Cardiac Catecholamine Concentrations and α1, β1, Ca^<2+>-Receptors in Patients of Hypertension or Heart Failure

An improved high performance liquid chromatographic procedure useing an electrochemical detector (HPLC-ECD) for the analysis of catecholamine in tissue is described. The separation of norepinephrine (NE), epinephrine (E), dopamine (DA) and 3, 4-dihydroxybenzylamine (internal standard) was achieved within 14min. Detection limits were 5 pg fbr NE, 15 pg for E and 20 pg for DA at a signal to noise ratio of 3, respectively. The recovery of these catecholamines eluted from the alumina was above 80% . Useing this method, the determination of cardiac catecholamine concentrations of Wistar-kyoto rat (WKY) and the spontaneously hypertensive rat (SHR) was carried out. In fetus of WKY and SHR, cardiac E concentration was high. With the growth of rats, cardiac E concentration went down, while a rapid increase of cardiac NE concentration appeared. Cardiac NE concentration of SHR became higher than that of WKY significantly in 16 week-old rats and cardiac NE concentration of pregnant SHR was higher than that of 16 week-old SHIR. Cardiac NE was lower in cardiomyopathic hamster (BIO 14.6) than in the control hamster. Coenzyme Q_10 was administered orally for 10 months tended to increase cardiac NE in cardiomyopathic hamster. These findings confirm the protective effect of Coenzyme Q_10 in myocardium of idiopathic dilated cardiomyopathy patients. Xamoterol, a β_1-partial agonist, was given orally for 7 days (100mg twice daily) to healthy volunteers and patients with heart failure. Lymphocyte β-receptor density (Bmax) and affinity were determined by radioligand binding assay using ^<125>I-ICYP berore and after the treatment. Bmax was lower in the patient group compared with control group. During treatment with xamoterol, Bmax increased markedly in both groups. Following withdrawal of the treament, Bmax deceased in both groups. Blood pressure rose slightiy in both groups. The ling-term effects after 3 and 12 months of treatment with xsmoterol were assessed. Xamoterol increased exercised tolerance after 12 months of treatment. Echocardiographic fractional shortening increased and pulmonary wedge pressure (PAW) during exercise at the same work load decreased at 3 months. Resting PAW and exercise heart rate decreased at 3 months. The density of the βーreceptors in lymphocytes increased at 3 and 12 months.To elucidate the mechanism by which the new inotropic agent dibutyryl cyclic AMP (DBcAMP) improves the cardiac functon, I examined multiple indices of the left ventricular systolic and diastolic functions before and during administration of DBcAMP to patients with congestive heart failure (CHF, NYHA II-IV). In 12 patients echocardiographic and radionuclide angiographic studies were performed during right heart catheterization. During intravenous administration of DBcAmP, there were no significant changes in the heart rate, left ventricular dimension, right ventricular ejection fraction, left ventricular peak systolic ejection rate. Left ventricular ejection fraction, left ventricular peak diastolic filling rate and cardiac index increased significantly during DBcAMP. Additionally, blood pressure, mean pulmonary wedge pressure and total peripheral vascular resisance decreaed significantly. In conclusion, an improved method for the determination of cardiac catechlamines by HPLC-ECD is presented. The relation between the progression of the hypertension or pregnant-toxicosis and cardiac catecholamine concentraions was strongly suggested. β-receptor in myocardium was lower in CHF compared with control. Xamoterol demonstrated both β-agonist and antagonist effects in CHF and DCM patients. β-receptors in lymphocytes were up-regurated during treatment with xamoterol without deterioration in cardiac function in the patient with CHF. DBcAMP improved systolic and diastolic functions in patients with CHF