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Biomedical subjects

L I Sinoway

Publications and source records attributed to L I Sinoway.

At least 55 records · Page 3Linked to original sources
PubMed1994

Sympathetic nerve activity during prolonged rhythmic forearm exercise.

Exercise is a potent stimulus to activate the sympathetic nervous system. Previous work suggests that metabolite-sensitive muscle afferents are activated near the point of fatigue, and, when activated, they determine the muscle sympathetic nerve activity (MSNA) response to isometric forearm exercise. Yet, studies using a more prolonged rhythmic exercise paradigm suggest that the sympathetic nervous system can be activated in a more graded fashion. The purpose of this study was to determine whether metaboreceptor stimulation would also be responsible for MSNA responses to prolonged rhythmic isotonic forearm exercise. Subjects (n = 16) performed rhythmic isotonic forearm exercise at 25% maximal voluntary contraction for 30 min as we measured MSNA (microneurography). We observed progressive increases in MSNA with a peak increase of 161 units from a baseline value of 180 units. We also performed posthandgrip circulatory arrest (PHG-CA) in nine of these subjects. This maneuver isolates the metaboreceptor contribution to MSNA. During PHG-CA, delta MSNA values were not different from those observed during a freely perfused recovery period (n = 7). We also compared MSNA responses during the rhythmic paradigm with those seen during a static protocol at 40% of maximal voluntary contraction in five subjects. The two types of exercise caused similar increases in MSNA, but only the static paradigm was associated with a sustained MSNA response during PHG-CA. Finally, 31P-nuclear magnetic resonance was used to evaluate muscle metabolic responses during rhythmic and static forearm exercise (n = 6). Static exercise caused muscle acidosis and an increase in H2PO4-, whereas rhythmic exercise had no effect on muscle metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Forearm compression during exercise increases sympathetic nerve traffic.

Previously, we showed that forearm venous congestion augmented muscle sympathetic nerve activity (MSNA) during static exercise. We postulated that venous congestion increased interstitial pressure, sensitizing mechanoreceptor afferents that led to a greater sympathoexcitation during exercise. In this study, we tested the hypothesis that forearm compression (FC) would increase interstitial pressure and selectively stimulate mechanically sensitive afferents. We measured MSNA during 2 min of ischemic static exercise (40% maximal voluntary contraction) and 2 min of posthandgrip circulatory arrest. Exercise was performed again after 5 min of FC induced by inflation of a forearm cuff to 90 mmHg (n = 6) and 110 mmHg (n = 7). FC without exercise had no effect on any of the hemodynamic variables. MSNA and mean arterial blood pressure responses were not augmented when exercise was performed with FC at 90 mmHg. However, static exercise coupled with FC at 110 mmHg did augment the reflex responses to static exercise (changes in MSNA before and after FC were 277 +/- 58 and 503 +/- 82 arbitrary units, respectively, P < 0.02; changes in mean arterial pressure before and after FC were 35 +/- 4 and 41 +/- 5 mmHg, respectively, P < 0.003). These responses were probably not due to greater metaboreceptor stimulation, since posthandgrip circulatory arrest responses were unaffected by FC. We postulate that FC sensitizes mechanoreceptors, leading to greater sympathoexcitation during exercise.

Adult↗
PubMed1993

Effects of contraction and lactic acid on the discharge of group III muscle afferents in cats.

1. In barbiturate-anesthetized cats we examined the interaction of lactic acid and static contraction on the discharge of group III muscle afferents. Only afferents whose receptive fields were located in the triceps surae muscles were studied. 2. Twelve of 20 afferents were stimulated by a 60-s static contraction. The majority of firing occurred within the first few seconds of contraction. Thirteen of 20 afferents were stimulated by femoral arterial injections of 24 mM lactic acid (1-4 ml) with the muscle at rest. Repeated injections of lactic acid with the muscle at rest led to tachyphylaxis. Lactic acid was then injected (24 mM; 4 ml) during the last 15 s of static contraction. In eight of nine afferents that were tachyphylactic to lactic acid with the muscle at rest, we noted a restored sensitivity to lactic acid during contraction. 3. In separate experiments we examined the effects of dichloroacetate (DCA) on the responses of group III muscle afferents to static contraction. DCA reduces the production of lactic acid by increasing levels of the active form of the enzyme pyruvate dehydrogenase. 4. DCA lowered arterial and venous lactate concentrations at rest and during contraction. DCA significantly decreased (31%; P < 0.05) the responses of the afferents to contraction. This effect was most prominent within the first 10 s of contraction and was not due to a reduced level of mechanical stimulation after DCA, because peak tension levels were the same during the two bouts of contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Glycogen depletion-induced lactate reductions attenuate reflex responses in exercising humans.

Post leg exercise circulatory arrest (PLE-CA) raises blood pressure (BP) and reduces peak forearm vascular conductance (C). This reflex is evoked by activation of muscle afferents that are often sensitive to lactic acid. We tested the hypothesis that lactic acid reductions induced by muscle glycogen depletion would attenuate the lower-limb metaboreceptor-mediated pressor and forearm vasoconstrictor responses. Eleven subjects had C measured (plethysmography) during post leg exercise circulatory arrest (PLE-CA) (supine bicycle exercise for 9 min, 10 s at 75% VO2max before and after undergoing a glycogen-depletion paradigm (24-h fast followed by 10 min of supine leg exercise at 75% VO2max). In six subjects with lower lactate values, C during PLE-CA was higher after glycogen depletion (0.39 +/- 0.05 vs. 0.21 +/- 0.01 ml.min-1.100 ml-1 x mmHg-1; P < 0.01) and BP was lower (113 +/- 6 vs. 128 +/- 6 mmHg, P < 0.01). In five subjects without attenuated lactate responses, C and BP during PLE-CA were not different. Muscle biopsies (n = 5) demonstrated that the paradigm lowered muscle glycogen concentrations. Thus glycogen depletion-induced reductions in muscle lactate are associated with reduced muscle metaboreceptor-mediated responses.

Adult↗
PubMed1992

Hydrogen ion concentration is not the sole determinant of muscle metaboreceptor responses in humans.

We examined the effects of exercise conditioning on muscle sympathetic nerve activity (MSNA) during handgrip and posthandgrip circulatory arrest (PHG-CA). Two conditioning stimuli were studied: forearm dominance and bodybuilding. Static handgrip at 30% maximal voluntary contraction followed by PHG-CA led to a rise in MSNA smaller in dominant than in nondominant forearms (99% vs. 222%; P less than 0.02) and in body builders than in normal volunteers (28% vs. 244%; P less than 0.01). Separate 31P NMR experiments showed no effect of dominance on forearm pH but a pH in bodybuilders higher (6.88) than in normal volunteers (6.79; P less than 0.02) during PHG-CA. Our second goal was to determine if factors besides attenuated [H+] contribute to this conditioning effect. If differences in MSNA during exercise were noted at the same pH, then other mechanisms must contribute to the training effect. We measured MSNA during ischemic fatiguing handgrip. No dominance or bodybuilding effect on pH was noted. However, we noted increases in MSNA smaller in dominant than nondominant forearms (212% vs. 322%; P less than 0.02) and in bodybuilders than in normal volunteers (161% vs. 334%; P less than 0.01). In summary, MSNA responses were less during exercise of conditioned limbs. Factors aside from a lessening of muscle acidosis contribute to this effect.

Adult↗
PubMed1991

Time-constant adaptations in heart failure.

The circulatory compensatory mechanisms designed to cope quickly with physiological stress (e.g. sympathetic nervous system and the Frank-Starling mechanism) are less effective when there is chronic pathological stress, such as congestive heart failure (CHF). Other mechanisms come into play that operate over a longer time (e.g. activation of the renin-angiotensin-aldosterone system, myocardial hypertrophy and physiological deconditioning). Changes in blood vessels and skeletal muscle metabolism that result from inadequate delivery of oxygenated blood to working muscles belong to the group of mechanisms that develop slowly. When CHF therapy is successful, the abnormalities produced by this latter group of mechanisms will improve, but slowly. The concept that compensatory mechanisms have either short or long time constants for activation and reversal may explain why exercise tolerance improves much later than haemodynamics, which can be reversed acutely with vasodilator therapy.

Adaptation, Physiological↗
PubMed1991

Norepinephrine kinetics and cardiac output during nonhypotensive lower body negative pressure.

Recently we have shown that arterial norepinephrine (NE) concentration increases significantly during lower body negative pressure (LBNP) of -15 mmHg. Interestingly, the increase was found to be related predominantly to a decrease in arterial NE clearance. We postulated that this reduction in clearance would be related to a reduction in cardiac output. Accordingly, we measured both cardiac output (2-dimensional echocardiographic/Doppler technique) and arterial NE kinetics ([3H]NE continuous infusion radiotracer technique) during LBNP of -15 mmHg. These measures of cardiac output and arterial NE spillover and clearance were obtained in 12 normal subjects at baseline, 5 and 10 min (Early) and 25 and 30 min (Late) of LBNP. We found that arterial NE concentration increased significantly, by 25% Early and 22% Late (P = 0.001). Spillover, however, did not change (P = 0.258), whereas clearance decreased by 12% Early and 19% Late (P = 0.014), and cardiac output decreased by 15% Early and 19% Late (P = 0.001). These reductions in clearance and cardiac output correlated significantly (r = 0.61, P = 0.001). No correlation was noted between spillover and cardiac output (r = 0.027, P = 0.874). We conclude that the increases in arterial NE concentration during nonhypotensive LBNP are predominantly due to decreased cardiac output with resultant decreases in systemic clearance of NE. These findings suggest that the ability to clear NE from the circulation is linked to the level of cardiac output and that low cardiac output states by themselves may lead to an elevation in arterial plasma NE concentrations.

Adult↗
PubMed1991

Skeletal muscle metaboreceptor exercise responses are attenuated in heart failure.

BACKGROUND: Resting sympathetic nervous system activity is increased in heart failure. Whether sympathetic nervous system responses during exercise are increased is controversial. Furthermore, the role of muscle metaboreceptors and central command in regulating sympathetic outflow has been largely unexplored. METHODS AND RESULTS: Muscle sympathetic nerve activity (MSNA, peroneal nerve) was measured in nine heart failure subjects and eight age-matched control subjects during static exercise (30% maximal voluntary contraction) for 2 minutes and during a period of posthandgrip regional circulatory arrest. This maneuver isolates the metaboreceptor contribution to sympathetic nervous system responses. MSNA responses were similar during static exercise in the two groups. During posthandgrip regional circulatory arrest we observed a marked attenuation in MSNA responses in the heart failure subjects (15% increase in heart failure versus 57% increase in control subjects). A cold pressor test demonstrated a normal MSNA response to a potent nonspecific stimulus in the heart failure subjects (heart failure subjects, 141% increase; control subjects, 215% increase; NS). Nuclear magnetic resonance spectroscopy studies in five separate heart failure subjects and five control subjects suggested that the attenuated metaboreceptor response in heart failure was not due to reduced H+ production. CONCLUSIONS: Skeletal muscle metaboreceptor responses are impaired in heart failure. Because MSNA responses during static exercise are similar in the two groups, mechanisms aside from metaboreceptor stimulation must be important in increasing sympathetic nervous system activity.

Exercise↗
PubMed1990

Reversible impairment of forearm vasodilation after forearm casting.

To examine whether the resumption of normal physical activity after forearm immobilization would reverse impaired vasodilation, the minimal vascular resistance was examined in six subjects who had forearm casts placed for broken forearm bones. Each subject was examined twice, once within 48 h after forearm cast removal and again approximately 29 days later. The formerly casted forearm and the opposite forearm (noncasted) were examined. Minimal vascular resistance decreased in the casted forearm from 3.0 +/- 0.4 to 2.6 +/- 0.5 mmHg.ml-1.min.100 ml (P less than 0.014). There was no change in the noncasted forearm: 2.5 +/- 0.3 vs. 2.5 +/- 0.3 mmHg.ml-1.min.100 ml. This study shows that maximal vasodilation improves with the resumption of normal physical activity and therefore demonstrates that immobilization is associated with a reduced forearm vasodilator capacity.

Adult↗
PubMed1990

Direct neurohumoral evidence for isolated sympathetic nervous system activation to skeletal muscle in response to cardiopulmonary baroreceptor unloading.

It has been postulated that cardiopulmonary baroreceptor unloading in humans results in nonuniform activation of the sympathetic nervous system. We reasoned that simultaneous measurements of arterial and venous norepinephrine (NE) spillover and clearance (using NE kinetics), muscle sympathetic neural activity (using microneurography), forearm blood flow (using plethysmography), and skin blood flow (using laser Doppler velocimetry) during lower body negative pressure at -15 mm Hg would isolate the location and extent of cardiopulmonary baroreceptor-mediated sympathetic nervous system activation. We exposed normal subjects (n = 8) to lower body negative pressure for 30 minutes, with measurements obtained at baseline, 5-10 minutes (EARLY), and 25-30 minutes (LATE). We found that arterial NE spillover, reflecting systemic sympathetic nervous system activation, did not increase significantly, whereas arterial NE clearance decreased significantly. In contrast, forearm venous NE spillover, reflecting skin and muscle sympathetic nervous system activation, increased by 17% and muscle sympathetic neural activity by 35% EARLY, whereas venous clearance did not change significantly. Although laser Doppler skin blood flow did not change, plethysmographic forearm blood flow (combined muscle and skin blood flow) decreased by 28%. All changes were sustained throughout 30 minutes of lower body negative pressure. Our data suggest that sympathetic vasoconstriction to muscle is greater than it is to skin in response to cardiopulmonary baroreceptor unloading. Moreover, our data suggest that reduced NE clearance in the arterial circulation is the primary mechanism by which arterial NE concentrations rise. Conversely, NE spillover appears to be the primary mechanism responsible for increasing venous NE concentrations measured from the forearm during cardiopulmonary baroreceptor unloading.

Adult↗
PubMed1990

Physiologic and structural indices of vascular function in paraplegics.

In an effort to determine whether chronic physical forearm activity would increase both structural and physiologic indices of peripheral forearm vasodilation, we studied a group (N = 7) of individuals chronically performing high levels of arm work, young wheelchair-confined paraplegics, and compared them with ten young, able bodied control subjects. The index of vasodilator capacity was the flow response following the release of 10 min of arterial occlusion, the peak reactive hyperemic blood flow response (RHBF). The index of a structural effect of training on the vasculature was the brachial artery diameter (cm) derived by simultaneous measurement of velocity and forearm blood flow (area = flow.forearm volume.velocity-1). Vascular function differed significantly between the groups, with a greater RHBF (paraplegics, 53.8 +/- 3.7; controls, 38.2 +/- 1.5 ml.min-1.100 ml-1; P less than 0.05) and a larger brachial artery diameter at rest (paraplegics, 0.4 +/- 0.01 vs controls, 0.3 +/- 0.02 cm; P less than 0.05) in the paraplegics. We conclude that chronic upper extremity activity leads to an enhanced capability to vasodilate resistance vessels acutely and to a structural dilation of large conductance vessels.

Adult↗
PubMed1989

Left subclavian flap aortoplasty for coarctation of the aorta: effects on forearm vascular function and growth.

This study evaluated vascular function and growth of the forearm in nine children (mean age 9.2 years) who had undergone left subclavian flap aortoplasty for the infantile type of coarctation of the aorta many years (mean 9.0) earlier. Variables used to investigate bilateral forearm vascular function included forearm blood flow and resistance measured by strain gauge plethysmography under rest conditions, in response to 30 s of static handgrip exercise at 40% maximal voluntary contraction and in response to 10 min of forearm arterial occlusion (that is, the reactive hyperemic blood flow response). Forearm growth was ascertained by measuring right and left forearm volumes, lengths, circumferences and skinfold thickness. Mean arterial pressure at rest in the right and left arms differed by 9% (right 78.2 +/- 2.1, left 71.0 +/- 2.7 mm Hg; p less than 0.05). Forearm blood flow, however, was not significantly different between the surgically altered left arm and the normal right arm under any of the study conditions. Likewise, forearm vascular resistance was not statistically different under any conditions, although the left arm tended to have a lower resistance at rest (right 23.5 +/- 3.2, left 18.7 +/- 2.0 mm Hg.min.100 ml/ml; p = 0.057). Left forearm anthropometric measurements showed a 9% reduction in volume and a 3% reduction in circumference and length. In addition, skinfold thickness tended to be larger on the left arm, suggesting that this limb had a smaller muscle mass. In conclusion, early repair with a subclavian flap does not impair vascular function in the altered limb and is associated with only minor reductions in forearm growth variables. Hence, left subclavian flap aortoplasty appears to be a safe and effective procedure for repair of coarctation of the aorta.

Aortic Coarctation↗
PubMed1989

Characteristics of flow-mediated brachial artery vasodilation in human subjects.

In an effort to determine whether arterial conductance vessels dilate in response to increased blood flow stimuli, brachial artery area (cm2) and diameter (cm) were derived by simultaneous measurement of forearm blood flow (ml/min.100 ml) and brachial artery blood flow velocity (cm/sec) following the release of arterial occlusion. Measurements were made at rest and at the time of maximal flow after the release of graded periods of forearm arterial occlusion (20 seconds to 10 minutes). These studies showed a graded large vessel dilation following occlusions of up to 1 minute (baseline diameter, 0.33 +/- 0.01; after 1 minute occlusion, 0.45 +/- 0.02 cm; p less than 0.05) after which time diameter plateaued (after 10 minutes of occlusion, 0.48 +/- 0.02 cm). In addition, the time course of diameter and flow changes after 3 minutes of arterial occlusion were examined. Flow was maximal at 5 seconds but diameter was maximal at 15-30 seconds after release. Furthermore, the half time for the return of diameter to baseline was longer than that for blood flow. We also measured the diameter after forearm heating (42 degrees C) and noted a substantial increase in diameter (before heating, 0.32 +/- 0.01; after heating, 0.39 +/- 0.02 cm; p less than 0.05). Finally, we applied pressure to the venous side of arteriovenous fistulae in five hemodialysis patients. This maneuver was associated with large reductions in forearm blood flow (baseline flow, 63.3 +/- 10.6; venous compression flow, 36.0 +/- 4.4 ml/min.100 ml; p less than 0.05) and a decrease in brachial artery size (baseline diameter, 0.63 +/- 0.07; venous compression diameter, 0.58 +/- 0.06 cm; p less than 0.05). We conclude that 1) the human brachial artery size changes in response to changes in blood flow, and 2) the maximal dilation occurs after maximal flow is noted. Although alternate explanations are possible for each of our observations, our results are most consistent with a flow-mediated, localized vasodilating process.

Adult↗
PubMed1989

The peripheral circulation.

In severe congestive heart failure, exercise capacity is reduced. This is not directly due to reduced ventricular function. We present evidence in this article that peripheral vascular abnormalities are important in determining exercise capacity. We believe the vascular abnormalities noted in heart failure may be related to both sodium retention and deconditioning. Moreover, we propose that in severe heart failure this vascular response may be protective.

Blood Circulation↗
PubMed1988

Regional blood flow in congestive heart failure: concept of compensatory mechanisms with short and long time constants.

With physiologic stress to the cardiovascular system, some circulatory compensatory mechanisms are designed to restore homeostasis quickly (e.g., sympathetic nervous system activation and the Frank-Starling mechanism). These compensatory mechanisms are not nearly as effective when there is a chronic pathologic stress such as congestive heart failure (CHF). In this circumstance, other mechanisms that operate with longer time constants come into play (e.g., activation of the renin-angiotensin-aldosterone system, myocardial hypertrophy and deconditioning). The most successful chronic drug therapies of CHF are those that are designed to reverse the latter group of compensatory mechanisms, a process that is slow. It takes especially long to reverse those CHF-induced changes in blood vessels and skeletal muscle metabolism that are activated to cope with inadequate delivery of oxygenated blood to working muscles. The concept that compensatory mechanisms have either short or long time constants for activation, effectiveness and reversal may help explain why the improvement in exercise tolerance with effective heart failure therapy lags behind hemodynamic improvement.

Adaptation, Physiological↗
PubMed1988

Effect of conditioning and deconditioning stimuli on metabolically determined blood flow in humans and implications for congestive heart failure.

Peripheral blood vessels do not dilate normally in congestive heart failure (CHF). The mechanisms responsible for this impairment are not well understood. In this review, a group of studies performed over the past 3 years aimed at examining these mechanisms further are described. These studies suggest that in CHF, fluid retention has a negative effect on vasodilator capacity, thereby limiting peak forearm blood flow. A second mechanism is described that is slowly reversing and not directly dependent on cardiac function; it is believed that this mechanism may be related to the vascular deconditioning associated with severe CHF. This postulate is based on studies that have shown that peak vasodilator capacity is higher in the trained arms of tennis players, that improved vasodilator capacity can be induced by a localized unilateral training program, and that vasodilator capacity is reduced by localized deconditioning. Furthermore, the level of conditioning on vasodilator capacity may be mediated by chronic changes in blood flow. Further studies are necessary to confirm these relations.

Blood Flow Velocity↗
PubMed1988

Delayed reversal of impaired vasodilation in congestive heart failure after heart transplantation.

The effects of changes in central cardiovascular function on peripheral vasodilation were investigated. Strain gauge plethysmography was used to measure the maximal blood flow response following release of forearm arterial occlusion and the peak reactive hyperemic blood flow response (ml/min.100 ml) before and twice after orthotopic heart transplantation in 10 subjects with severe congestive heart failure. The 2 posttransplantation studies were done before hospital discharge (mean 18 days after transplantation) and again after discharge (mean 114 days after transplantation). Transplantation led to a significant but delayed increase in maximal vasodilation (reactive hyperemic blood flow: pretransplant 21 +/- 3; predischarge 25 +/- 2; postdischarge 43 +/- 5) and a concurrent significant reduction in minimal forearm resistance. Although the improvement in peripheral vasodilator function may be linked to improvement in cardiac function, this linkage is not direct, nor is it immediate. If the normalization of maximal metabolic blood flow is related to resumption of normal physical activity postdischarge, then much of the basic abnormality in vasodilator capacity in congestive heart failure may be related to physical deconditioning.

Adult↗