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Biomedical subjects

Kenneth J Gustafson

Publications and source records attributed to Kenneth J Gustafson.

16 recordsLinked to original sources

Frequency-dependent selection of reflexes by pudendal afferents in the cat.

Activation of urethral or genital afferents of the pudendal nerve can elicit or inhibit micturition, and low frequency stimulation of the compound pudendal nerve (PN) is known to produce a continence response. The present study demonstrates that PN stimulation also can elicit a micturition-like response and that the response to PN stimulation is dependent on stimulation frequency. We measured the changes in bladder pressure and external urethral sphincter (EUS) electroneurogram (ENG) evoked by PN stimulation before and up to 16 h after spinal cord transection (SCT) in cats anaesthetized with alpha-chloralose. Low frequency (10 Hz) stimulation elicited a continence-like response, including inhibition of the bladder and activation of the EUS, but mid-frequency (33 Hz) stimulation produced a micturition-like response, including excitation of the bladder without activation of the EUS. The dependence of the response on stimulus frequency was linked to interpulse interval as the same number of pulses at 10, 33 and 100 Hz produced different responses. Stimulation of the PN at 33 Hz produced bladder contractions before and 8 h after SCT provided the bladder contained a minimum volume of fluid. Only mid-range frequency stimulation with sufficient stimulus train duration produced a reduction in EUS ENG activity before and after SCT. In addition to a continence-like response, PN stimulation can also elicit a micturition-like response, and this response is dependent on stimulation frequency, stimulus train duration, and bladder volume. The ability to control the two principal functions of the bladder by pudendal nerve stimulation is an exciting prospect for neurorehabilitation.

Afferent Pathways↗

High frequency electrical conduction block of the pudendal nerve.

A reversible electrical block of the pudendal nerves may provide a valuable method for restoration of urinary voiding in individuals with bladder-sphincter dyssynergia. This study quantified the stimulus parameters and effectiveness of high frequency (HFAC) sinusoidal waveforms on the pudendal nerves to produce block of the external urethral sphincter (EUS). A proximal electrode on the pudendal nerve after its exit from the sciatic notch was used to apply low frequency stimuli to evoke EUS contractions. HFAC at frequencies from 1 to 30 kHz with amplitudes from 1 to 10 V were applied through a conforming tripolar nerve cuff electrode implanted distally. Sphincter responses were recorded with a catheter mounted micro-transducer. A fast onset and reversible motor block was obtained over this range of frequencies. The HFAC block showed three phases: a high onset response, often a period of repetitive firing and usually a steady state of complete or partial block. A complete EUS block was obtained in all animals. The block thresholds showed a linear relationship with frequency. HFAC pudendal nerve stimulation effectively produced a quickly reversible block of evoked urethral sphincter contractions. The HFAC pudendal block could be a valuable tool in the rehabilitation of bladder-sphincter dyssynergia.

Animals↗

Performance of dynamic and isovolumetric trained skeletal muscle ventricles.

BACKGROUND: Dynamic training and maintaining muscle tension are important factors during skeletal muscle ventricle (SMV) conditioning that may improve SMV performance. This study sought to determine the effects of dynamic muscle training and progressive SMV resting pressure expansion on SMV pumping capability. MATERIALS AND METHODS: SMVs were constructed in 14 goats using the left latissimus dorsi muscle. SMVs were conditioned with a 40 ml constant-volume isovolumetric implant (n = 5, IsoVol group) or a compliant, pneumatic system that allowed dynamic shortening and direct exposure to resting pressures. Dynamic SMV resting pressure was either progressively increased from 40 to 100 to 120 mmHg (n = 5, HiP group) or maintained at 40 mmHg (n = 4, LowP group) during conditioning. After 8 to 10 weeks of electrical stimulation conditioning, SMVs were connected to a counterpulsation mock circulation system and SMV pumping performance evaluated across a range of pressures and stimulation parameters. RESULTS: SMV pumping performance was similar in each group. Stroke works generally increased with pressure and reached a plateau in all groups above 80 mmHg (120 msec contraction approximately 80 mJ/stroke; 480 msec contraction approximately 180 mJ/stroke). Stroke volumes decreased with pressure except at high stimulation levels where loading effects were observed. Chronic changes in SMV volume significantly effected pumping performance. CONCLUSIONS: These data suggest that acute pumping performance is not different between 8 to 10 weeks of dynamic or isovolumetric training if SMV volume is not constrained. A potentially improved SMV conditioning protocol is proposed that determines, positions, and maintains SMV volume near the initial volume for maximal isovolumetric pressure during conditioning.

Animals↗

Models of metabolic utilization predict limiting conditions for sustained power from conditioned skeletal muscle.

Application and development of muscle powered cardiac assist devices is limited by the ability to predict the sustainable power output of in situ conditioned muscle under the expected loading conditions and geometrical constraints. Empirical definition of the sustained power limits and representative models of the bounding conditions where continuous power can be obtained are needed for device design and optimization. The latissimus dorsi muscles of four goats were chronically conditioned for 11 weeks with an implanted myostimulator. The ability to sustain power under isotonic conditions was evaluated across a range of contraction durations (100-600 ms) and rates (10-120 contractions/min). Muscles were characterized both biomechanically and myothermically to develop and evaluate three increasingly complex empirically-based models of metabolic utilization per contraction based on (1) the duty cycle, (2) a linear function of activation time, and (3) a multivariate-derived function of contraction duration, muscle load, and shortening distance. A clearly defined boundary for sustainable stimulation conditions was observed and was best represented by the linear metabolic model. These data provide both an empirical measure of chronically sustainable muscle power and predictive metabolic models that may be used to optimize the power harnessed for skeletal muscle actuated devices.

Adaptation, Physiological↗

Electrode array for reversing the recruitment order of peripheral nerve stimulation: experimental studies.

One of the most challenging problems in peripheral nerve stimulation is the ability to activate selectively small axons without large ones. Electrical stimulation of peripheral nerve activates large diameter fibers before small ones. Currently available techniques for selective activation of small axons without large ones require long-duration stimulation pulses (>500 micros) and large stimulation amplitude, which shorten battery life of the implanted stimulator and could lead to electrode corrosion. In the current study, the hypothesis that small axons can be recruited before large ones with narrow pulse width (50 micros) using an electrode array was tested in both simulations simulation and experiments in the cat lateral gastrocnemius (LG) model. The LG nerve innervates both LG and soleus muscle groups with axons within 10-13 and 8-12 microm diameter ranges, respectively. A finite element model of LG nerve was constructed and simulations showed that, when activating 40% of LG, a conventional tripolar electrode activated only 9% of soleus whereas the electrode arrays of 5, 7, and 11 contacts activated 39, 46, and 60% of soleus respectively, suggesting that the arrays could activate small axons before fully recruiting large axons. In animal experiments, peak twitch force of LG and soleus were plotted as a function of stimulation amplitude to indicate the recruitment curve. At 40% activation of LG, a conventional tripolar electrode activated only 7% of soleus whereas the electrode arrays of 5, 7, and 11 contacts activated 43, 48, and 72% of soleus respectively. The electrode arrays also decreased significantly the recruitment curve slopes to only 10-20% of the value obtained for the tripolar electrode in both computer simulations and experiments. In conclusion, the 5-, 7-, and 11-contact arrays can be used to reverse the recruitment order of peripheral nerve stimulation with a narrow pulse.

Animals↗

Bladder emptying by intermittent electrical stimulation of the pudendal nerve.

Persons with a suprasacral spinal cord injury cannot empty their bladder voluntarily. Bladder emptying can be restored by intermittent electrical stimulation of the sacral nerve roots (SR) to cause bladder contraction. However, this therapy requires sensory nerve transection to prevent dyssynergic contraction of the external urethral sphincter (EUS). Stimulation of the compound pudendal nerve trunk (PN) activates spinal micturition circuitry, leading to a reflex bladder contraction without a reflex EUS contraction. The present study determined if PN stimulation could produce bladder emptying without nerve transection in cats anesthetized with alpha-chloralose. With all nerves intact, intermittent PN stimulation emptied the bladder (64 +/- 14% of initial volume, n = 37 across six cats) more effectively than either distention-evoked micturition (40 +/- 19%, p < 0.001, n = 27 across six cats) or bilateral intermittent SR stimulation (25 +/- 23%, p < 0.005, n = 4 across two cats). After bilateral transection of the nerves innervating the urethral sphincter, intermittent SR stimulation voided 79 +/- 17% (n = 12 across three cats), comparable to clinical results obtained with SR stimulation. Voiding via intermittent PN stimulation did not increase after neurotomy (p > 0.10), indicating that PN stimulation was not limited by bladder-sphincter dyssynergia. Intermittent PN stimulation holds promise for restoring bladder emptying following spinal injury without requiring nerve transection.

Animals↗

Detection of neurogenic detrusor contractions from the activity of the external anal sphincter in cat and human.

AIMS: Individuals with spinal cord injury or neurological disorders may develop bladder contractions at low volumes (neurogenic detrusor overactivity), which can lead to significant health problems. Present devices can inhibit unwanted contractions through continuous electrical stimulation of sensory nerves, but do not enable conditional stimulation only at the onset of bladder contractions. The objectives of this study were to determine the relationship between the electrical activity of external anal sphincter (EAS) and bladder pressure during neurogenic detrusor contractions and to determine whether EAS activity could be used to detect the onset of bladder contractions. METHODS: Bladder pressure and EAS electromyogram (EMG) were recorded in nine adult male cats. Retrospective clinical data consisting of bladder pressure and EAS EMG from 41 spinal cord injured individuals with neurogenic detrusor overactivity were analyzed. A CUSUM algorithm was used to detect the onset of bladder contractions from the EAS EMG. RESULTS: EAS EMG activity increased at the onset of bladder contractions in six cats (dyssynergic) and decreased (synergic) in three cats. The onset of bladder contractions was detected within 3 sec of the start of the contraction for both the synergic and dyssynergic data sets. The onset of bladder contractions was detected within 1 sec of the start of the bladder contraction for both synergic and dyssynergic human subjects. CONCLUSIONS: Recordings of the EAS EMG can be used to detect robustly the onset of neurogenic detrusor contractions. The EAS EMG is a suitable signal to control closed-loop inhibitory electrical stimulation to maintain urinary continence.

Anal Canal↗

Closed loop electrical control of urinary continence.

PURPOSE: Individuals with spinal cord injury or neurological disorders may have neurogenic detrusor contractions at low volumes (bladder hyperreflexia), which cause incontinence and can lead to significant health problems. Bladder contractions can be suppressed by electrical stimulation of inhibitory pathways but continuous activation may lead to habituation of the inhibitory reflex and loss of continence. We determined whether conditional stimulation with electrical stimulation of inhibitory pathways applied only at the onset of nascent bladder contractions allows the bladder to fill to a greater volume before continence is lost compared with continuous stimulation. MATERIALS AND METHODS: In 6 alpha-chloralose anesthetized cats cystometry was performed to compare the volume at which continence was lost under the conditions of no stimulation, continuous stimulation and conditional electrical stimulation of inhibitory pathways. PNT ENG was used to detect the onset of bladder contractions and it served as the input to an event triggered control system that regulated conditional stimulation to maintain continence. RESULTS: Conditional stimulation controlled by PNT ENG increased bladder capacity by 36% over no stimulation and by 15% over continuous stimulation (p <0.001 and 0.027, respectively). The event triggered control system decreased stimulation time by 67% compared to continuous stimulation. CONCLUSIONS: Conditional electrical stimulation of inhibitory pathways is more effective than continuous stimulation. A control system triggered by PNT ENG can maintain urinary continence.

Animals↗

Is skeletal muscle ventricle chronic stability dependent on wall stress? Design implications.

Chronic skeletal muscle ventricle (SMV) stability is essential for clinical implementation. SMVs in animal models have chronically expanded or collapsed when exposed to physiologic pressures. SMV wall stress is a more appropriate indicator than pressure or geometry to compare SMVs between studies. SMV wall tensions during conditioning were determined for SMVs that collapsed, expanded, or were isovolumetric in a previous study. Wall stresses in SMVs that expanded (2.76 +/- 0.803 N/cm(2)) were significantly greater than isovolumetric SMVs (0.89 +/- 0.450) and SMVs that collapsed (0.88 +/- 0.451). These data support the existence of minimum and maximum wall stresses for SMV volume stability and provide empiric estimates for SMV design. Scaling SMV designs from animal models with smaller volumes and similar pressures may result in greater wall stresses in clinical designs. Therefore, the use of volume limiting implants or an isovolumetric conditioning phase to increase the wall stress expansion threshold may be required.

Animals↗

Fascicular anatomy and surgical access of the human pudendal nerve.

The ability to access selectively distal nerve branches at the level of the compound pudendal nerve (PN) would allow control of multiple neural pathways and genitourinary functions at a single location. Nerve cuff electrodes can selectively stimulate individual fascicles; however the PN fascicular anatomy is unknown. The fascicular representation of distal branches was identified and traced proximally to create fascicle maps of 12 compound PNs in seven cadavers. Distal nerves were represented as groups of individual fascicles in the PN. Fascicle maps were consistent between specimens and along the PN within specimens. PN branch free length was 26+/-7.7 mm. PN cross-sections were relatively flat with major and minor diameters of 4.3+/-0.90 and 1.7+/-0.45 mm, respectively. Placing a nerve cuff on the PN is anatomically and surgically feasible. The PN fascicular anatomy, branch free length, and cross-section geometry are conducive to selective stimulation of distal nerves with a single nerve cuff electrode.

Aged↗

Detecting the onset of hyper-reflexive bladder contractions from the electrical activity of the pudendal nerve.

Individuals with a spinal cord injury or neurological disorders may develop involuntary bladder contractions at low volumes (bladder hyper-reflexia), which can lead to significant health problems. Present devices can inhibit unwanted contractions through continuous stimulation, but do not enable conditional stimulation only at the onset of bladder contractions. The objectives of this study were to determine the relationship between the electrical activity of the pudendal nerve trunk (PNT) and bladder pressure during hyper-reflexive bladder contractions and to determine whether PNT activity could be used to detect the contractions. Bladder pressure and PNT electroneurogram (ENG) were recorded in eight adult male cats. The PNT ENG activity increased at the onset of a bladder contraction and the activity during bladder contractions was greater than during the intercontraction interval (p < 0.001). Three algorithms were developed to detect the onset of a bladder contraction from the PNT ENG activity. A cumulative sum (CUSUM) algorithm performed better than either a constant threshold or a dynamic threshold algorithm, and enabled detection of reflex bladder contractions from the PNT ENG an average of 1.2 s after the contraction started with an average increase in pressure 7.1 cm H2 x O when evaluated on data not used to set detection parameters. These data demonstrated that recordings from the PNT could be used to detect hyper-reflexive bladder contractions and provide a signal to control closed-loop inhibitory stimulation.

Action Potentials↗

Spinal micturition reflex mediated by afferents in the deep perineal nerve.

Reflexes mediated by urethral sensory pathways are integral to urinary function. This study investigated the changes in bladder pressure and urethral sphincter activity resulting from electrical stimulation of afferents in the deep perineal nerve (DP), which innervates the urethra and surrounding muscles, before and after acute spinal cord transection (SCT) in cats anesthetized with alpha-chloralose monitored by blood pressure and heart rate. DP stimulation elicited bladder contractions before and after SCT but only if the bladder contained a sufficient volume of fluid (78% of the volume needed to cause distention-evoked reflex contractions). The volume dependency was mediated by a neuronal mechanism in the lumbosacral spinal cord and was not attributable to length-tension properties of the detrusor muscle. Stimulation at 2-40 Hz initiated bladder contractions, but 20-40 Hz was more effective than lower frequencies in evoking and sustaining bladder contractions for the duration of the stimulus train. Decreases in urethral sphincter activity occurred during sustained bladder contractions evoked by 20- to 40-Hz stimulation before and within 16 h after SCT. After SCT, average bladder pressure increases evoked by DP stimulation were smaller than those evoked before SCT, but in some animals, bladder pressures elicited by DP stimulation continued to increase as time after SCT increased and reached pretransection amplitudes at 8-16 h posttransection. These data confirm the presence of a spinal circuit that can mediate coordinated bladder-sphincter responses and show that afferents from the DP can activate this circuit under appropriate conditions.

Afferent Pathways↗

A urethral afferent mediated excitatory bladder reflex exists in humans.

An excitatory reflex between urethral flow receptors and the bladder has been established in animals, but attempts to demonstrate this reflex in humans using urethral fluid flow have been inconclusive. Intraurethral electrical stimulation has recently been shown to generate bladder contractions in animals and was applied to study the presence of an excitatory urethra to bladder reflex in humans. The prostatic urethra was stimulated electrically via a catheter-based electrode in five men with complete spinal cord injury. Bladder contractions were generated in four of five individuals, however, only when the bladder volume was sufficiently large. These results demonstrate the presence of a volume dependent excitatory bladder reflex mediated by urethral afferent nerve fibers and the lumbosacral spinal cord.

Adult↗

Skeletal muscle ventricle pressure-volume properties conform to dynamic and static conditioning.

BACKGROUND: Chronic changes in skeletal muscle ventricle (SMV) size and strength can directly affect performance and stability. These changes may depend on the conditioning protocol or implant system. Therefore the effects of conditioning protocols on SMV geometry and contractility must be identified for optimal SMV design and application. METHODS: Skeletal muscle ventricles were constructed in 14 goats using the left latissimus dorsi muscle. The SMVs were conditioned with a 40 mL constant-volume isovolumetric implant (n = 5, IsoVol group) or a compliant pneumatic system that allowed dynamic shortening and direct exposure to resting pressures. Dynamic SMV resting pressure was either progressively increased from 40 to 100 to 120 mm Hg (n = 5, high pressure [HiP] group) or maintained at 40 mm Hg (n = 4, low pressure [LowP] group) during conditioning. The SMV pressure and volume characteristics were monitored daily. RESULTS: All HiP SMVs expanded in volume during conditioning after exposure to physiologic pressures. Three of 4 LowP SMVs decreased in volume during conditioning. Skeletal muscle ventricle passive and active (isovolumetric evoked pressure) pressure-volume curves shifted toward the increasing, stable, and decreasing volumes in HiP, IsoVol, and LowP SMVs respectively. CONCLUSIONS: Frequent monitoring of SMV characteristics during conditioning enabled progressive pressure training and is a valuable tool to evaluate SMV conformation. Chronic SMV adaptation is dependent on the conditioning protocol or implant system utilized. Demonstration of SMV expansion at physiologic pressures suggests that clinical sized SMVs may be chronically unstable unless a supporting implant system is utilized or SMV compliance is reduced. Therefore the mechanisms effecting chronic expansion should be further defined to optimally design SMVs for clinical implementation.

Animals↗

A catheter based method to activate urethral sensory nerve fibers.

PURPOSE: The ability to control bladder activity would provide a valuable tool to assist individuals with neurological disorders or spinal cord injury (SCI). Recent studies in animal models have shown that bladder contractions can be evoked by electrical stimulation of urethral afferent nerves. We developed and validated in cats a minimally invasive method to stimulate electrically the sensory nerve fibers that innervate the urethra. MATERIALS AND METHODS: The urethra was stimulated electrically along its length via a catheter mounted circumferential electrode in 6 cats. The urethra was similarly stimulated in a male individual with complete SCI. RESULTS: Robust bladder contractions were generated via intraurethral electrical stimulation in all cat experiments. Peak responses were obtained in the proximal and prostatic urethra. In the individual with SCI bladder contractions were generated via intraurethral stimulation at a position 4 cm distal to the bladder. Responses in cats and the human depended on bladder volume. CONCLUSIONS: To our knowledge this study provides the first documentation of generating bladder contractions via intraurethral electrical stimulation in cats and humans. This method provides a research tool for future studies to investigate these pathways in humans. Preliminary human results suggest that urethral afferent mediated neural pathways demonstrated in animal models exist in humans and support the development of neural prostheses using electrical stimulation of these nerves to restore control of bladder function in individuals with neurological disorders or SCI.

Adult↗

Linear performance characteristics of latissimus dorsi muscle: potential for cardiac assistance.

Knowledge of the quantitative performance capabilities of skeletal muscle in a linear geometry is necessary to predict the performance and to optimize the design of linearly configured, skeletal muscle powered cardiac assist devices (MCADs). This study determined the performance characteristics of goat latissimus dorsi muscle (LDM) using a linear, ex vivo experimental apparatus. In five goats, the LDM (130.6 +/- 18.8 g) was dissected free of its distal attachments, connected to a series of weights (500 to 2250 g), and maximal tetanic contractions were elicited via thoracodorsal nerve stimulation. Second order polynomial equations were derived to represent each of the following variables versus load: muscle prestretch (range 1.5 to 5.4 cm), contraction duration (220 to 360 milliseconds), contraction shortening distance (13.5 to 10.9 cm), contraction velocity (60 to 31 cm/s), generated stroke power (3 to 7 W), and stroke work (0.7 to 2.4 J). Analysis of the potential stroke volumes obtained with a linearly configured, cylindrically shaped MCAD directly coupled to the circulation indicate that a feasible MCAD operating region exists based on the LDM performance data across a range of device geometries and mean ejection pressures.

Animals↗