Eisenmenger's syndrome (ES) is the most advanced form of pulmonary arterial hypertension related to congenital heart disease. Evolution of pulmonary vascular disease differs markedly between patients with atrial septal defects (ASD) versus ventricular septal defects (VSD), potentially affecting response to treatment. We compared the effects of bosentan and placebo in patients with isolated ASD (ASD subgroup) versus patients with isolated VSD or both defects (VSD subgroup).
Post-hoc analysis of a 16-week, multicenter, randomized, double-blind, placebo-controlled trial was performed. Fifty-four patients (13: ASDs, 36: VSDs, 5: VSD+ASD) were randomized to bosentan 62.5 mg bid for four weeks (uptitrated to 125 mg bid thereafter) or placebo. Main outcome measures were: indexed pulmonary vascular resistance (PVRi), exercise capacity, mean pulmonary artery pressure (mPAP), pulmonary blood flow index (Qpi), and changes in oxygen saturation (SpO2).
Placebo-corrected median (95% CI) treatment effects on PVRi were -544.0 dyn·s·cm?5 (-1593.8, 344.7) and -436.4 dyn·s·cm?5 (-960.0, 167.0) in the ASD and VSD subgroups, respectively. Effects of bosentan on exercise capacity and mPAP were similar in both subgroups. No changes in SpO2 or Qpi were observed in either bosentan or placebo subgroups.
Improvements in exercise capacity and cardiopulmonary hemodynamics, without desaturation, were observed in ES patients with both ASDs and VSDs. Although not reaching statistical significance, improvements were similar to those in the BREATHE-5 analyses, suggesting that the location of septal defects is not a key determinant of treatment response. These data further support the use of bosentan for the treatment of ES, independent of shunt location.
The use of a vasodilator selective to the pulmonary circulation may be beneficial in cases with right-ventricle failure, as it will decrease right-heart afterload without concurrent systemic hypotension. Adenosine has recently been advocated as such a drug, although its clinical efficacy in this respect is still in question. We therefore devised an experimental protocol of right-heart infarct to test the efficacy of adenosine in alleviating symptoms of right-heart failure. Right-heart infarct was induced experimentally in 17 young pigs. After hemodynamics had stabilized, preload was optimized with a dextrose-based colloid solution. A continuous infusion of adenosine was then begun at doses of 25, 50, 75, and 100 microg/kg/min in a study group of 10 animals, while the remaining seven were monitored as controls. Hemodynamic parameters were followed throughout the study, with particular attention paid to pulmonary and systemic vascular resistance indices (PVRI and SVRI), right ventricle ejection fraction (REF), cardiac index (CI), and heart rate (HR). Cardiac index (CI) showed a tendency to increase during the adenosine infusion, as did REF and stroke index (SI), whereas PVRI and mean pulmonary pressure (MPAP) were decreased. There was a marked decrease in SVRI as a result of the adenosine, as there was in mean arterial pressure at the higher infusion rates. HR remained unchanged by the infusion. Discontinuation of the drug resulted in a rapid increase in MAP, SVRI, MPAP, HR, left ventricle stroke work index (LVSWI), and PVRI and in a modest decrease in CI. The continuous infusion of adenosine appears to cause an effective arterial vasodilation, with a consequent unloading of right-heart afterload. Its use may be beneficial in the treatment of increased pulmonary vascular resistance after right-heart failure.
Labelling cigarettes as "light" or "mild" is claimed to be one of the biggest marketing scams in Canadian history. Arguably, such labelling implies that these varieties of cigarettes are less harmful than "regular" cigarettes. In Canada, a food product can be labelled "light" if there is a 25% reduction from the "reference food" and if the constituent being reduced is clearly identified (e.g., light in fat). Cigarette labelling does not comply with these regulations, however. To examine whether or not some tobacco constituents meet the 25% reduction criterion, we compared yields of 41 toxic and/or carcinogenic smoke constituents in six varieties of "light" cigarettes to the yields of "regular" cigarettes. We selected cigarettes from the two most popular Canadian brands, Du Maurier and Players.
Using a set of data provided by Imperial Tobacco Canada and made available to the public by the Government of British Columbia, we compared yields measured under a laboratory protocol (modified ISO) that was designed to provide a more rigorous evaluation of the differences between varieties of cigarettes and a more accurate assessment of smokers' potential smoke intake than the traditional protocol (standard ISO).
For all six varieties of "light" cigarettes, the yields of nicotine were higher by an average of 5% (range: 1% to 13%). The 25% reduction criterion was not met for any variety of "light" cigarettes concerning yields of tar. For all cigarettes tested, yields of tar were reduced on average by only 16% (range: 5% to 22%). For carbon monoxide (CO), only Player's Smooth Light had an over 25% reduction (30%) compared with Player's Regular. Conversely, yield of CO was 24% higher for Du Maurier Lights compared with Du Maurier Regular. As for the other smoke constituents, the majority (75%) were not reduced by 25% or more in "light" cigarettes, and a sizeable proportion of yields (e.g., acrylonitrile, benzene, chromium, m+p cresol, mercury, nickel, toluene) were larger in these varieties of cigarettes. Only yields of formaldehyde, crotonaldehyde, 1-aminonaphtalene, and proprionaldehyde were systematically reduced in all varieties of "light" cigarettes.
The six varieties of "light" cigarettes examined in this study do not differ substantially from "regular" cigarettes in terms of smoke yields. We argue that the modified ISO protocol should be implemented for a more valid comparison of potential smoke yields in all varieties of cigarettes and that labelling based on this protocol should be promoted.
Comment In: Can J Public Health. 2005 May-Jun;96(3):165-6, 18815913076