Neurally mediated hypotension and bradycardia are believed to be common causes of syncope. We used the "upright-tilt test" (duration, less than or equal to 10 minutes) with or without an infusion of exogenous catecholamine (isoproterenol [1 to 5 micrograms per minute], given intravenously) to elicit bradycardia, hypotension, or both in 24 patients with recurrent syncope and in 18 control subjects. A conventional electrophysiologic test performed before the tilt test was positive in 9 of the 24 patients, revealing arrhythmias that may have caused recurrent syncope, but was negative and thus nondiagnostic in 15 patients. The tilt test alone (i.e., without isoproterenol) induced symptomatic bradycardia or hypotension in 1 of the 9 patients with positive electrophysiologic tests (11 percent), 4 of the 15 patients with negative electrophysiologic tests (27 percent), and none of the controls. When the isoproterenol infusion was administered during the tilt test, 9 of the 11 patients with negative electrophysiologic and tilt tests had syncope, marked slowing of the heart rate, and hypotension. In contrast, isoproterenol was associated with tachycardia and only a slight decline in arterial pressure in the 8 remaining patients with positive electrophysiologic tests and the 18 control subjects, and syncope developed in only 1 of the 8 patients with positive electrophysiologic tests and negative tilt tests (13 percent) and 2 of the 18 control subjects (11 percent). We conclude that an isoproterenol infusion administered in conjunction with the upright-tilt test may be useful for identifying susceptibility to neurally mediated recurrent syncope.

Although it is recognized that the number of cardiac beta-adrenoceptors is reduced in human dilated cardiomyopathy, the mechanisms involved have not been defined. We examined the possible role of altered humoral immunity by comparing the effect of sera from patients with idiopathic dilated cardiomyopathy (n = 20), ischemic or valvular heart disease (n = 28), or controls with no known cardiac disease (n = 18) on the binding of radioligands to cardiac beta-receptors. The ability of sera from cardiomyopathic patients to inhibit the binding of [3H]dihydroalprenolol to rat cardiac membranes was significantly higher than that of the other two patient groups (40 +/- 5% at 50-fold serum dilution compared to 14 +/- 3% for the ischemic/valvular heart disease group, and 14 +/- 4% for the normal control group, p less than 0.001). A similar inhibition was exerted by IgG from cardiomyopathic patients. Only the number, not the affinity, of the beta-receptors was decreased by cardiomyopathic sera. This decrease could be prevented by preincubating the sera with anti-human IgG, indicating the presence of autoantibodies. Furthermore, the sera were ineffective against cardiac alpha 1-adrenoceptors and considerably less effective against lung beta 2-receptors. In addition to ligand binding inhibition, sera from cardiomyopathic patients could immunoprecipitate beta-adrenoceptors quantitatively from solubilized cardiac membranes. Positive sera inhibited significantly isoproterenol-stimulated adenylate cyclase with no effect on basal or NaF-stimulated activities. These results document the presence in sera from patients with idiopathic dilated cardiomyopathy of autoantibodies directed against the cardiac beta 1-adrenoceptor which may play an important role in the regulation of inotropic responsiveness to beta-agonists.

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To determine the biochemical basis of abnormal diastolic properties in human dilated cardiomyopathy calcium uptake by the sarcoplasmic reticulum in ventricular homogenates of biopsy specimens from 21 patients with dilated cardiomyopathy was compared with that in nine normal controls. As a group, patients with cardiomyopathy had considerably lower calcium uptake rates (3.3(0.6) nmol.mg-1.min-1 vs 6.5(0.5) nmol.mg-1.min-1, p less than 0.01). Calcium uptake rates correlated modestly with resting haemodynamic values and significantly with plasma noradrenaline concentrations but not with plasma renin activity. These results show that sarcoplasmic reticulum function is impaired in human dilated cardiomyopathy and that this impairment is related both to the severity of haemodynamic dysfunction and to the extent of sympathetic nervous system activation.

T-lymphocyte activation, as reflected in elevated sIL-2R levels, is frequent in patients with dilated cardiomyopathy and is associated with more severe disease. Cellular and humoral immune activation may correlate with progression of the disease process.

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