A recently introduced rate responsive cardiac pacing system is based on information derived from the intracardiac impedance signal containing information on the inotropic state of the ventricle. This study compared the inotropic state index (ISI) with muscle sympathetic activity (MSA), both being modulated by the autonomic nervous system. Nine patients (66 +/- 3 years, mean +/- SEM) with Inos2DR pacemakers were included. Each patient was studied at rest and during cold pressor test (CPT). Microneurography of the peroneal nerve was performed to measure MSA continuously, which was digitally stored along with continuous surface ECG and blood pressure. The intracardiac impedance signal was transmitted by the pacemaker and stored simultaneously. Linear correlation between ISI and MSA was calculated for the period of the CPT. During CPT, mean systolic blood pressure increased from 122 +/- 4 to 149 +/- 6 mmHg (P < 0.0001), diastolic blood pressure increased from 74 +/- 8 to 86 +/- 4 mmHg (P = 0.02), and intrinsic heart rate increased from 69 +/- 7 to 75 +/- 7 beats/mill (P = 0.019). ISI increased by 21 +/- 7% (P = 0.018), MSA by 26 +/- 6% (P = 0.004). ISI and MSA were positively correlated during the CPT in eight of nine patients (R2 = 0.86-0.99, P < 0.0001). Negative correlation was found in one patient (R2 = 0.94). This study demonstrates parallel increases of the ISI and MSA during CPT. ISI and MSA showed a close linear relationship during provoked changes of sympathetic activity. These results provide further evidence that the sympathetic nervous system is responsible for the observed ISI changes.