Citations

Experiments were designed to determine how changes in the ratio of specific vascular endothelium-derived factors might affect reactivity of bronchial smooth muscle. The epithelium was mechanically removed from rings of third-order canine bronchi, and the rings were suspended in organ chambers for measurement of isometric force. Rings of pulmonary artery were cut; in some the endothelium was mechanically removed. The arterial rings were everted and pairs, with and without endothelium, were incubated with control solution, NG-monomethyl-L-arginine (L-NMMA), indomethacin, or both L-NMMA and indomethacin for 90 min. They were then inserted into the lumen of the bronchial rings. Cumulative concentration-response curves to acetylcholine and 5-hydroxytryptamine were obtained. There was no significant difference in response between bronchi containing arteries with or without endothelium incubated with control solution. Contractions of bronchi containing arteries without endothelium, incubated in either L-NMMA or indomethacin, increased from control. However, in rings containing arteries with endothelium, incubation with either inhibitor decreased bronchial contractions. Incubation with both inhibitors eliminated the difference. These results suggest that the vascular endothelium produces factors that can both contract and relax bronchial smooth muscle. With inhibition of production of either nitric oxide with L-NMMA or prostanoids with indomethacin, release of other endothelium-derived factors occurs that attenuates contractions of bronchial smooth muscle. Therefore, an imbalance in the ratio of production of endothelium-derived factors may contribute to bronchospastic disorders.

To characterize α2-adrenergic control of motor and sensory functions of gastrointestinal tract and colon, we studied dose-related effects of clonidine (placebo or up to 0.3 mg po) by random assignment in 55 healthy humans. Gastrointestinal transit was measured in all subjects; in 35, we assessed colonic compliance, tone, and sensations of gas and pain during phasic distensions. Clonidine did not significantly alter gastrointestinal or colonic transit, but it increased colonic compliance and reduced fasting tone without altering colonic response to a meal. Clonidine significantly reduced aggregate sensation to distensions overall and had significant linear dose-related sensory effects at 8- and 24-mmHg distensions. Effect on pain (including dose-response relationship) was due to 0.3-mg dose for distensions at 24 mmHg. We confirmed that clonidine relaxes fasting colonic tone and reduces sensation of pain. In this study, gut transit was not altered by clonidine, and novel dose-response characteristics and clonidine's effect on gas sensation are provided. Doses as low as 0.05 mg may be effective and potentially useful in reducing colonic tone and gas sensation.

Background There is no consensus on the most effective and best tolerated first‐line antiarrhythmic treatment for fetal tachyarrhythmia. The purpose of this systematic review and meta‐analysis was to compare the efficacy, safety, and fetal–maternal tolerance of first‐line monotherapies for fetal supraventricular tachycardia and atrial flutter. Methods and Results A comprehensive search of several databases was conducted through January 2017. Only studies that made a direct comparison between first‐line treatments of fetal tachyarrhythmia were included. Outcomes of interest were termination of fetal tachyarrhythmia, fetal demise, and maternal complications. Ten studies met inclusion criteria, with 537 patients. Overall, 291 patients were treated with digoxin, 137 with flecainide, 102 with sotalol, and 7 with amiodarone. Digoxin achieved a lower rate of supraventricular tachycardia termination compared with flecainide (odds ratio [ OR ]: 0.773; 95% confidence interval [ CI ], 0.605–0.987; I 2 =34%). In fetuses with hydrops fetalis, digoxin had lower rates of tachycardia termination compared with flecainide ( OR : 0.412; 95% CI , 0.268–0.632; I 2 =0%). There was no significant difference in the incidence of maternal side effects between digoxin and flecainide groups ( OR : 1.134; 95% CI , 0.129–9.935; I 2 =80.79%). The incidence of maternal side effects was higher in patients treated with digoxin compared with sotalol ( OR : 3.148; 95% CI , 1.468–6.751; I 2 =0%). There was no difference in fetal demise between flecainide and digoxin ( OR : 0.767; 95% CI , 0.140–4.197; I 2 =44%). Conclusions Flecainide may be more effective treatment than digoxin as a first‐line treatment for fetal supraventricular tachycardia.

Background— Percutaneous closure of prosthetic mitral valve paravalvular leak (PVL) has emerged as an alternative to surgical treatment in high-risk patients. Limited data exist on the impact of successful percutaneous PVL closure on midterm outcomes. Methods and Results— We examined consecutive patients who underwent percutaneous mitral PVL closure at Mayo Clinic, Rochester, MN, between January 2006 and January 2017. Procedural success, in-hospital outcomes, and midterm mortality were assessed. A total of 231 patients underwent percutaneous mitral PVL repair at a mean age of 67±12 years. Mean time from mitral valve replacement to percutaneous PVL repair was 1.25 (0.31–7.25) years. One hundred sixty-two patients (70%) had ≤mild PVL after the procedure. Compared with those who had >mild residual PVL, patients with ≤mild residual PVL had lower rates of repeat surgical interventions (6% versus 17%; P =0.004) and lower all-cause mortality at 30 days (1% versus 14%; P <0.001) and 1 year (15% versus 39%; P <0.001). Survival at 3 years was 61% in patients who had ≤mild residual leak and 47% in patients with higher grade of residual PVL ( P =0.002). Conclusions— In a large consecutive cohort of patients undergoing percutaneous mitral PVL closure, successful percutaneous reduction of the PVL to mild or less was associated with significant midterm survival benefit.

Although improvement in cardiac output and hemodynamic parameters is routinely demonstrated in patients implanted with continuous-flow left ventricular assist devices (CF-LVADs), improvement in exercise capacity is inconsistently seen. Our purpose was to determine whether native cardiac factors, LVAD factors, or comorbid factors were associated with lack of improvement. Review of all patients undergoing preimplant cardiopulmonary exercise testing (CPET) and CPET on LVAD therapy at one institution was performed between 2007 and 2014 (n = 49). Comprehensive assessment of echocardiographic parameters, right heart catheterization data, medications, and comorbid illness was undertaken. There was no mean improvement in peak oxygen consumption (VO2; 11.8–12.4 ml/kg/min; p = 0.26), although exercise time (5.1 [46% predicted] to 5.8 min [56% predicted]; p = 0.02) and nadir of the ratio of minute ventilation to carbon dioxide production slope (VE/VCO2; 39–36; p = 0.001) improved. Factors most strongly associated with improvement in VO2 were Heartmate II pulsatility index (PI; R = 0.48; p = 0.001), power (R = −0.40; p = 0.009), pump flow (R = −0.40; p = 0.008), and pump speed (R = −0.32; p = 0.04). Peak heart rate (HR) was also associated with improvement in VO2 (R = 0.41; p = 0.004). Left ventricular ejection fraction (LVEF; R = 0.004; p = 0.77), right ventricular (RV) function (R = 0.22; p = 0.28), and aortic valve opening (R = 0.20; p = 0.57) were not associated with improvement in VO2. Our data suggest that less reliance on LVAD support was modestly associated with improvement in exercise capacity. Further studies should seek to determine the optimal level of device support prospectively in relation to exercise capacity.