Effects of intravenous theophylline on exercise-induced myocardial ischemia: II. A concentration-dependent phenomenon

AbstractObjectives. The effects of varying concentrations of theophylline on exercise-induced myocardial ischemia were evaluated in patients with stable coronary artery disease.Background. Theophylline is a competitive antagonist of adenosine and may have potential as an anti-ischemic medication. It is not known whether these effects on myocardial ischemia are concentration dependent.Methods. In a double-blind, randomized, crossover manner, 11 patients received, at 1-week intervals, placebo and each of three theophylline doses by intravenous infusion for 45 min. Graded exercise testing was performed before randomization and immediately after each infusion. Concurrent anti-ischemic medications were withheld for 24 h before each exercise test. Serum theophylline concentrations achieved were 3.9 ± 1.0 mg/liter (low), 8.2 ± 1.8 mg/liter (medium) and 13.2 ± 2.3 mg/liter (high).Results. Compared with placebo, none of the three theophylline infusions produced a significant alteration in rest heart rate, blood pressure, mean frequency or severity of ventricular ectopic activity or noncardiac symptoms. The time to onset of ischemia was progressively increased, with medium and high concentrations achieving statistical significance. Similar patterns were observed for oxygen uptake and the heart rate-systolic blood pressure product at the onset of ischemia. Total exercise duration was significantly prolonged with the medium and high concentrations.Conclusions. It is concluded that administration of varying doses of theophylline before exercise produces a clinically significant and concentration-dependent improvement in the indicators of myocardial ischemia in patients with chronic stable coronary artery disease

The pacing stress test: Thallium-201 myocardial imaging after atrial pacing. Diagnostic value in detecting coronary artery disease compared with exercise testing

Many patients suspected of having coronary artery disease are unable to undergo adequate exercise testing. An alternate stress, pacing tachycardia, has been shown to produce electrocardiographic changes that are as sensitive and specific as those observed during exercise testing. To compare thallium-201 imaging after atrial pacing stress with thallium imaging after exercise stress, 22 patients undergoing cardiac catheterization were studied with both standard exercise thallium imaging and pacing thallium imaging.Positive ischemic electrocardiographic changes (> 1 mm ST segment depression) were noted in 11 of 16 patients with coronary artery disease during exercise, and in 15 of the 16 patients during atrial pacing. One of six patients with normal or trivial coronary artery disease had a positive electrocardiogram with each test. Exercise thallium imaging was positive in 13 of 16 patients with coronary artery disease compared with 15 of 16 patients during atrial pacing. Three of six patients without coronary artery disease had a positive scan with exercise testing, and two of these same patients developed a positive scan with atrial pacing. Of those patients with coronary artery disease and an abnormal scan, 85% showed redistribution with exercise testing compared with 87% during atrial pacing. Segment by segment comparison of thallium imaging after either atrial pacing or exercise showed that there was a good correlation of the location and severity of the thallium defects (r = 0.83, p = 0.0001, Spearman rank correlation).It is concluded that the location and presence of both fixed and transient thallium defects after atrial pacing are closely correlated with the findings after exercise testing. Thus, atrial pacing may be used as a stress for myocardial perfusion scintigraphy in patients unable to complete a satisfactory exercise test

Iodofiltic Acid I 123 (BMIPP) Fatty Acid Imaging Improves Initial Diagnosis in Emergency Department Patients With Suspected Acute Coronary Syndromes A Multicenter Trial

ObjectivesThe aim of this study was to assess the performance of β-methyl-p-[123I]-iodophenyl-pentadecanoic acid (BMIPP) single-photon emission computed tomography (SPECT) to detect acute coronary syndromes (ACS) in emergency department patients with chest pain.BackgroundEmergency department diagnosis of chest pain is problematic, often requiring prolonged observation and stress testing. BMIPP SPECT detects abnormalities in fatty acid metabolism resulting from myocardial ischemia, even many hours after symptom cessation.MethodsEmergency department patients with suspected ACS were enrolled at 50 centers. Patients received 5 mCi BMIPP within 30 h of symptom cessation. BMIPP SPECT images were interpreted semiquantitatively by 3 blinded readers. Initial clinical diagnosis was based on symptoms, initial electrocardiograms, and troponin, whereas the final diagnosis was based on all available data (including angiography and stress SPECT) but not BMIPP SPECT. Final diagnoses were adjudicated by a blinded committee as ACS, intermediate likelihood of ACS, or negative for ACS.ResultsA total of 507 patients were studied and efficacy was evaluated in 448 patients with sufficient data. The sensitivity of BMIPP by 3 blinded readers for a final diagnosis of ACS and intermediate likelihood of ACS was 71% (95% confidence interval [CI]: 64% to 79%), 74% (95% CI: 68% to 81%), and 69% (95% CI: 62% to 77%); the corresponding specificity of BMIPP was 67% (95% CI: 61% to 73%), 54% (95% CI: 48% to 60%), and 70% (95% CI: 64% to 76%). Compared with the initial diagnosis alone, BMIPP + initial diagnosis increased sensitivity from 43% to 81% (p < 0.001), negative predictive value from 62% to 83% (p < 0.001), and positive predictive value from 41% to 58% (p < 0.001), whereas specificity was unchanged (61% to 62%, p = NS).ConclusionsThe addition of BMIPP data to the initially available clinical information adds incremental value toward the early diagnosis of an ACS, potentially allowing determination of the presence or absence of ACS to be made earlier in the evaluation process. (Safety and Efficacy Iodofiltic Acid I 123 in the Treatment of Acute Coronary Syndrome [Zeus-ACS]; NCT00514501

Search for sterile neutrino mixing in the MINOS long-baseline experiment

A search for depletion of the combined flux of active neutrino species over a 735 km baseline is reported using neutral-current interaction data recorded by the MINOS detectors in the NuMI neutrino beam. Such a depletion is not expected according to conventional interpretations of neutrino oscillation data involving the three known neutrino flavors. A depletion would be a signature of oscillations or decay to postulated noninteracting sterile neutrinos, scenarios not ruled out by existing data. From an exposure of 3.18×10^(20) protons on target in which neutrinos of energies between ∼500  MeV and 120 GeV are produced predominantly as ν_μ, the visible energy spectrum of candidate neutral-current reactions in the MINOS far detector is reconstructed. Comparison of this spectrum to that inferred from a similarly selected near-detector sample shows that of the portion of the ν_μ flux observed to disappear in charged-current interaction data, the fraction that could be converting to a sterile state is less than 52% at 90% confidence level (C.L.). The hypothesis that active neutrinos mix with a single sterile neutrino via oscillations is tested by fitting the data to various models. In the particular four-neutrino models considered, the mixing angles θ_(24) and θ_(34) are constrained to be less than 11° and 56° at 90% C.L., respectively. The possibility that active neutrinos may decay to sterile neutrinos is also investigated. Pure neutrino decay without oscillations is ruled out at 5.4 standard deviations. For the scenario in which active neutrinos decay into sterile states concurrently with neutrino oscillations, a lower limit is established for the neutrino decay lifetime τ_3/m_3>2.1×10^(-12) s/eV at 90% C.L

New constraints on muon-neutrino to electron-neutrino transitions in MINOS

This paper reports results from a search for ν_μ → ν_e transitions by the MINOS experiment based on a 7×10^(20) protons-on-target exposure. Our observation of 54 candidate ν_e events in the far detector with a background of 49.1±7.0(stat)±2.7(syst) events predicted by the measurements in the near detector requires 2sin^2(2θ_(13))sin^2θ_(23)<0.12(0.20) at the 90% C.L. for the normal (inverted) mass hierarchy at δ_(CP)=0. The experiment sets the tightest limits to date on the value of θ_(13) for nearly all values of δ_(CP) for the normal neutrino mass hierarchy and maximal sin^2(2θ_(23))