Higher prevalence of obstructive airway disease in patients with thoracic or abdominal aortic aneurysm

AbstractBackground and Aim: The risk factors of aortic aneurysm (AA) are comparable with those described for chronic obstructive pulmonary disease. This study was performed to determine whether patients with AA have a higher than average prevalence of obstructive airway disease. Methods: We performed pulmonary function tests in 240 consecutive patients (182 men and 58 women; age, 70 ± 10 years) with thoracic or abdominal AA. The results were compared with those in individuals without obvious cardiovascular disease (control) and in patients with coronary artery disease who were matched for age, gender, smoking status, and other atherosclerotic risk factors. Results: Patients in the AA group had a lower forced expiratory volume in 1 second/forced vital capacity (%) and carbon monoxide diffusing capacity (%/predicted value) than did the control group (P < .01). The proportion of patients with airway obstruction, defined as forced expiratory volume in 1 second/forced vital capacity of 70% or less, was higher in the AA group (100/240; 42%) than in the control (51/223; 23%) and coronary artery disease (43/238; 18%) groups. Multiple logistic regression analysis results revealed that the presence of an AA and male gender were associated with a higher risk of airway obstruction (odds ratio, 2.928; 95% CI, 1.722 to 4.979; and odds ratio, 1.622; 95% CI, 1.055 to 2.493, respectively). Conclusion: These data suggest that AA may be a risk factor indicative of the presence of chronic obstructive pulmonary disease. A higher prevalence of depressed pulmonary function should be suspected as a preoperative risk in presence of thoracic or abdominal AA as compared with other types of cardiovascular disorders. (J Vasc Surg 2002;36:35-40.

肺高血圧症に対するトロンボキサン合成阻害作用をもった新規長期作用型プロスタサイクリンアゴニストの経口投与

BACKGROUND: Continuous administration of prostacyclin has improved the survival of patients with pulmonary arterial hypertension (PAH). However, this treatment has some problems, including its short duration of activity and difficult delivery. Therefore, we developed ONO-1301, an orally active, long-acting prostacyclin agonist with thromboxane synthase inhibitory activity. METHODS AND RESULTS: We investigated whether oral administration of ONO-1301 can both prevent and reverse monocrotaline (MCT)-induced PAH in rats. Rats were randomly assigned to receive repeated oral administration of ONO-1301 twice daily beginning either 1 or 8 days after subcutaneous injection of MCT. A control group received oral saline, and a sham group received a subcutaneous injection of saline instead of MCT. MCT-treated controls developed significant pulmonary hypertension. Treatment with ONO-1301 from day 1 or 8 significantly attenuated the increases in right ventricular systolic pressure and the increase in medial wall thickness of pulmonary arterioles. Kaplan-Meier survival curves demonstrated that the effect of ONO-1301 was equivalent to that of an endothelin receptor antagonist and a phosphodiesterase-5 inhibitor. A single oral dose of ONO-1301 increased plasma cAMP levels for up to 6h. Treatment with ONO-1301 significantly decreased urinary 11-dehydro-thromboxane B2 and increased the plasma hepatocyte growth factor concentration. CONCLUSIONS: Oral administration of ONO-1301 ameliorated PAH in rats, an effect that may occur through cAMP and hepatocyte growth factor.博士（医学）・乙1326号・平成26年3月17日日本循環器学会の許諾を得て登録（2014年6月6日付）ジャーナル公式サイト（日本循環器学会HP内）：https://www.j-circ.or.jp/journal/公開サイト（J-STAGE）：https://www.jstage.jst.go.jp/browse/circj

Sympathetic stimulation produces a greater increase in both transmural and spatial dispersion of repolarization in LQT1 than LQT2 forms of congenital long QT syndrome

AbstractOBJECTIVESThe study compared the influence of sympathetic stimulation on transmural and spatial dispersion of repolarization between LQT1 and LQT2 forms of congenital long QT syndrome (LQTS).BACKGROUNDCardiac events are more associated with sympathetic stimulation in LQT1 than in LQT2 or LQT3 syndrome. Experimental studies have suggested that the interval between Tpeak and Tend (Tp-e) in the electrocardiogram (ECG) reflects transmural dispersion of repolarization across the ventricular wall.METHODSWe recorded 87-lead body-surface ECGs before and after epinephrine infusion (0.1 μg/kg/min) in 13 LQT1, 6 LQT2, and 7 control patients. The Q-Tend (QT-e), Q-Tpeak (QT-p), and Tp-e were measured automatically from 87-lead ECGs, corrected by Bazett’s method (QTc-e, QTc-p, Tcp-e), and averaged among all 87-leads and among 24-leads, which reflect the potential from the left ventricular free wall. As an index of spatial dispersion of repolarization, the dispersion of QTc-e (QTc-eD) and QTc-p (QTc-pD) were obtained among 87-leads and among 24-leads, and were defined as the interval between the maximum and the minimum of the QTc-e and the QTc-p, respectively.RESULTSEpinephrine significantly increased the mean QTc-e but not the mean QTc-p, resulting in a significant increase in the mean Tcp-e in both LQT1 and LQT2, but not in control patients. The epinephrine-induced increases in the mean QTc-e and Tcp-e were larger in LQT1 than in LQT2, and were more pronounced when the averaged data were obtained from 24-leads than from 87-leads. Epinephrine increased the maximum QTc-e but not the minimum QTc-e, producing a significant increase in the QTc-eD in both LQT1 and LQT2 patients, but not in control patients. The increase in the QTc-eD was larger in LQT1 than in LQT2 patients.CONCLUSIONSOur data suggest that sympathetic stimulation produces a greater increase in both transmural and spatial dispersion of repolarization in LQT1 than in LQT2 syndrome, and this may explain why LQT1 patients are more sensitive to sympathetic stimulation

Differential effects of beta-blockade on dispersion of repolarization in the absence and presence of sympathetic stimulation between the lqt1 and lqt2 forms of congenital long qt syndrome

AbstractObjectivesThis study compared the effects of beta-blockade on transmural and spatial dispersion of repolarization (TDR and SDR, respectively) between the LQT1 and LQT2 forms of congenital long QT syndrome (LQTS).BackgroundThe LQT1 form is more sensitive to sympathetic stimulation and more responsive to beta-blockers than either the LQT2 or LQT3 forms.MethodsEighty-seven-lead, body-surface electrocardiograms (ECGs) were recorded before and after epinephrine infusion (0.1 μg/kg body weight per min) in the absence and presence of oral propranolol (0.5–2.0 mg/kg per day) in 11 LQT1 patients and 11 LQT2 patients. The Q-Tendinterval, the Q-Tpeakinterval and the interval between Tpeakand Tend(Tp-e), representing TDR, were measured and averaged from 87-lead ECGs and corrected by Bazett’s method (corrected Q-Tendinterval [cQTe], corrected Q-Tpeakinterval [cQTp] and corrected interval between Tpeakand Tend[cTp-e]). The dispersion of cQTe(cQTe-D) was obtained among 87 leads and was defined as the interval between the maximum and minimum values of cQTe.ResultsPropranolol in the absence of epinephrine significantly prolonged the mean cQTpvalue but not the mean cQTevalue, thus decreasing the mean cTp-evalue in both LQT1 and LQT2 patients; the differences with propranolol were significantly larger in LQT1 than in LQT2 (p < 0.05). The maximum cQTe, minimum cQTeand cQTe-D were not changed with propranolol. Propranolol completely suppressed the influence of epinephrine in prolonging the mean cQTe, maximum cQTeand minimum cQTevalues, as well as increasing the mean cTp-eand cQTe-D values in both groups.ConclusionsBeta-blockade under normal sympathetic tone produces a greater decrease in TDR in the LQT1 form than in the LQT2 form, explaining the superior effectiveness of beta-blockers in LQT1 versus LQT2. Beta-blockers also suppress the influence of sympathetic stimulation in increasing TDR and SDR equally in LQT1 and LQT2 syndrome

Epinephrine unmasks latent mutation carriers with LQT1 form of congenital long-QT syndrome

n/

Ghrelin Treatment of Cachectic Patients with Chronic Obstructive Pulmonary Disease: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

BACKGROUND: Pulmonary cachexia is common in advanced chronic obstructive pulmonary disease (COPD), culminating in exercise intolerance and a poor prognosis. Ghrelin is a novel growth hormone (GH)-releasing peptide with GH-independent effects. The efficacy and safety of adding ghrelin to pulmonary rehabilitation (PR) in cachectic COPD patients were investigated. METHODOLOGY/PRINCIPAL FINDINGS: In a multicenter, randomized, double-blind, placebo-controlled trial, 33 cachectic COPD patients were randomly assigned PR with intravenous ghrelin (2 µg/kg) or placebo twice daily for 3 weeks in hospital. The primary outcomes were changes in 6-min walk distance (6-MWD) and the St. George Respiratory Questionnaire (SGRQ) score. Secondary outcomes included changes in the Medical Research Council (MRC) scale, and respiratory muscle strength. At pre-treatment, serum GH levels were increased from baseline levels by a single dose of ghrelin (mean change, +46.5 ng/ml; between-group p<0.0001), the effect of which continued during the 3-week treatment. In the ghrelin group, the mean change from pre-treatment in 6-MWD was improved at Week 3 (+40 m, within-group p = 0.033) and was maintained at Week 7 (+47 m, within-group p = 0.017), although the difference between ghrelin and placebo was not significant. At Week 7, the mean changes in SGRQ symptoms (between-group p = 0.026), in MRC (between-group p = 0.030), and in maximal expiratory pressure (MEP; between-group p = 0.015) were better in the ghrelin group than in the placebo group. Additionally, repeated-measures analysis of variance (ANOVA) indicated significant time course effects of ghrelin versus placebo in SGRQ symptoms (p = 0.049) and MEP (p = 0.021). Ghrelin treatment was well tolerated. CONCLUSIONS/SIGNIFICANCE: In cachectic COPD patients, with the safety profile, ghrelin administration provided improvements in symptoms and respiratory strength, despite the lack of a significant between-group difference in 6-MWD. TRIAL REGISTRATION: UMIN Clinical Trial Registry C000000061