Cerebrovascular reactivity after cessation of menopausal hormone treatment.

OBJECTIVE: Women who are currently using menopausal hormone therapy (MHT) have higher cerebrovascular reactivity when compared with postmenopausal women who are not taking MHT; however, the effect of cessation of MHT on cerebrovascular reactivity is not known. Given that MHT can have structural and activational effects on vascular function, this study was performed to characterize cerebrovascular reactivity following cessation of MHT in women at low risk for cerebrovascular disease. METHODS: Cerebrovascular reactivity was measured in a subset of women from the Kronos Early Estrogen Prevention Study (KEEPS) 3 years after cessation of the study drug (oral conjugated equine estrogen, transdermal 17ß-estradiol, or placebo [PLA]). RESULTS: Age, body mass index, and blood pressure were comparable among groups. At rest, the middle cerebral artery velocity (MCAv), cerebrovascular conductance index, mean arterial pressure, and cerebral pulsatility index did not differ among groups. Slope-based summary measures of cerebrovascular reactivity did not differ significantly among groups. However, utilizing repeated-measures modeling, there was a significant upward shift in MCAv responses (p = 0.029) in the combined MHT group compared with the PLA group. CONCLUSION: MHT has a marginal sustained effect on cerebrovascular reactivity when measured 3 years after cessation of hormone treatment.

Sex differences in elite swimming with advanced age are less than marathon running.

The sex difference in marathon performance increases with finishing place and age of the runner but whether this occurs among swimmers is unknown. The purpose was to compare sex differences in swimming velocity across world record place (1st-10th), age group (25-89 years), and event distance. We also compared sex differences between freestyle swimming and marathon running. The world's top 10 swimming times of both sexes for World Championship freestyle stroke, backstroke, breaststroke, and butterfly events and the world's top 10 marathon times in 5-year age groups were obtained. Men were faster than women for freestyle (12.4 ± 4.2%), backstroke (12.8 ± 3.0%), and breaststroke (14.5 ± 3.2%), with the greatest sex differences for butterfly (16.7 ± 5.5%). The sex difference in swimming velocity increased across world record place for freestyle (P < 0.001), breaststroke, and butterfly for all age groups and distances (P < 0.001) because of a greater relative drop-off between first and 10th place for women. The sex difference in marathon running increased with the world record place and the sex difference for marathon running was greater than for swimming (P < 0.001). The sex difference in swimming increased with world record place and age, but was less than for marathon running. Collectively, these results suggest more depth in women's swimming than marathon running.

Integrative mechanisms of blood pressure regulation in humans and rats: cross-species similarities.

As our understanding of the importance of individualized medicine continues to grow, the clinical relevance of interindividual variability in hemodynamic variables is receiving increasing attention. However, it is not known whether the rat, which is often used for studies of cardiovascular regulation, exhibits similar interindividual variability. In the present study, we evaluated whether the magnitude of interindividual variability in cardiac output (CO) and total peripheral resistance (TPR) was similar in humans and in rats. We assessed interindividual variability of mean arterial pressure (MAP), CO, and TPR during control conditions in normotensive humans (n = 40) and during normotension and deoxycorticosterone acetate-salt hypertension in Sprague-Dawley rats (n = 16). Humans and rats showed marked interindividual variability in CO and TPR but low variability in MAP. During deoxycorticosterone acetate-salt hypertension, CO was maintained, but TPR was elevated compared with the baseline period. We conclude that the magnitudes of interindividual variability of MAP, CO, and TPR are quantitatively similar in humans and rats, providing support for the relevance of this variability in both species and suggesting that studies in rats could be designed to address questions specific to individualized medicine in hypertension.

Gait and balance of transfemoral amputees using passive mechanical and microprocessor-controlled prosthetic knees.

BACKGROUND: Microprocessor-controlled knee joints appeared on the market a decade ago. These joints are more sophisticated and more expensive than mechanical ones. The literature is contradictory regarding changes in gait and balance when using these sophisticated devices. METHODS: This study employed a crossover design to assess the comparative performance of a passive mechanical knee prosthesis compared to a microprocessor-controlled knee joint in 15 subjects with an above-knee amputation. Objective measurements of gait and balance were obtained. RESULTS: Subjects demonstrated significantly improved gait characteristics after receiving the microprocessor-controlled prosthetic knee joint (p<0.01). Improvements in gait were a transition from a hyperextended knee to a flexed knee during loading response which resulted in a change from an internal knee flexor moment to a knee extensor moment. The participants' balance also improved (p<0.01). All conditions of the Sensory Organization Test (SOT) demonstrated improvements in equilibrium score. The composite score also increased. CONCLUSIONS: Transfemoral amputees using a microprocessor-controlled knee have significant improvements in gait and balance.

Influence of the menstrual cycle on sympathetic activity, baroreflex sensitivity, and vascular transduction in young women.

BACKGROUND: Our goal was to test sympathetic and cardiovagal baroreflex sensitivity and the transduction of sympathetic traffic into vascular resistance during the early follicular (EF) and midluteal (ML) phases of the menstrual cycle. METHODS AND RESULTS: Sympathetic baroreflex sensitivity was assessed by lowering and raising blood pressure with intravenous bolus doses of sodium nitroprusside and phenylephrine. It was defined as the slope relating muscle sympathetic nerve activity (MSNA; determined by microneurography) and diastolic blood pressure. Cardiovagal baroreflex sensitivity was defined as the slope relating R-R interval and systolic blood pressure. Vascular transduction was evaluated during ischemic handgrip exercise and postexercise ischemia, and it was defined as the slope relating MSNA and calf vascular resistance (determined by plethysmography). Resting MSNA (EF, 1170+/-151 U/min; ML, 2252+/-251 U/min; P<0.001) and plasma norepinephrine levels (EF, 240+/-21 pg/mL; ML, 294+/-25 pg/mL; P=0. 025) were significantly higher in the ML than in the EF phase. Furthermore, sympathetic baroreflex sensitivity was greater during the ML than the EF phase in every subject (MSNA/diastolic blood pressure slopes: EF, -4.15; FL, -5.42; P=0.005). No significant differences in cardiovagal baroreflex sensitivity or vascular transduction were observed. CONCLUSIONS: The present study suggests that the hormonal fluctuations that occur during the normal menstrual cycle may alter sympathetic outflow but not the transduction of sympathetic activity into vascular resistance.

Sympathetic activity and baroreflex sensitivity in young women taking oral contraceptives.

BACKGROUND: We tested sympathetic and cardiovagal baroreflex sensitivity during the placebo or "low-hormone" phase (LH) and 2 to 3 weeks later during the "high-hormone" phase (HH) of oral contraceptive (OC) use in 9 women. METHODS AND RESULTS: Sympathetic baroreflex sensitivity was assessed by intravenous doses of sodium nitroprusside and phenylephrine and defined as the slope relating muscle sympathetic nerve activity (by microneurography) and diastolic blood pressure. Cardiovagal baroreflex sensitivity was defined as the slope relating R-R interval and systolic blood pressure. No difference was observed for resting muscle sympathetic nerve activity or plasma norepinephrine levels. However, sympathetic baroreflex sensitivity was greater and mean arterial pressure was higher during the LH than in the HH phase. Similarly, cardiovagal baroreflex sensitivity was greater in the LH than in the HH phase. CONCLUSIONS: Sympathetic and cardiovagal baroreflex sensitivities change during the 28-day course of OC use. Furthermore, changes in baroreflex sensitivity with OC differ from changes in baroreflex sensitivity during the normal menstrual cycle.

Response of upper limb blood flow to handgrip exercise after Blalock-Taussig operation (for tetralogy of Fallot) or subclavian flap operation (for aortic isthmic coarctation).

To evaluate the effects of long-term reductions in perfusion pressure on blood flow responses to increased functional demand, 5 patients (aged 12 to 26 years) without normal aortic to subclavian artery blood flow to 1 arm as a result of surgery to treat congenital heart disease were studied. Five age- and sex-matched healthy (control) subjects were also studied. In the patients, forearm blood flow was not different in the surgical and normal arms at rest (3.6 +/- 0.6 vs 4.0 +/- 0.7 ml/min/100 ml, respectively, mean +/- standard error, difference not significant) despite lower systolic blood pressure in the surgical arm (87 +/- 2 vs 115 +/- 2 mm Hg, p less than 0.05). The increases in heart rate, systolic blood pressure, forearm electromyographic activity (index of muscle fatigue) and postexercise forearm blood flow (index of muscle oxygen deficit) were not different in response to 2.5 minutes of submaximal rhythmic handgrip exercise (50% of maximal force) performed with the surgical versus the normal arms. Peak forearm blood flow elicited by combined ischemia and maximal isometric handgrip exercise was not significantly different in surgical and normal arms in the group as a whole (39 +/- 4 vs 43 +/- 3 ml/min/100 ml, difference not significant), although some bilateral deficit (20 to 38%) was observed in 2 patients. No bilateral differences were observed in the control subjects under any condition. The finding of normal physiologic adjustments to submaximal rhythmic handgrip exercise with the surgical arm suggests that oxygen delivery during exercise was adequate.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute response to submaximal and maximal exercise consequent to beta-adrenergic blockade: implications for the prescription of exercise.

Forty-seven healthy male subjects, 17 to 34 years old, completed a test to exhaustion on a motor-driven treadmill to determine their maximal oxygen uptake. A second test was administered 2 days later during which the subject walked for 20 to 25 minutes at a steady-state level representing 60% of the maximal oxygen uptake as determined in the first test. The grade was then increased every 2 minutes until the subject reached the state of exhaustion. After the second test, the subjects were randomly assigned, in a double-blind manner, to either placebo, propranolol (160 mg/day), or atenolol (100 mg/day) treatment for 7 days. Exactly 1 week from the time of the second test, and 3 hours after the last medication, the subjects completed the final exercise test using the same treadmill protocol administered in the second test. Heart rate and systolic blood pressure at rest and during submaximal steady-state exercise were significantly reduced by both drugs, whereas diastolic pressure was unaffected. During submaximal steady-state exercise, cardiac output was reduced in both the placebo and atenolol groups, stroke volume was increased in both atenolol and propranolol groups, oxygen uptake was reduced in the atenolol group, pulmonary ventilation was reduced in both propranolol and atenolol groups, and the respiratory exchange ratio remained unchanged. With maximal exercise, treadmill time was significantly reduced with propranolol, pulmonary ventilation and heart rate were reduced significantly with both drugs, but maximal oxygen uptake remained unchanged. Thus, beta blockade does not appear to limit ability to exercise. However, there appears to be a significant advantage to using a cardioselective rather than a nonselective beta-blocking agent.

Effects of cardioselective and nonselective beta-adrenergic blockade on the performance of highly trained runners.

Twenty-five highly trained runners with a maximal oxygen uptake (VO2 max) of 64.7 +/- 4.3 ml . kg-1. min-1 were administered clinically equivalent doses of a nonselective (propranolol) and a cardioselective (atenolol) beta-blocking agent as well as a placebo. The subjects performed a horizontal treadmill test on the eighth day and a 10-km track race on the tenth day of each treatment. Beta blockade decreased submaximal heart rate and propranolol caused the largest decrease. Beta blockade caused a decrease in maximal heart rate, VO2 max, maximal ventilation, maximal respiratory exchange ratio and treadmill time. Propranolol caused a greater decrease than atenolol in each of these values. The 10-km race times were significantly slower during beta blockade, and propranolol race times were significantly slower than atenolol race times. It is concluded that the performance of highly trained distance runners is significantly altered by beta-adrenergic blockade and that nonselective agents reduce performance to a greater extent than cardioselective agents.

Cardiorespiratory alterations consequent to endurance exercise training during chronic beta-adrenergic blockade with atenolol and propranolol.

A study was undertaken to determine if normal healthy subjects can increase their endurance capacity consequent to endurance training during chronic beta-adrenergic blockade. Forty-seven subjects, 17 to 34 years of age, were randomly assigned to 1 of 3 treatments (placebo, propranolol, 160 mg/day, and atenolol, 100 mg/day) and then completed a 15-week aerobic exercise training program. All groups reduced their submaximal steady-state heart rates consequent to training; submaximal oxygen uptake was slightly reduced; submaximal stroke volume was increased only in the placebo and atenolol groups; submaximal cardiac output was generally lower; and arterial-mixed venous oxygen difference was increased after training in all 3 groups, suggesting decreased muscle blood flow and increased oxidative capacity. Maximal oxygen uptake and maximal treadmill time were increased in all 3 groups after training. However, while still on medication the atenolol group had significantly greater increases in maximal oxygen uptake and maximal treadmill time compared with the propranolol group. Because most patients will remain on medication, these results suggest a distinct advantage for cardioselective blocking agents. It is concluded that beta-adrenergic blockade does not reduce the ability of normal healthy subjects to gain the benefits associated with cardiorespiratory endurance training.

The effect of changing transfusion practice on rates of perioperative stroke and myocardial infarction in patients undergoing carotid endarterectomy: a retrospective analysis of 1114 Mayo Clinic patients. Mayo Perioperative Outcomes Group.

OBJECTIVE: To evaluate changes in the institution's red blood cell (RBC) transfusion practice during the past 15 years and the influence of these changes on neurologic or cardiac morbidity after carotid endarterectomy. PATIENTS AND METHODS: Based on a retrospective analysis of the Mayo Clinic database, 1,114 patients who underwent carotid endarterectomy were stratified into 1 of 2 groups: (1) 1980 to 1985 (ie, pre-human immunodeficiency virus screening, early-practice group [n=552]) and (2) 1990 to 1995 (ie, recent-practice group [n=562]). Data were compared between time periods using the chi2 test for categorical variables and the rank sum test for continuous variables. Logistic regression was used to assess the association between perioperative transfusion practice and the occurrence of stroke or myocardial infarction. Two-tailed P values < or = 05 were considered statistically significant. RESULTS: Patients in the recent-practice group were significantly older (mean +/- SD age, 69.6 +/- 8.7 years) vs 65.9 +/- 8.3 years in the early-practice group (P<.001). The proportion of patients receiving perioperative RBC transfusion decreased dramatically from 72.9% in 1980-1985 to 8.7% in 1990-1995 (P<.001). Additionally, the mean +/- SD number of RBC units transfused decreased from 1.10 +/- 1.30 U in 1980-1985 to 0.27 +/- 1.22 U in 1990-1995 (P<.001). Mean +/- SD discharge hemoglobin concentration decreased from 13.7 +/- 1.4 g/dL in 1980-1985 to 11.8 +/- 1.5 g/dL in 1990-1995 (P<.001). Rates of perioperative stroke and myocardial infarction did not differ between the 2 time periods (early-practice group vs recent-practice group: stroke, 5.1% vs 3.6% [P=.22]; myocardial infarction, 1.5% vs 2.3% [P=.29]). CONCLUSIONS: Our results suggest that elderly patients undergoing carotid endarterectomy (ie, individuals known to be at high risk for cerebral and cardiac ischemia) can tolerate modest perioperative anemia despite a considerable change in the institution's transfusion practice (lower "transfusion trigger," the hemoglobin concentration or hematocrit value below which RBC transfusion is indicated).

Modeling: optimal marathon performance on the basis of physiological factors.

This paper examines current concepts concerning "limiting" factors in human endurance performance by modeling marathon running times on the basis of various combinations of previously reported values of maximal O2 uptake (VO2max), lactate threshold, and running economy in elite distance runners. The current concept is that VO2max sets the upper limit for aerobic metabolism while the blood lactate threshold is related to the fraction of VO2max that can be sustained in competitive events greater than approximately 3,000 m. Running economy then appears to interact with VO2max and blood lactate threshold to determine the actual running speed at lactate threshold, which is generally a speed similar to (or slightly slower than) that sustained by individual runners in the marathon. A variety of combinations of these variables from elite runners results in estimated running times that are significantly faster than the current world record (2:06:50). The fastest time for the marathon predicted by this model is 1:57:58 in a hypothetical subject with a VO2max of 84 ml.kg-1.min-1, a lactate threshold of 85% of VO2max, and exceptional running economy. This analysis suggests that substantial improvements in marathon performance are "physiologically" possible or that current concepts regarding limiting factors in endurance running need additional refinement and empirical testing.

Does the pressor response to ischemic exercise improve blood flow to contracting muscles in humans?

The purpose of this study was to determine in humans 1) the gain for the reflex pressor response that occurs when perfusion pressure to rhythmically contracting muscles is reduced and 2) whether the pressor response improves blood flow to the contracting muscles. Six normal subjects performed light, moderate, and heavy rhythmic forearm contractions (30/min) with the forearm enclosed in a Plexiglas box. Pressure in the box was increased 10 mmHg each minute up to 50 mmHg to reduce transmural pressure in the arterial system of the forearm. Mean arterial pressure (MAP) was measured continuously. During light exercise no reflex increase in MAP occurred until box pressure was 50 mmHg. During moderate and heavy exercise MAP began to increase with only 10- to 20-mmHg increases in box pressure. The slope of this increase was 3.5-3.9 mmHg per 10 mmHg of box pressure (approximately 60% of that in dogs). In a further study on six subjects a deep vein draining the active forearm muscles was cannulated and deep venous O2 saturation measured to assess how a 50-mmHg increase in box pressure and subsequent reflex increase in MAP altered blood flow to the contracting muscles during heavy rhythmic exercise. The increase in box pressure reduced blood flow to contracting forearm muscles by 20-25% and was followed by a 19-mmHg increase in MAP that did not appear to improve perfusion of the active muscles. This finding was unexpected, because studies in dogs suggest that the pressor response to rhythmic exercise with restricted muscle blood flow can improve perfusion of the active muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased muscle perfusion reduces muscle sympathetic nerve activity during handgripping.

This study sought to determine whether increasing blood flow to active muscles can blunt the normal rise in muscle sympathetic nerve activity (MSNA) during heavy rhythmic forearm exercise in humans. Subjects performed 5- to 6-min exercise bouts of handgripping (30/min) at 40-50% of maximum voluntary contraction (MVC). Blood flow was increased by application of suction (50 mmHg) around the forearm. Suction increased deep venous oxygen saturation in blood draining the forearm from 34 +/- 4 to 45 +/- 4%, indicating that muscle blood flow had risen by approximately 20%. Suction had no impact on the heart rate, perceived exertion, or electromyographic responses to the handgripping. During 6 min of exercise at 50% of MVC, MSNA rose from 376 +/- 67 to 970 +/- 125 units during the control trial vs. 396 +/- 69 to 729 +/- 94 units during the suction trial, and the difference was maintained during 2 min of postexercise ischemia (P < 0.05; suction < control). Mean arterial pressure (MAP) rose from 99 +/- 4 to 129 +/- 6 mmHg during control vs. 99 +/- 4 to 126 +/- 6 mmHg during the suction trial, and these responses were only different (P < 0.05; suction < control) during the final minute of the exercise bouts. During postexercise ichemia, MAP was 122 +/- 6 mmHg after the control trial but was only 112 +/- 4 mmHg after the suction trial. These results indicate that forearm suction augmented muscle blood flow, limited the activation of chemosensitive muscle afferents, and blunted the rise in MSNA during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Skeletal muscle mass and the reduction of VO2max in trained older subjects.

The role of skeletal muscle mass in the age-associated decline in maximal O2 uptake (VO2max) is poorly defined because of confounding changes in muscle oxidative capacity and in body fat and the difficulty of quantifying active muscle mass during exercise. We attempted to clarify these issues by examining the relationship between several indexes of muscle mass, as estimated by using dual-energy X-ray absorptiometry and treadmill VO2max in 32 chronically endurance-trained subjects from four groups (n = 8/group): young men (20-30 yr), older men (56-72 yr), young women (19-31 yr), and older women (51-72 yr). VO2max per kilogram body mass was 26 and 22% lower in the older men (45.9 vs. 62.0 ml.kg-1.min-1) and older women (40.0 vs. 51.5 ml.kg-1.min-1). These age differences were reduced to 14 and 13%, respectively, when VO2max was expressed per kilogram of appendicular muscle. When appropriately adjusted for age and gender differences in appendicular muscle mass by analysis of covariance, whole body VO2max was 0.50 +/- 0.09 l/min less (P < 0.001) in the older subjects. This effect was similar in both genders. These findings suggest that the reduced VO2max seen in highly trained older men and women relative to their younger counterparts is due, in part, to a reduced aerobic capacity per kilogram of active muscle independent of age-associated changes in body composition, i.e., replacement of muscle tissue by fat. Because skeletal muscle adaptations to endurance training can be well maintained in older subjects, the reduced aerobic capacity per kilogram of muscle likely results from age-associated reductions in maximal O2 delivery (cardiac output and/or muscle blood flow).

Nitric oxide and vasodilation in human limbs.

Both the skeletal muscle and skin of humans possess remarkable abilities to vasodilate. Marked vasodilation can be seen in these vascular beds in response to a variety of common physiological stimuli. These stimuli include reactive hyperemia (skin and muscle), exercise hyperemia (muscle), mental stress (muscle), and whole body heating (skin). The physiological mechanisms that cause vasodilation in response to these stimuli are poorly understood, and the substance(s) responsible for it remain unclear. In this context, recent attention has been focused on the possible contribution of nitric oxide (NO) to the regulation of hyperemic responses in human skin and skeletal muscle. The emerging picture is that NO is not an essential component of the dilator response seen during reactive hyperemia. However, it does appear that NO may play a modest role in exercise hyperemia. NO appears to play a major role in the skeletal muscle vasodilation seen in response to mental stress in humans. Preliminary evidence also indicates that NO is not essential for the normal dilator responses observed in the cutaneous circulation during body heating in humans, but this issue needs further study. There are a number of possible mechanisms that might mediate NO release in humans, and the role of these mechanisms in the various hyperemic responses is also poorly understood. The role of altered NO-mediated vasodilation in some disease states is also discussed. Whereas NO is a potent vasodilating substance, the actions of NO alone do not explain a variety of poorly understood vasodilator mechanisms in conscious humans. Much work remains for those interested in the role of NO in the regulation of blood flow to the skin and skeletal muscle of humans.

Electrical activation of expiratory muscles increases with time in pentobarbital-anesthetized dogs.

Although the pentobarbital-anesthetized dog is often used as a model in studies of respiratory muscle activity during spontaneous breathing, there is no information regarding the stability of the pattern of breathing of this model over time. The electromyograms of several inspiratory and expiratory muscle groups were measured in six dogs over a 4-h period by use of chronically implanted electrodes. Anesthesia was induced with pentobarbital sodium (25 mg/kg iv), with supplemental doses to maintain constant plasma pentobarbital concentrations. Phasic electrical activity increased over time in the triangularis sterni, transversus abdominis, and external oblique muscles (expiratory muscles). The electrical activity of the costal diaphragm, crural diaphragm, and parasternal intercostal muscles (inspiratory muscles) was unchanged. These changes in electrical activity occurred despite stable plasma levels of pentobarbital and arterial PCO2. They were associated with changes in chest wall motion and an increased tidal volume with unchanged breathing frequency. We conclude that expiratory muscle groups are selectively activated with time in pentobarbital-anesthetized dogs lying supine. Therefore the duration of anesthesia is an important variable in studies using this model.

Reductions in blood pressure after acute exercise by hypertensive rats.

Postexercise reductions in blood pressure at rest have been reported for hypertensive subjects. To determine whether post-exercise hypotension would occur in spontaneously hypertensive rats and to test the hypothesis that any reductions would result because of decreases in regional vascular resistances, hypertensive rats (n = 19) were instrumented with indwelling arterial catheters and Doppler probes to measure regional blood flows from the iliac, superior mesenteric, and renal arteries. Data were collected from animals who performed a 20- and a 40-min treadmill test at between 60 and 70% of their maximum O2 uptake. When the animals ran for 20 min, there was a pre- to postexercise drop in mean arterial pressure (MAP) from 158 +/- 3.6 to 150 +/- 3.6 mmHg (P less than 0.05), which was recorded 30 min after the exercise had ceased. The pre- to postexercise reduction in MAP after 40 min of treadmill running was from 154 +/- 3.1 to 138 +/- 3.0 mmHg (P less than 0.05) as recorded 30 min postexercise. Postexercise heart rate was significantly lower after the 40-min exercise bout, from a preexercise mean of 351 +/- 3 beats/min to 324 +/- 5 beats/min 30 min after the treadmill had stopped. Surprisingly, marked pre- to postexercise reductions in regional vascular resistance were not observed in either the iliac, superior mesenteric, or renal vascular beds. These data demonstrated the existence of postexercise hypotension in genetic hypertensive rats and suggested that reductions in cardiac output were the primary hemodynamic mechanism for this finding.