Adrenal gland-released vasostatin-I is a myocardial depressant factor

Abstract

Pheochromocytoma crisis is an exceptional consequence of the release of storage vesicles of the adrenal medulla. It is complicated by fulminant adrenergic myocarditis. It offers a unique opportunity to detect inotropic negative factors from neuroendocrine origin. Our objectives were (a) to describe a pheochromocytoma crisis, (b) to investigate in vivo myocardial depressant activities for the N-terminal 1-76 Chromogranin A-derived peptide, vasostatin-I (VS-I). A patient with a pheochromocytoma crisis was treated, including extracorporeal membrane oxygenation, until mass resection. Plasma concentrations of VS-I were time-dependently assessed with a specific immunoassay; correlations with invasive cardiovascular parameters were investigated. Increased VS-I concentrations were observed over 7 days until tumour resection. VS-I concentrations correlated positively with Chromogranin A levels, negatively with cardiac output and left ventricular stroke work index, but not with heart rate. This case illustrates the pharmacokinetics of VS-I in a pheochromocytoma crisis. It highlights myocardial depressant activity for this peptide at high concentrations.

Keywords: Chromogranin A; myocardial depressant factor; pheochromocytoma, crisis; vasostatin-I.

Figure 1

Time‐dependent changes in plasma VS‐I concentrations and cardiac index from admission to surgery. Plasma concentrations of VS‐I are diamond‐shaped for the patient (n = 1) and squared for healthy controls (n = 13, median (IQ 1; 3): 2.85 (2.47; 3.22)). Cardiac index is represented as triangles connected by a solid line. The arrow indicates the time of surgical removal of the tumour. Note that emergency extracorporeal membrane oxygenation was started 8 hours after admission and removed at day 7. On admission, concentrations of normetanephrines and metanephrines in urine were at 29 460 nmol/24 h (normal range 600‐2293/24 h) and 333 970 nmol/24 h (normal range 353‐1515/24 h), respectively, reflecting the endogenous production of catecholamines. Immediately (ie, 24 hours) after tumour resection, these figures were stable as far normetanephrines were concerned (30 054 nmol/24 h), but they decreased by 80% as far as metanephrines were concerned (59 173 nmol/24 h). By day 15 after surgical resection, they were back within normal range. After surgical resection, plasma CGA concentration declined over 5 days to 89 μg/L¹ (normal range <102 μg/L) and so did VS‐I concentration (1.74 ng/mL): the latter does not appear in Figure 1 because no cardiac output was assessed simultaneously to biological sampling (pulmonary arterial catheter removal at day 1 after surgery)