F. Vitek

Kinetic study of atrial natriuretic peptide in patients with idiopathic dilated cardiomyopathy: evidence for resistance to biologic effects of the hormone even in patients with mild myocardial involvement.

Atrial natriuretic peptide (ANP) kinetics was studied in 12 patients with idiopathic dilated cardiomyopathy at different sodium excretion (30-175 mmol/day) and variable degrees of hemodynamic dysfunction [New York Heart Association (NYHA) class range I-III] to investigate whether differences in renewal and distribution of this hormone (as compared with those of a control group) play a role in pathogenesis and evolution of heart failure. [125I]Labeled ANP was injected as a bolus, and a high-performance liquid chromatography (HPLC) procedure was used to purify the labeled hormone in venous plasma samples collected for < or = 50 min after injection; the main ANP kinetic parameters were then derived from the disappearance curve of the labeled hormone. As in controls, a positive linear regression between ANP metabolic clearance rate (MCR, ml/min/m2) values and daily urinary excretion of sodium (NaUE, mmol/day) was noted in patients. The different linear regression coefficients between normal subjects (MCR = 365 +/- 8.08 NaUE, r = 0.986, p < 0.0001) and patients (MCR = 497 + 18.5 NaUE, r = 0.867, p = 0.001) indicate that in patients a higher peptide clearance rate is needed to obtain the same biologic effect (sodium excretion) and suggest that resistance to biologic effects of the hormone exists in patients at an early stage of disease (NYHA class I). When the efficiency of the ANP system in excreting sodium was expressed as the ratio of NaUE to ANP production rate (PR = MCR x ANP plasma concentration, microgram/day/m2) patients showed significantly lower values (p = 0.0126) than normal volunteers, thus confirming resistance to the hormone effects. Significantly lower values for ANP total distribution volume (16.5 +/- 8.4 L/m2), mean residence time in the sampling space (4.04 +/- 1.14 min), mean residence time in the body (7.25 +/- 2.13 min), and fewer recycles through the initial (sampling) space (0.27 +/- 0.16) were noted in patients, indicating an altered mechanism regulating distribution of the hormone. The positive correlations between ANP MCR (L/min/m2) values and cardiac index (CI, L/min/m2) (MCR = -1.24 + 1.17 CI, r = 0.689, p = 0.0092) and between initial distribution volume (IDV, L/m2) and CI (IDV = -11.2 + 6.85 CI, r = 0.730, p = 0.0046) in all patients indicate that hemodynamic factors contribute to the progressive reduction in MCR and IDV values throughout the progression of myocardial involvement.(ABSTRACT TRUNCATED AT 400 WORDS)

Peripheral thyroid hormone metabolism in patients with complex ventricular arrhythmias.

Abstract In conclusion, our kinetic data indicate that patients with complex ventricular arrhythmias show a peculiar alteration of thyroid hormone metabolism, characterized by increased T 4 to T 3 conversion and reduced T 4 production, and resulting in a relatively increased availability of T 3 at the cellular level. Therefore, our data support the hypothesis that an altered peripheral metabolism of thyroid hormones may play a role in the pathogenesis of complex ventricular arrhythmias, even if further studies are required to confirm this hypothesis and to supply information for their interpretation.

Peripheral Resistance to Atrial Natriuretic Peptide in Patients with Idiopathic Dilated Cardiomyopathy

Atrial natriuretic peptide (ANP) has been suggested to play an important role in asymptomatic left ventricular dysfunction, preserving cardiorenal homeostasis through the maintenance of the sodium balance and the inhibition of the detrimental effects of the neurohormonal vasoconstrictor system. The current study was designed to investigate whether differences in the renewal and distribution of ANP may play a role in the pathogenesis and evolution of heart failure in idiopathic dilated cardiomyopathy (IDC). A tracer method was used to study ANP kinetics in the steady-state condition in 10 normal subjects and in 13 patients with IDC with different degrees of hemodynamic dysfunction at variable sodium intakes. [125I]-labeled ANP was bolus injected and high-pressure liquid chromatography (HPLC) was used to purify the labeled hormone in venous plasma samples collected up to 50 min after injection. The main ANP kinetic parameters were then derived from the disappearance curve of the labeled hormone. Patients with IDC showed a gradual reduction in the total distribution volume (on average from 20.5 ± 4.51/m2 to 12.2 ± 7.21/m2, p < 0.0279) with the progression of disease, mainly due to a contraction of the peripheral distribution spaces in the early phases of the disease and to a reduction in both the initial distribution volume and the peripheral spaces in the late phases of the disease. Moreover, the ANP production rate, which was in the normal range (120.0 ± 104.7 ng/ min/m2) in the early stages (99.8 ± 52.3ng/min/m2), greatly (more then three times, p < 0.0055) increased in patients with more severe myocardial involvement (378.9 ± 189.1 ng/min/m2). Different relationships between the metabolic clearance rate (MCR) values and daily sodium excretion were observed in patients (r = 0.837, p < 0.0001) and controls (r = 0.962, p < 0.0001). The significantly (p < 0.02) different linear regression coefficients (slopes) indicate that, on average, for each millimole rise in sodium excretion, the ANP MCR increased by 17ml/min/m2 in the patients, that is, there was an increase of about twofold with respect to the controls. Our study demonstrates a markedly altered peripheral distribution and degradation of ANP in patients with IDC, even those in the early phase of the disease (NYHA class I and II), who have plasma levels in the normal range. This alteration of ANP metabolism indicates the presence of a peripheral resistance to hormone effects and also suggests disturbed renal handling of sodium in patients with IDC and asymptomatic left ventricular dysfunction.