The role of adenosine and its cellular source in isoproterenol-induced coronary vasodilatation was investigated in isolated perfused rat hearts prelabelled with [3H]adenosine. Time courses (times for half-maximal increase) were measured for changes in oxygen consumption (2.23 +/- 0.22 min), coronary flow (3.30 +/- 0.33 min), concentrations of effluent radioactivity (3.92 +/- 0.30 min) and adenosine and its metabolites (inosine, hypoxanthine and xanthine) (2.00 +/- 0.23 min). Isoproterenol stimulation decreased the cellular energy state and increased the concentration of tissue adenosine and its metabolites. Coronary flow was linearly correlated with tissue adenosine (r = 0.85) and phosphorylation potential (r = -0.82) and tissue adenosine also showed a linear correlation with phosphorylation potential (r = -0.84) and tissue free [AMP] (r = 0.79). The specific radioactivities of tissue nucleotides remained constant, but those of adenosine, inosine and hypoxanthine + xanthine were decreased by 42%, 26% and 46%, respectively. Purine compound concentrations increased during isoproterenol stimulation from basal values of 56 +/- 23, 98 +/- 33 and 44 +/- 19 nM to 388 +/- 173, 583 +/- 156 and 178 +/- 27 nM, respectively. The basal specific radioactivity ratio of adenosine:inosine:(hypoxanthine + xanthine) in the effluent perfusate was 1:0.5:7, but the specific radioactivities decreased rapidly upon isoproterenol stimulation, and at 3 min the ratio had changed to 1:2.5:16.5. The time courses of release and the changes in the specific radioactivities of the nucleosides indicate that adenosine release occurred mainly from cardiomyocytes, and that the release of adenosine and its metabolites from the cardiomyocytes preceded that from the endothelium. It is also shown that adenosine release during catecholamine stimulation occurs concomitantly with a decrease in the cellular energy state and AMP accumulation. This is in accord with the adenosine hypothesis of coronary vasoregulation.
INTRODUCTION: Adenosine is an endogenous nucleoside that has an important role in the diagnosis and treatment of several cardiac arrhythmias. However, its effects on inappropriate sinus tachycardia (IST) are not well established. METHODS AND RESULTS: In this study, the response to intravenous adenosine (0.1 to 0.15 mg/kg) was studied in 18 patients (age 46+/-15 years) with IST. In a subset of patients (n = 5), the direct effects of adenosine were assessed during pharmacologic beta-adrenergic and cholinergic blockade. Atrial cycle length (ACL) was measured before adenosine injection, at the time of the greatest cycle length prolongation, and during the maximum rebound acceleration of heart rate. Eighteen subjects (age 46+/-11 years) with normal sinus rhythm undergoing clinically indicated electrophysiologic study served as controls. Adenosine did not terminate IST in any patient. The maximum dose of adenosine prolonged the sinus interval significantly, from 780+/-128 msec to 985+/-225 msec (P
Cardiac Arrhythmias and Risk Stratification after Myocardial infarction (CARISMA) is a prospective multicenter trial designed to document the incidence of cardiac arrhythmias after acute myocardial infarction (AMI), and to assess the predictive accuracy of various arrhythmic risk markers. In this substudy of the CARISMA trial, microvolt T-wave alternans (TWA) was assessed with specific equipment 6 weeks after AMI during bicycle exercise, atrial (A) pacing, and simultaneous ventricular and atrial (V + A) pacing in 80 patients with left ventricular ejection fraction (LVEF)
The FinPAC trial showed that the strategy of uninterrupted oral anticoagulation (OAC) was non-inferior to interrupted OAC for the primary outcome of bleeding and thromboembolic complications in patients undergoing cardiac rhythm management device (CRMD) implantation.
We conducted a post hoc analysis of the FinPAC data to explore the incidence and predictors of significant (> 100 cm(2)) pocket hematoma after CRMD implantation among the study population (n = 447). A total of 213 patients were on OAC, 128 were on aspirin, and 106 on no antithrombotic therapy.
The incidence of significant pocket hematoma during hospital stay was significantly higher among patients using OAC (5.6%) and aspirin (5.5%) than in those with no antithrombotic medications (0.9%), but only one patient (0.8%) in the aspirin group needed revision of hematoma. Two patients (0.9%) in the OAC group and one (0.8%) in the aspirin group needed blood products. In multivariable regression analysis, no pre- procedural features predicted the significant hematoma in any of the groups.
Clinically significant pocket hematoma is a rare complication after CRMD implantation in patients with ongoing therapeutic OAC. The incidence of significant pocket hematoma formation is similar in patients using OAC and those using aspirin.
The quality of warfarin therapy and CHA2DS2-VASc score associate with the incidence of myocardial infarction and cardiovascular outcome in patients with atrial fibrillation: data from the nationwide FinWAF Registry.
The impact of the quality of warfarin therapy on cardiovascular outcomes excluding stroke is largely unknown. The aims of this study were to evaluate the association between the warfarin control and the incidence and outcome of myocardial infarction (MI) and to validate the predictive value of the CHA2DS2-VASc score for MI in atrial fibrillation (AF) patients taking warfarin.
The nationwide FinWAF Registry consists of 54?568 AF patients (mean age 73.31?±?10.7?years, 52% men) taking warfarin. The quality of warfarin therapy was assessed continuously by calculating the time in therapeutic range within a 60-day window using the Rosendaal method (TTR60). Adjusted Cox proportional hazards models were prepared for the incidence of MI and cardiovascular mortality in six different TTR60 categories. During the 3.2?±?1.6?years of follow-up, the annual incidence of MI (95% confidence interval) was 3.3% (3.0-3.5%), 2.9% (2.6-3.3%), 2.4% (2.1-2.7%), 1.9% (1.7-2.2%), 1.7% (1.5-2.0%), and 1.2% (1.1-1.3%) among patients with TTR60 80%, respectively. Well-managed warfarin therapy (TTR60?>?80%) was associated also with a lower cardiovascular mortality, whereas a high CHA2DS2-VASc score correlated with poor outcome.
Cardiovascular outcome was superior among AF patients with good warfarin control and in those with a low CHA2DS2-VASc score. The inverse association between the TTR60 and incidence of MI and cardiovascular mortality indicate that in AF patients the quality of warfarin therapy is critical not only for prevention of stroke but also with regard to cardiovascular outcome.
AIMS: Chronic atrial fibrillation causes mechanical remodelling of the atria, but it is uncertain whether self-terminating episodes of paroxysmal atrial fibrillation (PAF) alter atrial mechanical function during normal sinus rhythm. This study was designed to assess the relationship between the frequency of symptomatic arrhythmic episodes and pulmonary venous flow (PVF) pattern among patients with PAF. METHODS AND RESULTS: The effect of symptomatic arrhythmic episodes on PVF was studied in 85 patients with lone PAF (age 48+/-8 years, 66 men). PVF was measured with transthoracic echocardiography during sinus rhythm. Adequate recordings of PVF were achieved in 81 (95%) patients. Peak systolic PVF had an inverse correlation (r=-0.35, P=0.002) with the frequency of PAF episodes. The peak systolic PVF was 76+/-14 cm/s vs 62+/-12 cm/s (P=0.008) among the quartiles with the most and the least frequent episodes of PAF, respectively. There were no significant differences in the other echocardiographic measurements or demographic variables. CONCLUSIONS: Frequent arrhythmic episodes significantly diminished systolic PVF among patients with PAF, suggesting that PAF results in gradual mechanical remodelling of the atrium, which may favour recurrence and perpetuation of AF and/or formation of atrial thrombus.