3‐year follow‐up of 100 consecutive coronary bifurcation lesions treated with Taxus stents and the crush technique

Objectives : To determine the 3 year safety and efficacy of crush‐stenting with paclitaxel‐eluting stents. Background : The optimum two‐stent strategy for treatment of coronary bifurcation lesions is undetermined. Crush‐stenting is advocated to minimize restenosis through complete circumferential stent coverage; long‐term follow‐up data are lacking. Methods and Results : In a single center prospective registry, 100 consecutive patients with bifurcation lesions were treated with the Crush technique. The vast majority (93%) were true bifurcations, predominantly involving the left anterior descending and diagonal arteries. Technical success was 98%. Final kissing balloon dilatation, which became standard practice during the study, was attempted in 68 patients and successful in 51. Abciximab was used in all cases. There were no peri‐procedural stent thromboses. Follow‐up was 100% at 3 years. Symptom‐driven target lesion revascularisation was 8% at 3 years. Cumulative 3‐year major adverse cardiac events was 28% (7 cardiac deaths, 15 myocardial infarctions, 11 target vessel revascularisations). Absence of a final kissing inflation predicted repeat revascularisation but not death, infarction or stent thrombosis. Three probable stent thromboses occurred, of which two were very late. Conclusion : Where a two‐stent bifurcation strategy is required, Crush‐stenting with paclitaxel‐eluting stents is safe and effective in the long‐term. Failure to perform a final kissing dilatation increases the likelihood of revascularisation but not other adverse events. © 2009 Wiley‐Liss, Inc.     

Vasculature of various locations of canine gastrointestinal tract responds differently to intravenous isoproterenol

In this study we investigated the relative vascular response of different locations of the gastrointestinal tract to continuous intravenous infusion of isoproterenol (0.1 microgram kg-1 min-1 for 10 min). The vascular response of some nonsplanchnic organs was also examined. Blood flow of the arteries was measured by electromagnetic flowmetry and that of the tissues by 15-micron microspheres. Isoproterenol increased (P less than 0.05) blood flow of the axillary artery (+52%), and the superior mesenteric artery (+45%), but not that of the inferior mesenteric artery. In the nongastrointestinal tissues, isoproterenol increased (P less than 0.05) the blood flow of the left (+46%), and right ventricle (+85%), and the skeletal muscle (+100%). In the gastrointestinal tract, isoproterenol increased (P less than 0.05) blood flow in the esophagogastric junction (+505%) and antrum (+1511%) only, but not in the gastric body or in any location of the small or large intestine. The drug also caused a large fall in resistance in the esophagogastric junction (-74%) and antrum (-94%), and a small, but significant fall in the duodenum, jejunum, and in the mid-small intestine. It had no significant effect on vascular resistance in the gastric body, ileum, or colon. In those locations of the gastrointestinal tract where isoproterenol caused an increase in blood flow, this effect was confined to the combined mucosal plus submucosal layer, and the drug had no effect on the muscularis. These data suggest that different locations of the gastrointestinal tract respond differently to the same circulating concentration of isoproterenol. The mechanism of this difference in response merits further investigation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Management of recurrent ventricular tachyarrhythmias associated with Q-T prolongation

Eleven patients with acquired prolongation of the Q-Tc interval and recurrent ventricular tachyarrhythmias were studied. Five patients required 5 to 44 direct current shocks to correct prolonged ventricular tachyarrhythmias, and five were given at least two antiarrhythmic agents in an attempt to control the arrhythmias. In 4 of the 11 patients, when thioridazine, diuretic drugs and antiarrhythmic agents were withdrawn and hypokalemia or hypocalcemia corrected, ventricular tachyarrhythmias did not recur. The Q-Tc interval normalized in 2 to 3 days. Ventricular tachyarrhythmias were recurrent in the remaining seven patients, despite withdrawal of the drugs that caused the Q-Tc prolongation, attempted correction of hypokalemia when present and the administration of antiarrhythmic agents to four of the seven. All antiarrhythmic agents were then withdrawn in this group.

Immediately on the establishment of overdrive ventricular or atrioventricular sequential pacing in these patients, ventricular tachyarrhythmias were abolished. No breakthrough ventricular tachyarrhythmias occurred during temporary pacing. Temporary pacing was required for an average of 10 days and the Q-Tc interval normalized an average of 5 days from the onset of pacing. Three patients required a permanent pacemaker, one because of chronic complete heart block, one because of the sick sinus syndrome, and one because of frequent ventricular ectopic complexes complicating ischemic heart disease. All 11 patients survived their period of hospitalization.     

Canine electrophysiology of encainide, a new antiarrhythmic drug

Encainide, a new benzanillide derivative with high potency and a good therapeutic/toxic ratio, was evaluated with the use of standard His bundle recording techniques to determine its effects on the cardiac conduction system in closed chest animals. Twenty mongrel dogs weighing 18 to 29 kg were anesthetized with 4 percent chloralose and classified into groups: group 1, a control group and groups 2,3, and 4, which were given 0.3, 0.9 and 2.7 mg/kg body weight, respectively, of encalnide In an intravenous infusion over a 15 minute period. Plasma concentration, blood pressure, surface electrocardiogram and atrlal and His bundle electrograms were recorded before, during and after drug infusion for a total of 120 minutes. Heart rate, A-H and H-V intervals, the QRS complex and Q-Tc interval were measured every 5 minutes during sinus rhythm and with constant atrial pacing. In addition, sinus nodal recovery time and atrial, atrioventrlcular (A-V) nodal and left ventricular refractory periods were measured before and immediately after infusion and every 30 minutes for 2 hours. Peak plasma concentration averaged 450 ng/ml in group 2,1,300 ng/ml in group 3 and 4,000 ng/ml in group 4. Blood pressure was not altered at any dose level throughout the study. The QRS complex and H-V interval were significantly prolonged (P < 0.005) at doses of 0.9 mg/kg and greater. These effects correlated well with plasma concentration. There was no significant change in heart rate, corrected sinus nodal recovery time, A-H interval, Q-Tc Interval atrial, A-V nodal or left ventricular refractory period. It is concluded that, unlike other antiarrhythmic agents, encainide prolongs His-Purkinje system conduction without significantly affecting conduction or refractoriness of other parts of the cardiac conduction system in animals.     

Sleep disordered breathing – a new component of syndrome x?

Sleep disordered breathing (SDB) is a complication of obesity estimated to occur in about 4–6% of overweight individuals. These respiratory disturbances during sleep incorporate a number of conditions including snoring, upper airway resistance syndrome and obstructive sleep apnoea syndrome (OSAS). It is thought that as well as having deleterious effects on sleep quality these conditions may also promote cardiovascular and hormonal changes leading to an elevated blood pressure and an increased incidence of cardiovascular morbidity. Evidence reviewed here points to an alteration in sympathovagal balance, baroreceptor sensitivity, insulin resistance and leptin, growth hormone and lipid levels. Whether these changes are a consequence of the associated obesity or the SDB itself remains to be proven.     

Targeting Nitric Oxide With Drug Therapy

Increasing knowledge of the role of nitric oxide (NO) in physiology and disease has stimulated efforts to target the NO pathway pharmacologically. These therapeutic strategies include NO donors that directly or indirectly release NO and agents that increase NO bioactivity. Traditional organic nitrates such as nitroglycerin, which indirectly release NO, were believed to have limited long-term efficacy and tolerability, chiefly because of nitrate tolerance. Recent studies, however, suggest more effective ways of using these agents and new applications for them. Nicorandil, a hybrid organic nitrate that also activates potassium channels, has demonstrated significant benefits in acute coronary syndromes. Other nitrates are being investigated for use in neurodegenerative diseases. Direct NO donors include NO gas, which is useful in respiratory disorders, and the more recent classes of diazeniumdiolates, sydnonimines, and S-nitrosothiols. Preliminary data suggest that these agents may be effective as anti-atherosclerotic agents as well as in other disease states. In addition, hybrid agents that consist of an NO donor coupled with a parent anti-inflammatory drug, including nonsteroidal anti-inflammatory drugs, have demonstrated enhanced efficacy and tolerability compared with the anti-inflammatory parent drug alone in diverse experimental models. Established drugs that enhance NO bioactivity include antihypertensive agents, particularly angiotensin-converting enzyme inhibitors, calcium channel blockers, and newer vasodilating β-blockers. In addition, 3-methylglutaryl coenzyme A reductase inhibitors (statins) promote NO bioactivity, both through and independent of lipid lowering. The NO-promoting actions of these established drugs provide some insight into their known benefits and suggest possible therapeutic potential.