Cardiac sympathetic neuroimaging
For cardiac sympathetic neuroimaging the subject was positioned supine, feet-first in a GE Advance scanner (General Electric, Milwaukee, WI), with the thorax in the gantry. After positioning the patient with the thorax in the scanner and transmission scanning for attenuation correction, 6-[18F]fluorodopamine (usual dose 1 mCi, specific activity 1.0 to 4.0 Ci/mmole, in about 10 mL normal saline) was infused intravenously at a constant rate for 3 min, and dynamic scanning data were obtained for thoracic radioactivity, with the midpoint of the scanning interval at 7.5 min after injection of the tracer (data collection interval between 5 and 10 min). Cardiac sympathetic denervation was defined by low concentrations of 6-[18F] fluorodopamine-derived radioactivity in the interventricular septum (< 5,000 nCi-kg/cc-mCi) or left ventricular free wall (< 4,000 nCi-kg/cc-mCi) corresponding to about 2 SD below the normal means.
Cardiac norepinephrine spillover
Subgroups of subjects (3 PD + NOH, 3 MSA, 3 PAF, 5 normal volunteers) underwent right heart catheterization for measurement of cardiac norepinephrine spillover. 3H-Norepinephrine was infused intravenously, and arterial and coronary sinus blood was sampled and coronary sinus blood flow was measured by thermodilution for measurements of cardiac norepinephrine spillover as described previously.18 In some subjects, yohimbine was infused during cardiac catheterization. Patients with chronic autonomic failure received the doses described above; normal volunteers and patients with chronic orthostatic intolerance received twice the doses described above.
Statistical analyses were performed using StatView version 5.0.1. (SAS Institute, Cary, NC). Mean values in the baseline condition for the several subject groups were compared using single-factor ANOVA. Responses to drugs were analyzed by dependent-means t tests. Differences in response to pharmacologic tests among subject groups were compared using repeated measures analyses of variance. Relationships between individual hemodynamic values were assessed by linear regression and calculation of Pearson correlation coefficients. Post-hoc testing consisted of the Fisher PLSD test. Multiple regression analysis was done on the individual data, with the log of LF power as the dependent measure and the log of baroreflex slope and septal 6-[18F] fluorodopamine-derived radioactivity as independent measures. Mean values were expressed ± SEM.
Across the 7 subject groups (N = 98), LF power was unrelated to subject group (F = 1.2). When individual subjects were stratified in terms of cardiac sympathetic denervation or innervation, based on concentrations of 6-[18F]fluorodopamine-derived radioactivity more than 2 SD below the normal mean, then LF power was lower in the Denervated group (mean 221 ± 55 msec2/Hz, N = 34) than in the Innervated group (516 ± 93 msec2/Hz, N = 64, F = 4.8, P = 0.03). LF power normalized for total power, HF normalized for total power, and the ratio of LF:HF were not related to 6-[18F]fluorodopamine-derived radioactivity.
When subjects were stratified in terms of BRS, then LF power was lower in the Low BRS group (223 ± 105 msec2/Hz, N = 46) than in the Normal BRS group (617 ± 97 msec2/Hz, N = 25, F = 6.1, P = 0.02). The Low BRS group did not differ from the Normal BRS group in normalized LF power (F = 0.8).
From multiple regression analysis for the log of LF power as the dependent measure and the log of baroreflex slope and septal 6-[18F]fluorodopamine-derived radioactivity as independent measures, the regression coefficient for the log of baroreflex slope was 0.92 (P < 0.0001), whereas the regression coefficient for 6-[18F] fluorodopamine-derived radioactivity was 3 ×10−6.
At baseline, the log of HF power correlated positively with the log of LF power (r = 0.77, P < 0.0001). HF power varied with the subject group (F = 4.9, P = 0.004). As with LF power, HF power was greater in the Innervated-Normal BRS than in the Innervated-Low BRS (P = 0.001, Table 2). As expected, the log of HF power correlated positively with the log of BRS (r = 0.60, P < 0.0001). The log of HF power also correlated negatively with the magnitude of decrease in systolic pressure during the Valsalva maneuver (r = −0.24, P = 0.02) and positively with the orthostatic change in systolic pressure (r = 0.40, P = 0.004).