Relationship of diaphragmatic contractility to diaphragmatic blood flow in newborn lambs

We determined the relationship of diaphragmatic contraction rate to diaphragmatic blood flow (Qdi), metabolism, and contractility in nine open-chested mechanically ventilated newborn lambs. The diaphragm was paced for 15 min at slow (20/min) and fast (100/min) contraction rates each followed by a 30-min rest period. There was a mild reduction in transdiaphragmatic pressure (Pdi) during the slow contraction period accompanied by a shift to the right of the curve relating stimulation frequency (10-100 Hz) to Pdi. Pdi returned to control at the start of the fast contraction period, but then fell by 30% within 2 min with continued fast contraction rates. The frequency-Pdi curve was significantly shifted to the right. Qdi, O2 transport, and O2 consumption increased during slow contraction and to an even greater extent during fast contraction. Fractional O2 extraction reached an apparent maximum during slow contraction. Lactate efflux from the right phrenic vein during slow contraction remained unchanged from control. During fast contraction lactate efflux rose proportionately more than did O2 consumption. We conclude that the energy demands at fast rates of diaphragmatic contraction in newborn lambs cannot be met by aerobic metabolism alone despite increasing O2 transport to the diaphragm.     

Stimulation characteristics that determine arteriolar dilation in skeletal muscle

To determine the skeletal muscle stimulation parameters that are most important in establishing vasodilation in the microvasculature, I tested whether arteriolar diameter during 2 min of repetitive, short-duration, tetanic skeletal muscle contractions increased with changes in stimulus frequency, stimulation train duration, and contraction frequency. To test this, the diameter of transverse arterioles approximately perpendicular to small bundles of cremaster muscle fibers in situ of anesthetized Golden Syrian hamsters was used as a bioassay system. Arteriolar diameter was measured before and during different stimulation patterns that consisted of a contraction frequency [6, 12, or 24 contractions per minute (cpm)], a stimulation train duration (250, 500, or 750 ms) and a stimulus frequency (4, 8, 10, 15, 20, 30, 40, 60, and 80 Hz). The magnitude of the dilation significantly increased with stimulus frequency but not in a simple linear manner. The average rate of increase was 0.32 +/- 0.02 microm/Hz from 4 to 20 Hz and 0.09 +/- 0.02 microm/Hz from 30 to 80 Hz. The magnitude of the dilation increased significantly with the contraction frequency where the dilation at 6 cpm was significantly smaller than the dilation at 24 cpm across all stimulus frequencies. Changing the train duration from 250 to 750 ms did not significantly affect the magnitude of the dilation. These observations suggest that stimulation parameters are important in determining the magnitude of the microvascular dilation and that the magnitude of the dilation was dependent on both the contraction frequency and stimulus frequency but was independent of train duration.     

Factors determining post-stimulation dilatation

Post-stimulation dilatation (PSD) of the femoral artery and vein after cessation of postganglionic sympathetic stimulation were related to the frequency and pulse number of the preceding stimulation. It was found that: 1) A minimum number of pulses (MNP) is needed to evoke PSD. MNP is inversely related to the stimulation frequency. A marked PSD develops after stimulation at 1 Hz when only 100 pulses were applied, whereas, if stimulated at 4 Hz or at higher frequencies, even 2,000 pulses fail to induce PSD. 2) The maximum value, the maximum rate and the overall diameter change of PSD (expressed either in absolute values or in relation to the preceding contraction) are a) directly related to the number of pulses at a constant stimulation frequency, b) for a constant number of pulses the above values are inversely related to the stimulation frequency. 3) The relation of PSD values to the stimulation parameters contradict the assumption that PSD is elicited either by a neurogenic transmitter released by the stimulation, or by an extraneuronal transmitter whose release is associated with the release of noradrenaline. PSD is suggested to be due to a decreased noradrenaline level within the synaptic cleft due to persistence of the reuptake after the release of noradrenaline had ceased.     

Potentiation of vagal contractile response by thromboxane mimetic U-46619

We studied the effect of the thromboxane mimetic U-46619 on tracheal smooth muscle contraction caused by bilateral stimulation of the vagus nerves in 14 mongrel dogs in situ. The parasympathetic contractile response was studied isometrically after beta-adrenergic blockade with 2 mg/kg iv propranolol plus 20 micrograms X kg-1 X min-1 continuous intravenous infusion and blockade of endogenous prostaglandin synthesis with 5 mg/kg iv indomethacin. An initial frequency-response curve was generated by electrical stimulation of the caudal ends of cut cervical vagi over the range of frequencies 2-25 Hz (constant 25 V) at 15-s intervals. In five dogs, 10(-10) to 10(-8) mol of the thromboxane mimetic (15S)-hydroxyl-11 alpha,9 alpha-(epoxymethano)prosta-5Z,13E-dienoic acid (U-46619) was injected selectively into the tracheal arterial circulation, causing a transient contractile response (less than or equal to 10 g/cm). Additional frequency response studies were generated 7 min before and 1, 15, 30, 45, and 60 min after U-46619. Substantial augmentation of tracheal contraction to efferent vagal stimulation was observed after U-46619 for all frequencies greater than 4 Hz (P less than 0.02). Augmentation of vagally mediated contraction was not observed in four other dogs after equivalent tracheal contraction was elicited without U-46619. Similarly, in four separate dogs, augmentation of tracheal contraction was not observed when acetylcholine was given instead of vagal stimulation after U-46619. We conclude that the thromboxane analogue, U-46619, causes augmentation of tracheal contractile response induced by efferent vagus nerve stimulation. Potentiation is caused by a prejunctional action of U-46619 and is not induced by nonspecific precontraction with another agonist.     

Tetanic force development of adductor pollicis muscle in anesthetized man.

The tetanic force development of the human adductor pollicis muscle was studied under light anesthesia with nitrous oxide, oxygen, and Demerol, by the use of tetanic stimulation of the ulnar nerve at frequencies ranging from 10 to 100 Hz. The time necessary for the tetanic contraction to reach a plateau was longest at frequencies between 15 and 20 Hz. Fusion of tetanus occurred between 40 and 45 Hz. The mean maximal force of 6.92 kg was developed at a mean frequency of approximately 75 Hz. The maximal force was well maintained up to a stimulation frequency of 100 Hz. The results indicate that in lightly anesthetized man, the maximal force is developed at higher stimulation frequencies than those observed in conscious man and that it is well sustained at higher frequencies.     

Interaction between cell shape and contraction pattern in the Physarum plasmodium

The relationship between cell shape and rhythmic contractile activity in the large amoeboid organism Physarum polycephalum was studied. The organism develops intricate networks of veins in which protoplasmic sol moved to and fro very regularly. When migrating on plain agar, the plasmodium extends like a sheet and develops dendritic veins toward the rear. After a particular stimulation, the vein organization changes into veinless or vein-network structures. In both structures, the mixing rate of the protoplasm, which is related to communication among contraction oscillators, decreased compared with that of the dendritic one. Accompanying these changes in vein structure, the spatio-temporal pattern of the rhythmic contraction changed into a small-structured pattern from a synchronized one. In the above process, cell shape affects the contraction pattern, but, conversely, the contraction pattern effects the cell shape. To demonstrate this, a phase difference in the rhythmic contraction was induced artificially by entraining the intrinsic rhythm to external temperature oscillations. New veins then formed along the direction parallel to the phase difference of the rhythm. Consequently, the vein organization of the cell interacts with the contractile activity to form a feedback loop in a mechanism of contraction pattern formation.     

The release of catecholamines from the adrenal medulla and its modulation by alpha 2-adrenoceptors in the anaesthetized dog

The adrenal nerve of anaesthetized and vagotomized dogs was electrically stimulated (10 V pulses of 2 ms duration for 10 min) at frequencies of 1, 3, 10, and 25 Hz. There was a correlation between the frequency of stimulation and the plasma concentrations of epinephrine, norepinephrine, and dopamine in the adrenal vein, mainly after the 1st min of stimulation and the maximal concentration was reached sooner with higher frequencies of stimulation. Moreover, the relative percentage of catecholamines released in response to the electrical stimulation was not changed by the frequency of stimulation. To test the hypothesis that a local negative feedback mechanism mediated by alpha 2-adrenoceptors exists in the adrenal medulla, the effects of the systemic administration of clonidine (alpha 2-antagonist) on the concentrations of catecholamines in the adrenal vein were evaluated during the electrical stimulation of the adrenal nerve (5 V pulses of 2 ms duration for 3 min) at 3 Hz. Moreover, the effects of the systemic injections of more specific alpha 2-agonist and antagonist (oxymetazoline and idazoxan) were tested on the release of catecholamines in the adrenal vein in response to electrical stimulation of the splanchnic nerve at 1 and 3 Hz frequencies. The injection of 0.5 mg/kg of yohimbine caused a significant increase in the concentrations of epinephrine and norepinephrine in the adrenal vein induced by the electrical stimulation of the adrenal nerve and the injection of 15 micrograms/kg of clonidine had no effects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuromodulation in a rat model of the bladder micturition reflex

A rat model of bladder reflex contraction (BRC) was used to determine the optimal frequency and intensity of spinal nerve (SN) stimulation to produce neuromodulation of bladder activity and to assess the therapeutic mechanisms of this neuromodulation. In anesthetized female rats (urethane 1.2 g/kg ip), a wire electrode was used to produce bilateral stimulation of the L6 SN. A cannula was placed into the bladder via the urethra, and the urethra was ligated to ensure an isovolumetric bladder. Saline infusion induced BRC. Electrical stimulation of the SN produced a frequency- and intensity-dependent attenuation of the frequency of bladder contractions. Ten-herz stimulation produced maximal inhibition; lower and higher stimulation frequency produced less attenuation of BRC. Attenuation of bladder contraction frequency was directly proportional to the current intensity. At 10 Hz, stimulation using motor threshold pulses (T(mot)) produced a delayed inhibition of the frequency of bladder contractions to 34 ± 11% of control. Maximal bladder inhibition appeared at 10 min poststimulation. High current intensity at 0.6 mA (～6 * T(mot)) abolished bladder contraction during stimulation, and the inhibition was sustained for 10 min poststimulation (prolonged inhibition). Furthermore, in rats pretreated with capsaicin (125 mg/kg sc), stimulation produced a stronger inhibition of BRC. The inhibitory effects on bladder contraction may be mediated by both afferent and efferent mechanisms. Lower intensities of stimulation may activate large, fast-conducting fibers and actions through the afferent limb of the micturition reflex arc in SN neuromodulation. Higher intensities may additionally act through the efferent limb.     

Effects of contraction frequency and duty cycle on diaphragmatic blood flow

The effects of diaphragmatic contraction frequency (no. of intermittent tetanic contractions/min) at a given tension-time index and of duty cycle (contraction time/total cycle time) on diaphragmatic blood flow were measured in anesthetized mongrel dogs during bilateral supramaximal phrenic nerve stimulation. Diaphragmatic blood flow was measured by the radionuclide-labeled microsphere method. Contraction frequency was varied between 10 and 160/min at duty cycles of 0.25 and 0.75. Diaphragmatic blood flow increased with contraction frequency from 1.47 +/- 0.13 ml X min-1 X g-1 (mean +/- SE) at an average of 18/min to 2.65 +/- 0.16 ml X min-1 X g-1 at 74/min (P less than 0.01) with a duty cycle of 0.25 and from 1.32 +/- 0.19 ml X min-1 X g-1 at an average of 15/min to 1.96 +/- 0.15 ml X min-1 X g-1 at 80/min (P less than 0.02) with a duty cycle of 0.75. At higher contraction frequencies diaphragmatic blood flow did not increase further at both duty cycles. In addition, diaphragmatic blood flow was higher with a duty cycle of 0.25 than 0.75 at all contraction frequencies. We conclude that frequency of contraction is a major determinant of diaphragmatic blood flow and that high duty cycle impedes diaphragmatic blood flow.     

Response of isolated rat iris dilator to adrenergic and cholinergic agents and electrical stimulation

Responses of isolated rat iris dilator to some agents and to electrical stimulation were examined. Norepinephrine and epinephrine produced contraction, which was antagonized by 0.03 μM phentolamine. Acetylcholine produced relaxation at low concentrations (1 nM ? 1 μM) as great as 80 % of the resting tone while contraction at high concentrations (≥1 μM). Both responses were suppressed by 0.02 μM atropine and enhanced by 0.03 μM physostigmine. Electrical stimulation at low voltage or low frequency (up to 10 Hz) elicited relaxation while stimulation at high voltage or high frequency (30 Hz) produced contraction. Stimulation with intermediate strength elicited biphasic response. The contraction and relaxation induced by electrical stimulation were abolished by 3 μM phentolamine or by 0.05 μM atropine, respectively. Both phases were abolished by tetrodotoxin (0.3 μM). It is suggested that in the rat the cholinergic relaxation of the dilator may assist the cholinergic contraction of the sphincter (1). The pronounced cholinergic relaxation of nonvascular tissue is to be noted.     

Excessive reflexes in spinal cord injury triggered by electrical stimulation

Interaction of electrocutaneous stimulation with an impaired human motor control system may result in unstable reflex loops causing excessive spastic reactions. These contractions are usually excluded from analysis since the presence of spasm is one of the criteria commonly applied for discarding a contraction. They may, however, provide interesting information on the nature of spasticity. The dorsiflexor muscles of four SCI subjects were activated by means of surface electrical stimulation and the isometric ankle moment was measured. Short bursts of constant stimulation frequency at seven different frequencies (8, 12, 16, 20, 25, 33, 50 Hz) triggered spastic reactions in all subjects. The onset times of spastic activity during an electrically elicited contraction shortened with increased stimulation frequency. A stimulation burst may also have a spasticity reduction effect on a subsequent burst, indicating potential short term therapeutic effects of stimulation on spasticity in isometric conditions.     

Electrically induced narcotic-like dependence in the isolated guinea-pig ileum

Segments of guinea-pig ileum stimulated at 10 Hz (0.5 msec, supramaximal voltage) for periods of 15 min respond with an intense, dose-dependent contraction to the $\text{in}$$\text{vitro}$ administration of naloxone. The antagonist produced only a very modest contraction in control segments (0.1 Hz stimulation). Comparison of dose-response curves for naloxone indicated that the sensitizing effect of electrical stimulation at 10 Hz was on the order of 100-fold. The addition of naloxone to the bath immediately before the stimulatory period at 10Hz completely prevented the development of this effect. Moreover, atropine produced a dose-dependent inhibition of the contraction. It was also found that the magnitude of the naloxone-induced contraction is a function of the duration of the stimulatory period and is maximal after about 15 min. The data presented indicate that the contraction induced by naloxone in ilea stimulated at 10 Hz has many similarities to the response produced by the same antagonist in narcotic-dependent preparations. Thus, it is possible that electrical stimulation at high frequencies induces a state of narcotic-like dependence in this tissue. Acetylcholine may be the mediator of the naloxone-induced contraction.     

弥猴单侧软腭肌肉对针式电极刺激的反应

目的建立针电极口内刺激猴软腭肌肉诱发腭咽闭合运动的模式,取得软腭肌肉运动的有效刺激数值,为软腭肌肉功能重建奠定基础。方法通过解剖成年猕猴软腭的五组肌肉,确定其体表位置;利用实验动物用腭部肌肉电极定位刺激器及针式电极对软腭肌肉进行有效刺激;结合鼻咽纤维镜、头颅侧位X片及软腭造影技术观察、记录肌肉收缩及腭咽闭合动作。结果在猕猴口内定位目标肌肉进行针电极刺激可诱发肌肉收缩。刺激电压为3 V、刺激频率为20 Hz时均能诱发单侧软腭肌肉的有效收缩;单侧腭帆提肌在刺激电压为5 V、20 Hz时可发生腭咽闭合动作。咽腭肌、舌腭肌在刺激电压5 V、刺激频率100 Hz时发生软腭下降动作。腭帆张肌仅发生收缩,而未发生腭咽闭合。应用鼻咽纤维镜和X线成像技术配合能记录腭咽闭合动作。结论弥猴可作为研究软腭肌肉运动模式的实验动物。应用电极刺激软腭肌肉,可初步建立腭咽闭合的动作模式。     

On the existence of parasympathetic motor nerves to the submaxillary gland of the dog

Duct pressure and salivary flow were recorded in submaxillary glands of anaesthetized dogs, to study whether parasympathetic stimulation caused effects referable to activity in myoepithelial cells. At fairly low frequency of stimulation, e.g. 3 Hz, the pressure curve had two distinct components, with initial steep and a secondary gradual rise. It resembled that obtained on sympathetic stimulation, where the first phase is ascribed to myoepithelial contraction, the second phase to secretion. When parasympathetic stimulation ceased, there was first a steep fall, then a more gradual decline of the pressure. The steep fall was of the same magnitude as the steep rise; both increased with the frequency of stimulation. The size of the initial fall was fairly independent of the pressure level from which it started. Such a steep fall did not occur subsequent to parasympathetic stimulation if the myoepithelial cells were already in a state of strong contraction caused by sympathetic impulses or bradykinin. The phase of steep fall was inferred to be due mainly to relaxation of contracted myoepithelial cells, the following decline to back-flow of fluid into the gland. The salivary flow rate was highest at the beginning of a period of parasympathetic stimulation, particularly if the duct system was well filled and the saliva thin. It was concluded that myoepithelial contraction had initially expelled saliva. A brief period of parasympathetic stimulation while a slow basal secretion at constant rate was going on was found to accelerate this flow, and afterwards there was a transient deceleration of the flow. Acceleration was attributed partly to myoepithelial contraction, mainly to superimposed secretion; retardation to myoepithelial relaxation. The effect appeared independently of the way in which the basal flow was evoked, and the retardation resembled that seen after sympathetic stimulation or bradykinin.     

Effect of low frequency fatigue on human muscle strength and fatigability during subsequent stimulated activity

Fatiguing contractions of the adductor pollicis muscle were produced by intermittent supramaximal stimulation of the ulnar nerve in a set frequency pattern, in six normal subjects. At the end of an initial fatiguing contraction series, low frequency fatigue (LFF) had been induced and persisted at 15 min of recovery. Stimulated fatiguing activity was then repeated in an identical fashion to the initial series. At high frequencies, declines in force were similar for both series. At low frequencies, declines in force were greater during the second series despite similar changes in compound muscle action potential amplitude. This confirmation that LFF persists during subsequent stimulated activity, and reduces low but not high frequency fatigue resistance, suggests that the impaired endurance of fatigued muscle during voluntary activity primarily results from peripheral changes at low frequency. These findings also have implications for therapeutic electrical stimulation of muscle.     

Role of contraction duration in inducing fast‐to‐slow contractile and metabolic protein and functional changes in engineered muscle

The role of factors such as frequency, contraction duration and active time in the adaptation to chronic low‐frequency electrical stimulation (CLFS) is widely disputed. In this study we explore the ability of contraction duration (0.6, 6, 60, and 600 sec) to induce a fast‐to‐slow shift in engineered muscle while using a stimulation frequency of 10 Hz and keeping active time constant at 60%. We found that all contraction durations induced similar slowing of time‐to‐peak tension. Despite similar increases in total myosin heavy (MHC) levels with stimulation, increasing contraction duration resulted in progressive decreases in total fast myosin. With contraction durations of 60 and 600 sec, MHC IIx levels decreased and MHC IIa levels increased. All contraction durations resulted in fast‐to‐slow shifts in TnT and TnC but increased both fast and slow TnI levels. Half‐relaxation slowed to a greater extent with contraction durations of 60 and 600 sec despite similar changes in the calcium sequestering proteins calsequestrin and parvalbumin and the calcium uptake protein SERCA. All CLFS groups resulted in greater fatigue resistance than control. Similar increases in GLUT4, mitochondrial enzymes (SDH and ATPsynthase), the fatty acid transporter CPT‐1, and the metabolic regulators PGC‐1α and MEF2 were found with all contraction durations. However, the mitochondrial enzymes cytochrome C and citrate synthase were increased to greater levels with contraction durations of 60 and 600 sec. These results demonstrate that contraction duration plays a pivotal role in dictating the level of CLFS‐induced contractile and metabolic adaptations in tissue‐engineered skeletal muscle. J. Cell. Physiol. 230: 2489–2497, 2015. © 2015 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.     

The response of fast and slow nuclear bag fibres and nuclear chain fibres in isolated cat muscle spindles to fusimotor stimulation, and the effect of intrafusal contraction on the sensory endings.

1. The mechanical behaviour of intrafusal muscle fibres during fusimotor stimulation and passive stretch was observed directly in muscle spindles isolated from the cat tenuissimus muscle. 2. Mammalian intrafusal muscle fibres are of three functional types. Most spindles contain one slow nuclear bag fibre, one fast nuclear bag fibre, and four or five nuclear chain fibres. 3. Contraction in slow nuclear bag fibres is characterized by a long latency and very slow initial velocity, whereas the latency for the other intrafusal fibres is short and the inital velocity rapid. The mean time for maximum contraction (at 75 Hz to 100 Hz) and relaxation is significantly longer for slow nuclear bag fibres (0-8s) than for other intrafusal fibres (0-5 s). The contraction time of fast nuclear bag fibres is sometimes longer than that of nuclear chain fibres but the mean values are not significantly different; a difference in the time to attain 90% contraction is more obvious. 4. At low stimulation frequencies (10 Hz) contraction in slow nuclear bag fibres and in most fast nuclear bag fibres is smooth whereas nuclear chain fibres exhibit marked oscillations. Single stimuli elicit small local twitches in nuclear chain fibres and occasionally in fast nuclear bag fibres but produce no visible effect in slow nuclear bag fibres. 5. Maximum contraction of slow and fast nuclear bag fibres at body temperature is attained at a stimulation frequency of 75 Hz to 100 Hz, whereas a frequency of 150 Hz or more is required for maximum contraction of nuclear chain fibres. At 50 Hz at body temperature contraction in nuclear bag fibres is at least half the maximum, whereas in many spindles nuclear chain fibres show only a very small contraction at this frequency. 6. Contraction in slow nuclear bag fibres occurs at one or two discrete foci, most of which lie in the intracapsular region beyond the end of the fluid space. Weak contraction extends the primary sensory spiral by a small amount (2%-8%) at a low velocity (5%-10%s-1). When the fibre is passively stretched the spiral opens and then creeps back to about 75% of the extension at the end of the stretch due to yielding in the poles of fibre; creep is complete in 0-5s to 2-5s. 7. Contraction in fast nuclear bag fibres also occurs at one or two discrete foci, most of which lie in the intracapsular region beyond the end of the fluid space. Shortening of sarcomeres at the foci and extension of the sensory spiral are, however, up to eight times greater (up to 25%) than in slow nuclear bag fibres, and the velocity of stretch of the spiral is three to eight times greater (25%-40%s-1). Fast nuclear bag fibres exhibit little or no creep following passive stretch. 8. Contraction in the nuclear chain fibre bundle is localized to the intracapsular region, centered on a point in the intracapsular region between 0-9 mm and 1-6 mm from the spindle equator. Maximal contraction stretches primary and secondary sensory endings by 15% to 20%, at 30% to 40% s-1...     

The muscle sound properties of different muscle fiber types during voluntary and electrically induced contractions.

Soundmyogram (SMG) and electromyogram signals were recorded simultaneously from the relatively fast medial gastrocnemius (MG) and slow soleus (SOL) during voluntary and electrically induced contractions. Using a spike-triggered averaging technique, the averaged elementary sound and corresponding MU spikes were also obtained from about 35 different MUs identified. The rms-SMG of MG increased as a function of force (P < 0.01). On the contrary, these values for SOL increased up to 60% MVC (P < 0.01), but decreased at 80% MVC. The relationship between the peak to peak amplitude of SMG and MU spike indicated significant positive correlations (r = 0.631 to approximately 0.657, P < 0.01). During electrical stimulation at 5 Hz, the SMG power spectral peak frequency (PF) was matched with stimulation frequency in both muscles. At higher stimulation frequencies, e.g., > 15 Hz, only in the MG was SMG-PF synchronized with stimulation frequency; the slow SOL did not show such synchronization. Our data suggest that the SMG frequency components might reflect active motor unit firing rates, and that the SMG amplitude depends upon mechanical properties of contraction, muscle fiber composition, and firing rate during voluntary and electrically induced contractions.     

Potentiation of the responses to transmural nerve stimulation by alpha-agonists: a possible role in vivo

This study was undertaken to assess the effects of exogenous alpha-agonists on the effector response to transmural nerve stimulation in canine saphenous vein rings. The response to a fixed train (5 s duration) of transmural nerve stimulation (8 Hz, 0.3 ms, 9 V) applied every 5 min was determined in the control state and in the presence of subthreshold (for contraction) concentrations of noradrenaline, adrenaline, clonidine, and methoxamine. The maximum potentiations achieved by the three drugs were 246.2 +/- 36.9, 220.5 +/- 38.8, 384.3 +/- 78.7, and 353.3 +/- 68.0%, respectively. The potentiation observed was significantly inhibited by indomethacin (10(-6) mol/L) and propranolol (5 X 10(-6) mol/L). Both indomethacin and propranolol potentiated the response to transmural nerve stimulation. The potentiation of the responses to transmural nerve stimulation by alpha-agonists suggests that, presynaptic alpha 2-inhibition by circulating catecholamines is likely to be of limited biological significance in modulating the effector responses in the canine saphenous vein.     

Neurovascular activation requires conduction through vessels

In experiments on rats, a hind leg was transected except for the femoral nerve, artery and vein. The femoral nerve was stimulated by electrical pulses, with one electrode attached to the nerve in the amputation gap and another placed in the inferior caval vein. At each pulse of stimulation, contraction could be recorded in femoral muscles. Ligation of the femoral vessels suspended the contractions within a fraction of a second; contractions resumed when ligation ended. Propagation of neural stimuli to femoral muscles therefore required an intact electrical communication through associated vessels. This is possible because conducting blood plasma and its capillary junction with the interstitial fluid form an "external" closed circuit branch of low resistance with the neuromuscular unit. In testing the interstitial tissue fluid as an alternative to the vascular "outer" communication, a higher voltage of stimulation was required for muscle contractions.