ABSTRACT
BACKGROUND: Exertional dyspnea is a frequent limiting symptom in patients with chronic heart failure. Furthermore, dyspnea and a plateau in VO(2) (oxygen consumption) at peak exercise often co-exist in chronic heart failure, especially in patients with severe regurgitant valvular heart disease (RVHD), their relevance to hemodynamics and subjective symptoms during exercise have not been fully understood. OBJECTIVES: The purpose of this study was to examine the determinant factor of exercise capacity in patients with RVHD. METHODS: We performed a symptom-limited cardiopulmonary exercise test using a sitting cycle ergometer with right heart catheterization in 20 patients with severe RVHD. VO(2) and hemodynamics were measured at rest and during exercise, and symptomatic end-point at peak exercise was evaluated by using Borg's score. RESULTS: Of the 20 patients, 11 attained a plateau in VO(2) at peak exercise (Group 1). At peak exercise, pulmonary arterial pressure (PAP) was higher, and cardiac output (CO) and VO(2) were lower in Group 1 than in patients without a plateau in VO(2) (Group 2) (mean PAP: 60+/-10 vs. 48+/-9 mm Hg, P=0.05; CO: 8.3+/-2.6 vs. 11.2+/-2.6 l/min, P=0.01; VO(2): 1059+/-259 vs. 1359+/-328 ml/min, P=0.01). In Group 1, 6 patients complaining of dyspnea rather than leg fatigue at peak exercise had lower CO (7.1+/-1.8 vs. 9.7+/-3.0 l/min, P=0.05) and higher slope of mean PAP-CO relation (P-Q slope) (10.6+/-3.6 vs. 5.4+/-1.7, P=0.01), compared with the other 5 patients with leg fatigue. CONCLUSIONS: Development of pulmonary hypertension during exercise is the important limiting factor for exercise capacity in patients with RVHD. The limitation of increase in CO concomitant with pulmonary hypertension could be an important factor in the appearance of dyspnea.
Subject(s)
Aortic Valve Insufficiency/physiopathology , Exercise Tolerance/physiology , Mitral Valve Insufficiency/physiopathology , Aortic Valve Insufficiency/epidemiology , Comorbidity , Dyspnea/physiopathology , Exercise Test , Female , Humans , Hypertension, Pulmonary/epidemiology , Male , Middle Aged , Mitral Valve Insufficiency/epidemiology , Oxygen Consumption , Pulmonary Artery/physiopathologyABSTRACT
A simple HPLC method for the direct chiral separation of troglitazone stereoisomers was developed. The separation was performed on a reversed-phase cellulose-derivertized chiral column (Chiralcel OJ-R) using a mobile phase consisting of methanol-acetic acid (1000:1, v/v) at a flow rate of 0.5 ml/min. The peak areas of stereoisomers separated from 0.13 to 0.75 mg/ml of troglitazone had good linearity, with correlation coefficients > 0.999 in the reversed-phase mode. The repeatability of the ratios of stereoisomers isolated from 0.5 mg/ml of troglitazone had a relative standard deviation of 0.1-0.2%. The relative sensitivities of the four isomers at UV 285 nm were similar, as each response factor was within the range of 0.99-1.01. Troglitazone racemized at the chiral center of the thiazolidine ring in methanol solution, but was found to be stable for 24 h in methanol-acetic acid (1000:1, v/v). This method was applied to the stereoisomeric analysis of troglitazone in pharmaceutical formulations and used to evaluate the constancy of the stereoisomer ratio in the manufacturing process and stability testing.
