Analysis of rhythm variation during spontaneous cardioinhibitory neurally-mediated syncope. Implications for RDR pacing optimization: an ISSUE 2 substudy.

BACKGROUND: Little is known of the variations of the heart rate during spontaneous cardioinhibitory neurally-mediated syncope. Their knowledge has both academic and practical implications for the optimization of rate drop response (RDR) pacing mode. METHODS AND RESULTS: We describe variations of the rhythm occurring during 48 syncopal episodes documented by implantable loop recorder. The presyncopal phase of 18 s (interquartile range 9-65) was characterized by a fall in heart rate from 83 +/- 20 bpm to maximal bradycardia or (multiple) asystolic pauses which lasted a median of 19 s (10-30). The recovery phase lasted 22 s (7-52). The total duration of the cardioinhibitory reflex was 85 s (47-116). We then calculated the potential increase in benefit that an optimally programmed drop rate detection could provide compared with a reference Lower Rate detection. Compared with Lower Rate detection (defined as two consecutive beats at 40 bpm), drop rate detection (assumed to be drop size = 20 bpm, detection window = 1 min, and drop rate = 50 bpm) would have been able to introduce intervention pacing, a median of 5.7 s (interquartile range -5.1- -10.4) earlier in 28 cases (58%). CONCLUSION: Cardioinhibitory neurally-mediated reflex varies widely from a few seconds to some minutes. In our data the total duration was <2 min. Optimal RDR programming, being potentially able to anticipate the detection of the cardioinhibitory reflex by a few seconds, could provide an increase in benefit for cardiac pacing therapy in prevention of syncope.

Clinical experience of a new rate drop response algorithm in the treatment of vasovagal and carotid sinus syncope.

Dual chamber pacing has proven beneficial in patients with sudden drops in heart rate as seen in vasovagal syncope and carotid sinus syndrome. Newer algorithms for faster detection of an insidious drop in heart rate and short lasting intervention pacing at a high rate, as in the rate drop response algorithm in the Medtronic Kappa series of pacemakers, might improve the effect of pacing. Two case reports, that demonstrate the use of these rate drop response algorithms, are presented. A 24-year-old woman with recurrent episodes of syncope and repeated tilt-table tests with vasovagal cardioinhibitory outcomes had a Medtronic Kappa 400 pacemaker implanted. Syncope was abolished during repeat tilt-table testing following pacemaker implantation and proper functioning of the rate drop response algorithm. The patient has been free of syncope during follow-up apart from a single episode that occurred due to neglect of vasovagal warning symptoms. A 52-year-old man with coronary artery disease developed recurrent blackouts. Carotid sinus massage resulted in 5.5 s of asystole and presyncope. A Medtronic Kappa 700 pacemaker with a rate drop response algorithm was implanted and the patient became asymptomatic. The rate drop response algorithm is discussed in detail based upon the case reports, and recommendations are given for the use of this algorithm in patients with vasovagal syncope and carotid sinus syndrome.

Topical and systemic absorption of sodium pyrithione following topical application to the nails of the rhesus monkey.

A study was performed to investigate the local penetration into the nail, the systemic absorption into the rest of the body, and the routes of excretion of sodium pyrithione following topical application to the nail. Approximately 20 microliters of a film-forming 3% sodium 14C-pyrithione solution was applied once daily to 5 fingernails and 5 toenails of 4 rhesus monkeys for 6 or 7 days. Following dose removal on study day 7, 2 animals were sacrificed, and the treated nails were analyzed for radioactivity. The other 2 monkeys received the topical dose for 1 more day and were monitored during the postdosing period. Sodium 14C-pyrithione was absorbed slowly into and across the nail following topical application, with the nails serving as reservoirs for the drug. Further evidence of the slow movement of sodium pyrithione across the nail was provided by peak plasma 14C equivalents obtained on day 9, 1 day after the last dose had been removed from the nails. Only slight drug concentrations were measurable in plasma, with no radioactivity observed beyond day 12. The urinary excretion data exhibited a delay in peak urinary excretion (days 8 and 9), and an elimination half-life of 2 days, so that approximately 90% of the absorbed drug was eliminated within 1 week following treatment. Including a minor excretion pathway through the feces, total excretion as a percent of dosage was 8.5%, indicating that less than 10% of the applied topical dose of sodium pyrithione was absorbed systemically.(ABSTRACT TRUNCATED AT 250 WORDS)