Multivariate modeling of cognitive-motor stimulation on neurovascular coupling: transcranial Doppler used to characterize myogenic and metabolic influences

Neural activation induces changes in cerebral blood flow velocity (CBFV) with separate contributions from resistance-area product (V(RAP)) and critical closing pressure (V(CrCP)). We modeled the dependence of V(RAP) and V(CrCP) on arterial blood pressure (ABP), end-tidal CO(2) (EtCO(2)), and cognitive stimulation to test the hypothesis that V(RAP) reflects myogenic activity while V(CrCP) reflects metabolic pathways. In 14 healthy subjects, CBFV was measured with transcranial Doppler ultrasound, ABP with the Finapres device and EtCO(2) with infrared capnography. Two different paradigms (word or puzzle) were repeated 10 times (30 s on-off), and the corresponding square-wave signal was used, together with ABP and EtCO(2), as inputs to autoregressive-moving average (ARMA) models, which allowed identification of the separate contributions of the three inputs to either V(RAP) or V(CrCP). For both paradigms, the contribution of ABP was mainly manifested through V(RAP) (P < 0.005 for word; P < 0.004 for puzzle), while stimulation mainly contributed to V(CrCP) (P < 0.002 for word; P < 0.033, for puzzle). The contribution of EtCO(2) was relatively small (<10%) with greater contribution to V(CrCP) (P < 0.01 for puzzle; not significant for word). Separate step responses were also obtained for each of the three inputs. ARMA modeling of V(RAP) and V(CrCP) allows the separation of the effects of cerebral autoregulation and CO(2) reactivity from the main effects of cognitive-motor stimulation and have the potential to improve the diagnostic value of neurovascular coupling testing in physiological and clinical studies.     

Transcranial Doppler estimation of cerebral blood flow and cerebrovascular conductance during modified rebreathing.

Clinical transcranial Doppler assessment of cerebral vasomotor reactivity (CVMR) uses linear regression of cerebral blood flow velocity (CBFV) vs. end-tidal CO(2) (Pet(CO(2))) under steady-state conditions. However, the cerebral blood flow (CBF)-Pet(CO(2)) relationship is nonlinear, even for moderate changes in CO(2). Moreover, CBF is increased by increases in arterial blood pressure (ABP) during hypercapnia. We used a modified rebreathing protocol to estimate CVMR during transient breath-by-breath changes in CBFV and Pet(CO(2)). Ten healthy subjects (6 men) performed 15 s of hyperventilation followed by 5 min of rebreathing, with supplemental O(2) to maintain arterial oxygen saturation constant. To minimize effects of changes in ABP on CVMR estimation, cerebrovascular conductance index (CVCi) was calculated. CBFV-Pet(CO(2)) and CVCi-Pet(CO(2)) relationships were quantified by both linear and nonlinear logistic regression. In three subjects, muscle sympathetic nerve activity was recorded. From hyperventilation to rebreathing, robust changes occurred in Pet(CO(2)) (20-61 Torr), CBFV (-44 to +104% of baseline), CVCi (-39 to +64%), and ABP (-19 to +23%) (all P < 0.01). Muscle sympathetic nerve activity increased by 446% during hypercapnia. The linear regression slope of CVCi vs. Pet(CO(2)) was less steep than that of CBFV (3 vs. 5%/Torr; P = 0.01). Logistic regression of CBF-Pet(CO(2)) (r(2) = 0.97) and CVCi-Pet(CO(2)) (r(2) = 0.93) was superior to linear regression (r(2) = 0.91, r(2) = 0.85; P = 0.01). CVMR was maximal (6-8%/Torr) for Pet(CO(2)) of 40-50 Torr. In conclusion, CBFV and CVCi responses to transient changes in Pet(CO(2)) can be described by a nonlinear logistic function, indicating that CVMR estimation varies within the range from hypocapnia to hypercapnia. Furthermore, quantification of the CVCi-Pet(CO(2)) relationship may minimize the effects of changes in ABP on the estimation of CVMR. The method developed provides insight into CVMR under transient breath-by-breath changes in CO(2).     

Cerebral and systemic hemodynamic changes during cognitive and motor activation paradigms

Cognitive and/or sensorimotor stimulations of the brain induce increases in cerebral blood flow that are usually associated with increased metabolic demand. We tested the hypothesis that changes in arterial blood pressure (ABP) and arterial Pco(2) also take place during brain activation protocols designed to induce hemispheric lateralization, leading to a pressure-autoregulatory response in addition to the metabolic-driven changes usually assumed by brain stimulation paradigms. Continuous recordings of cerebral blood flow velocity [CBFV; bilateral, middle cerebral artery (MCA)], ABP, ECG, and end-tidal Pco(2) (Pet(CO(2))) were performed in 15 right-handed healthy subjects (aged 21-43 yr), in the seated position, at rest and during 10 repeated presentations of a word generation and a constructional puzzle paradigm that are known to induce differential cortical activation. Derived variables included heart rate, cerebrovascular resistance, critical closing pressure, resistance area product, and the difference between the right and left MCA recordings (CBFV(R-L)). No adaptation of the CBFV(R-L) difference was detected for the repeated presentation of 10 activation tasks, for either paradigm. During activation with the word generation tasks, CBFV changed by (mean +/- SD) 9.0 +/- 3.7% (right MCA, P = 0.0007) and by 12.3 +/- 7.6% (left MCA, P = 0.0007), ABP by 7.7 +/- 6.0 mmHg (P = 0.0007), heart rate by 7.1 +/- 5.3 beats/min (P = 0.0008), and Pet(CO(2)) by -2.32 +/- 2.23 Torr (P = 0.002). For the puzzle paradigm, CBFV changed by 13.9 +/- 6.6% (right MCA, P = 0.0007) and by 11.5 +/- 6.2% (left MCA, P = 0.0007), ABP by 7.1 +/- 8.4 mmHg (P = 0.0054), heart rate by 7.9 +/- 4.6 beats/min (P = 0.0008), and Pet(CO(2)) by -2.42 +/- 2.59 Torr (P = 0.001). The word paradigm led to greater left hemispheric dominance than the right hemispheric dominance observed with the puzzle paradigm (P = 0.004). We concluded that significant changes in ABP and Pet(CO(2)) levels occur during brain activation protocols, and these contribute to the evoked change in CBFV. A pressure-autoregulatory response can be observed in addition to the hemodynamic changes induced by increases in metabolic demand. Simultaneous changes in Pco(2) and heart rate add to the complexity of the response, indicating the need for more detailed modeling and better understanding of brain activation paradigms.     

End-tidal carbon dioxide tension reflects arterial carbon dioxide tension in the heat-stressed human with and without simulated hemorrhage

End-tidal carbon dioxide tension (Pet(CO(2))) is reduced during an orthostatic challenge, during heat stress, and during a combination of these two conditions. The importance of these changes is dependent on Pet(CO(2)) being an accurate surrogate for arterial carbon dioxide tension (Pa(CO(2))), the latter being the physiologically relevant variable. This study tested the hypothesis that Pet(CO(2)) provides an accurate assessment of Pa(CO(2)) during the aforementioned conditions. Comparisons between these measures were made: 1) after two levels of heat stress (N = 11); 2) during combined heat stress and simulated hemorrhage [via lower-body negative pressure (LBNP), N = 8]; and 3) during an end-tidal clamping protocol to attenuate heat stress-induced reductions in Pet(CO(2)) (N = 7). Pet(CO(2)) and Pa(CO(2)) decreased during heat stress (P < 0.001); however, there was no group difference between Pa(CO(2)) and Pet(CO(2)) (P = 0.36) nor was there a significant interaction between thermal condition and measurement technique (P = 0.06). To verify that this nonsignificant trend for the interaction was not due to a type II error, Pet(CO(2)) and Pa(CO(2)) at three distinct thermal conditions were also compared using paired t-tests, revealing no difference between Pa(CO(2)) and Pet(CO(2)) while normothermic (P = 0.14) and following a 1.0 ± 0.2°C (P = 0.21) and 1.4 ± 0.2°C (P = 0.28) increase in internal temperature. During LBNP while heat stressed, measures of Pet(CO(2)) and Pa(CO(2)) were similar (P = 0.61). Likewise, during the end-tidal carbon dioxide clamping protocol, the increases in Pet(CO(2)) (7.5 ± 2.8 mmHg) and Pa(CO(2)) (6.6 ± 3.4 mmHg) were similar (P = 0.31). These data indicate that mean Pet(CO(2)) reflects mean Pa(CO(2)) during the evaluated conditions.     

Cerebral blood flow during orthostasis: role of arterial CO2

Reductions in end-tidal Pco(2) (Pet(CO(2))) during upright posture have been suggested to be the result of hyperventilation and the cause of decreases in cerebral blood flow (CBF). The goal of this study was to determine whether decreases in Pet(CO(2)) reflected decreases in arterial Pco(2) (Pa(CO(2))) and their relation to increases in alveolar ventilation (Va) and decreases in CBF. Fifteen healthy subjects (10 women and 5 men) were subjected to a 10-min head-up tilt (HUT) protocol. Pa(CO(2)), Va, and cerebral flow velocity (CFV) in the middle and anterior cerebral arteries were examined. In 12 subjects who completed the protocol, reductions in Pet(CO(2)) and Pa(CO(2)) (-1.7 +/- 0.5 and -1.1 +/- 0.4 mmHg, P < 0.05) during minute 1 of HUT were associated with a significant increase in Va (+0.7 +/- 0.3 l/min, P < 0.05). However, further decreases in Pa(CO(2)) (-0.5 +/- 0.5 mmHg, P < 0.05), from minute 1 to the last minute of HUT, occurred even though Va did not change significantly (-0.2 +/- 0.3 l/min, P = not significant). Similarly, CFV in the middle and anterior cerebral arteries decreased (-7 +/- 2 and -8 +/- 2%, P < 0.05) from minute 1 to the last minute of HUT, despite minimal changes in Pa(CO(2)). These data suggest that decreases in Pet(CO(2)) and Pa(CO(2)) during upright posture are not solely due to increased Va but could be due to ventilation-perfusion mismatch or a redistribution of CO(2) stores. Furthermore, the reduction in Pa(CO(2)) did not fully explain the decrease in CFV throughout HUT. These data suggest that factors in addition to a reduction in Pa(CO(2)) play a role in the CBF response to orthostatic stress.     

Cerebral blood flow velocity during mental activation: interpretation with different models of the passive pressure-velocity relationship.

The passive relationship between arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV) has been expressed by a single parameter [cerebrovascular resistance (CVR)] or, alternatively, by a two-parameter model, comprising a resistance element [resistance-area product (RAP)] and a critical closing pressure (CrCP). We tested the hypothesis that the RAP+CrCP model can provide a more consistent interpretation to CBFV responses induced by mental activation tasks than the CVR model. Continuous recordings of CBFV [bilateral, middle cerebral artery (MCA)], ABP, ECG, and end-tidal CO(2) (EtCO(2)) were performed in 13 right-handed healthy subjects (aged 21-43 yr), in the seated position, at rest and during 10 repeated presentations of a word generation and a constructional puzzle paradigm that are known to induce differential cortical activation. Due to its small relative change, the CBFV response can be broken down into standardized subcomponents describing the relative contributions of ABP, CVR, RAP, and CrCP. At rest and during activation, the RAP+CrCP model suggested that RAP might reflect myogenic activity in response to the ABP transient, whereas CrCP was more indicative of metabolic control. These different influences were not reflected by the CVR model, which indicated a predominantly metabolic response. Repeated-measures multi-way ANOVA showed that CrCP (P = 0.025), RAP (P = 0.046), and CVR (P = 0.002) changed significantly during activation. CrCP also had a significant effect of paradigm (P = 0.045) but not hemispheric dominance. Both RAP (P = 0.039) and CVR (P = 0.0008) had significant effects of hemispheric dominance but were not sensitive to the different paradigms. Subcomponent analysis can help with the interpretation of CBFV responses to mental activation, which were found to be dependent on the underlying model of the passive ABP-CBFV relationship.     

Multiple coherence of cerebral blood flow velocity in humans

The coherence function has been used in transfer function analysis of dynamic cerebral autoregulation to assess the statistical significance of spectral estimates of gain and phase frequency response. Interpretation of the coherence function and choice of confidence limits has not taken into account the intrinsic nonlinearity represented by changes in cerebrovascular resistance due to vasomotor activity. For small spontaneous changes in arterial blood pressure (ABP), the relationship between ABP and cerebral blood flow velocity (CBFV) can be linearized, showing that corresponding changes in cerebrovascular resistance should be included as a second input variable. In this case, the standard univariate coherence function needs to be replaced by the multiple coherence, which takes into account the contribution of both inputs to explain CBFV variability. With the use of two different indicators of cerebrovascular resistance index [CVRI = ABP/CBFV and the resistance-area product (RAP)], multiple coherences were calculated for 42 healthy control subjects, aged 20 to 40 yr (28 +/- 4.6 yr, mean +/- SD), at rest in the supine position. CBFV was measured in both middle cerebral arteries, and ABP was recorded noninvasively by finger photoplethysmography. Results for the ABP + RAP inputs show that the multiple coherence of CBFV for frequencies <0.05 Hz is significantly higher than the corresponding values obtained for univariate coherence (P < 10(-5)). Corresponding results for the ABP + CVRI inputs confirm the principle of multiple coherence but are less useful due to the interdependence between CVRI, ABP, and CBFV. The main conclusion is that values of univariate coherence between ABP and CBFV should not be used to reject spectral estimates of gain and phase, derived from small fluctuations in ABP, because the true explained power of CBFV in healthy subjects is much higher than what has been usually predicted by the univariate coherence functions.     

Impaired cerebral CO2 vasoreactivity: association with endothelial dysfunction

Conflicting data exist on the role of nitric oxide (NO) in cerebral blood flow (CBF) autoregulation. Previous studies involving human and animal subjects seem to indicate that NO involvement is limited to the CO(2)-dependent mechanism (chemoregulation) and not to the pressure-dependent autoregulation (mechanoregulation). We tested this hypothesis in patients with impaired endothelial function compared with healthy controls. Blood pressure, heart rate, end-tidal Pco(2), CBF velocities (CBFV), forearm blood flow, and reactive hyperemia were assessed in 16 patients with diabetes mellitus and/or hypertension and compared with 12 age- and sex-matched healthy controls. Pressure-dependent autoregulation was determined by escalating doses of phenylephrine. CO(2) vasoreactivity index was extrapolated from individual slopes of mean CBFV during normocapnia, hyperventilation, and CO(2) inhalation. Measurements were repeated after sodium nitroprusside infusion. Indexes of endothelial function, maximal and area under the curve (AUC) of forearm blood flow (FBF) changes, were significantly impaired in patients (maximal flow: 488 +/- 75 vs. 297 +/- 31%; P = 0.01, AUC DeltaFBF: 173 +/- 17 vs. 127 +/- 11; P = 0.03). Patients and controls showed similar changes in cerebrovascular resistance during blood pressure challenges (identical slopes). CO(2) vasoreactivity was impaired in patients compared with controls: 1.19 +/- 0.1 vs. 1.54 +/- 0.1 cm.s(-1).mmHg(-1); P = 0.04. NO donor (sodium nitroprusside) offsets this disparity. These results suggest that patients with endothelial dysfunction have impaired CO(2) vasoreactivity and preserved pressure-dependent autoregulation. This supports our hypothesis that NO is involved in CO(2)-dependent CBF regulation alone. CBFV chemoregulation could therefore be a surrogate of local cerebral endothelial function.     

Impaired cerebrovascular autoregulation and reduced CO₂ reactivity after long duration spaceflight

Long duration habitation on the International Space Station (ISS) is associated with chronic elevations in arterial blood pressure in the brain compared with normal upright posture on Earth and elevated inspired CO(2). Although results from short-duration spaceflights suggested possibly improved cerebrovascular autoregulation, animal models provided evidence of structural and functional changes in cerebral vessels that might negatively impact autoregulation with longer periods in microgravity. Seven astronauts (1 woman) spent 147 ± 49 days on ISS. Preflight testing (30-60 days before launch) was compared with postflight testing on landing day (n = 4) or the morning 1 (n = 2) or 2 days (n = 1) after return to Earth. Arterial blood pressure at the level of the middle cerebral artery (BP(MCA)) and expired CO(2) were monitored along with transcranial Doppler ultrasound assessment of middle cerebral artery (MCA) blood flow velocity (CBFV). Cerebrovascular resistance index was calculated as (CVRi = BP(MCA)/CBFV). Cerebrovascular autoregulation and CO(2) reactivity were assessed in a supine position from an autoregressive moving average (ARMA) model of data obtained during a test where two breaths of 10% CO(2) were given four times during a 5-min period. CBFV and Doppler pulsatility index were reduced during -20 mmHg lower body negative pressure, with no differences pre- to postflight. The postflight indicator of dynamic autoregulation from the ARMA model revealed reduced gain for the CVRi response to BP(MCA) (P = 0.017). The postflight responses to CO(2) were reduced for CBFV (P = 0.056) and CVRi (P = 0.047). These results indicate that long duration missions on the ISS impaired dynamic cerebrovascular autoregulation and reduced cerebrovascular CO(2) reactivity.     

Effect of central CO(2) drive on lung inflation responses of expiratory bulbospinal neurons in dogs

The purpose of these studies is to better understand the nature of the reflex interactions that control the discharge patterns of caudal medullary, expiratory (E) bulbospinal neurons. We examined the effect of central chemodrive inputs measured as arterial CO(2) tension (Pa(CO(2))) during hyperoxia on the excitatory and inhibitory components of the lung inflation responses of these neurons in thiopental sodium-anesthetized, paralyzed dogs. Data from slow ramp inflation and deflation test patterns, which were separated by several control inflation cycles, were used to produce plots of neuronal discharge frequency (F(n)) versus transpulmonary pressure (P(t)). P(t) was used as an index of the activity arising from the slowly adapting pulmonary stretch receptors (PSRs). Changes in inspired CO(2) concentrations were used to produce Pa(CO(2)) levels that ranged from 20 to 80 mmHg. The data obtained from 41 E neurons were used to derive an empirical model that quantifies the average relationship for F(n) versus both P(t) and Pa(CO(2)). This model can be used to predict the time course and magnitude of E neuronal responses to these inputs. These data suggest that the interaction between Pa(CO(2)) and PSR-mediated excitation and inhibition of F(n) is mainly additive, but synergism between Pa(CO(2)) and excitatory inputs is also present. The implications of these findings are discussed.     

Effects of age and exercise on physiological dead space during simulated dives at 2.8 ATA.

Physiological dead space (Vds), end-tidal CO(2) (Pet(CO(2))), and arterial CO(2) (Pa(CO(2))) were measured at 1 and 2.8 ATA in a dry hyperbaric chamber in 10 older (58-74 yr) and 10 younger (19-39 yr) air-breathing subjects during rest and two levels of upright exercise on a cycle ergometer. At pressure, Vd (liters btps) increased from 0.34 +/- 0.09 (mean +/- SD of all subjects for normally distributed data, median +/- interquartile range otherwise) to 0.40 +/- 0.09 (P = 0.0060) at rest, 0.35 +/- 0.13 to 0.45 +/- 0.11 (P = 0.0003) during light exercise, and 0.38 +/- 0.17 to 0.45 +/- 0.13 (P = 0.0497) during heavier exercise. During these conditions, Pa(CO(2)) (Torr) increased from 33.8 +/- 4.2 to 35.7 +/- 4.4 (P = 0.0059), 35.3 +/- 3.2 to 39.4 +/- 3.1 (P < 0.0001), and 29.6 +/- 5.6 to 37.4 +/- 6.5 (P < 0.0001), respectively. During exercise, Pet(CO(2)) overestimated Pa(CO(2)), although the absolute difference was less at pressure. Capnography poorly estimated Pa(CO(2)) during exercise at 1 and 2.8 ATA because of wide variability. Older subjects had higher Vd at 1 ATA but similar changes in Vd, Pa(CO(2)), and Pet(CO(2)) at pressure. These results are consistent with an effect of increased gas density.     

Dynamic cerebral autoregulation remains stable during physical challenge in healthy persons

The effects of physical activity on cerebral blood flow (CBF) and cerebral autoregulation (CA) have not yet been fully evaluated. There is controversy as to whether increasing heart rate (HR), blood pressure (BP), and sympathetic and metabolic activity with altered levels of CO2 might compromise CBF and CA. To evaluate these effects, we studied middle cerebral artery blood flow velocity (CBFV) and CA in 40 healthy young adults at rest and during increasing levels of physical exercise. We continuously monitored HR, BP, end-expiratory CO2, and CBFV with transcranial Doppler sonography at rest and during stepwise ergometric challenge at 50, 100, and 150 W. The modulation of BP and CBFV in the low-frequency (LF) range (0.04-0.14 Hz) was calculated with an autoregression algorithm. CA was evaluated by calculating the phase shift angle and gain between BP and CBFV oscillations in the LF range. The LF BP-CBFV gain was then normalized by conductance. Cerebrovascular resistance (CVR) was calculated as mean BP adjusted to brain level divided by mean CBFV. HR, BP, CO2, and CBFV increased significantly with exercise. Phase shift angle, absolute and normalized LF BP-CBFV gain, and CVR, however, remained stable. Stable phase shift, LF BP-CBFV gain, and CVR demonstrate that progressive physical exercise does not alter CA despite increasing HR, BP, and CO2. CA seems to compensate for the hemodynamic effects and increasing CO2 levels during exercise.     

CT灌注评价高碳酸血症模型下正常大鼠脑组织血流动力学变化

目的探讨CT灌注评价高碳酸血症模型下正常大鼠脑组织血流动力学变化的可行性;研究大鼠CT灌注参数变化率与α-SMA表达之间的相关性。方法 10只雄性SD大鼠,体质量250～300g,在吸入空气和吸入高浓度CO2混合气体(10%CO2和90%空气组成)后15min,分别使用GE16层Light Speed CT扫描仪对大鼠脑尾状核层面进行CT灌注扫描,原始图像经GE ADW4.2工作站Perfusion3.0脑部灌注软件处理后产生灌注曲线及伪彩图像,两次扫描前均测定大鼠的血液CO2分压、pH值等血气分析指标。检查结束后24h内,大鼠取脑固定,在尾状核中心层面切片,进行脑组织HE染色及鼠特异性SMA抗体免疫组化染色。应用SPSS11.5统计学软件进行分析:采用配对t检验,比较正常大鼠右侧尾状核在吸入空气和吸入高浓度CO2混合气体后CT灌注参数脑血容量(CBV)、脑血流量(CBF)、血管表面通透性(PS)和平均透过时间(MTT)的变化有无差异;采用Pearson相关分析分别检测大鼠右侧尾状核的SMA阳性血管染色计数与灌注参数CBV和CBF在CO2分压升高前后的变化率相关性。结果所有大鼠在吸入含10%CO2和90%空气的混合气体15min后,动脉血CO2分压均明显升高(t=9.39,P0.001),血浆pH值降低(t=13.49,P0.001)。正常SD大鼠右侧基底节区CBV、CBF、PS每100g组织分别为(10.28±4.01)mL、(304.95±88.77)mL/min、(0.26±0.37)mL/min,MTT值为(1.48±0.07)s;吸入10%CO2和90%空气的混合气体后右侧基底节区CBV、CBF值明显增加,每100g组织分别为(19.25±8.42)mL(t=4.92,P=0.001)和(507.33±167.94)mL/min(t=6.75,P0.001);吸入混合气体前后CBV、CBF增加百分比分别为(87.14±46.45)%、(65.75±22.05)%;PS及MTT变化不显著(P均0.05)。大鼠脑组织α-SMA阳性染色血管计数为(12.7±3.23)条/高倍视野。Pearson相关分析显示,正常脑组织的CBV和CBF变化率与其α-SMA阳性计数之间呈显著相关(r分别为0.652和0.890,P均0.05)。结论 CT灌注技术在改变血液CO2分压的条件下可以反映脑组织血流动力学变化;大鼠正常脑组织高碳酸血症前后CT灌注参数变化率与成熟血管数量相关。     

Effects of cross-education on the muscle after a period of unilateral limb immobilization using a shoulder sling and swathe

The purpose of this study was to apply cross-education during 4 wk of unilateral limb immobilization using a shoulder sling and swathe to investigate the effects on muscle strength, muscle size, and muscle activation. Twenty-five right-handed participants were assigned to one of three groups as follows: the Immob + Train group wore a sling and swathe and strength trained (n = 8), the Immob group wore a sling and swathe and did not strength train (n = 8), and the Control group received no treatment (n = 9). Immobilization was applied to the nondominant (left) arm. Strength training consisted of maximal isometric elbow flexion and extension of the dominant (right) arm 3 days/wk. Torque (dynamometer), muscle thickness (ultrasound), maximal voluntary activation (interpolated twitch), and electromyography (EMG) were measured. The change in right biceps and triceps brachii muscle thickness [7.0 ± 1.9 and 7.1 ± 2.2% (SE), respectively] was greater for Immob + Train than Immob (0.4 ± 1.2 and -1.9 ± 1.7%) and Control (0.8 ± 0.5 and 0.0 ± 1.1%, P < 0.05). Left biceps and triceps brachii muscle thickness for Immob + Train (2.2 ± 0.7 and 3.4 ± 2.1%, respectively) was significantly different from Immob (-2.8 ± 1.1 and -5.2 ± 2.7%, respectively, P < 0.05). Right elbow flexion strength for Immob + Train (18.9 ± 5.5%) was significantly different from Immob (-1.6 ± 4.0%, P < 0.05). Right and left elbow extension strength for Immob + Train (68.1 ± 25.9 and 32.2 ± 9.0%, respectively) was significantly different from the respective limb of Immob (1.3 ± 7.7 and -6.1 ± 7.8%) and Control (4.7 ± 4.7 and -0.2 ± 4.5%, P < 0.05). Immobilization in a sling and swathe decreased strength and muscle size but had no effect on maximal voluntary activation or EMG. The cross-education effect on the immobilized limb was greater after elbow extension training. This study suggests that strength training the nonimmobilized limb benefits the immobilized limb for muscle size and strength.     

Influence of noninvasive peripheral arterial blood pressure measurements on assessment of dynamic cerebral autoregulation.

Assessment of dynamic cerebral autoregulation (CA) requires continuous recording of arterial blood pressure (ABP). In humans, noninvasive ABP recordings with the Finapres device have often been used for this purpose. We compared estimates of dynamic CA derived from Finapres with those from invasive recordings in the aorta. Measurements of finger noninvasive ABP (Finapres), intra-aortic ABP (Millar catheter), surface ECG, transcutaneous CO2, and bilateral cerebral blood flow velocity (CBFV) in the middle cerebral arteries were simultaneously and continuously recorded in 27 patients scheduled for percutaneous coronary interventions. Phase, gain, coherence, and CBFV step response from both the Finapres and intra-arterial catheter were estimated by transfer function analysis. A dynamic autoregulation index (ARI) was also calculated. For both hemispheres, the ARI index and the CBFV step response recovery at 4 s were significantly greater for the Finapres-derived estimates than for the values obtained from aortic pressure. The transfer function gain for frequencies <0.1 Hz was significantly smaller for the Finapres estimates. The phase frequency response was significantly greater for the Finapres estimates at frequencies >0.1 Hz, but not at lower frequencies. The Finapres gives higher values for the efficiency of dynamic CA compared with values derived from aortic pressure measurements, as indicated by biases in the ARI index, CBFV step response, gain, and phase. Despite the significance of these biases, their relatively small amplitude indicates a good level of agreement between indexes of CA derived from the Finapres compared with corresponding estimates obtained from invasive measurements of aortic ABP.     

Cerebral blood flow velocity response to induced and spontaneous sudden changes in arterial blood pressure

The influence of different types of maneuvers that can induce sudden changes of arterial blood pressure (ABP) on the cerebral blood flow velocity (CBFV) response was studied in 56 normal subjects (mean age 62 yr, range 23-80). ABP was recorded in the finger with a Finapres device, and bilateral recordings of CBFV were performed with Doppler ultrasound of the middle cerebral arteries. Recordings were performed at rest (baseline) and during the thigh cuff test, lower body negative pressure, cold pressor test, hand grip, and Valsalva maneuver. From baseline recordings, positive and negative spontaneous transients were also selected. Stability of PCO2 was monitored with transcutaneous measurements. Dynamic autoregulatory index (ARI), impulse, and step responses were obtained for 1-min segments of data for the eight conditions by fitting a mathematical model to the ABP-CBFV baseline and transient data (Aaslid's model) and by the Wiener-Laguerre moving-average method. Impulse responses were similar for the right- and left-side recordings, and their temporal pattern was not influenced by type of maneuver. Step responses showed a sudden rise at time 0 and then started to fall back to their original level, indicating an active autoregulation. ARI was also independent of the type of maneuver, giving an overall mean of 4.7 +/- 2.9 (n = 602 recordings). Amplitudes of the impulse and step responses, however, were significantly influenced by type of maneuver and were highly correlated with the resistance-area product before the sudden change in ABP (r = -0.93, P < 0.0004). These results suggest that amplitude of the CBFV step response is sensitive to the point of operation of the instantaneous ABP-CBFV relationship, which can be shifted by different maneuvers. Various degrees of sympathetic nervous system activation resulting from different ABP-stimulating maneuvers were not reflected by CBFV dynamic autoregulatory responses within the physiological range of ABP.     

Pulmonary gas exchange during exercise in highly trained cyclists with arterial hypoxemia.

The causes of exercise-induced hypoxemia (EIH) remain unclear. We studied the mechanisms of EIH in highly trained cyclists. Five subjects had no significant change from resting arterial PO(2) (Pa(O(2)); 92.1 +/- 2.6 Torr) during maximal exercise (C), and seven subjects (E) had a >10-Torr reduction in Pa(O(2)) (81.7 +/- 4.5 Torr). Later, they were studied at rest and during various exercise intensities by using the multiple inert gas elimination technique in normoxia and hypoxia (13.2% O(2)). During normoxia at 90% peak O(2) consumption, Pa(O(2)) was lower in E compared with C (87 +/- 4 vs. 97 +/- 6 Torr, P < 0.001) and alveolar-to-arterial O(2) tension difference (A-aDO(2)) was greater (33 +/- 4 vs. 23 +/- 1 Torr, P < 0. 001). Diffusion limitation accounted for 23 (E) and 13 Torr (C) of the A-aDO(2) (P < 0.01). There were no significant differences between groups in arterial PCO(2) (Pa(CO(2))) or ventilation-perfusion (VA/Q) inequality as measured by the log SD of the perfusion distribution (logSD(Q)). Stepwise multiple linear regression revealed that lung O(2) diffusing capacity (DL(O(2))), logSD(Q), and Pa(CO(2)) each accounted for approximately 30% of the variance in Pa(O(2)) (r = 0.95, P < 0.001). These data suggest that EIH has a multifactorial etiology related to DL(O(2)), VA/Q inequality, and ventilation.     

Effects of five consecutive nocturnal hypoxic exposures on the cerebrovascular responses to acute hypoxia and hypercapnia in humans.

The effects of discontinuous hypoxia on cerebrovascular regulation in humans are unknown. We hypothesized that five nocturnal hypoxic exposures (8 h/day) at a simulated altitude of 4,300 m (inspired O2 fraction = approximately 13.8%) would elicit cerebrovascular responses that are similar to those that have been reported during chronic altitude exposures. Twelve male subjects (26.6 +/- 4.1 yr, mean +/- SD) volunteered for this study. The technique of end-tidal forcing was used to examine cerebral blood flow (CBF) and regional cerebral O2 saturation (Sr(O2)) responses to acute variations in O2 and CO2 twice before, immediately after, and 5 days after the overnight hypoxic exposures. Transcranial Doppler ultrasound was used to assess CBF, and near-infrared spectroscopy was used to assess Sr(O2). Throughout the nocturnal hypoxic exposures, end-tidal Pco2 decreased (P < 0.001) whereas arterial O2 saturation increased (P < 0.001) compared with overnight normoxic control measurements. Symptoms associated with altitude illness were significantly greater than control values on the first night (P < 0.001) and second night (P < 0.01) of nocturnal hypoxia. Immediately after the nocturnal hypoxic intervention, the sensitivity of CBF to acute variations in O2 and CO2 increased 116% (P < 0.01) and 33% (P < 0.05), respectively, compared with control values. Sr(O2) was highly correlated with arterial O2 saturation (R2 = 0.94 +/- 0.04). These results show that discontinuous hypoxia elicits increases in the sensitivity of CBF to acute variations in O2 and CO2, which are similar to those observed during chronic hypoxia.     

Sex differences in the respiratory response to hemorrhage in the conscious, New Zealand white rabbit

In conscious animals, the response to hemorrhage is biphasic. During phase 1, arterial pressure is maintained. Phase 2 is characterized by profound hypotension. Despite allied roles, less is known about the integrated cardiovascular and respiratory response to blood loss in conscious animals. We evaluated cardiorespiratory changes during hemorrhage to test the hypotheses that 1) respiratory rate (RR) and blood gases do not change during phase 1; 2) RR increases during phase 2; and 3) RR and blood gas changes during hemorrhage are similar in males and females. We measured mean arterial pressure, RR, and blood gases during hemorrhage in 16 conscious, chronically prepared, male and female New Zealand white rabbits. We removed venous blood until mean arterial pressure was < or =40 mmHg. Sex did not affect mean arterial pressure, heart rate, Pa(O(2)), Pa(CO(2)), or pH during hemorrhage or the blood loss required to induce phase 2. Pa(CO(2)) decreased significantly from 37 +/- 1 to 33 +/- 1 and 29 +/- 1 mmHg (P < 0.001) during phase 1 and 2, respectively. Before hemorrhage, Pa(O(2)) was 87 +/- 2 mmHg. Pa(O(2)) was unchanged in phase 1 (92 +/- 2 mmHg) but increased in phase 2 (101 +/- 2 mmHg; P < 0.001). Body temperature, Pv(CO(2)) (thoracic vena cava), and ventilation-perfusion mismatch (A-a gradient) were unchanged during phases 1 and 2. Neither sex increased RR during phase 1. While males doubled RR during phase 2, RR in females did not change (P < 0.001). Thus, while Pa(CO(2)) decreases in phase 1 and phase 2, the decreases are achieved in different ways across the two phases and in the two sexes.     

Effect of range of motion on muscle strength and thickness

The purpose of this investigation was to compare partial range-of-motion vs. full range-of-motion upper-body resistance training on strength and muscle thickness (MT) in young men. Volunteers were randomly assigned to 3 groups: (a) full range of motion (FULL; n = 15), (b) partial range of motion (PART; n = 15), or (c) control (CON; n = 10). The subjects trained 2 d · wk(-1) for 10 weeks in a periodized program. Primary outcome measures included elbow flexion maximal strength measured by 1 repetition maximum (1RM) and elbow flexors MT measured by ultrasound. The results indicated that elbow flexion 1RM significantly increased (p < 0.05) for the FULL (25.7 ± 9.6%) and PART groups (16.0 ± 6.7%) but not for the CON group (1.7 ± 5.5%). Also, FULL 1RM strength was significantly greater than the PART 1RM after the training period. Average elbow flexor MT significantly increased for both training groups (9.65 ± 4.4% for FULL and 7.83 ± 4.9 for PART). These data suggest that muscle strength and MT can be improved with both FULL and PART resistance training, but FULL may lead to greater strength gains.