82Rb cardiac PET allows the assessment of myocardial perfusion using a column generator in clinics that lack a cyclotron. We and others have previously shown that quantitation of myocardial blood flow (MBF) and coronary flow reserve (CFR) is feasible using dynamic 82Rb PET and factor and compartment analyses. The aim of the present work was to determine the intra- and inter-observer variability of MBF estimation using 82Rb PET as well as the reproducibility of our generalized factor + compartment analyses methodology to estimate MBF and assess its accuracy by comparing, in the same subjects, 82Rb estimates of MBF to those obtained using 13N-ammonia. Methods Twenty-two subjects were included in the reproducibility and twenty subjects in the validation study. Patients were injected with 60±5mCi of 82Rb and imaged dynamically for 6 minutes at rest and during dipyridamole stress Left and right ventricular (LV+RV) time-activity curves were estimated by GFADS and used as input to a 2-compartment kinetic analysis that estimates parametric maps of myocardial tissue extraction (K1) and egress (k2), as well as LV+RV contributions (fv,rv). Results Our results show excellent reproducibility of the quantitative dynamic approach itself with coefficients of repeatability of 1.7% for estimation of MBF at rest, 1.4% for MBF at peak stress and 2.8% for CFR estimation. The inter-observer reproducibility between the four observers that participated in this study was also very good with correlation coefficients greater than 0.87 between any two given observers when estimating coronary flow reserve. The reproducibility of MBF in repeated 82Rb studies was good at rest and excellent at peak stress (r2=0.835). Furthermore, the slope of the correlation line was very close to 1 when estimating stress MBF and CFR in repeated 82Rb studies. The correlation between myocardial flow estimates obtained at rest and during peak stress in 82Rb and 13N-ammonia studies was very good at rest (r2=0.843) and stress (r2=0.761). The Bland-Altman plots show no significant presence of proportional error at rest or stress, nor a dependence of the variations on the amplitude of the myocardial blood flow at rest or stress. A small systematic overestimation of 13N-ammonia MBF was observed with 82Rb at rest (0.129 ml/g/min) and the opposite, i.e., underestimation, at stress (0.22 ml/g/min). Conclusions Our results show that absolute quantitation of myocardial bloof flow is reproducible and accurate with 82Rb dynamic cardiac PET as compared to 13N-ammonia. The reproducibility of the quantitation approach itself was very good as well as inter-observer reproducibility.

The effects of bolus injections of recombinant single-chain tissue-type plasminogen activator (rt-PA) and of F(ab')2 fragments of a murine monoclonal antibody (7E3) Bleeding times remained unchanged after injection of rt-PA alone and were moderately (about twofold) prolonged after the injection of 7E3-F(ab')2 at a dose of 0.1 to 0.4 mg/kg. With 0.6 mg/kg 7E3-F(ab')2 the bleeding time prolonged approximately four times and was greater than 30 min in four of nine dogs. At 0.8 mg/kg the bleeding time was consistently prolonged to more than 30 min; this dose blocked 83 -+ 5% of the GPIIb/IIIa receptors on the platelet surface. Thus, injection of F(ab')2 fragments of the monoclonal antibody 7E3, directed against the platelet GPIIb/IIIa receptor, accelerates thrombolysis with rt-PA and prevents reocclusion. Antagonists of the platelet GPIIb/IIIa receptor may constitute useful adjunctive therapy for coronary arterial thrombolysis in patients with acute myocardial infarction.

Purpose:To evaluate the accuracy of 64-section multidetector computed tomography (CT) for the assessment of perfusion defects (PDs), regional wall motion (RWM), and global left ventricular (LV) function. Materials and Methods:All myocardial infarction (MI) patients signed informed consent. The IRB approved the study and it was HIPAAcompliant. Cardiac multidetector CT was performed in 102 patients (34 with recent acute MI and 68 without). Multidetector CT images were analyzed for myocardial PD, RWM abnormalities, and LV function. Global LV function and RWM were compared with transthoracic echocardiography (TTE) by using multidetector CT. PD was detected by using multidetector CT and was correlated with cardiac biomarkers and single photon emission CT (SPECT) myocardial perfusion imaging. Multidetector CT diagnosis of acute MI was made on the basis of matching the presence of PD with RWM abnormalities compared with clinical evaluation. Results:Correlation between multidetector CT and TTE for global function (r ϭ 0.68) and RWM ( ϭ 0.79) was good. The size of PD on multidetector CT had a moderate correlation against SPECT (r ϭ 0.48, Ϫ7% Ϯ 9). There was good to excellent correlation between cardiac biomarkers and the percentage infarct size by using multidetector CT (r ϭ 0.82 for creatinine phosphokinase, r ϭ 0.76 for creatinine phosphokinase of the muscle band, and r ϭ 0.75 for troponin). For detection of acute MI in patients, multidetector CT sensitivity was 94% (32 of 34) and specificity was 97% (66 of 68). Multidetector CT had an excellent interobserver reliability for ejection fraction quantification (r ϭ 0.83), as compared with TTE (r ϭ 0.68). Conclusion:Patients with acute MI can be identified by using multidetector CT on the basis of RWM abnormalities and PD.

Localized thrombosis was produced in the left anterior descending (LAD) coronary artery of open chest dogs by constricting a segment so as to produce > 90% stenosis (reducing blood flow to 40±10% of baseline), and placing a thrombus in the segment immediately proximal to the stenosis by inducing endothelial cell injury and instilling a mixture of blood and thrombin.Intravenous infusion of recombinant tissue-type plasminogen activator (rt-PA) at a rate of 15-30 ,g/kg per min for 30 or 60 min in eight dogs induced coronary artery reperfusion within 23±7 min (mean±SD), but reocclusion occurred despite heparin anticoagulation in all but one of these dogs within 7±5 mi.

In patients with unstable angina, argatroban inhibits clotting (aPTT prolongation) and thrombin activity toward fibrinogen (fibrinopeptide A decrease), but in vivo thrombin (thrombin-antithrombin III complex) formation is not suppressed. However, cessation of infusion is associated with rebound thrombin (thrombin-antithrombin III complex) generation and with an early dose-related recurrence of unstable angina. Although the mechanism of this clinical and biochemical rebound phenomenon remains to be determined, its implication for the clinical use of specific thrombin inhibitors in the management of ischemic coronary syndromes may be significant.