Sulfoconjugated and free plasma catecholamine levels at rest and during exercise in patients with idiopathic dilated cardiomyopathy

Abstract

Plasma levels of sulfoconjugated (sc) catecholamines (CA) have been shown to be increased with activation of the sympathoadrenal system in a number of clinical settings. We evaluated the relation between scCA and clinical or hemodynamic parameters of patients with idiopathic dilated cardiomyopathy (IDC) at rest and during incremental exercise testing. Eleven healthy subjects, nine patients in New York Heart Association (NYHA) functional class I (IDC-A group) and 11 in NYHA functional class II and III (IDC-B group) performed a symptom-limited, graded bicycle exercise test. Resting, peak and various postexercise levels of plasma free and scCA were determined by high-pressure liquid chromatography. Resting CA levels obtained in the supine position were remarkable for elevations of free norepinephrine (NE) in IDC-B patients (355 +/- 157 ng/l) as compared to IDC-A patients (177 +/- 54, p = 0.006) or healthy controls (193 +/- 74, p = 0.007). Similarly, scNE was highest in IDC-B patients with 1856 +/- 1089 ng/l, followed by IDC-A (1028 +/- 187, p = 0.025) and control subjects (1109 +/- 440, p = 0.025). There was a highly significant correlation between free and scNE (r = 0.76, p < 0.0005). Whereas resting free dopamine (DA) levels were comparable in all three groups, scDA was found to be elevated clearly in IDC-B patients (8772 +/- 2097 ng/l) and significantly different to IDC-A (5786 +/- 2481, p = 0.01) or control subjects (4892 +/- 1575, p = 0.0005). The NYHA functional class and maximum exercise performance correlated best with resting scDA (r = 0.68, p = 0.001 and r = 0.56, p = 0.005, respectively). At peak exercise, IDC-B patients exhibited a significant decrease in scNE and sc epinephrine (E) (from 1856 +/- 1089 to 1495 +/- 932 ng/l, p < 0.005 and from 491 +/- 173 to 282 +/- 143 ng/l, p < 0.01) compared to controls (from 1109 +/- 444 to 1094 +/- 548 ng/l and from 379 +/- 200 to 329 +/- 134 ng/l). In IDC-B patients this decrease in scNE and scE at peak exercise was related inversely to the rise in free NE and E (r = -0.81, p < 0.005 and r = -0.68, p < 0.05). Resting hemodynamic indices generally were reflected better by some free CA rather than by conjugated forms or by parameters of clinical performance. These findings suggest that in addition to free or scNE levels, resting scDA is elevated in symptomatic patients with IDC.(ABSTRACT TRUNCATED AT 400 WORDS)

Association of High Levels of Plasma Free Dopamine With Future Coronary Events in Patients With Coronary Artery Disease

“…9,[18][19][20] Although the precise regulatory mechanisms for the activity of these enzymes remain unclear, the deconjugation of conjugated dopamine to free dopamine is known to increase in patients with chronic heart failure, 21 in whom sympathetic activation occurs chronically. This finding is compatible with previous reports 9,22 showing that plasma free dopamine levels are increased by sympathetic nervous activation. The circulating concentration of conjugated dopamine is the highest among the concentrations of the circulating catecholamines, usually 5-to 10-fold higher than all others, conjugated or free norepinephrine and epinephrine.…”

“…The circulating concentration of conjugated dopamine is the highest among the concentrations of the circulating catecholamines, usually 5-to 10-fold higher than all others, conjugated or free norepinephrine and epinephrine. 21,22 Therefore, free dopamine levels are greatly influenced by the deconjugation of conjugated dopamine, and this conjugation is also stimulated by cortisol, 23 which is released in the condition of heart failure. Furthermore, the transient increase in free dopamine levels after physiological stress is less as compared with norepinephrine.…”

“…Furthermore, the transient increase in free dopamine levels after physiological stress is less as compared with norepinephrine. 22 In this context, free dopamine levels may reflect well the steady state of cardiovascular compensation in patients with heart failure.…”

Relationship between Depressed Baroreflex Function and Exaggerated Sympathetic Response to Exercise in Patients with Heart Failure

“…A reduced rate of NE increase during exercise in patients with HF in comparison to controls was first described by Francis [4]. Similar results were reported by Dobnig et al [5]. Conversely, other authors observed a more marked increase in plasma NE during exercise in patients with HF compared to normal subjects [6, 7].…”

Peripheral dopamine in hypertension and associated conditions

“…85 In patients with idiopathic dilated cardiomyopathy exposed to exercise, plasma DA sulfate proved to be an even better marker of sympathetic discharge than free NA. 86 DA receptors were found not only in the kidney but also in the heart 87 and to be involved in heart failure. Increased DA is probably balanced by DA receptor downregulation in the failing heart protecting it against further DA stimulation.…”