Context Metabolife 356, a multicomponent dietary supplement containing ephedra and caffeine (DSEC) in addition to several other components, is the top-selling dietary weight loss supplement. Given its common use, anecdotal reports of cardiovascular and cerebrovascular adverse events, and paucity of safety data, further research with this DSEC was warranted. Objective To determine the impact of the DSEC on corrected QT (QTc) interval duration and systolic blood pressure (SBP). Design Randomized, double-blind, placebo-controlled, crossover study conducted from January to May 2003.

The efficacy of n-3 PUFAs in preventing recurrence of atrial fibrillation (AF) is controversial and their effects on inflammation and oxidative stress in this population are not known. This study examined the effects of high-dose marine omega-3 polyunsaturated fatty acids (n-3 PUFAs) added to conventional therapy on the recurrence of AF and on markers of inflammation and oxidative stress. Patients with paroxysmal or persistent AF were randomized to n-3 PUFAs (4g/d) (n=126) or placebo (n=64) in a 2:1 ratio in a prospective, double-blind, placebo-controlled, parallel group study. The primary outcome was time to recurrence of AF. Secondary outcomes were changes in biomarkers of inflammation (serum interleukin (IL)-6, IL-8, IL-10, tissue necrosis factor alpha (TNFα), monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor (VEGF)), N-terminal-pro-brain type natriuretic peptide (NTpBNP), and oxidative stress (urinary F2–isoprostanes (IsoPs)). Atrial fibrillation recurred in 74 (58.7%) patients randomized to n3-PUFAs and in 30 (46.9%) who received placebo; time to recurrence of AF did not differ significantly in the two groups (hazard ratio 1.20; 95% CI 0.76 - 1.90, adjusted P=0.438). Compared to placebo, n3-PUFAs did not result in clinically meaningful changes in concentrations of inflammatory markers, NTpBNP or F2-Isops. In conclusion, in patients with paroxysmal or persistent AF treatment with n3-PUFAs 4g/day did not reduce the recurrence of AF, nor was it associated with clinically important effects on concentrations of markers of inflammation and oxidative stress.

The involuntary respiratory muscle contractions that occur during breath holding were found in almost all of 52 subjects and were regular in a majority. In detailed studies, subjects rebreathed a mixture of 8% CO2 in O2 and then held their breath on an occluded mouthpiece, with glottis open, at functional residual capacity. Contractions monitored as waves of negative pressure were reproducible and increased in amplitude and frequency through the breath hold, but the breakpoint did not always correspond to the same pressure or frequency. Frequency and the time derivative of pressure (dP/dt) of contractions were much higher during breath holding than frequency of breathing and dP/dt of occluded breaths at the same gas tensions during rebreathing. Contractions were reduced in amplitude after the subject took three breaths without altering gas tensions. The results are consistent with the hypothesis that contractions contribute to dyspnea in breath breath holding, but there is not a simple correlation between their magnitude and the degree of dyspnea.

The regular involuntary inspiratory muscle contractions that occur in normal conscious men during breath holding were quantified by means of the waves of intrathoracic pressure that they produced. A stream of cool air circulated through the nose and mouth reproducibly inhibited the contractions. The degree of inhibition increased with increasing nasal flow in the range of normal resting respiratory flow and with lower temperature of circulating gas. The effect depended on the phase of respiration in which flow occurred and was abolished by local anesthesia of the nose and pharynx. The results demonstrate that the upper airway contains flow-sensitive receptors, the discharge of which can have a marked influence on respiration.

Levosimendan is a novel calcium sensitizing agent in development for the treatment of acute and chronic heart failure. The agent increases myocardial force without increasing myocyte calcium concentrations, thus reducing the possibility for myocardial necrosis. In addition, the agent also causes vasodilation of coronary and peripheral vessels to improve coronary blood flow and reduce afterload. The short half-life is a benefit for intravenous administration but could be problematic for the drug's use in chronic heart failure. The risk of the development of arrhythmias from levosimendan appears small secondary to an increase in the QTc interval of 15 msec but needs to be evaluated in light of the ability of levosimendan to open adenosine triphosphate (ATP)-sensitive potassium channels. In addition, the agent has not been studied in patients with additional risks for torsades de pointes. Levosimendan has been shown to have beneficial survival effects in several populations; its use improves patient outcomes relative to the standard of care and has the potential to reduce hospital costs associated with heart failure.