Wendy L. Eubank

The effect of changes in cardiac output on middle cerebral artery mean blood velocity at rest and during exercise

We examined the relationship between changes in cardiac output and middle cerebral artery mean blood velocity (MCA Vmean) in seven healthy volunteer men at rest and during 50% maximal oxygen uptake steady‐state submaximal cycling exercise. Reductions in were accomplished using lower body negative pressure (LBNP), while increases in were accomplished using infusions of 25% human serum albumin. Heart rate (HR), arterial blood pressure and MCA Vmean were continuously recorded. At each stage of LBNP and albumin infusion was measured using an acetylene rebreathing technique. Arterial blood samples were analysed for partial pressure of carbon dioxide tension (P  a,CO 2. During exercise HR and were increased above rest (P < 0.001), while neither MCA Vmean nor P  a,CO 2 was altered (P > 0.05). The MCA Vmean and were linearly related at rest (P < 0.001) and during exercise (P= 0.035). The slope of the regression relationship between MCA Vmean and at rest was greater (P= 0.035) than during exercise. In addition, the phase and gain between MCA Vmean and mean arterial pressure in the low frequency range were not altered from rest to exercise indicating that the cerebral autoregulation was maintained. These data suggest that the associated with the changes in central blood volume influence the MCA Vmean at rest and during exercise and its regulation is independent of cerebral autoregulation. It appears that the exercise induced sympathoexcitation and the change in the distribution of between the cerebral and the systemic circulation modifies the relationship between MCA Vmean and .

Autonomic Neural Control of the Cerebral Vasculature Acute Hypotension

Background and Purpose— The effect of antihypertensive drugs on autonomic neural control of the cerebral circulation remains unclear. This study was designed to compare middle cerebral artery mean blood velocity responses to acute hypotension with and without &agr;1-adrenoreceptor blockade (Prazosin) in young, healthy humans. Methods— Acute hypotension was induced nonpharmacologically in 6 healthy subjects (mean±SE; 28±2 years) by releasing bilateral thigh cuffs after 9 minutes of suprasystolic resting ischemia before and after an oral dose of Prazosin (1 mg/20 kg body weight). Results— Prazosin had no effect on thigh cuff release-induced reductions in mean arterial pressure and middle cerebral artery mean blood velocity. However, Prazosin attenuated the amount of peripheral vasoconstriction through the arterial baroreflex as evidenced by a slower return of mean arterial pressure to baseline (P=0.03). Immediately after cuff release, cerebral vascular conductance index increased through cerebral autoregulation and returned to resting values as a result of an increased perfusion pressure mediated through arterial baroreflex mechanisms. The rate of regulation, an index of cerebral autoregulation, was attenuated with Prazosin (control versus Prazosin; rate of regulation=0.204±0.020 versus 0.006±0.053/s, P=0.037). In addition, as mean arterial pressure was returning to resting values, the rate of change in cerebral vascular conductance index was decreased with Prazosin (0.005±0.006/s) compared with control (0.025±0.005/s; P=0.010). Conclusions— These data suggest that during recovery from acute hypotension, decreases in cerebral vascular conductance index were mediated by increases in arterial blood pressure and sympathetically mediated cerebral vasoconstriction.

α1‐Adrenergic receptor control of the cerebral vasculature in humans at rest and during exercise

•  What is the central question of this study? Despite the abundance of sympathetic nerve fibres emanating from the cervical and stellate ganglia that innervate the cerebral arteries, the role of the sympathetic nervous system in regulation of cerebral vasculature in humans remains equivocal. •  What is the main finding and its importance? The findings from this study support the role of the sympathetic nervous system, mediated by activation of α1‐adrenoreceptors, in dynamic cerebral autoregulation and cerebral vascular tone at rest and during moderate dynamic exercise. Blockade of the α1‐adrenoreceptors impaired dynamic cerebral autoregulation and attenuated any increases in cerebral vascular tone during moderate dynamic exercise in healthy humans.

The effects of aerobic fitness and β1-adrenergic receptor blockade on cardiac work during dynamic exercise

The purpose of this investigation was to determine whether cardiovascular adaptations characteristic of long-term endurance exercise compensate more effectively during cardioselective beta(1)-adrenergic receptor blockade-induced reductions in sympathoadrenergic-stimulated contractility. Endurance-trained (ET) athletes (n = 8) and average-trained (AT; n = 8) subjects performed submaximal cycling exercise at moderate [45% maximum oxygen uptake (Vo(2max))] and heavy (70% Vo(2max)) workloads, with and without metoprolol. Cardiac output (Qc), heart rate (HR), and systolic blood pressure were recorded at rest and during exercise. Cardiac work was calculated from the triple product of HR, stroke volume, and systolic blood pressure, and myocardial efficiency is represented as cardiac work for a given total body oxygen consumption. Metoprolol reduced Qc at 45% Vo(2max) (P = 0.004) and 70% Vo(2max) (P = 0.022) in ET subjects, but did not alter Qc in the AT subjects. In ET subjects at 45% Vo(2max), metoprolol-induced reductions in Qc were a result of decreases in HR (P < 0.05) and the absence of a compensatory increase in stroke volume (P > 0.05). The cardiac work and calculated cardiac efficiency were reduced with metoprolol in ET subjects at both exercise intensities and in the AT subjects during the high-intensity workload (P < 0.01). The cardiac work and the calculated cardiac efficiency were not affected by metoprolol in the AT subjects during the 45% Vo(2max) exercise. Therefore, in AT subjects, beta-blockade reduced the amount of pressure generation necessary to produce the same amount of work during moderate-intensity exercise. In patients with heart disease receiving metoprolol, a decrease in the generation of cardiac pressure necessary to perform a given amount of work during mild-to-moderate exercise would prove to be beneficial.

N-Acetylcysteine reduces hyperacute intermittent hypoxia-induced sympathoexcitation in human subjects

What is the central question of this study? This study evaluated the following central question: does N‐acetylcysteine (N‐AC), an antioxidant that readily penetrates the blood–brain barrier, have the capability to reduce the increase in sympathetic nerve activity observed during hyperacute intermittent hypoxia? What is the main finding and its importance? We demonstrate that N‐AC decreases muscle sympathetic nerve activity in response to hyperacute intermittent hypoxia versus placebo control. This finding suggests that antioxidants, such as N‐AC, have therapeutic potential in obstructive sleep apnoea.