Passive Muscle Stretch Research Articles

P2X receptor blockade attenuates the sympathetic response to exercise in humans

Animal studies suggest that ATP may play a role in evoking the muscle reflex via stimulating P2X receptors on sensory neurons. No data about the role of P2X receptors in the muscle pressor reflex in humans has been reported. We hypothesized that P2X receptor blockade attenuates the exercise pressor response in humans. Blood pressure (Finometer), heart rate, and muscle sympathetic nerve activity (MSNA) from peroneal nerve were assessed during fatiguing isometric handgrip, post exercise muscle ischemia (PEMI), and passive muscle stretch during PEMI in 8 young healthy volunteers. The protocol was performed before and after local infusion of vitamin B6 (Pyridoxine Hydrochloride, a non‐specific blocker of P2 receptors) in saline via Bier block. In the second experiment, the same amount of saline was infused via the Bier block. After Vitamin B6, the MSNA responses to fatiguing handgrip (Δ342±78 vs. Δ548±102), PEMI (Δ280±43 vs. Δ451±85) and passive stretch (Δ338±62 vs. Δ559±107 units/min, all P<0.05) were significantly less than those before B6. The blood pressure responses were also significantly (all P<0.05) less than those before B6. Saline Bier block had no similar effects on the MSNA and blood pressure responses. These data verified our hypothesis that P2X receptor blockade attenuates the exercise pressor response in humans. Supported by AHA 0635245 N, NIH P01 HL077670, and M01 RR010732.

Evaluation of the Catch in Spasticity Assessment in Children With Cerebral Palsy

van den Noort JC, Scholtes VA, Becher JG, Harlaar J. Evaluation of the catch in spasticity assessment in children with cerebral palsy. Objective To evaluate whether the catch in clinical spasticity assessment in cerebral palsy (CP) is the consequence of a sudden velocity-dependent increase in muscle activity, resulting from hyperexcitability of the stretch reflex in spasticity. Design Cross-sectional study. Setting A special school for children with physical disabilities. Participants Children with CP (N=20; age range, 5–14y; mean weight ± SD, 35±14kg; mean length ± SD, 139±19cm). Interventions Spasticity assessment tests (using slow and fast passive stretch) were performed in the medial hamstrings, soleus, and medial gastrocnemius muscles of the children by 2 experienced examiners. Main Outcome Measures Surface electromyography (EMG) was recorded and joint motion was simultaneously measured using 2 inertial sensors. The encounter of a catch by the examiner was compared with the presence of a sudden increase in muscle activity (“burst”). The average rectified value (ARV) of the EMG signal was calculated for each test. Results The study shows a sudden increase in muscle activity in fast passive stretch, followed by a catch (hamstrings 100%, soleus 95%, gastrocnemius 84%). The ARV in slow passive stretch was significantly lower. Conclusions The results confirm that in children with CP, an increase in muscle activity is primarily responsible for a catch in fast passive muscle stretch.

Reliability of the Tardieu Scale for Assessing Spasticity in Children With Cerebral Palsy

Gracies J-M, Burke K, Clegg NJ, Browne R, Rushing C, Fehlings D, Matthews D, Tilton A, Delgado MR. Reliability of the Tardieu Scale for assessing spasticity in children with cerebral palsy. Objective To measure the Tardieu Scale's reliability in children with cerebral palsy (CP) when used by raters with and without experience in using the scale, before and after training. Design Single-center, intrarater and interrater reliability study. Setting Institutional ambulatory care. Participants Referred children with CP in the pretraining phase (n=5), during training (n=3), and in the posttraining phase (n=15). Interventions The Tardieu Scale involves performing passive muscle stretch at 2 velocities, slow and fast. The rater derives 2 parameters; the Spasticity Angle X is the difference between the angles of arrest at slow speed and of catch-and-release or clonus at fast speed; the Spasticity Grade Y is an ordinal variable that grades the intensity (gain) of the muscle reaction to fast stretch. In phase 1, experienced raters without formalized training in the scale graded elbow, knee, and ankle plantar flexors bilaterally, without and with a goniometer. In phase 2, after training, the experienced and nonexperienced raters graded the same muscles unilaterally. Main Outcome Measures Intrarater and interrater reliability of the Tardieu Scale. Results After training, nonexperienced raters had mean ± SD intrarater and interrater agreement rates across all joints and parameters of 80%±14% and 74%±16%, respectively. For experienced raters, intrarater and interrater agreement rates before training were 77%±13% and 66%±15%, respectively, versus 90%±8% and 81%±13%, respectively, after training ( P<.001 for both). Specific angle measurements at the knee were less reliable for the angles of catch measured at fast speed. Across all joints, agreement rates were similar using visual or goniometric measurements. Conclusions Both parameters of the Tardieu Scale have excellent intrarater and interrater reliability when assessed at the elbow and ankle joints of children with CP, with no difference noted between visual and goniometric measurements. Angle measurements were less reliable at the knee joints. Training was associated with a highly significant improvement in reliability.

Spike sorting of muscle spindle afferent nerve activity recorded with thin-film intrafascicular electrodes.

Afferent muscle spindle activity in response to passive muscle stretch was recorded in vivo using thin-film longitudinal intrafascicular electrodes. A neural spike detection and classification scheme was developed for the purpose of separating activity of primary and secondary muscle spindle afferents. The algorithm is based on the multiscale continuous wavelet transform using complex wavelets. The detection scheme outperforms the commonly used threshold detection, especially with recordings having low signal-to-noise ratio. Results of classification of units indicate that the developed classifier is able to isolate activity having linear relationship with muscle length, which is a step towards online model-based estimation of muscle length that can be used in a closed-loop functional electrical stimulation system with natural sensory feedback.

고혈압 전단계자들에 대한 골격근 Group III 자극 시 시간에 따른 심혈관 반응

본 연구는 고혈압전단계자들에 대한 지속적인 건 스트레치시 시간에 따른 생리학적 반응을 분석하여 정상혈압자와 고혈압전단계자에 대한 EPR의 한 요소인 기계적 수용기가 혈압 및 혈역학 반응에 어떠한 영향을 주는지를 검토하였다. 그 결과, 안정 시와 시간에 따른 혈압 반응은 고혈압전단계자에 있어 SBP, MAP가 평균 20sec에서 통계적으로 가장 높은 경향을 보였으며(p<0.05), 정상혈압자에서는 SBP, DBP, MAP가 평균 45sec에서 가장 높은 경향을 보였다(p<0.05). 이는 고혈압 전단계자의 지속적인 수동적 건 스트레치 시 정상혈압자에 비해 Group III mechanoreceptors의 역기능에 따른 상승된 혈압 반응이 초기에 나타내었다고 사료된다. 또한 혈역학 반응에서 안정 시와 비교하여 지속적인 수동적건 스트레치 시 고혈압전단계자에서의 HR, SV, CO, TPR 모두 유의한 차이를 보이지 않았으나 정상혈압자에서 SV, CO가 통계적으로 유의한 차이를 보였다(p<0.05). 이는 CO, SV, HR, TPR이 정상혈압자에 비해 고혈압전단계자에 있어 높은 경향을 나타내었지만, 혈역학 반응은 본 연구를 통해 차이를 보이지 않아 앞으로 연구가 필요할 것으로 사료된다. The purpose of this study was to investigate whether group III muscle afferents play an important role eliciting abnormal blood pressure response mediated during passive muscle stretch in prehypertensive individuals. Eleven middle-aged prehypertensive men (average BP 133/80 mmHg) and nine middle-aged normotensive men (average BP 119/74 mmHg) participated in this study. After 1 min rest baseline data collection, the subject's foot was flexed (dorsiflexion) by an automated cybex for one minute. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP), heart rate, stroke volume, cardiac output, and total peripheral resistance were continuously measured on a beat-by-beat basis from a finger via a Finapres device for 1 minute. To evaluate the role of mechanoreflex, a component of exercise pressor reflex, SBP, DBP, and MAP responses over the course of time were examined. The results showed that the pressor response mediated by the muscle mechanoreflex was faster in prehypertensive individuals compared to the normotensive individuals. The substantial pressor response was observed within mean 20 sec of the onset of passive stretch in prehypertension, while mean 45 sec in normotension (p<0.05). It is concluded that excessive pressor response produced during exercise in prehypertension may be due to the dysfunction of the mechano-receptors.

Development of the Hypertonia Assessment Tool (HAT)

Spasticity and dystonia, the two common forms of hypertonia in children, can be easily distinguished on neurological examination by knowledgable practitioners. Spasticity is an isokinetic form of hypertonia and is identified by palpation of the increased resistance to passive muscle stretch at various speeds. Dystonia is a hyperkinetic form of hypertonia and is identified by observation of the involuntary sustained muscle contractions that result in twisting and abnormal postures. Many practitioners do not recognize dystonia; multiple publications report that dystonia occurs in only 10% to 15% children with cerebral palsy (CP), far less than in reality. Other publications state that rigidity is seen with appreciable frequency in CP, when in fact, rigidity of the classic form seen in juvenile parkinsonism, is virtually never seen in CP. Standardized scales are available to grade the severity of spasticity and dystonia once they are diagnosed. Gordon et al.1 have reported quantitative methods to distinguish spasticity and dystonia. Apart from these, no tool has been available to distinguish the two, nor to distinguish them from rigidity (or athetosis, a hyperkinetic, hypertonic movement disorder). Jethwa et al.'s aim was to develop such a tool.2 An expert panel generated a list of 14 diagnostic items and identified seven items that agreed with the diagnoses of an experienced movement disorders pediatric neurologist more than 50% of the time. The seven items comprise the Hypertonia Assessment Tool (HAT): two items to diagnose spasticity, three to diagnose dystonia, and two to diagnose rigidity. The HAT was administered to children with hypertonia by two experienced physicians: a developmental pediatrician and a pediatric physiatrist. Their evaluations and those of the pediatric neurologist were compared to determine interrater reliability and validity. The HAT found only moderate to good validity for spasticity, and for dystonia, only fair interrater reliability and wide variations in validity. The strengths of the HAT are its simplicity and clarity. However, the following observations need to be made (1). The authors stated that ‘the neurological exam lacks standardization and the outcome is often influenced by the experience of the clinician’– yet they used a single experienced clinician as the criterion standard in developing the HAT. (2) The HAT is administered with the child supine on the examination table. The rationale for deciding on that position was not stated and it is well known that dystonia scores often differ substantially between lying and sitting. (3) Items 3 and 4 in the HAT – velocity dependent resistance to stretch and the presence of a spastic catch – are the standard techniques to diagnose and grade spasticity. (4) Items 2 and 6, used to identify dystonia, cannot be evaluated in the majority of children with dystonic CP, who are in Manual Ability Classification System and Gross Motor Function Classification System levels IV and V and unable therefore to voluntarily carry out purposeful movements. Children who are nonverbal and children with severe cognitive impairments would also be unable to perform these items. The HAT evaluation of dystonia was performed only in the extremities and not in other common sites (trunk, neck, orofacial). The use of a tactile stimulus in evaluating dystonia is controversial as dystonia is typically considered to be spontaneous, involuntary hypertonia. In fact, children with severe spastic quadriparesis – without dystonia – often have greater flexion of their upper extremities when their forearms are touched. (5) Items 5 and 7 are designed to evaluate rigidity, which almost never occurs in childhood; the authors found no child with rigidity to assess the HAT. Some children with spasticity on both sides of a joint, i.e. the biceps and triceps, or with a sustained dystonic posture, could be mistakenly diagnosed as having rigidity. The goal of developing a tool to distinguish spasticity and the hyperkinetic movement disorders is clearly worthwhile. The limitations of the HAT noted above indicate that additional work on its development is needed.

Interpretation of Muscle Spindle Afferent Nerve Response to Passive Muscle Stretch Recorded With Thin-Film Longitudinal Intrafascicular Electrodes

In this study, we explored the feasibility of estimating muscle length in passive conditions by interpreting nerve responses from muscle spindle afferents recorded with thin-film longitudinal intrafascicular electrodes. Afferent muscle spindle response to passive stretch was recorded in ten acute rabbit experiments. A newly proposed first-order model of muscle spindle response to passive sinusoidal muscle stretch manages to capture the relationship between afferent neural firing rate and muscle length. We demonstrate that the model can be used to track random motion trajectories with bandwidth from 0.1 to 1 Hz over a range of 4 mm with a muscle length estimation error of 0.3 mm (1.4 degrees of joint angle). When estimation is performed using four-channel ENG there is a 50% reduction in estimate variation, compared to using single-channel recordings.

The enhancing effect of propofol anesthesia on skeletal muscle mechanoreflex in conscious cats

To test the hypothesis that a muscle mechanosensitive reflex is suppressed in the conscious condition, we examined the effect of propofol anesthesia on the cardiovascular responses to passive mechanical stretch of the hindlimb triceps surae muscle in five conscious cats. The triceps surae muscle was manually stretched for 30 s by extending the hip and knee joints and subsequently by dorsiflexing the ankle joint. Mean arterial blood pressure (MAP) and heart rate (HR) slightly increased or decreased during passive mechanical stretch of the muscle in the conscious condition. At 5–17 min after intravenously administering propofol (8.5 ± 1 mg/kg), the identical passive stretch of the triceps surae muscle was able to induce the substantial cardiovascular responses; HR and MAP increased by 13 ± 3 beats/min and 25 ± 4 mm Hg, respectively, and the cardiovascular responses were sustained throughout the passive stretch. In contrast, stretching skin on the triceps surae muscle evoked a smaller pressor response in the anesthetized condition. When propofol anesthesia became light in the recovery period and the animals started to show spontaneous body movement, the cardiovascular responses to passive muscle stretch were blunted again. It is therefore concluded that passive mechanical stretch of skeletal muscle is capable of evoking the reflex cardiovascular responses, which is suppressed in the conscious condition but enhanced by propofol anesthesia.

Influence of central command and muscle afferent activation on anterior cerebral artery blood velocity responses to calf exercise in humans

The purpose of the present study was to determine the relative importance of peripheral feedback from mechanically (mechanoreflex) and metabolically (metaboreflex) sensitive muscle afferents and central signals arising from higher centers (central command) to the exercise-induced increases in regional cerebral perfusion. To accomplish this, anterior cerebral artery (ACA) mean blood velocity (V(mean)) responses were assessed during sustained and rhythmic passive calf muscle stretch (mechanoreflex), volitional calf exercise (mechanoreflex, metaboreflex, and central command), and electrically stimulated calf exercise (mechanoreflex and metaboreflex but no central command) at 35% of maximum voluntary contraction (n = 16). In addition, a period of postexercise muscle ischemia (PEMI) was used to isolate the metaboreflex. Blood pressure, cardiac output, and the end-tidal partial pressure of carbon dioxide (Pet(CO2)) were also measured. ACA V(mean) was unchanged from rest during either sustained or rhythmic calf muscle stretch (P > 0.05). However, ACA V(mean) was increased from rest during both isometric (+15 +/- 1%) and rhythmic (+15 +/- 2%, voluntary exercise P < 0.05) but remained unchanged during stimulated exercise (P > 0.05). Isometric and rhythmic exercise-induced increases in blood pressure and cardiac output were similar during voluntary and stimulated exercise (P > 0.05 between conditions). Blood pressure remained elevated during PEMI after all exercise conditions (P < 0.05 vs. rest), whereas cardiac output and ACA V(mean) were not different from rest (P > 0.05). Pet(CO2) was unchanged from rest throughout. These data suggest that selective activation of skeletal muscle afferents (i.e., stretch, PEMI, or stimulated exercise) does not increase ACA V(mean) and that increases in ACA V(mean) during volitional contractions of an exercising calf muscle are dependent on the presence of central command.

Evaluation of clinical spasticity assessment in Cerebral palsy using inertial sensors

Spasticity is clinically assessed using goniometry to measure the joint angle of the catch (AOC) during fast passive muscle stretch. The precision and accuracy of the goniometric AOC measurements are questionable, because of the inevitable joint repositioning after occurrence of the catch. This study aims to evaluate the use of goniometry in estimating the AOC in spasticity assessment of the medial hamstrings, soleus and gastrocnemius in twenty children with Cerebral palsy (CP), using inertial sensors (IS) as reference system. The IS were initially validated with an optoelectronic system to measure 3d-orientation and proved to be accurate within 1°. To evaluate the precision and accuracy of the goniometry, the joint angle measured with the goniometer after repositioning was compared to the joint angle measured simultaneously with the IS, and to the true AOC, detected and measured with the IS during the fast muscle stretch. Results showed that goniometry is an imprecise method to measure the true AOC in spasticity assessment. The error is mainly due to joint repositioning after the fast muscle stretch. For spasticity assessment, it is advised to apply inertial sensors when a precise measurement of the angle of catch is required.

Afferents contributing to autogenic inhibition of gastrocnemius following electrical stimulation of its tendon

Electrical stimulation of the Achilles tendon produced strong reflex inhibition of the ongoing voluntary EMG activity in the two heads of the gastrocnemius (GA) muscle in all tested subjects. The inhibition was seen clearly in both averaged and single sweep surface EMG records. The inhibitory response was produced without electrical (M wave) or mechanical, (muscle twitch) signs of direct muscle stimulation. The onset latency and duration for the first period of inhibition (I 1) were 47–49 ms and 67 ms, respectively. A second inhibition (I 2) had an onset latency of 187–193 ms and duration under 40 ms. Non-noxious stimuli in the range of 2.6–7.6 × mean perceptual threshold, when delivered to four locations over the GA tendon, all produced clear inhibition of the voluntary muscle activity. The inhibition was maximal when the cathode was a large metal plate located near the musculotendinous junction and decreased approximately linearly with distances more distal to that site. The effect of passive muscle stretch on the electrically induced tendon reflex inhibition (TRE) was tested at ankle joint angles incremented in steps of 20°. It was found that TRE is strongly dependent on joint angle, being maximal in the fully stretched muscle. TRE was lost completely after partial tibial nerve block. In comparison, GA inhibition produced by cutaneous (sural) nerve stimulation was of a higher threshold, longer latency and persisted after partial tibial nerve block. We thus demonstrated a powerful autogenic inhibition in the lower limb arising from tendon afferents in conscious subjects that is increased by passive muscle stretch and likely to originate from group I tendon afferents.

Adenosine receptor blockade accentuates the responses of muscle sympathetic nerve activity to fatiguing exercise

The role adenosine plays in evoking the exercise pressor reflex in humans remain controversial. Interestingly, animal studies suggest that adenosine can inhibit type 1 vanilloid receptors activity. Thus, we hypothesized that adenosine receptor blockade would accentuate muscle sympathetic nerves activity (MSNA) response to fatiguing exercise in humans. Blood pressure (Finometer), heart rate, and MSNA from peroneal nerve were assessed in 11 healthy young volunteers during fatiguing isometric handgrip, post exercise muscle ischemia (PEMI), and passive muscle stretch during PEMI. The protocol was performed before and after adenosine receptor blockade by local infusion of 40 mg aminophylline in saline via forearm Bier block (regional intravenous anesthesia). In the second experiment, the same amount of saline was infused via the Bier block. After aminophylline, the MSNA and blood pressure responses to fatiguing handgrip, PEMI and passive stretch (all P&lt;0.05) were significantly greater than those in control condition. Saline Bier block had no similar effects on the MSNA and blood pressure responses. These data verified our hypothesis, and suggest that adenosine may act to inhibit MSNA response in exercise pressor reflex. Supported by NIH P01 HL077670, M01 RR010732 and AHA 0635245 N.

Local metabolite accumulation augments passive muscle stretch‐induced modulation of carotid–cardiac but not carotid–vasomotor baroreflex sensitivity in man

We examined the effects of muscle mechanoreflex stimulation by passive calf muscle stretch, at rest and during concurrent muscle metaboreflex activation, on carotid baroreflex (CBR) sensitivity. Twelve subjects either performed 1.5 min one-legged isometric plantarflexion at 50% maximal voluntary contraction with their right or left calf [two ischaemic exercise (IE) trials, IER and IEL] or rested for 1.5 min [two ischaemic control (IC) trials, ICR and ICL]. Following exercise, blood pressure elevation was partly maintained by local circulatory occlusion (CO). 3.5 min of CO was followed by 3 min of CO with passive stretch (STR-CO) of the right calf in all trials. Carotid baroreflex function was assessed using rapid pulses of neck pressure from +40 to -80 mmHg. In all IC trials, stretch did not alter maximal gain of carotid-cardiac (CBR-HR) and carotid-vasomotor (CBR-MAP) baroreflex function curves. The CBR-HR curve was reset without change in maximal gain during STR-CO in the IEL trial. However, during the IER trial maximal gain of the CBR-HR curve was smaller than in all other trials (-0.34+/-0.04 beats min(-1) mmHg(-1) in IER versus -0.76+/-0.20, -0.94+/-0.14 and -0.66+/-0.18 beats min(-1) mmHg(-1) in ICR, IEL and ICL, respectively), and significantly smaller than in IEL (P<0.05). The CBR-MAP curves were reset from CO values by STR-CO in the IEL and IER trials with no changes in maximal gain. These results suggest that metabolite sensitization of stretch-sensitive muscle mechanoreceptive afferents modulates baroreflex control of heart rate but not blood pressure.

Mechanoreceptors In Skeletal Muscles Lead To A Greater Blood Pressure Increase During Exercise In Prehypertension

Previous studies strongly indicate that the exercise pressor reflex (EPR) plays an important role in the cardiovascular responses to dynamic exercise. Exercise elicits excessive pressor response in hypertension. However, it is not clear that the exaggerated cardiovascular response to exercise is mediated by EPR overactivity in hypertensive people. PURPOSE: To investigate the effects of mechanoreceptors (a component of EPR) on the cardiovascular responses during brief passive dorsiflexion of the foot in prehypertensive individuals. METHODS: Twenty healthy volunteers (12 prehypertension and 8 normotension) with a mean age of 46.7±1.0 years were recruited for this study. All subjects were instrumented to measure cardiac output (CO), mean arterial pressure (MAP) and heart rate (HR) and the responses before and after passive muscle stretch were observed in the same subjects. RESULTS: MAP increased with passive muscle stretch in both normotensive and prehypertensive conditions, however, MAP was significantly higher in prehypertensive individuals. The higher MAP in prehypertensive individuals was due to higher levels of total peripheral resistance.CONCLUSIONS: This study suggests that the enhanced cardiovascular response to exercise in hypertension may be mediated by excessive EPR. The EPR enhances vasoconstrictor tone during exercise in prehypertension causing larger increases in MAP despite depressed CO. Supported by Korea Research Foundation Grant funded by the Korean Government (KRF-2007-314-G00008

Acute compartment syndrome: reducing the risk

Acute limb compartment syndrome is a surgical emergency characterized by raised pressure within an unyielding tissue compartment. Although there is commonly a history of trauma there are a number of causes of compartment syndrome, which includes iatrogenic insults. The key clinical feature of a compartment syndrome in the conscious patient is severe pain out of proportion to the injury and aggravated by passive muscle stretch. Intracompartmental pressure measurements remain the only objective method of diagnosing an acute compartment syndrome. Although it is subject to false positives, interpreting the pressures in relation to the systemic blood pressure helps confirm the diagnosis when the clinical findings are equivocal and provides essential information in unconscious or uncooperative patients. Successful treatment of an acute compartment syndrome involves prompt, early diagnosis followed by an adequate surgical decompression of all four compartments of the leg by fasciotomies. Delay in diagnosis is almost invariably associated with a poor outcome and loss of limb function. As acute compartment syndromes typically occur in young patients with an average work–life expectancy of up to 30 years, a poor outcome results in severe loss of productivity.

Cyclooxygenase inhibition attenuates sympathetic responses to muscle stretch in humans

Passive muscle stretch performed during a period of post-exercise muscle ischemia (PEMI) increases muscle sympathetic nerve activity (MSNA), and this suggests that the muscle metabolites may sensitize mechanoreceptors in healthy humans. However, the responsible substance(s) has not been studied thoroughly in humans. Human and animal studies suggest that cyclooxygenase products sensitize muscle mechanoreceptors. Thus we hypothesized that local cyclooxygenase inhibition in exercising muscles could attenuate MSNA responses to passive muscle stretch during PEMI. Blood pressure (Finapres), heart rate, and MSNA (microneurography) responses to passive muscle stretch were assessed in 13 young healthy subjects during PEMI before and after cyclooxygenase inhibition, which was accomplished by a local infusion of 6 mg ketorolac tromethamine in saline via Bier block. In the second experiment, the same amount of saline was infused via the Bier block. Ketorolac Bier block decreased prostaglandin synthesis to approximately 34% of the baseline. Before ketorolac Bier block, passive muscle stretch evoked significant increases in MSNA (P < 0.005) and mean arterial blood pressure (P < 0.02). After ketorolac Bier block, passive muscle stretch did not evoke significant responses in MSNA (P = 0.11) or mean arterial blood pressure (P = 0.83). Saline Bier block had no effect on the MSNA or blood pressure response to ischemic stretch. These observations indicate that cyclooxygenase inhibition attenuates MSNA responses seen during PEMI and suggest that cyclooxygenase products sensitize the muscle mechanoreceptors.

Muscle progenitor cells proliferation doesn’t sufficiently contribute to maintaining stretched soleus muscle mass during gravitational unloading

Skeletal muscle work hypertrophy is usually connected with muscle progenitor satellite cells (SC) activation with subsequent incorporation of their nuclei into myofibers. Passive stretch of unloaded muscle was earlier established to prevent atrophic processes and is accompanied by enhanced protein synthesis. We hypothesized that elimination of SC proliferation capacity by γ -irradiation would partly avert stretched muscle fiber capability to maintain their size under the conditions of gravitational unloading. To assess the role of muscle progenitor (satellite) cells in development of passive stretch preventive effect SC proliferation was suppressed by local exposing to ionized radiation (2500 rad), subsequent hindlimb suspension or hindlimb suspension with concomitant passive stretch were carried out. Reduction of myofiber cross-sectional area and decrease in myonuclei number accompanying unloaded muscle atrophy were completely abolished by passive stretch both in irradiated and sham-treated animals. We conclude that SC did not make essential contribution to passive stretch preventive action under the conditions of simulated weightlessness.

Local prostaglandin blockade attenuates muscle mechanoreflex-mediated renal vasoconstriction during muscle stretch in humans

During exercise, muscle mechanoreflex-mediated sympathoexcitation evokes renal vasoconstriction. Animal studies suggest that prostaglandins generated within the contracting muscle sensitize muscle mechanoreflexes. Thus we hypothesized that local prostaglandin blockade would attenuate renal vasoconstriction during ischemic muscle stretch. Eleven healthy subjects performed static handgrip before and after local prostaglandin blockade (6 mg ketorolac tromethamine infused into the exercising forearm) via Bier block. Renal blood flow velocity (RBV; Duplex Ultrasound), mean arterial pressure (MAP; Finapres), and heart rate (HR; ECG) were obtained during handgrip, post-handgrip muscle ischemia (PHGMI) followed by PHGMI with passive forearm muscle stretch (PHGMI + stretch). Renal vascular resistance (RVR, calculated as MAP/RBV) was increased from baseline during all paradigms except during PHGMI + stretch after the ketorolac Bier block trial where RVR did not change from baseline. Before Bier block, RVR rose more during PHGMI + stretch than during PHGMI alone (P < .01). Similar results were found after a saline Bier block trial (Delta53 +/- 13% vs. Delta35 +/- 10%; P < 0.01). However, after ketorolac Bier block, RVR was not greater during PHGMI + stretch than during PHGMI alone [Delta39 +/- 8% vs. Delta40 +/- 12%; P = not significant (NS)]. HR and MAP responses were similar during PHGMI and PHGMI + stretch (P = NS). Passive muscle stretch during ischemia augments renal vasoconstriction, suggesting that ischemia sensitizes mechanically sensitive afferents. Inhibition of prostaglandin synthesis eliminates this mechanoreceptor sensitization-mediated constrictor responses. Thus mechanoreceptor sensitization in humans is linked to the production of prostaglandins.

Muscle mechanosensitive reflex is suppressed in the conscious condition: effect of anesthesia

To test the hypothesis that a muscle mechanosensitive reflex is suppressed in the conscious condition, we examined the effect of anesthesia on the cardiovascular responses to passive mechanical stretch of the triceps surae muscle in six conscious cats. The triceps surae muscle was manually stretched for 30s by extending the hip and knee joints and subsequently by dorsiflexing the ankle joint; the lateral gastrocnemius muscle was lengthened by 19 ± 3 mm. Heart rate (HR) and mean arterial blood pressure (MAP) did not change significantly during passive stretch of the muscle in the conscious condition. At 10–40 min after intravenously administering sodium pentobarbital (20–25 mg/kg), the identical passive stretch of the triceps surae muscle was able to induce the cardiovascular responses; HR and MAP were increased by 14 ± 1 beats/min and 14 ± 1 mmHg, respectively. In contrast, vigorous stretching skin on the triceps surae muscle elicited no significant changes in HR and MAP in the anesthetized condition, indicating that if cutaneous nociceptors and/or mechanoreceptors might be activated by the skin stretch, pain‐induced reflex cardiovascular responses would be inhibited by anesthesia. We conclude that passive mechanical stretch of skeletal muscle is capable of evoking the reflex cardiovascular response, which is suppressed in the conscious condition but exaggerated by anesthesia. This study was supported by a Grant‐in‐Aid for Scientific Research (B) from the Japan Society for the Promotion of Science.

Cyclooxygenase inhibition attenuates muscle sympathetic nerve responses to passive muscle stretch

Previous studies suggest the muscle metabolites may sensitize muscle mechanoreceptors. However, the responsible substance(s) has not been studied thoroughly in humans. This study tested the hypothesis that local cyclooxygenase (COX) inhibition in exercising muscles could attenuate muscle sympathetic nerve activity (MSNA) responses to passive muscle stretch during post exercise muscle ischemia (PEMI). Responses of blood pressure (BP), heart rate, and MSNA to passive stretch of hand and forearm muscles were assessed in 13 healthy subjects during PEMI before and after COX inhibition by local infusion of 6 mg ketorolac tromethamine in saline via Bier block. In the second experiment, the same amount of saline was infused via the Bier block. Ketorolac Bier block significantly decreased the synthesis of COX products. Before ketorolac Bier block, passive stretch evoked significant increase in MSNA (P&lt;0.005) and mean BP (P&lt;0.02). After ketorolac Bier block, passive muscle stretch did not evoke significant responses in MSNA (P=0.11) or in mean BP (P=0.83). Saline Bier block did not attenuate the MSNA responses. These observations indicate that COX inhibition attenuates MSNA responses to stretch during PEMI, and suggest that COX products sensitize muscle mechanoreceptors in humans. Supported by NIH P01 HL077670, M01 RR010732 and AHA 0635245 N.