Isoproterenol induced cardiovascular hypersensitiviy in nonpheochromocytoma patients with paroxysmal hyperadrenergic symptoms

Abstract

The objective of this study was to determine whether graded isoproterenol infusion test identifies a specific hypersensitivity response of the LV diastolic relaxation properties in nonpheochromocytoma patients with paroxysmal symptoms of hyperadrenergic surges. We hypothesized that patients with hyperadrenergic surges, not due to pheochromocytoma, have hypersensitivity of cardiac beta-adrenergic receptor responses to exogenous catecholamines, resulting in enhancement of LV relaxation. We assessed the physiological beta 1 and beta 2 receptor responsiveness to graded isoproterenol infusion (0.01, 0.02, 0.03 and 0.04 microgram/kg per min) in 32 patients presented with hyperadrenergic surges not due to pheochromocytoma. Two major observations were made. First, systemic hemodynamic evaluation using 99m Technetium first pass method revealed hyperkinetic state only in 21 patients (20 females and 1 male; aged 31 +/- 9 years); the other 11 patients were without hyperkinetic circulatory state (10 females and 1 male; aged 41 +/- 9 years). At baseline, plasma catecholamines were not significantly different between the two groups. The baseline corrected LV peak filling and ejection rates (cPFR and cPER) were significantly higher in hyperkinetic group (cPFR: 10 +/- 2 vs 8 +/- 2 x 10(-2) Hz/ms, P = 0.03; cPER: 11 +/- 2 vs 8 +/- 1 x 10(-2) Hz/ms, P = 0.002) and their baseline HR was faster (85 +/- 16 vs 70 +/- 9 beats/min, P = 0.006). Second, the cardiac and vascular responses to isoproterenol infusion were compared between these two groups. During the graded isoproterenol infusion, the response of HR, systolic, and diastolic BP were not significantly different between the two groups at all doses of isoproterenol, but cPFR and cPER had a more marked response to the lowest dose of 0.01 mg/kg per min in the hyperkinetic group. Thus, the graded isoproterenol infusion test can differentiate between two groups of nonpheochromocytoma patients presenting with paroxysmal symptoms of hyperadrenergic surges. Only patients with baseline hyperkinetic hemodynamic profile had accentuated cardiac hyperresponsiveness to a low dose of isoproterenol. We concluded that cPFR and cPER is a more sensitive index to assess the response to isoproterenol, because of metabolic determinants affecting the rate of change in LV volume.