Dysfunction of the right ventricle (RV) is closely related to prognosis for patients with RV failure. Therefore, strategies to improve failing RV function are significant. In a mouse RV failure model, we previously reported that α1-adrenergic receptor (α1-AR) inotropic responses are increased. The present study determined the roles of both predominant cardiac α1-AR subtypes (α1A and α1B) in upregulated inotropy in failing RV. We used the mouse model of bleomycin-induced pulmonary fibrosis, pulmonary hypertension, and RV failure. We assessed the myocardial contractile response in vitro to stimulation of the α1A-subtype (using α1A-subtype-selective agonist A61603) and α1B-subtype [using α1A-subtype knockout mice and nonsubtype selective α1-AR agonist phenylephrine (PE)]. In wild-type nonfailing RV, a negative inotropic effect of α1-AR stimulation with PE (force decreased ≈50%) was switched to a positive inotropic effect (PIE) with bleomycin-induced RV injury. Upregulated inotropy in failing RV occurred with α1A-subtype stimulation (force increased ≈200%), but not with α1B-subtype stimulation (force decreased ≈50%). Upregulated inotropy mediated by the α1A-subtype involved increased activator Ca(2+) transients and increased phosphorylation of myosin regulatory light chain (a mediator of increased myofilament Ca(2+) sensitivity). In failing RV, the PIE elicited by the α1A-subtype was appreciably less when the α1A-subtype was stimulated in combination with the α1B-subtype, suggesting functional antagonism between α1A- and α1B-subtypes. In conclusion, upregulation of α1-AR inotropy in failing RV myocardium requires the α1A-subtype and is opposed by the α1B-subtype. The α1A subtype might be a therapeutic target to improve the function of the failing RV.

OBJECTIVES

To examine trends in tuberculosis (TB) incidence and to compare demographic and clinical characteristics of nursing home (NH) residents and community-dwelling older adults.

DESIGN

Prospective TB surveillance.

SETTING

TB cases reported in California from 2000 to 2009.

PARTICIPANTS

TB patients aged 65 and older.

MEASUREMENTS

Trends in TB incidence per 100,000 population were assessed using Poisson regression. Demographic and clinical characteristics were compared using the chi-square or Wilcoxon rank-sum test. Among NH residents, risk factors for death during TB treatment were identified using logistic regression.

RESULTS

From 2000 to 2009, TB incidence rates decreased significantly, from 15.9/100,000 to 8.4/100,000 (-44%, 95% confidence interval (CI) = -66% to -7%) for NH residents and from 21.2/100,000 to 15.0/100,000 (-27%, 95% CI = -29% to -24%) for community-dwelling older adults. Overall, 211 TB cases among NH residents and 6,518 cases among community-dwelling older adults were reported. NH residents were more likely than community-dwelling older adults to be older (median age 81 vs 75, P < .001), have a negative acid-fast bacilli sputum smear and positive culture (37% vs 28%, P < .001), and die while undergoing TB treatment (44% vs 14%, P < .001), and were less likely to have a positive tuberculin skin test (TST) (28% vs 44%, P < .001) and have TB care provided by a health department (20% vs 59%, P < .001). In multivariable analysis, NH residents who had a positive TST were less likely to die while undergoing TB treatment (odds ratio = 0.39, 95% CI = 0.16-0.96).

CONCLUSION

TB incidence rates were lower, and reductions in incidence were greater among NH residents; community-dwelling older adults had higher TB rates and smaller reductions in incidence. Interventions that promote timely detection and treatment of TB infection and disease may be needed to reduce morbidity and mortality among NH residents.