The effects of photosensitizers and ultraviolet irradiation on the biosynthesis and metabolism of prostaglandins

Prostaglandin biosynthesis from arachidonic acid by skin microsomal fraction preparation was enhanced by UV～irradiation at wavelengths of 254 and 360 nm. In the presence of S-methoxy psoralen (8 MOP) and coal tar, prostaglandin biosynthesis was further enhanced approximately 2-fold by UV-irradiation at 254 nm. Stimulation was less by UV-irradiation at 360 nm. 8-MOP enhanced the conversion of PGE, into PGF_2α by PGE₂-9-ketoreductase prepared from skin high speed supernatant fractions. UV-irradiation at 254 nm and 360 nm with or without the photosensitizers had no effect on the activity of the PGE₂-9-ketoreductase. These data therefore indicate that the action of UV-irradiation, 8-methoxy psoralen and coal tar on the skin may in part be due to their regulation of the biosynthesis and metabohsm of prosta-glandins in this tissue.     

Mitral Valve Prolapse and Pre-Excitation

Two out of 118 patients with mitral valve prolapse were found to have pre-excitaiton. The presence of mitral valve prolapse in one patient with Lown-Ganong-Levine syndrome and the persistence of prolapse in (he presence and absence of pre-excitation in another patient with intermittent type B Wolff-Parkinson-White syndrome suggest that mitral valve prolapse in pre-excitation syndrome may not be secondary to the abnormal activation pattern of the left ventricle, which has been suggested as a possible mechanism by some investigators. (PACE, Vol. 5, September-October, 1982)     

Perioperative Management of Anticoagulation during Device Implantation—The UK Perspective

Background: Increasing numbers of patients taking oral anticoagulation are presenting for device implantation. Cessation of anticoagulation in the perioperative period may expose patients to increased risk of thromboembolic events, while continuing anticoagulation may increase the risk of bleeding. There are few guidelines or randomized controlled trials to guide perioperative management. Methods: We carried out a questionnaire‐based study of all cardiologists implanting devices in the United Kingdom to establish if there was consensus on management of anticoagulation in patients undergoing pacemaker implantation. Results: There is significant variation in management of these patients. Eighty‐nine percent of doctors stop oral anticoagulation a mean 3.7 days prior to pacemaker implantation in patients with a mechanical mitral valve, with 94% using heparin to provide preoperative anticoagulation: 58% unfractionated heparin, 40% low molecular weight heparin. The maximum accepted international normalized ratio for implantation ranged from 1.4 to 3 (median 1.8). Postoperatively, 86% restart heparin after a mean 8.5 hours. Only 11% continue oral anticoagulation throughout the implantation period. There is a hierarchy of perceived embolic risk with doctors using progressively less anticoagulation in patients with prosthetic aortic valve, high‐risk, and low‐risk atrial fibrillation. In contrast, only 7% of implanters stop theinopyridines prior to device implantation in patients with a 2‐month‐old drug eluting stent. Conclusion: Perioperative anticoagulation management of patients undergoing device procedures is currently performed with little consensus. This emphasizes the need for careful national and international audit of periprocedural anticoagulation management and its associated complications with a view to developing international consensus guidelines. (PACE 2010; 389–393)     

Clinical Experience with Thera DR Rate-Drop Response Pacing Algorithm in Carotid Sinus Syndrome and Vasovagal Syncope

This study examined the effectiveness of cardiac pacing using the Thera DR rate-drop response algorithm for prevention of recurrent symptoms in patients with carotid sinus syndrome (CSS) or vasovagal syncope. The algorithm comprises both diagnostic and treatment elements. The diagnostic element consists of a programmable "window" used to identify heart rate changes compatible with an evolving neurally mediated syncopal episode. The treatment arm consists of pacing at a selectable rate and for a programmable duration. Forty-three patients (mean age 53 ± 20.4 years) with CSS alone (n = 8), CSS in conjunction with vasovagal syncope (n = 4), or vasovagal syncope alone (n = 31) were included. Thirty-nine had recurrent syncope, while the remaining four reported multiple presyncopal events. Prior to pacing, 40 ± 152 syncopal episodes (range from 1 to approximately 1,000 syncopal events) over the preceding 56 ± 84.5 months. Postpacing follow-up duration was 204 ± 172 days. Three patients have been lost to follow-up and in one patient the algorithm was disabled. Among the remaining 39 individuals, 31 (80%) indicated absence or diminished frequency of symptoms, or less severe symptoms. Twenty-three patients (23/29, or 59%) were asymptomatic with respect to syncope or presyncope. Sixteen patients had symptom recurrences. Of these, seven experienced syncope (7/39, or 18%) and 9 (29%) had presyncope: the majority of patients with recurrences (6/7 syncope and 7/9 presyncope) were individuals with a history of vasovagal syncope. Consequently, although symptoms were observed during postpacing follow-up, they appeared to be of reduced frequency and severity. Thus, our findings suggest that a transient period of high rate pacing triggered by the Thera DR rate-drop response algorithm was beneficial in a large proportion of highly symptomatic patients with CSS or vasovagal syncope.     

Physiological Benefits of a Pacemaker with Dual Chamber Pacing at Low Heart Rates and Single Chamber Rate Responsive Pacing During Exercise

Dual chamber rate responsive pacing may be an ideal mode but may result in high current drain and premature battery depletion. To minimize battery drain during exercise, this study compared a combination pacing mode of IDDD and ventricular rate responsive pacing (WIR). Nine patients were studied who had complete heart block, sinus rhythm, DDD pacemakers, and a reduced mean left ventricular ejection fraction of 44%. Patients were exercised in DDD, WIR, and a combination of DDD at low heart rates and WIR at mean heart rates over 89 bpm. Blood pressure, heart rate, exercise duration, work rate, oxygen uptake, anaerobic threshold, and oxygen pulse were measured. There was no difference in symptoms or in mean cardiopulmonary function indices including exercise duration 10.7. 10.3. 10.3 minutes; heart rate 127. 133. 136 bpm; oxygen uptake 1.4. 1.5. 1.5 L/minute; or anaerobic threshold 5.6, 5.5, 5.7 minutes (p > 0.05) in any mode. A pacemaker that provides atrioventricular synchrony at low heart rates with ventricular rate responsiveness at high heart rates may be an alternative mode for some patients.     

Comparison of Intrinsic Versus Paced Ventricular Function

There is increasing evidence supporting the benefits of providing optimum AV delay in cardiac pacing, though controversy exists regarding its value and the benefits of intrinsic versus paced ventricular activation. This study compared various AV delays at rest in patients whose native AV delays were 200 msec. Only patients with DDD pacemakers who had intact AV conduction and normal ventricular activation were included in the study. Nine patients were studied. Methods: Ten studies were performed. Evaluation was done in AAI and DDD modes at paced heart rates of 60/min or as close as possible to the intrinsic heart rate if this was > 60/min. Stroke volume (SV) and cardiac output (COJ were measured. Results: When AV sequential pacing in the DDD mode with an optimum AV delay was compared to AAI pacing with a prolonged AV interval, the average optimum AV delay in the DDD mode was 157 msec and ranged from 125 to 175 msec. The average AV interval in the AAI mode was 245 msec and ranged from 212 to 300 msec. In the DDD mode, there was an overall significant improvement in CO of 11% and SV of 9%. Patients with intrinsic AV conduction times of > 220 msec showed an overall significant improvement in CO of 13% and SV of 11%. In patients with intrinsic AV conduction times of < 220 msec, an improvement in CO of 6% and SV of 4% was seen. Conclusions: (1) An optimum AV delay is an important component of hemodynamic performance; and (2) AV sequential pacing at rest with an optimum AV delay may provide better hemodynamic performance than atrial pacing with intrinsic ventricular conduction when native AV conduction is prolonged > 220 msec.