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Clinical InvestigationsIs Sick Sinus Syndrome an Adenosine—Mediated Disease?: Effects of Intravenous Aminophylline on Sick Sinus Node Function after Pharmacologic Autonomic Blockade
Section snippets
Study Patients
Twelve patients with the diagnosis of sick sinus syndrome were enrolled in this study. There were six men and six women ranging in age from 40 to 78 years (mean, 59.9 ± 10.0 years). The diagnosis of sick sinus syndrome was based on the presence of sinus bradycardia, sinus arrest and the bradytachycardia syndrome documented in the 24-h ambulatory electrocardiographic Holter recordings. None of the patients had glaucoma, urinary retention or contraindications to using beta-blockers. After
Definitions
Maximum sinus node recovery time was defined as the longest interval from the last paced high right atrial electrogram to the first spontaneous sinus atrial electrogram after termination of any rate of pacing.
Maximum corrected SNRT was calculated by subtracting the mean sinus cycle length from the maximum SNRT.
Sinoatrial conduction time was estimated by a continuous pacing method as proposed by Narula et al.21 The high right atrium was paced for eight beats at a cycle length slightly shorter
Control Measurements
During the control state, the mean sinus cycle length was 1,012.9 ± 208.1 ms (range 680 to 1,390 ms [Table 1]). The mean maximum SNRT and mean maximum corrected SNRT were 2,392 ± 817 and 1,379 ± 703 ms, respectively. The maximum corrected SNRT was abnormal (>525 ms) in 11 of 12 patients. The SACT was abnormal (>125 ms) in 9 of 12 patients with a mean SACT of 156 ± 66 ms.
Autonomic Blockade
After administration of pharmacologic autonomic blockade, the mean sinus cycle length was 953 ± 175 ms, corresponding to the
Discussion
If adenosine played a role in the pathogenesis of sick sinus syndrome, intravenous aminophylline would improve the sinus node function by competitively antagonizing the adenosine effect through extracellular adenosine receptors.16 In this study, intravenous aminophylline in a dosage of 5 mg/kg did not improve sinus node function as shown by clinical electrophysiologic measurements in patients with sick sinus syndrome. These results indicate that intrinsic adenosine may not play an important
Conclusion
Thus, intravenous aminophylline after pharmacologic autonomic blockade cannot improve the sinus node function in patients with chronic and advanced sick sinus syndrome. Endogenous adenosine may not play an important role in the pathogenesis of advanced sick sinus syndrome. Clinically, aminophylline does not increase the intrinsic heart rate in patients with advanced sick sinus syndrome and pacemaker therapy is still the first choice for patients with symptomatic sick sinus syndrome.
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Adenosine and its receptors in the heart: Regulation, retaliation and adaptation
2011, Biochimica et Biophysica Acta - BiomembranesCitation Excerpt :The actions of adenosine are also consistent with a role in sick sinus syndrome [70], though mechanistic involvement is yet to be fully established. The poorly selective AR antagonists aminophylline and theophylline do suppress symptoms in aged patients with this disorder [71,72]. Decay of ventricular fibrillation is accelerated by A1AR antagonism in a swine model [73], though this effect of endogenous adenosine does not impact on short-term outcomes [74].
Effects of oral theophylline on sick sinus syndrome
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1993, The American Journal of CardiologyNegative dromotropism of adenosine under beta-adrenergic stimulation with isoproterenol
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Manuscript received June 21; revision accepted September 14.