INTRODUCTION

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CARDIOVASCULAR RESPONSES to muscle activity include concomitant elevations of heart rate and blood pressure (1), which are initially caused by a reduced vagal outflow to the heart and which are followed by an increase in sympathetic outflow to the heart and the resistance vessels (11, 18, 23) as the muscle activity persists. Central command, mechanoreceptors, and muscle chemoreceptors are considered to provide important inputs to cardiovascular control centers (1, 7, 9). At the same time, arterial baroreflexes maintain short-term control by means of inputs from arterial baroreceptors and efferents to the heart and the vasculature. The integration of arterial baroreflex function on one hand and other inputs more specific for muscle activity on the other hand have been subject to varying conclusions from researchers utilizing different experimental paradigms. Thus the sensitivity of the arterial baroreflexes during dynamic leg exercise has been described as both decreased (24) and increased (8, 22), although most recent work suggests that the sensitivity is unchanged compared with rest (15, 19, 22, and 25). Data from dynamic exercise in large muscle groups are not necessarily representative of isometric arm contraction, which is an equally common mode of muscle activity in daily life. Isometric arm contraction involves much smaller muscle groups and is associated with time-dependent ischemic components as the contraction impedes muscle blood flow (10). Although arterial baroreflexes modify cardiovascular responses from voluntary muscle activations and muscle afferents (28), data on arterial baroreflex sensitivity and other baroreflex response characteristics during isometric arm contraction are sparse and incomplete (4, 15). We attempted to elucidate the separate effects of voluntary motor activation and muscle ischemia on arterial baroreflexes by determining complete sets of baroreflex response parameters during sudden alterations of carotid sinus distending pressure in men during rest, during isometric arm contractions, and during postcontraction ischemia.

	MATERIALS AND METHODS

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Subjects. Ten healthy men, with an average age of 24 (range 22-25) yr, weight 73.5 (60-96) kg, and height 1.79 (1.69-1.90) m volunteered for the study. All were nonsmokers, and none was currently taking any medication. They all had normal findings in a physical examination, normal resting electrocardiograms (ECG), and normal blood pressure. The experiments were performed either in the morning, 2 h after a light caffeine-free breakfast, or in the afternoon, 2 h after a light caffeine-free lunch. Ambient temperature ranged from 22 to 24°C, adjusted to the comfort of each subject. The subjects had given their informed consent for the protocol, and the experimental procedures had been approved by the Ethical Committee of Karolinska Institutet.

Carotid stimulation. Changes in the carotid sinus distending pressure (CDP) were generated by the application of positive or negative pressure in a lead neck chamber. The chamber enclosed both sides and the front of the neck from the mandibular level to the sternum and clavicles (5). Each stimulation consisted of a 15-s period of constant (nonpulsatile) pressure or suction. Two levels of neck pressure (NP) (+20 and +40 mmHg) and four levels of neck suction (NS) (20, 40, 60, and 80 mmHg) were applied. Pressures were generated by two vacuum cleaners, with one blowing and the other sucking air through a series of adjustable resistances. The pump system was installed in an adjacent room to eliminate acoustic noise. Carotid stimulations were controlled with the use of an R wave triggered circuit operating a large-bore three-way solenoid valve (type 323, Bürkert, Ingelfingen, Germany) with a 40-ms delay. Thus the neck chamber could alternately be vented to the ambient air or connected to a manually operated manifold connecting the solenoid to one of six preset pressure levels. The pressure in the neck chamber was monitored by a pressure transducer (Hewlett-Packard 1280 with amplifier 311a). The rate of pressure change in the chamber was 800 mmHg/s.

Cardiovascular measurements. An ECG was acquired from chest electrodes and a combined amplifier and beat-to-beat tachometer (Biotach ECG, model 20-4615-65, Gould, Valley View, OH). A continuous beat-to-beat recording of arterial blood pressure in the left-hand middle finger was obtained by using a photoplethysmographic device (Finapres 2300, Ohmeda, Englewood, CO). The Finapres provides continuous recordings of mean arterial blood pressure (MAP) in close agreement with concomitant invasive recordings (12).

Procedure. Each subject was seated comfortably in an armchair in a semireclining position, with the back of the seat tilted 10° backward. The experiment operator and the equipment were outside the view of the subject. The subject held a hand dynamometer (Vigorimeter, Martin, Tuttlingen, Germany) in his lap in the right, dominant hand. Immediately upon the subject's arrival, the maximal contraction force was determined from three 2-s-long maximal voluntary contractions. A contraction force of 30% of maximum was used during subsequent tests.

Data acquisition and analysis. Beat-to-beat heart rate (HR), continuous arterial blood pressure, and neck chamber pressure were recorded with a personal computer-based data collection system (Biopac Systems, Goleta, CA). The calibrated data were recorded at 100 Hz per channel and subsequently stored and analyzed with an AcqKnowledge 3.1 software package (Biopac Systems). Data were stored starting 10 s before and until 15 s after the end of each NS or NP stimulus.

View larger version (19K): [in this window] [in a new window]   Fig. 1.   Six-segment carotid baroreflex response curves. A: curves are linear interpolations between group mean values for mean arterial pressure (MAP, at level of the heart) responses to changes in carotid distending pressure (CDP) elicited by application of pressures of +40, +20, 20, 40, 60, and 80 mmHg in a neck chamber during rest, isometric lower arm contraction, and postcontraction ischemia (occlusion). Third data point from left for each curve represents prevailing MAP and CDP, i.e., with no external neck pressure. Open symbols represent estimated optimum points at which a given absolute CDP change will result in equal responses in both directions. Data are means ± SE; n = 10 subjects. B: responses of heart rate (HR) during same conditions as in A.

View larger version (18K): [in this window] [in a new window]   Fig. 2.   A: schematic representation of carotid-MAP baroreflex response curves based on same data as in Fig. 1. Logistic curves (13) have been computed from group mean curve parameters as given in Table 1. Open symbols represent optimum points. Gray arrows indicate significant shifts of curve position between conditions, as determined from shifts of optimum points. Black arrow indicates a shift of prevailing MAP and CDP along response curve during occlusion to a value below and to right of optimum point. * indicate threshold and saturation computed according to Chen et al. (3). B: schematic representation of carotid-cardiac baroreflex curves presented as in A.

Statistics. Differences among conditions were analyzed using a paired Student's t-test for dependent variables (Statistica, Statsoft, Tulsa, OK). Significance was accepted at the 5% level and with Bonferroni correction for repeated comparisons.

	RESULTS

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Ten subjects participated in the study. All subjects reported that they came close to fatigue at the end of the periods of static handgrip.

Group mean results are shown in Figs. 1 and 2 and in Table 1. For all conditions, prevailing and optimum points for HR did not differ significantly. This was also true for MAP during rest and during static contraction; however, during occlusion prevailing MAP was 2 mmHg lower and prevailing CDP was 6 mmHg higher than corresponding values at the optimum point. Ranges and maximum slopes for HR and MAP baroreflex response curves did not differ among conditions.

The HR time delay to the initial maximal response averaged 6.0 ± 2.7 s, and the MAP delay averaged 10.8 ± 2.4 s (means ± SD) in the group of subjects.

Figure 2 summarizes schematically the statistically significant differences among the baroreflex response curves from the three conditions. Group mean data from Table 1 have been utilized to synthesize logistic curves illustrating carotid-cardiac (Fig. 2B) and carotid-MAP (Fig. 2A) baroreflex response curves for the three conditions. Compared with rest, contraction caused a displacement of the carotid-cardiac response curve to a 14 beats/min higher HR and to a 9-mmHg higher CDP as given by the displacement of the optimum point. Corresponding values for MAP were +20 mmHg and +18 mmHg, respectively.

During occlusion, the carotid-cardiac response curve was displaced vertically compared with that during contraction, i.e., to the same HR level as during rest but to a 14-mmHg higher CDP level than during rest. At the same time, the carotid-MAP response curve was displaced horizontally to 8-mmHg lower CDP values compared with those during contraction.

	DISCUSSION

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The distinctive feature of this study was the definition of complete sets of curve parameters for arterial baroreflex response curves during both isometric arm contraction and postcontraction ischemia in humans. The changes of the hemodynamics induced by isometric arm contraction have been defined (for reviews see Refs. 6, 14, 26, and 28). Our contribution has been to define the optimum points of the arterial baroreflex response curves for HR and MAP, thereby enabling us to determine to what extent arterial baroreflex curves are shifted to the right along the CDP axis and upward in terms of HR and MAP responses and to determine that the maximum slopes were not changed. We also showed that the prevailing points were at or slightly below the optimum points and that arterial baroreflex sensitivity as defined by the maximum slope at the optimum points of HR and MAP was not altered compared with that during rest.

Limitations of study. Most of our subjects reported that they found it more difficult to maintain the required force during the final experimental sequences than during the first, and it is likely that the level of central command was increased accordingly. With the present randomization of the order of the neck chamber pressures, we assume that this effect of repetition had little or no effect on our results.

Hemodynamic responses to isometric arm contraction and postcontraction ischemia. Hemodynamic responses to isometric arm contractions include concomitant tachycardia and elevated arterial blood pressure (1). There is an increase of muscle sympathetic nerve activity after the first minute (17, 30, 34) and a decreased radial artery diameter (20), suggesting vasoconstriction in important vascular beds. However, determinations of total peripheral resistance have shown no difference from resting control (23). This apparent paradox may be explained by passive widening of resistance vessels caused by the markedly elevated systemic arterial pressure as suggested by Eckberg et al. (5) and Olesen et al. (20). Thus one key component of the hemodynamic response to isometric arm contraction is an increase of cardiac output (23) equal in size to that of the MAP increase.

Arterial baroreflex responses during isometric arm contraction and postcontraction ischemia. Although the most important stimuli behind the cardiovascular responses to muscle activity have been identified, the mechanisms by which central command, mechanoreflexes, and the muscle chemoreflex interact with other major afferent input such as arterial baroreceptor stimuli need to be elucidated. Ludbrook et al. (15) and Ebert (4) determined the slopes of both the hypotensive and hypertensive parts of the carotid-cardiac baroreflex response curve and found no differences between rest and isometric lower arm contraction. Other curve parameters were not analyzed, so it is not obvious from these studies whether the change toward higher HR and blood pressures represents an upward shift or a rightward shift, or both, of the arterial baroreflex response curves for HR and blood pressure. Also, it was not ascertained that the recorded slopes were the maximum slopes. To our knowledge, the full ranges of baroreflex response curves have not previously been characterized during both isometric lower arm contraction and postcontraction ischemia.

Positions of prevailing points on baroreflex response curves. In resting man the prevailing points of HR and MAP are at the optimum point of the arterial baroreflex response curves (6, 29). Thus hypotensive and hypertensive carotid stimuli elicit approximately equal responses. Dynamic exercise, however, results in a shift of the position of the prevailing point upward and to the left of the optimum point (8, 25). Such a shift would be associated with reduced responses to hypotensive stimuli and might suggest that the baroreflex control of HR during dynamic exercise would be operating primarily against hypertensive deviations of CDP. This shift of operational point has been identified in the study of vagally induced HR responses to relatively brief (5-10 s) CDP perturbations (8, 25, 32). However, responses to more extended (~20 s) CDP perturbations (21), which include both vagally and sympathetically induced chronotropic responses (33), have not shown such a shift in the position of the operational point on the baroreflex response curves. We determined the initial vagally induced HR responses to sudden baroreceptor loading and unloading. Thus our HR results should be compared with those obtained by Potts et al. (25), Sundblad and Linnarsson (32), and Eiken et al. (8) rather than with those of Rowell's group (21, 22). Thus our observations suggest that there is a significant reserve of potential vagal withdrawal after 2 min of isometric arm contraction and under the influence of combined somatomotor activation and muscle chemoreflex stimulation. There are observations in support of the notion that the tachycardic response to isometric contraction is not due entirely to vagal withdrawal but may also be the result of increased sympathetic output to the heart. Martin et al. (18) and Hume et al. (11) observed that parasympathetic blockade with atropine eliminated the initial, rapid but not the late, tachycardic response. Pawelczyk et al. (23), while studying normal subjects performing isometric handgrip under partial neuromuscular blockade, found elevated plasma norepinephrine concentrations during the contraction phase, but not during postcontraction ischemia, and concluded that the somatomotor activation influence on cardiac output may be directed by way of the sympathetic nerve system.