Safety Factor for Precordial Pacing: Minimum Current Thresholds for Pacing and for Ventricular Fibrillation by Vulnerable-period Stimulation

Temporary cardiac pacing by means of rapidly applied, precordial electrodes can be of great value in selected patients suffering cardiac arrest or profound bradycardia, post-defibrillation atrioventricular block, or digitalis intoxication. This study provides data pertaining to the safety of precordial pacing measured as the ratio of the minimum current required to induce ventricular fibrillation (VF) to the minimum current required to pace the ventricular myocardium. Single rectangular pulse stimuli having durations of 1–50 ms were evaluated. In 6 anesthetized dogs, a cutaneous electrode was centered over the shaved apex beat area of the left chest and paired with a larger electrode sutured to the right chest wall. Using a specially fabricated, synchronized, high-energy pulse generator, the "most vulnerable" time in the cardiac cycle at which the least current was required to induce VF with a single shock was identified. This current was compared to the much lower current required to pace the heart in the diastolic interval. While the current required to produce either fibrillation or pacing decreased as pulse duration increased, the safety factor (i.e., the ratio of fibrillation current to pacing current) remained nearly constant, averaging 12.6 for all pulse durations examined. That is, on the average, a stimulus of any given duration between 1 and 50 ms required at least 12 times the current required for pacing to produce ventricular fibrillation. We conclude that in normal canine hearts, the risk of inducing VF during precordial pacing is small.     

Efficacy and safety of intracavernosal alprostadil alfadex in the treatment of erectile dysfunction

Background Prostaglandin E₁ (PGE₁) is well established as an effective treatment for erectile dysfunction with at least 70% and up to 100% of patients achieving erections adequate for sexual intercourse.
Methods This multicentre, open-label, non-controlled study of intracavernosal alprostadil alfadex (up to 20 μg) was conducted in the UK in 123 male patients with erectile dysfunction for at least 6 months. Following a screening and in-office titration period (period 1) patients entered a 6–10-week self-injection home-treatment phase (period 2) followed by a 34–38-week follow-up period (period 3). A patient was considered to be a `responder' if he had erections adequate for sexual intercourse with at least 75% of injections. Secondary measures of efficacy included clinical assessment of erection using a five-grade scale and Buckling Test.
Results A total of 106 patients entered the titration period. In period 2, 72% of patients were responders and 77% of injections resulted in an erection adequate for sexual intercourse. According to the five-grade scale, 73% of patients gained an optimal response and 48–79% of patients were found to have a positive Buckling Test, both during period 1. During follow up (period 3), 83% of patients were responders. There were a total of 403 penile pain events related to the study drug procedure; almost all were rated as mild (49%) or moderate (49%). Only two patients discontinued treatment owing to pain. Couples reported that the treatment was easy to use, with 81% of patients rating the treatment as good to excellent.
Conclusions Alprostadil alfadex is effective, well tolerated and easy to use.     

EFFECT OF DILTIAZEM AND DANTROLENE ON THE CONTRACTILITY OF ISOLATED MALIGNANT HYPERPYREXIA-SUSCEPTIBLE PORCINE SKELETAL MUSCLE

Diltiazem inhibited and antagonized the abnormal contracturesinduced by halothane, caffeine and potassium chloride in isolatedskeletal muscle from pigs susceptible to malignant hyperpyrexia(MHS). Contractile responses to caffeine and electrical stimulationalso were suppressed by diltiazem in control tissue. Similareffects were obtained in the presence of dantrolene. In bothMHS and control preparations, diltiazem antagonized caffeine-inducedcontractures in the presence of maximal effective concentrationsof dantrolene, and the converse was true also. In MHS and controlpreparations detubulated by glycerol, diltiazem did not inhibitor antagonize caffeine-induced contractures while dantrolenedid. Diltiazem seems to modify contractile responses at thelevel of the transverse tubule membrane by inhibiting the inwardflow of extracellular Ca²⁺, while dantrolene inhibits Ca²⁺ releasedirectly from the sarcoplasmic reticulum. Ca²⁺ influx throughtransverse tubules may be important in the aetiology of theMH syndrome.