Recording of neural firing from single-unit muscle sympathetic nerve activity (MSNA) is a new strategy offering information about the frequency of pure sympathetic firing. However, it is uncertain whether and when single-unit MSNA would be more useful than multiunit MSNA for analysis of various physiological stresses in humans. In 15 healthy subjects, we measured single-unit and multiunit MSNA before and during handgrip exercise at 30% of maximum voluntary contraction for 3 min and during the Valsalva maneuver at 40 mmHg expiratory pressure for 15 s. Shapes of individual single-unit MSNA were proved to be consistent and suitable for further evaluation. Single-unit and multiunit MSNA exhibited similar responses during handgrip exercise. However, acceleration of neural firing determined from single-unit MSNA became steeper than multiunit MSNA during the Valsalva maneuver. During the Valsalva maneuver, unlike handgrip exercise, the distribution of multiunit burst between 0, 1, 2, 3, and 4 spikes was significantly shifted toward multiple spikes within a given burst ( P < 0.05). These results indicated that evaluation of single-unit MSNA could provide more detailed and accurate information concerning the role and responses of neuronal discharges induced by various physiological stresses in humans, especially amid intense sympathetic activity.

Sympathetic activation in chronic heart failure (CHF) is greatly augmented at rest but the response to exercise remains controversial. We previously demonstrated that single-unit muscle sympathetic nerve activity (MSNA) provides a more detailed description of the sympathetic response to physiological stress than multi-unit nerve recordings. The purpose of this study was to determine whether the reflex response and discharge properties of single-unit MSNA are altered during handgrip exercise (HG, 30% of maximum voluntary contraction for 3 min) in CHF patients (New York Heart Association functional class II or III, n = 16) compared with age-matched healthy control subjects (n = 13). At rest, both single-unit and multi-unit indices of sympathetic outflow were augmented in CHF compared with controls (P < 0.05). However, the percentage of cardiac intervals that contained one, two, three or four single-unit spikes were not different between the groups. Compared to the control group, HG elicited a larger increase in multi-unit total MSNA ( 1002 ± 50 compared with 636 ± 76 units min −1 , P < 0.05) and single-unit MSNA spike incidence ( 27 ± 5 compared with 8 ± 2 spikes (100 heart beats) -1 ), P < 0.01) in the CHF patients. More importantly, the percentage of cardiac intervals that contained two or three single-unit spikes was increased (P < 0.05) during exercise in the CHF group only ( 8 ± 2% and 5 ± 1% for two and three spikes, respectively). These results suggest that the larger multi-unit total MSNA response observed during HG in CHF is brought about in part by an increase in the probability of multiple firing of single-unit sympathetic neurones.

Non-technical summary Augmentation of sympathetic nerve activity plays an important role in the deterioration of heart failure (HF). Atrial fibrillation (AF) is a well known and common complication in chronic HF. However, it remains unclear the relationship between sympathetic nerve activity and irregular ventricular rhythm induced by AF in HF. We examined the different sympathetic firing characteristics between HF patients with and without AF using a single-unit muscle sympathetic nerve activity (MSNA) method, which is a newly developed assessment of direct recording of sympathetic nerve activity. The firing frequency of single-unit MSNA was increased in HF patients with AF compared with HF patients without AF; particularly, those with a prolonged long RR interval showed multiple firings of single-unit MSNA. More intense single-unit MSNA within one cardiac interval occurred in HF patients with AF than patients without AF, even in AF patients receiving heart rate control therapy. Accordingly, our results suggest that AF per se augments central sympathetic activity and the restoration of sinus rhythm may be more effective in the treatment of HF patients with AF.Abstract Atrial fibrillation (AF) is a common complication in heart failure (HF) patients. However, it remains unclear whether irregular ventricular response patterns induced by AF increase sympathetic nerve activity. We measured resting multi-and single-unit muscle sympathetic nerve activity (MSNA) in 21 age-matched HF patients with chronic AF (n = 11) rhythm or sinus rhythm (SR, n = 10). The multi-unit MSNA, which was expressed as total activity, was similar between HF + AF patients and HF + SR patients. However, the single-unit MSNA in HF + AF patients was significantly greater than that in HF + SR patients (62 ± 9 spikes min −1 vs. 42 ± 4 spikes min −1 , P < 0.05). Moreover, the incidence of multiple firing of single-unit MSNA within a given burst was augmented in HF + AF patients as compared with HF + SR patients (48 ± 8% vs. 26 ± 3%, P < 0.01). A significant negative relationship was observed between the reduced diastolic pressure induced by a prolonged cardiac interval in AF subjects and single-unit MSNA frequency within one cardiac interval in each HF + AF subject. The firing characteristics of single-unit MSNA were different between HF patients with AF and HF patients with SR; particularly, those with a prolonged long RR interval showed multiple firings of single-unit MSNA. These findings suggest that AF per se leads to the instantaneous augmentation of single-unit MSNA induced by decreased diastolic pressure, which might partially contribute to disease progression in HF patients.

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Effects of H1-receptor stimulation on coronary arterial diameter and coronary hemodynamics were examined in 11 patients with angiographically normal coronary arteries and without variant angina or resting angina. Selective H1-receptor stimulation was achieved by infusing histamine into the left coronary artery at a rate of 2.0 1£g/min for 5 minutes after pretreatment with cimetidine (25 mg/kg). Plasma histamine concentration in the coronary sinus, coronary sinus blood flow, heart rate, and aortic pressure were measured before, during, and after the histamine infusion. Coronary arterial diameter was measured by cinevideodensitometric analysis of coronary arteriograms performed before and immediately after the histamine infusion. During the histamine infusion, plasma histamine concentration in the coronary sinus increased from 0.33+±0.06 to 5.86±0.71 ng/ml (p<0.01); coronary sinus blood flow increased from 98±12 to 124±13 ml/min (p<0.01), and coronary vascular resistance decreased from 1,113±+117 to 851±91 mm Hg. min/l (p