Inhaled iloprost reverses vascular remodeling in chronic experimental pulmonary hypertension

RATIONALE: Inhaled iloprost is an effective therapy for pulmonary arterial hypertension (PAH). However, no study to date has addressed the effects of inhaled iloprost on changes to pulmonary vascular structure that occur in PAH. OBJECTIVES: The present study was designed to investigate chronic antiremodeling effects of inhaled iloprost in monocrotaline (MCT)-induced PAH in rats. Methods: Four weeks after a single injection of MCT, after full establishment of PAH, rats were nebulized with iloprost at a dose of 6 microg . kg(-1) . day(-1), or underwent sham nebulization with saline. RESULTS: After 2 weeks of inhalation therapy, right ventricular pressure and pulmonary vascular resistance were reversed in rats treated with iloprost, but not in sham-treated control animals. Systemic arterial pressure was unaffected. In addition, right heart hypertrophy, the degree of pulmonary artery muscularization, and the medial wall thickness of intraacinar pulmonary arteries regressed in response to iloprost. Furthermore, the MCT-induced increase in matrix metalloproteinase-2 and -9 activities and tenascin-C expression was suppressed. CONCLUSIONS: We conclude that the inhalation of iloprost reverses PAH and vascular structural remodeling in MCT-treated rats. This regimen suggests the possibility of an antiremodeling therapy in PAH.     

Assessing coronary stenosis. Quantitative coronary angiography versus visual estimation from cine-film or pharmacological stress perfusion images

Visual judgment of stenosis severity from cine-film or single-photonemission computed tomographic dipyrida-mole perfusion imageswas compared to assessment of stenosis severity as measuredwith digital quantitative coronary angiography. Thirty patientswith angiographically verified single-vessel disease underwentdipyridamole thallium stress testing within 90 days of angiography. RESULTS: A percent diameter stenosis of 50%, a percent area stenosisof 75% and a stenotic flow reserve of <3·75 measuredby quantitative coronary angiography (CMS, version 1·1,Medis Inc.) corresponded to haemodynamically significant stenosisas evaluated by visual estimates from cine-film or perfusionimages. Quantitative coronary angiography percent diameter stenosis(51·2% ± 12·6%) correlated closely (r=0·74)but underestimated significantly visual assessment of stenosisseverity from cine-film (69·3% ±21·2% p=0·0001).However, quantitative coronary angiography percent area stenosis(74·7% ± 11·7%) more closely reflectedvisual estimates from cine-film (P=0·19). Quantitativecoronary angiography stenotic flow reserve showed the highestpositive and negative predictive value regarding visual estimatesfrom cine-film (88%, 86%) or perfusion images (88% 64%) followedby percent diameter stenosis (86% 75% 86% 56%) and percent areastenosis (87% 80% 87% 60%), respectively. CONCLUSION: Evaluation of coronary lesions by quantitative coronary angiographycorresponds closely with visual estimates from cine-film andhaemodynamic significance as evaluated by dipyridamole perfusionimages. (Eur Heart J 1996; 17: 1167–1174)     

Antigen expression determines adenoviral vaccine potency independent of IFN and STING signaling

Recombinant adenoviral vectors (rAds) are lead vaccine candidates for protection against a variety of pathogens, including Ebola, HIV, tuberculosis, and malaria, due to their ability to potently induce T cell immunity in humans. However, the ability to induce protective cellular immunity varies among rAds. Here, we assessed the mechanisms that control the potency of CD8 T cell responses in murine models following vaccination with human-, chimpanzee-, and simian-derived rAds encoding SIV-Gag antigen (Ag). After rAd vaccination, we quantified Ag expression and performed expression profiling of innate immune response genes in the draining lymph node. Human-derived rAd5 and chimpanzee-derived chAd3 were the most potent rAds and induced high and persistent Ag expression with low innate gene activation, while less potent rAds induced less Ag expression and robustly induced innate immunity genes that were primarily associated with IFN signaling. Abrogation of type I IFN or stimulator of IFN genes (STING) signaling increased Ag expression and accelerated CD8 T cell response kinetics but did not alter memory responses or protection. These findings reveal that the magnitude of rAd-induced memory CD8 T cell immune responses correlates with Ag expression but is independent of IFN and STING and provide criteria for optimizing protective CD8 T cell immunity with rAd vaccines.