a good reproducibility for intra- and interassay (CV <4 and 8%, respectively) and all the procedure demonstrated an excellent analytical recovery (from 98.3 to 99 %). The method suitability was proved both on red blood cells and in spermatozoa. We compared our proposed method to a spectrophotometric assay, by measuring ATP levels in 40 spermatozoa samples. The obtained data were analyzed by the Passing and Bablok regression and Bland-Altman test. PMID:18551716

  20. 21 CFR 864.7040 - Adenosine triphosphate release assay.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Adenosine triphosphate release assay. 864.7040 Section 864.7040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages §...

  1. 21 CFR 864.7040 - Adenosine triphosphate release assay.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Adenosine triphosphate release assay. 864.7040 Section 864.7040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages §...

  2. 21 CFR 864.7040 - Adenosine triphosphate release assay.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Adenosine triphosphate release assay. 864.7040 Section 864.7040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages §...

  3. 21 CFR 864.7040 - Adenosine triphosphate release assay.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Adenosine triphosphate release assay. 864.7040 Section 864.7040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages §...

  4. CD39/Adenosine Pathway Is Involved in AIDS Progression

    PubMed Central

    Limou, Sophie; Younas, Mehwish; Kök, Ayrin; Huë, Sophie; Seddiki, Nabila; Hulin, Anne; Delaneau, Olivier; Schuitemaker, Hanneke; Herbeck, Joshua T.; Mullins, James I.; Muhtarova, Maria; Bensussan, Armand; Zagury, Jean-François; Lelievre, Jean-Daniel; Lévy, Yves

    2011-01-01

    HIV-1 infection is characterized by a chronic activation of the immune system and suppressed function of T lymphocytes. Regulatory CD4+ CD25high FoxP3+CD127low T cells (Treg) play a key role in both conditions. Here, we show that HIV-1 positive patients have a significant increase of Treg-associated expression of CD39/ENTPD1, an ectoenzyme which in concert with CD73 generates adenosine. We show in vitro that the CD39/adenosine axis is involved in Treg suppression in HIV infection. Treg inhibitory effects are relieved by CD39 down modulation and are reproduced by an adenosine-agonist in accordance with a higher expression of the adenosine A2A receptor on patients' T cells. Notably, the expansion of the Treg CD39+ correlates with the level of immune activation and lower CD4+ counts in HIV-1 infected patients. Finally, in a genetic association study performed in three different cohorts, we identified a CD39 gene polymorphism that was associated with down-modulated CD39 expression and a slower progression to AIDS. PMID:21750674

  5. Adenosine receptor modulation of seizure susceptibility in rats

    SciTech Connect

    Szot, P.

    1987-01-01

    Adenosine is considered to be a neuromodulator or cotransmitter in the periphery and CNS. This neuromodulatory action of adenosine may be observed as an anticonvulsant effect. Dose-response curves for R-phenylisopropyladenosine (PIA), cycohexyladenosine (CHA), 2-chloroadenosine (2-ClAdo), N-ethylcarboxamidoadenosine (NECA) and S-PIA were generated against PTZ seizure thresholds in the rat. The rank order of potency for adenosine agonists to elevate PTZ seizure threshold was R-PIA > 2-ClAdo > NECA > CHA > S-PIA. R-PIA was approximately 80-fold more potent than S-PIA. This 80-fold difference in potency between the diasteriomers of PIA was consistent with an A{sub 1} adenoise receptor-mediated response. The anticonvulsant action of 2-ClAdo was reversed by pretreatment with theoplylline. Chronic administration of theophylline significantly increased the specific binding of {sup 3}H-cyclohexyladenosine in membranes of the cerebral cortex and cerebellum of the rat. Chronic exposure to theophylline produced a significant increase in the densities of both the high- and low-affinity forms of A{sub 1} adenosine receptors in the cerebral cortex.

  6. [Assessing myocardial perfusion with positron emission tomography].

    PubMed

    vom Dahl, J

    2001-11-01

    Positron emission tomography (PET) of the heart has gained widespread scientific and clinical acceptance with regard to two indications: 1) The detection of perfusion abnormalities by qualitative and semiquantitative analyses of perfusion images at rest and during physical or pharmacological stress using well-validated perfusion tracers, such as N-13 ammonia, Rb-82 rubidium chloride, or O-15 labeled water. 2) Viability imaging of myocardial regions with reduced contractility by combining perfusion measurements with substrate metabolism as assessed from F-18 deoxyglucose utilization. This overview summarizes the use of PET as a perfusion imaging method. With a sensitivity > 90% in combination with high specificity, PET is today the best-validated available nuclear imaging technique for the diagnosis of coronary artery disease (CAD). The short half-life of the perfusion tracers in combination with highly sophisticated hard- and software enables rapid PET studies with high patient throughput. The high diagnostic accuracy and the methological advantages as compared to conventional scintigraphy allows one to use PET perfusion imaging to detect subtle changes in the perfusion reserve for the detection of CAD in high risk but asymptomatic patients as well as in patients with proven CAD undergoing various treatment forms such as risk factor reduction or coronary revascularization. In patients following orthotopic heart transplantation, evolving transplant vasculopathy can be detected at an early stage. Quantitative PET imaging at rest allows for detection of myocardial viability since cellular survival is based on maintenance of a minimal perfusion and structural changes correlate to the degree of perfusion reduction. Furthermore, quantitative assessment of the myocardial perfusion reserve detects the magnitude and competence of collaterals in regions with occluded epicardial collaterals and, thus, imaging of several coronary distribution territories in one noninvasive

  7. Myocardial fibre calcification.

    PubMed Central

    McClure, J; Pieterse, A S; Pounder, D J; Smith, P S

    1981-01-01

    Three cases of myocardial fibre calcification found at post-mortem examination are described. In one case there was antemortem hypercalcaemia and hyperphosphataemia and the case was clearly an example of metastatic calcification. In the other two cases there was ischaemic myocardial necrosis and calcification was seen in fibres which were not overtly necrotic, but which were both in proximity to (the majority) and remote from the necrotic zones. Since renal failure with hyperphosphataemia was present in both cases, these were considered to be examples of augmented (by the hyperphosphataemia) dystrophic calcification. The histological, histochemical and ultrastructural features were identical in the three cases. Hydroxyapatite formation was observed initially in mitochondria, followed by spillage of crystals into the cytosol and ultimately into the interstitium. It is suggested that the fundamental lesion is a dysfunction of the fibre membrane; the similarity of this reaction with the calcification seen in skeletal muscle fibres in various myopathies is noted and a unifying hypothesis of the mechanism of skeletal and cardiac muscle fibre calcification is thereby suggested. Images PMID:7309897

  8. Valsartan after myocardial infarction.

    PubMed

    Güleç, Sadi

    2014-12-01

    One of the important problems of the patients undergoing acute myocardial infarction (MI) is early development of heart failure. It has been revealed in various studies that renin-angiotensin-aldosterone system (RAAS) has a significant role in this process. The studies conducted with angiotensin converting enzyme (ACE) inhibitors have resulted in decreased mortality rate. Another RAAS blocker which was discovered about ten years later than other ACE inhibitors in historical process is angiotensin receptor blockers (ARB) inhibiting the efficiency of angiotensin 2 by binding to angiotensin 1 receptor. Valsartan is one of the molecules of this group, which has higher number of large-scale randomized clinical studies. In this review, following presentation of a general overview on heart failure after acute MI, the efficiency of ARBs in this patient group will be discussed. This discussion will mostly emphasize the construction, outcomes and clinical importance of VALIANT (VALsartan In Acute myocardial iNfarcTion), which is the study on valsartan after acute MI heart failure. PMID:25604205

  9. Trauma induced myocardial infarction.

    PubMed

    Lolay, Georges A; Abdel-Latif, Ahmed K

    2016-01-15

    Chest Trauma in athletes is a common health problem. However, myocardial infarction secondary to coronary dissection in the setting of blunt chest trauma is extremely rare. We report a case of acute inferior wall myocardial infarction following blunt chest trauma. A 32-year-old male with no relevant medical problems was transferred to our medical center for retrosternal chest pain after being elbowed in the chest during a soccer game. Few seconds later, he started experiencing sharp retrosternal chest pain that was severe to that point where he called the emergency medical service. Upon arrival to the trauma department patient was still complaining of chest pain. ECG demonstrated ST segment elevation in the inferior leads with reciprocal changes in the lateral leads all consistent with active ischemia. After rolling out aortic dissection, patient was loaded with ASA, ticagerlor, heparin and was emergently taken to the cardiac catheterization lab. Coronary angiography demonstrated 100% thrombotic occlusion in the distal right coronary artery with TIMI 0 flow distally. After thrombus aspiration, a focal dissection was noted on the angiogram that was successfully stented. Two days after admission patient was discharged home. Echocardiography prior to discharge showed inferior wall akinesis, normal right ventricular systolic function and normal overall ejection fraction.

  10. B‐type natriuretic peptide identifies silent myocardial ischaemia in stroke survivors

    PubMed Central

    Wong, K Y K; McSwiggan, S; Kennedy, N S J; MacWalter, R S; Struthers, A D

    2006-01-01

    Objective To test the hypothesis that B‐type natriuretic peptide (BNP) predicts reversible myocardial ischaemia in stroke survivors who do not have chest pain or previous myocardial infarction. Methods 56 stroke survivors (mean (SE) age 68 (8) years) underwent tetrofosmin myocardial perfusion scanning with dipyridamole as the stressor. The degree of ischaemia was assessed by a scoring system (out of 64) by an experienced observer blinded to the results of BNP. Results In the whole cohort, BNP was significantly correlated with the degree of myocardial ischaemia on stress scanning (Spearman's r  =  −0.475, p < 0.001). BNP also correlated with the degree of reversible ischaemia (stress score − rest score; Spearman's r  =  0.28, two tailed p  =  0.049). In the cohort who did not have left ventricular systolic dysfunction (n  =  44), BNP remained higher in patients with relevant myocardial ischaemia (mean (SE) BNP 20.9 pg/ml, 95% confidence interval (CI) 15.2 to 26.5 v 12.2 pg/ml, 95% CI 5.95 to 18.5; p  =  0.046); 33 of the 44 patients had no chest pain or history of myocardial infarction. The relation between resting BNP and both inducible ischaemia and dipyridamole stress score remained significant (Spearman's r  =  0.37 and −0.38, respectively). Conclusions BNP correlates with the degree of reversible myocardial ischaemia in patients who do not have chest pain or a history of myocardial infarction or evidence of left ventricular systolic dysfunction. Stroke survivors with a high BNP deserve further investigations to rule out significant reversible myocardial ischaemia, in order to reduce their risk of cardiac death. PMID:16216865

  11. The Relationship Between Some Complete Blood Count Parameters and Myocardial Perfusion: A Scintigraphic Approach

    PubMed Central

    Ozdemir, Semra; Barutcu, Ahmet; Gazi, Emine; Tan, Yusuf Ziya; Turkon, Hakan

    2015-01-01

    Recent studies have shown that there is a relationship between some inflammatory and biochemical markers derived from complete blood count (CBC) such as neutrophil/lymphocyte (N/L) ratio, platelet/lymphocyte (P/L) ratio, platelet distribution width (PDW), red blood cell distribution width (RDW), and coronary artery disease (CAD). The aim of this study was to determine N/L ratio, P/L ratio, PDW values, and RDW values, which are associated with myocardial perfusion in patients diagnosed with CAD. This study included 262 patients (149 with myocardial ischemia/infarction and 113 with normal myocardial perfusion) undergoing myocardial perfusion scintigraphy (MPS) with CBC within 90 days of MPS. Myocardial perfusion parameters such as summed stress score and summed difference score (SDS) were compared with N/L ratio, P/L ratio, PDW values, and RDW values. Neutrophil counts and N/L ratios were significantly higher in patients diagnosed with myocardial ischemia and/or infarct. However, there was no statistically significant relationship between myocardial perfusion abnormalities and P/L ratio, PDW values, and RDW values. This study showed that N/L ratio is related to myocardial ischemia/infarction and correlated to left ventricular ejection fraction (LVEF). PMID:26420991

  12. Positron emission tomography detects tissue metabolic activity in myocardial segments with persistent thallium perfusion defects

    SciTech Connect

    Brunken, R.; Schwaiger, M.; Grover-McKay, M.; Phelps, M.E.; Tillisch, J.; Schelbert, H.R.

    1987-09-01

    Positron emission tomography with /sup 13/N-ammonia and /sup 18/F-2-deoxyglucose was used to assess myocardial perfusion and glucose utilization in 51 myocardial segments with a stress thallium defect in 12 patients. Myocardial infarction was defined by a concordant reduction in segmental perfusion and glucose utilization, and myocardial ischemia was identified by preservation of glucose utilization in segments with rest hypoperfusion. Of the 51 segments studied, 36 had a fixed thallium defect, 11 had a partially reversible defect and 4 had a completely reversible defect. Only 15 (42%) of the 36 segments with a fixed defect and 4 (36%) of the 11 segments with a partially reversible defect exhibited myocardial infarction on study with positron tomography. In contrast, residual myocardial glucose utilization was identified in the majority of segments with a fixed (58%) or a partially reversible (64%) thallium defect. All of the segments with a completely reversible defect appeared normal on positron tomography. Apparent improvement in the thallium defect on delayed images did not distinguish segments with ischemia from infarction. Thus, positron emission tomography reveals evidence of persistent tissue metabolism in the majority of segments with a fixed or partially resolving stress thallium defect, implying that markers of perfusion alone may underestimate the extent of viable tissue in hypoperfused myocardial segments.

  13. Loss of ATP-Sensitive Potassium Channel Surface Expression in Heart Failure Underlies Dysregulation of Action Potential Duration and Myocardial Vulnerability to Injury.

    PubMed

    Gao, Zhan; Sierra, Ana; Zhu, Zhiyong; Koganti, Siva Rama Krishna; Subbotina, Ekaterina; Maheshwari, Ankit; Anderson, Mark E; Zingman, Leonid V; Hodgson-Zingman, Denice M

    2016-01-01

    The search for new approaches to treatment and prevention of heart failure is a major challenge in medicine. The adenosine triphosphate-sensitive potassium (KATP) channel has been long associated with the ability to preserve myocardial function and viability under stress. High surface expression of membrane KATP channels ensures a rapid energy-sparing reduction in action potential duration (APD) in response to metabolic challenges, while cellular signaling that reduces surface KATP channel expression blunts APD shortening, thus sacrificing energetic efficiency in exchange for greater cellular calcium entry and increased contractile force. In healthy hearts, calcium/calmodulin-dependent protein kinase II (CaMKII) phosphorylates the Kir6.2 KATP channel subunit initiating a cascade responsible for KATP channel endocytosis. Here, activation of CaMKII in a transaortic banding (TAB) model of heart failure is coupled with a 35-40% reduction in surface expression of KATP channels compared to hearts from sham-operated mice. Linkage between KATP channel expression and CaMKII is verified in isolated cardiomyocytes in which activation of CaMKII results in downregulation of KATP channel current. Accordingly, shortening of monophasic APD is slowed in response to hypoxia or heart rate acceleration in failing compared to non-failing hearts, a phenomenon previously shown to result in significant increases in oxygen consumption. Even in the absence of coronary artery disease, failing myocardium can be further injured by ischemia due to a mismatch between metabolic supply and demand. Ischemia-reperfusion injury, following ischemic preconditioning, is diminished in hearts with CaMKII inhibition compared to wild-type hearts and this advantage is largely eliminated when myocardial KATP channel expression is absent, supporting that the myocardial protective benefit of CaMKII inhibition in heart failure may be substantially mediated by KATP channels. Recognition of Ca

  14. Psychological rehabilitation after myocardial infarction: multicentre randomised controlled trial.

    PubMed Central

    Jones, D. A.; West, R. R.

    1996-01-01

    OBJECTIVE: To evaluate rehabilitation after myocardial infarction. DESIGN: Randomised controlled trial of rehabilitation in unselected myocardial infarction patients in six centres, baseline data being collected on admission and by structured interview (of patients and spouses) shortly after discharge and outcome being assessed by structured interview at six months and clinical examination at 12 months. SETTING: Six district general hospitals. SUBJECTS: All 2328 eligible patients admitted over two years with confirmed myocardial infarction and discharged home within 28 days. INTERVENTIONS: Rehabilitation programmes comprising psychological therapy, counselling, relaxation training, and stress management training over seven weekly group outpatient sessions for patients and spouses. MAIN OUTCOME MEASURES: Anxiety, depression, quality of life, morbidity, use of medication, and mortality. RESULTS: At six months there were no significant differences between rehabilitation patients and controls in reported anxiety (prevalence 33%) or depression (19%). Rehabilitation patients reported a lower frequency of angina (median three versus four episodes a week), medication, and physical activity. At 12 months there were no differences in clinical complications, clinical sequelae, or mortality. CONCLUSIONS: Rehabilitation programmes based on psychological therapy, counselling, relaxation training, and stress management seem to offer little objective benefit to patients who have experienced myocardial infarction compared with previous reports of smaller trials. PMID:8978226

  15. Hydrogen Sulfide Donor GYY4137 Protects against Myocardial Fibrosis

    PubMed Central

    Meng, Guoliang; Zhu, Jinbiao; Xiao, Yujiao; Huang, Zhengrong; Zhang, Yuqing; Tang, Xin; Xie, Liping; Chen, Yu; Shao, Yongfeng; Ferro, Albert; Wang, Rui; Moore, Philip K.; Ji, Yong

    2015-01-01

    Hydrogen sulfide (H2S) is a gasotransmitter which regulates multiple cardiovascular functions. However, the precise roles of H2S in modulating myocardial fibrosis in vivo and cardiac fibroblast proliferation in vitro remain unclear. We investigated the effect of GYY4137, a slow-releasing H2S donor, on myocardial fibrosis. Spontaneously hypertensive rats (SHR) were administrated with GYY4137 by intraperitoneal injection daily for 4 weeks. GYY4137 decreased systolic blood pressure and inhibited myocardial fibrosis in SHR as evidenced by improved cardiac collagen volume fraction (CVF) in the left ventricle (LV), ratio of perivascular collagen area (PVCA) to lumen area (LA) in perivascular regions, reduced hydroxyproline concentration, collagen I and III mRNA expression, and cross-linked collagen. GYY4137 also inhibited angiotensin II- (Ang II-) induced neonatal rat cardiac fibroblast proliferation, reduced the number of fibroblasts in S phase, decreased collagen I and III mRNA expression and protein synthesis, attenuated oxidative stress, and suppressed α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1) expression as well as Smad2 phosphorylation. These results indicate that GYY4137 improves myocardial fibrosis perhaps by a mechanism involving inhibition of oxidative stress, blockade of the TGF-β1/Smad2 signaling pathway, and decrease in α-SMA expression in cardiac fibroblasts. PMID:26078813

  16. Feed-Forward Inhibition of CD73 and Upregulation of Adenosine Deaminase Contribute to the Loss of Adenosine Neuromodulation in Postinflammatory Ileitis

    PubMed Central

    Magalhães-Cardoso, Maria Teresa; Ferreirinha, Fátima; Dias, Ana Sofia; Pelletier, Julie

    2014-01-01

    Purinergic signalling is remarkably plastic during gastrointestinal inflammation. Thus, selective drugs targeting the “purinome” may be helpful for inflammatory gastrointestinal diseases. The myenteric neuromuscular transmission of healthy individuals is fine-tuned and controlled by adenosine acting on A2A excitatory receptors. Here, we investigated the neuromodulatory role of adenosine in TNBS-inflamed longitudinal muscle-myenteric plexus of the rat ileum. Seven-day postinflammation ileitis lacks adenosine neuromodulation, which may contribute to acceleration of gastrointestinal transit. The loss of adenosine neuromodulation results from deficient accumulation of the nucleoside at the myenteric synapse despite the fact that the increases in ATP release were observed. Disparity between ATP outflow and adenosine deficit in postinflammatory ileitis is ascribed to feed-forward inhibition of ecto-5′-nucleotidase/CD73 by high extracellular ATP and/or ADP. Redistribution of NTPDase2, but not of NTPDase3, from ganglion cell bodies to myenteric nerve terminals leads to preferential ADP accumulation from released ATP, thus contributing to the prolonged inhibition of muscle-bound ecto-5′-nucleotidase/CD73 and to the delay of adenosine formation at the inflamed neuromuscular synapse. On the other hand, depression of endogenous adenosine accumulation may also occur due to enhancement of adenosine deaminase activity. Both membrane-bound and soluble forms of ecto-5′-nucleotidase/CD73 and adenosine deaminase were detected in the inflamed myenteric plexus. These findings provide novel therapeutic targets for inflammatory gut motility disorders. PMID:25210228

  17. Mechanism of A2 adenosine receptor activation. I. Blockade of A2 adenosine receptors by photoaffinity labeling

    SciTech Connect

    Lohse, M.J.; Klotz, K.N.; Schwabe, U.

    1991-04-01

    It has previously been shown that covalent incorporation of the photoreactive adenosine derivative (R)-2-azido-N6-p-hydroxy-phenylisopropyladenosine ((R)-AHPIA) into the A1 adenosine receptor of intact fat cells leads to a persistent activation of this receptor, resulting in a reduction of cellular cAMP levels. In contrast, covalent incorporation of (R)-AHPIA into human platelet membranes, which contain only stimulatory A2 adenosine receptors, reduces adenylate cyclase stimulation via these receptors. This effect of (R)-AHPIA is specific for the A2 receptor and can be prevented by the adenosine receptor antagonist theophylline. Binding studies indicate that up to 90% of A2 receptors can be blocked by photoincorporation of (R)-AHPIA. However, the remaining 10-20% of A2 receptors are sufficient to mediate an adenylate cyclase stimulation of up to 50% of the control value. Similarly, the activation via these 10-20% of receptors occurs with a half-life that is only 2 times longer than that in control membranes. This indicates the presence of a receptor reserve, with respect to both the extent and the rate of adenylate cyclase stimulation. These observations require a modification of the models of receptor-adenylate cyclase coupling.

  18. The effects of methylmercury on motor activity are sex- and age-dependent, and modulated by genetic deletion of adenosine receptors and caffeine administration.

    PubMed

    Björklund, Olga; Kahlström, Johan; Salmi, Peter; Ogren, Sven Ove; Vahter, Marie; Chen, Jiang-Fan; Fredholm, Bertil B; Daré, Elisabetta

    2007-11-30

    Adenosine and its receptors are, as part of the brain stress response, potential targets for neuroprotective drugs. We have investigated if the adenosine receptor system affects the developmental neurotoxicity caused by the fish pollutant methylmercury (MeHg). Behavioral outcomes of low dose perinatal MeHg exposure were studied in mice where the A(1) and A(2A) adenosine receptors were either partially blocked by caffeine treatment or eliminated by genetic modification (A(1)R and A(2A)R knock-out mice). From gestational day 7 to day 7 of lactation dams were administered doses that mimic human intake via normal diet, i.e. 1microM MeHg and/or 0.3g/l caffeine in the drinking water. This exposure to MeHg resulted in a doubling of brain Hg levels in wild type females and males at postnatal day 21 (PND21). Open field analysis was performed at PND21 and 2 months of age. MeHg caused time-dependent behavioral alterations preferentially in male mice. A decreased response to amphetamine in 2-month-old males pointed to disturbances in dopaminergic functions. Maternal caffeine intake induced long-lasting changes in the offspring evidenced by an increased motor activity and a modified response to psychostimulants in adult age, irrespectively of sex. Similar alterations were observed in A(1)R knock-out mice, suggesting that adenosine A(1) receptors are involved in the alterations triggered by caffeine exposure during development. Perinatal caffeine treatment and, to some extent, genetic elimination of adenosine A(1) receptors, attenuated the behavioral consequences of MeHg in males. Importantly, also deletion of the A(2A) adenosine receptor reduced the vulnerability to MeHg, consistent with the neuroprotective effects of adenosine A(2A) receptor inactivation observed in hypoxia and Parkinson's disease. Thus, the consequences of MeHg toxicity during gestation and lactation can be reduced by adenosine A(1) and A(2A) receptor inactivation, either via their genetic deletion or by

  19. Metabolic changes of cultured DRG neurons induced by adenosine using confocal microscopy imaging

    NASA Astrophysics Data System (ADS)

    Zheng, Liqin; Huang, Yimei; Chen, Jiangxu; Wang, Yuhua; Yang, Hongqin; Zhang, Yanding; Xie, Shusen

    2012-12-01

    Adenosine exerts multiple effects on pain transmission in the peripheral nervous system. This study was performed to use confocal microscopy to evaluate whether adenosine could affect dorsal root ganglia (DRG) neurons in vitro and test which adenosine receptor mediates the effect of adenosine on DRG neurons. After adding adenosine with different concentration, we compared the metabolic changes by the real time imaging of calcium and mitochondria membrane potential using confocal microscopy. The results showed that the effect of 500 μM adenosine on the metabolic changes of DRG neurons was more significant than others. Furthermore, four different adenosine receptor antagonists were used to study which receptor mediated the influences of adenosine on the cultured DRG neurons. All adenosine receptor antagonists especially A1 receptor antagonist (DPCPX) had effect on the Ca2+ and mitochondria membrane potential dynamics of DRG neurons. The above studies demonstrated that the effect of adenosine which may be involved in the signal transmission on the sensory neurons was dose-dependent, and all the four adenosine receptors especially the A1R may mediate the transmission.

  20. Modulation of bladder function by luminal adenosine turnover and A1 receptor activation

    PubMed Central

    Prakasam, H. Sandeep; Herrington, Heather; Roppolo, James R.; Jackson, Edwin K.

    2012-01-01

    The bladder uroepithelium transmits information to the underlying nervous and musculature systems, is under constant cyclical strain, expresses all four adenosine receptors (A1, A2A, A2B, and A3), and is a site of adenosine production. Although adenosine has a well-described protective effect in several organs, there is a lack of information about adenosine turnover in the uroepithelium or whether altering luminal adenosine concentrations impacts bladder function or overactivity. We observed that the concentration of extracellular adenosine at the mucosal surface of the uroepithelium was regulated by ecto-adenosine deaminase and by equilibrative nucleoside transporters, whereas adenosine kinase and equilibrative nucleoside transporters modulated serosal levels. We further observed that enriching endogenous adenosine by blocking its routes of metabolism or direct activation of mucosal A1 receptors with 2-chloro-N6-cyclopentyladenosine (CCPA), a selective agonist, stimulated bladder activity by lowering the threshold pressure for voiding. Finally, CCPA did not quell bladder hyperactivity in animals with acute cyclophosphamide-induced cystitis but instead exacerbated their irritated bladder phenotype. In conclusion, we find that adenosine levels at both surfaces of the uroepithelium are modulated by turnover, that blocking these pathways or stimulating A1 receptors directly at the luminal surface promotes bladder contractions, and that adenosine further stimulates voiding in animals with cyclophosphamide-induced cystitis. PMID:22552934

  1. Fast-scan Cyclic Voltammetry for the Characterization of Rapid Adenosine Release

    PubMed Central

    Nguyen, Michael D.; Venton, B. Jill

    2014-01-01

    Adenosine is a signaling molecule and downstream product of ATP that acts as a neuromodulator. Adenosine regulates physiological processes, such as neurotransmission and blood flow, on a time scale of minutes to hours. Recent developments in electrochemical techniques, including fast-scan cyclic voltammetry (FSCV), have allowed direct detection of adenosine with sub-second temporal resolution. FSCV studies have revealed a novel mode of rapid signaling that lasts only a few seconds. This rapid release of adenosine can be evoked by electrical or mechanical stimulations or it can be observed spontaneously without stimulation. Adenosine signaling on this time scale is activity dependent; however, the mode of release is not fully understood. Rapid adenosine release modulates oxygen levels and evoked dopamine release, indicating that adenosine may have a rapid modulatory role. In this review, we outline how FSCV can be used to detect adenosine release, compare FSCV with other techniques used to measure adenosine, and present an overview of adenosine signaling that has been characterized using FSCV. These studies point to a rapid mode of adenosine modulation, whose mechanism and function will continue to be characterized in the future. PMID:26900429

  2. Exogenous adenosine 5'-phosphoramidate behaves as a signal molecule in plants; it augments metabolism of phenylpropanoids and salicylic acid in Arabidopsis thaliana seedlings.

    PubMed

    Pietrowska-Borek, Małgorzata; Nuc, Katarzyna; Guranowski, Andrzej

    2015-09-01

    Cells contain various congeners of the canonical nucleotides. Some of these accumulate in cells under stress and may function as signal molecules. Their cellular levels are enzymatically controlled. Previously, we demonstrated a signaling function for diadenosine polyphosphates and cyclic nucleotides in Arabidopsis thaliana and grape, Vitis vinifera. These compounds increased the expression of genes for and the specific activity of enzymes of phenylpropanoid pathways resulting in the accumulation of certain products of these pathways. Here, we show that adenosine 5'-phosphoramidate, whose level can be controlled by HIT-family proteins, induced similar effects. This natural nucleotide, when added to A. thaliana seedlings, activated the genes for phenylalanine:ammonia lyase, 4-coumarate:coenzyme A ligase, cinnamate-4-hydroxylase, chalcone synthase, cinnamoyl-coenzyme A:NADP oxidoreductase and isochorismate synthase, which encode proteins catalyzing key reactions of phenylpropanoid pathways, and caused accumulation of lignins, anthocyanins and salicylic acid. Adenosine 5'-phosphofluoridate, a synthetic congener of adenosine 5'-phosphoramidate, behaved similarly. The results allow us to postulate that adenosine 5'-phosphoramidate should be considered as a novel signaling molecule.

  3. Efficacy of cimetidin in the prevention of ulcer formation in the stomach during immobilization stress

    NASA Technical Reports Server (NTRS)

    Dorofeyev, G. I.; Litovskiy, I. A.; Gavrovskaya, L. K.; Ivashkin, V. T.

    1982-01-01

    The effect of stress on the formation of ulcers in the mucous membrane of the stomach, the increase in cyclic adenosine monophosphate level in the gastric tissues, and parietal cell structure alteration. Use of cimetidin prevents these effects

  4. Exercise stress testing

    NASA Technical Reports Server (NTRS)

    Schuster, B.

    1975-01-01

    Positive maximum stress tests in the management of coronary patients are discussed. It is believed that coronary angiography would be the ultimate test to predict the future of patients with coronary heart disease. Progression of angina, myocardial infarction, and death due to heart disease were analyzed.

  5. Myocardial Infarction: Symptoms and Treatments.

    PubMed

    Lu, Lei; Liu, Min; Sun, RongRong; Zheng, Yi; Zhang, Peiying

    2015-07-01

    Myocardial infarction (MI) is a term used for an event of heart attack which is due to formation of plaques in the interior walls of the arteries resulting in reduced blood flow to the heart and injuring heart muscles because of lack of oxygen supply. The symptoms of MI include chest pain, which travels from left arm to neck, shortness of breath, sweating, nausea, vomiting, abnormal heart beating, anxiety, fatigue, weakness, stress, depression, and other factors. The immediate treatment of MI include, taking aspirin, which prevents blood from clotting, and nitro-glycerin to treat chest pain and oxygen. The heart attack can be prevented by taking an earlier action to lower those risks by controlling diet, fat, cholesterol, salt, smoking, nicotine, alcohol, drugs, monitoring of blood pressure every week, doing exercise every day, and loosing body weight. The treatment of MI includes, aspirin tablets, and to dissolve arterial blockage injection of thrombolytic or clot dissolving drugs such as tissue plasminogen activator, streptokinase or urokinase in blood within 3 h of the onset of a heart attack. The painkillers such as morphine or meperidine can be administered to relieve pain. Nitroglycerin and antihypertensive drugs such as beta-blockers, ACE inhibitors or calcium channel blockers may also be used to lower blood pressure and to improve the oxygen demand of heart. The ECG, coronary angiography and X-ray of heart and blood vessels can be performed to observe the narrowing of coronary arteries. In this article the causes, symptoms and treatments of MI are described. PMID:25638347

  6. Myocardial Infarction: Symptoms and Treatments.

    PubMed

    Lu, Lei; Liu, Min; Sun, RongRong; Zheng, Yi; Zhang, Peiying

    2015-07-01

    Myocardial infarction (MI) is a term used for an event of heart attack which is due to formation of plaques in the interior walls of the arteries resulting in reduced blood flow to the heart and injuring heart muscles because of lack of oxygen supply. The symptoms of MI include chest pain, which travels from left arm to neck, shortness of breath, sweating, nausea, vomiting, abnormal heart beating, anxiety, fatigue, weakness, stress, depression, and other factors. The immediate treatment of MI include, taking aspirin, which prevents blood from clotting, and nitro-glycerin to treat chest pain and oxygen. The heart attack can be prevented by taking an earlier action to lower those risks by controlling diet, fat, cholesterol, salt, smoking, nicotine, alcohol, drugs, monitoring of blood pressure every week, doing exercise every day, and loosing body weight. The treatment of MI includes, aspirin tablets, and to dissolve arterial blockage injection of thrombolytic or clot dissolving drugs such as tissue plasminogen activator, streptokinase or urokinase in blood within 3 h of the onset of a heart attack. The painkillers such as morphine or meperidine can be administered to relieve pain. Nitroglycerin and antihypertensive drugs such as beta-blockers, ACE inhibitors or calcium channel blockers may also be used to lower blood pressure and to improve the oxygen demand of heart. The ECG, coronary angiography and X-ray of heart and blood vessels can be performed to observe the narrowing of coronary arteries. In this article the causes, symptoms and treatments of MI are described.

  7. Myocardial accumulation of iodinated beta-methyl-branched fatty acid analogue, iodine-125-15-(p-iodophenyl)-3-(R,S)methylpentadecanoic acid (BMIPP), in relation to ATP concentration

    SciTech Connect

    Fujibayashi, Y.; Yonekura, Y.; Takemura, Y.; Wada, K.; Matsumoto, K.; Tamaki, N.; Yamamoto, K.; Konishi, J.; Yokoyama, A. )

    1990-11-01

    To clarify the relationship between the myocardial accumulation of {sup 125}I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) and intracellular adenosine-5'-triphosphate (ATP) content, the effect of 2,4-dinitrophenol (DNP, an electron transport uncoupler) on myocardial BMIPP accumulation was studied, in comparison with that of thallium-201-chloride ({sup 201}Tl-Cl). In the mouse myocardium, DNP decreased the intracellular ATP and ADP levels, without affecting either acyl-CoA synthetase activity or the level of CoA-SH. Following treatment with DNP, decreases in myocardial BMIPP accumulation correlated well with those of ATP, while {sup 201}Tl-Cl showed slightly increased accumulation in the myocardium. Thus, in some diseases, BMIPP may be useful in evaluating myocardial ATP levels.

  8. Effects of metabolic and myocardial microcirculatory abnormalities on the pathogenesis of cardiac autonomic neuropathy in type 2 diabetes mellitus: A prospective study in Japanese patients*

    PubMed Central

    Komori, Hiromi

    2005-01-01

    Background: In diabetic patients, cardiac autonomic neuropathy is an important factor affecting prognosis. Whether this condition in diabetic patients is caused directly by neurovisceral metabolic disorder and/or indirectly by micro circulation remains to be clarified. Objective: The aim of this study was to determine whether cardiac sympathetic nerve dysfunction can be detected using adenosine triphosphate (ATP) testing, while also investigating the effects of metabolic and/or myocardial microcirculatory abnormalities on the pathogenesis of cardiac autonomic nerve dysfunction in patients with type 2 diabetes mellitus (DM-2) in Japan. Methods: This prospective study was performed at the Division of Diabetology Department of Internal Medicine, Toho University, Ohashi Hospital, Tokyo, Japan. Patients aged ≥ 18 years with DM-2 with no abnormalities on electrocardiography (ECG) or echocardiography were enrolled. An ATP thallium (Tl)-201 myocardial scintigraphy test (ATP test) and iodine (I)-123 metaiodobenzylguanidine (MIBG) scintigraphy were performed. ATP was administered by continuous IV infusion over 6 minutes at 0.16 mg/kg · min. Five minutes after the ATP infusion was started, T1-201 111 MBq IV was administered. Single-photon emission computed tomography (SPECT) imaging was begun immediately after the end of ATP infusion and was completed 3 hours after stress to show washout from stress to rest. I-123 MIBG 111 MBq IV was administered. A planar image from the front side and a SPECT image (early phase) was obtained 15 to 30 minutes later. After 3 hours, a planar image from the front side and a SPECT image (late phase) were obtained to show washout from stress to rest. The mean TI washout rate (ATP-WR) and heart-to-mediastinum (H/M) ratio in the late-phase scintigraphic images and the washout rate of MIBG (MIBG-WR) in the left ventricle was determined. The correlations of these measurements with the mean values of glycosylated hemoglobin (HbA1c) and fasting

  9. Adenosine Inhibition of Mesopontine Cholinergic Neurons: Implications for EEG Arousal

    PubMed Central

    Rainnie, Donald G.; Grunze, Heinz C. R.; McCarley, Robert W.; Greene, Robert W.

    2013-01-01

    Increased discharge activity of mesopontine cholinergic neurons participates in the production of electroencephalographic (EEG) arousal; such arousal diminishes as a function of the duration of prior wakefulness or of brain hyperthermia. Whole-cell and extracellular recordings in a brainstem slice show that mesopontine cholinergic neurons are under the tonic inhibitory control of endogenous adenosine, a neuromodulator released during brain metabolism. This inhibitory tone is mediated postsynaptically by an inwardly rectifying potassium conductance and by an inhibition of the hyperpolarization-activated current. These data provide a coupling mechanism linking neuronal control of EEG-arousal with the effects of prior wakefulness, brain hyperthermia, and the use of the adenosine receptor blockers caffeine and theophylline. PMID:8303279

  10. Adenosine: an endogenous mediator in the pathogenesis of psoriasis*

    PubMed Central

    Festugato, Moira

    2015-01-01

    It is known that inflammatory and immune responses protect us from the invasion of micro-organisms and eliminate "wastes" from the injured sites, but they may also be responsible for significant tissue damage. Adenosine, as a purine nucleoside, which is produced in inflamed or injured sites, fulfills its role in limiting tissue damage. Although, it may have a pleiotropic effect, which signals it with a proinflammatory state in certain situations, it can be considered a potent anti-inflammatory mediator. The effects of adenosine, which acts through its receptors on T cell, on mast cell and macrophages, on endothelial cells, on neutrophils and dendritic cells, as they indicate TNF-alpha and cytokines, show that this mediator has a central role in the pathogenesis of psoriasis. The way it acts in psoriasis will be reviewed in this study. PMID:26734868

  11. Structure–Activity Relationships of 9-Alkyladenine and Ribose-Modified Adenosine Derivatives at Rat A3 Adenosine Receptors†

    PubMed Central

    Jacobson, Kenneth A.; Siddiqi, Suhaib M.; Olah, Mark E.; Ji, Xiao-duo; Melman, Neli; Bellamkonda, Kamala; Meshulam, Yakov; Stiles, Gary L.; Kim, Hea O.

    2012-01-01

    9-Alkyladenine derivatives and ribose-modified N6-benzyladenosine derivatives were synthesized in an effort to identify selective ligands for the rat A3 adenosine receptor and leads for the development of antagonists. The derivatives contained structural features previously determined to be important for A3 selectivity in adenosine derivatives, such as an N6-(3-iodobenzyl) moiety, and were further substituted at the 2-position with halo, amino, or thio groups. Affinity was determined in radioligand binding assays at rat brain A3 receptors stably expressed in Chinese hamster ovary (CHO) cells, using [125I]AB-MECA (N6-(4-amino-3-iodobenzyl)adenosine-5′-(N-methyluronamide)), and at rat brain A1 and A2a receptors using [3H]-N6-PIA ((R)-N6-phenylisopropyladenosine) and [3H]CGS 21680 (2-[[[4-(2-carboxyethyl)-phenyl]ethyl]amino]-5′-(N-ethylcarbamoyl)adenosine), respectively. A series of N6-(3-iodobenzyl) 2-amino derivatives indicated that a small 2-alkylamino group, e.g., methylamino, was favored at A3 receptors. N6-(3-Iodobenzyl)-9-methyl-2-(methylthio)adenine was 61-fold more potent than the corresponding 2-methoxy ether at A3 receptors and of comparable affinity at A1 and A2a receptors, resulting in a 3–6-fold selectivity for A3 receptors. A pair of chiral N6-(3-iodobenzyl) 9-(2,3-dihydroxypropyl) derivatives showed stereoselectivity, with the R-enantiomer favored at A3 receptors by 5.7-fold. 2-Chloro-9-(β-d-erythrofuranosyl)-N6-(3-iodobenzyl)adenine had a Ki value at A3 receptors of 0.28 µM. 2-Chloro-9-[2-amino-2,3-dideoxy-β-d-5-(methylcarbamoyl)-arabinofuranosyl]-N6-(3-iodobenzyl)adenine was moderately selective for A1 and A3 vs A2a receptors. A 3′-deoxy analogue of a highly A3-selective adenosine derivative retained selectivity in binding and was a full agonist in the inhibition of adenylyl cyclase mediated via cloned rat A3 receptors expressed in CHO cells. The 3′-OH and 4′-CH2OH groups of adenosine are not required for activation at A3 receptors. A

  12. Targeting the A2B adenosine receptor during gastrointestinal ischemia and inflammation

    PubMed Central

    Eltzschig, Holger K; Rivera-Nieves, Jesus; Colgan, Sean P

    2014-01-01

    Extracellular adenosine functions as an endogenous distress signal via activation of four distinct adenosine receptors (A1, A2A, A2B and A3). Conditions of limited oxygen availability or acute inflammation lead to elevated levels of extracellular adenosine and enhanced signaling events. This relates to a combination of four mechanisms: i) increased production of adenosine via extracellular phosphohydrolysis of precursor molecules (particularly ATP and ADP); ii) increased expression and signaling via hypoxia-induced adenosine receptors, particularly the A2B adenosine receptor; iii) attenuated uptake from the extracellular towards the intracellular compartment; and iv) attenuated intracellular metabolism. Due to their large surface area, mucosal organs are particularly prone to hypoxia and ischemia associated inflammation. Therefore, it is not surprising that adenosine production and signaling plays a central role in attenuating tissue inflammation and injury during intestinal ischemia or inflammation. In fact, recent studies combining pharmacological and genetic approaches demonstrated that adenosine signaling via the A2B adenosine receptor dampens mucosal inflammation and tissue injury during intestinal ischemia or experimental colitis. This review outlines basic principles of extracellular adenosine production, signaling, uptake and metabolism. In addition, we discuss the role of this pathway in dampening hypoxia-elicited inflammation, specifically in the setting of intestinal ischemia and inflammation. PMID:19769545

  13. Ticagrelor potentiates adenosine-induced stimulation of neutrophil chemotaxis and phagocytosis.

    PubMed

    Alsharif, Khalaf F; Thomas, Mark R; Judge, Heather M; Khan, Haroon; Prince, Lynne R; Sabroe, Ian; Ridger, Victoria C; Storey, Robert F

    2015-08-01

    In the PLATO study, ticagrelor was associated with fewer pulmonary infections and subsequent deaths than clopidogrel. Neutrophils are a first-line defence against bacterial lung infection; ticagrelor inhibits cellular uptake of adenosine, a known regulator of neutrophil chemotaxis and phagocytosis. We assessed whether the inhibition of adenosine uptake by ticagrelor influences neutrophil chemotaxis and phagocytosis. Neutrophils and erythrocytes were isolated from healthy volunteers. Concentration-dependent effects of adenosine on IL-8-induced neutrophil chemotaxis were investigated and the involved receptors identified using adenosine receptor antagonists. The modulatory effects of ticagrelor on adenosine-mediated changes in neutrophil chemotaxis and phagocytosis of Streptococcus pneumoniae were determined in the presence of erythrocytes to replicate physiological conditions of cellular adenosine uptake. Low-concentration adenosine (10(-8)M) significantly increased IL-8-induced neutrophil chemotaxis (% neutrophil chemotaxis: adenosine 28.7%±4.4 vs. control 22.6%±2.4; p<0.01) by acting on the high-affinity A1 receptor. Erythrocytes attenuated the effect of adenosine, although this was preserved by ticagrelor and dipyridamole (another inhibitor of adenosine uptake) but not by control or by cangrelor. Similarly, in the presence of erythrocytes, a low concentration of adenosine (10(-8)M) significantly increased neutrophil phagocytic index compared to control when ticagrelor was present (37.6±6.6 vs. 28.0±6.6; p=0.028) but had no effect in the absence of ticagrelor. We therefore conclude that the inhibition of cellular adenosine reuptake by ticagrelor potentiates the effects of a nanomolar concentration of adenosine on neutrophil chemotaxis and phagocytosis. This represents a potential mechanism by which ticagrelor could influence host defence against bacterial lung infection.

  14. Ticagrelor potentiates adenosine-induced stimulation of neutrophil chemotaxis and phagocytosis

    PubMed Central

    Alsharif, Khalaf F.; Thomas, Mark R.; Judge, Heather M.; Khan, Haroon; Prince, Lynne R.; Sabroe, Ian; Ridger, Victoria C.; Storey, Robert F.

    2015-01-01

    In the PLATO study, ticagrelor was associated with fewer pulmonary infections and subsequent deaths than clopidogrel. Neutrophils are a first-line defence against bacterial lung infection; ticagrelor inhibits cellular uptake of adenosine, a known regulator of neutrophil chemotaxis and phagocytosis. We assessed whether the inhibition of adenosine uptake by ticagrelor influences neutrophil chemotaxis and phagocytosis. Neutrophils and erythrocytes were isolated from healthy volunteers. Concentration-dependent effects of adenosine on IL-8-induced neutrophil chemotaxis were investigated and the involved receptors identified using adenosine receptor antagonists. The modulatory effects of ticagrelor on adenosine-mediated changes in neutrophil chemotaxis and phagocytosis of Streptococcus pneumoniae were determined in the presence of erythrocytes to replicate physiological conditions of cellular adenosine uptake. Low-concentration adenosine (10− 8 M) significantly increased IL-8-induced neutrophil chemotaxis (% neutrophil chemotaxis: adenosine 28.7% ± 4.4 vs. control 22.6% ± 2.4; p < 0.01) by acting on the high-affinity A1 receptor. Erythrocytes attenuated the effect of adenosine, although this was preserved by ticagrelor and dipyridamole (another inhibitor of adenosine uptake) but not by control or by cangrelor. Similarly, in the presence of erythrocytes, a low concentration of adenosine (10− 8 M) significantly increased neutrophil phagocytic index compared to control when ticagrelor was present (37.6 ± 6.6 vs. 28.0 ± 6.6; p = 0.028) but had no effect in the absence of ticagrelor. We therefore conclude that the inhibition of cellular adenosine reuptake by ticagrelor potentiates the effects of a nanomolar concentration of adenosine on neutrophil chemotaxis and phagocytosis. This represents a potential mechanism by which ticagrelor could influence host defence against bacterial lung infection. PMID:25869515

  15. Effects of adenosine metabolism in astrocytes on central nervous system oxygen toxicity.

    PubMed

    Chen, Yu-liang; Zhang, Ya-nan; Wang, Zhong-zhuang; Xu, Wei-gang; Li, Run-ping; Zhang, Jun-dong

    2016-03-15

    Hyperbaric oxygen (HBO) is widely used in military operations, especially underwater missions. However, prolonged and continuous inhalation of HBO can cause central nervous system oxygen toxicity (CNS-OT), which greatly limits HBO's application. The regulation of astrocytes to the metabolism of adenosine is involved in epilepsy. In our study, we aimed to observe the effects of HBO exposure on the metabolism of adenosine in the brain. Furthermore, we aimed to confirm the possible mechanism underlying adenosine's mediation of the CNS-OT. Firstly, anesthetized rats exposed to 5 atm absolute HBO for 80 min. The concentrations of extracellular adenosine, ATP, ADP, and AMP were detected. Secondly, free-moving rats were exposed to HBO at the same pressure for 20 min, and the activities of 5'-nucleotidase and ADK in brain tissues were measured. For the mechanism studies, we observed the effects of a series of different doses of drugs related to adenosine metabolism on the latency of CNS-OT. Results showed HBO exposure could increase adenosine content by inhibiting ADK activity and improving 5'-nucleotidase activity. And adenosine metabolism during HBO exposure may be a protective response against HBO-induced CNS-OT. Moreover, the improvement of adenosine concentration, activation of adenosine A1R, or suppression of ADK and adenosine A2AR, which are involved in the prevention of HBO-induced CNS-OT. This is the first study to demonstrate HBO exposure regulated adenosine metabolism in the brain. Adenosine metabolism and adenosine receptors are related to HBO-induced CNS-OT development. These results will provide new potential targets for the termination or the attenuation of CNS-OT. PMID:26806404

  16. Pharmacology of the Adenosine A3 Receptor in the Vasculature and Essential Hypertension

    PubMed Central

    Ho, Ming-Fen; Low, Leanne M.; Rose’Meyer, Roselyn B.

    2016-01-01

    Background Essential hypertension is considered to be a multifactorial disorder and its aetiology has yet to be clearly identified. As the adenosine receptors have a significant role in mediating vasodilation, alterations in their structures or signalling pathways may be involved in the development of hypertension. This study aimed to measure the expression of adenosine A3 receptors in a range of cardiovascular tissues and determine whether they could be altered with essential hypertension, and to functionally test responses to adenosine A3 receptor agonists in coronary blood vessels using the isolated perfused heart preparation. Methods mRNA samples from cardiovascular tissues and a range of blood vessels were collected from 10 week old male spontaneously hypertensive rats and age-gender matched Wistar rats (n = 8). The Langendorff heart perfusion preparation was used to characterise adenosine A3 receptor mediated coronary vasodilation in the rat heart. Results Adenosine A3 receptor agonists induced coronary vasodilation. The expression of adenosine A3 receptors in cardiovascular tissues was altered in a tissue-specific pattern. Specifically, down-regulation of adenosine A3 receptor expression occurred in hypertensive hearts, which might be associated with attenuated vasodilator responses observed in coronary vessels to adenosine A3 receptor agonists. Conclusions This study demonstrated alterations in the expression of adenosine A3 receptors occurred in a tissue specific mode, and reduced adenosine A3 receptor mediated coronary vasodilation in hearts from spontaneously hypertensive rats. Our findings with regard to changes in the adenosine A3 receptor in hypertensive hearts suggest that adenosine A3 receptor might play a role in the physiopathology of essential hypertension and potentially open the way to pharmacologic manipulation of vasomotor activity by the use of adenosine A3 receptor agonists. PMID:26907173

  17. Identification of widespread adenosine nucleotide binding in Mycobacterium tuberculosis

    SciTech Connect

    Ansong, Charles; Ortega, Corrie; Payne, Samuel H.; Haft, Daniel H.; Chauvigne-Hines, Lacie M.; Lewis, Michael P.; Ollodart, Anja R.; Purvine, Samuel O.; Shukla, Anil K.; Fortuin, Suereta; Smith, Richard D.; Adkins, Joshua N.; Grundner, Christoph; Wright, Aaron T.

    2013-01-24

    The annotation of protein function is almost completely performed by in silico approaches. However, computational prediction of protein function is frequently incomplete and error prone. In Mycobacterium tuberculosis (Mtb), ~25% of all genes have no predicted function and are annotated as hypothetical proteins. This lack of functional information severely limits our understanding of Mtb pathogenicity. Current tools for experimental functional annotation are limited and often do not scale to entire protein families. Here, we report a generally applicable chemical biology platform to functionally annotate bacterial proteins by combining activity-based protein profiling (ABPP) and quantitative LC-MS-based proteomics. As an example of this approach for high-throughput protein functional validation and discovery, we experimentally annotate the families of ATP-binding proteins in Mtb. Our data experimentally validate prior in silico predictions of >250 ATPases and adenosine nucleotide-binding proteins, and reveal 73 hypothetical proteins as novel ATP-binding proteins. We identify adenosine cofactor interactions with many hypothetical proteins containing a diversity of unrelated sequences, providing a new and expanded view of adenosine nucleotide binding in Mtb. Furthermore, many of these hypothetical proteins are both unique to Mycobacteria and essential for infection, suggesting specialized functions in mycobacterial physiology and pathogenicity. Thus, we provide a generally applicable approach for high throughput protein function discovery and validation, and highlight several ways in which application of activity-based proteomics data can improve the quality of functional annotations to facilitate novel biological insights.

  18. Agonist Derived Molecular Probes for A2A Adenosine Receptors

    PubMed Central

    Jacobson, Kenneth A.; Pannell, Lewis K.; Ji, Xiao-duo; Jarvis, Michael F.; Williams, Michael; Hutchison, Alan J.; Barrington, William W.; Stiles, Gary L.

    2011-01-01

    The adenosine agonist 2-(4-(2-carboxyethyl)phenylethylamino)-5′-N-ethylcarboxamidoadenosine (CGS21680) was recently reported to be selective for the A2A adenosine receptor subtype, which mediates its hypotensive action. To investigate structurelactivity relationships at a distal site, CGS21680 was derivatized using a functionalized congener approach. The carboxylic group of CGS21680 has been esterified to form a methyl ester, which was then treated with ethylenediamine to produce an amine congener. The amine congener was an intermediate for acylation reactions, in which the reactive acyl species contained a reported group, or the precursor for such. For radioiodination, derivatives of p-hydroxyphenylpropionic, 2-thiophenylacetic, and p-aminophenylacetic acids were prepared. The latter derivative (PAPA-APEC) was iodinated electrophilically using [125I]iodide resulting in a radioligand which was used for studies of competition of binding to striatal A, adenosine receptors in bovine brain. A biotin conjugate and an aryl sulfonate were at least 350-fold selective for A, receptors. For spectroscopic detection, a derivative of the stable free radical tetramethyl-1-piperidinyloxy (TEMPO) was prepared. For irreversible inhibition of receptors, meta- and para-phenylenediisothiocyanate groups were incorporated in the analogs. We have demonstrated that binding at A2A receptors is relatively insensitive to distal structural changes at the 2-position, and we report high affinity molecular probes for receptor characterization by radioactive, spectroscopic and affinity labelling methodology. PMID:2561548

  19. Patterns of disturbed myocardial perfusion in patients with coronary artery disease. Regional myocardial perfusion in angina pectoris

    SciTech Connect

    Selwyn, A.P.; Forse, G.; Fox, K.; Jonathan, A.; Steiner, R.

    1981-07-01

    Fifty patients who presented with angina pectoris were studied to examine the disturbances of regional myocardial perfusion during stress. Each patient underwent 16-point precordial mapping of the ECG during an exercise test, and coronary and left ventricular angiography. Regional myocardial perfusion was assessed using an atrial pacing test and a short-lived radionuclide, krypton-81m. Eleven patients had negative exercise tests and uniform increases in myocardial activity of krypton-81m of 98 +/- 18.0% during pacing. Ten patients performed 30,000-43,000 J in positive exercise tests. These patients showed abnormal coronary anatomy and increases in myocardial activity of krypton-81m to remote and jeopardized myocardium at the onset of pacing. However, further pacing produced a decrease in activity in the affected segment of 68.0 +/- 9.0% accompanied by ST-segment depression and angina. Twelve patients achieved 26,000-32,000 J in positive exercise tests and had significant coronary artery disease. Atrial pacing produced increased activity of krypton-81m to remote myocardium. The jeopardized segment at first showed no change and then a decrease in regional activity of krypton-81m (89.0 +/- 17%) accompanied by ST-segment depression and chest pain. Seventeen patients achieved only 7000-22,000 J in positive exercise tests. These patients showed abnormal coronary anatomy and developed decreases in regional activity of krypton-81m to the affected segment of myocardium starting at the onset of atrial pacing and decreasing by 88 +/- 0 7.0% below control. We conclude that different patterns of disturbed myocardial distribution of krypton-81m are present during stress-induced ischemia in patients with coronary artery disease. There was a close temporal relationship between these disturbances and ST-segment depression.

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