Nicotine impairs reflex renal nerve and respiratory activity in deoxycorticosterone acetate-salt rats.

Smoking exacerbates the increase in arterial pressure in hypertension. The effect of nicotine on the baroreceptor-mediated reflex responses of renal nerve activity (RNA), heart rate, and respiratory activity (minute diaphragmatic activity [MDA]) after bolus injections of phenylephrine was compared in deoxycorticosterone acetate (DOCA)-salt sensitive and normotensive rats. Osmotic minipumps that dispensed either nicotine (2.4 mg/kg/day) or saline were implanted in DOCA and normotensive rats for 18 days. Anesthetized DOCA-nicotine, DOCA-saline, control-nicotine, and control-saline rats had mean arterial pressures (MAP) of 117 +/- 3, 110 +/- 9, 90 +/- 3, and 89 +/- 5 mm Hg, respectively. Nicotine decreased the sensitivity (p less than 0.05) of baroreceptor reflex control of RNA (% delta RNA/delta MAP) in the DOCA-nicotine rats (-0.92 +/- 0.08) compared with the DOCA-saline (-1.44 +/- 0.16), control-nicotine (-1.45 +/- 0.08), or control-saline (-1.45 +/- 0.21) rats. The reflex decrease in respiratory activity (% delta MDA/delta MAP x 100) was impaired (p less than 0.01) in both control-nicotine (-24.5 +/- 3.3) and DOCA-nicotine (-18.2 +/- 4.6) rats compared with control-saline (-59.2 +/- 9.1) and DOCA-saline (-52.5 +/- 9.9) rats. The reflex decrease in heart rate (absolute delta HR/delta MAP) in both DOCA-nicotine (1.56 +/- 0.17) and control-nicotine (1.54 +/- 0.24) rats was augmented compared with DOCA-saline and control-saline rats (0.91 +/- 0.12 and 0.97 +/- 0.14).(ABSTRACT TRUNCATED AT 250 WORDS)

Gas exchange and lactate anaerobic thresholds: inter- and intraevaluator agreement.

Twenty-four coded graph sets of gas exchange variables and blood lactate concentration (LA) plotted against time at 15-s intervals were analyzed by nine evaluators who determined the gas exchange (ATGE) and LA (ATLA) anaerobic thresholds. In addition, ATGE and ATLA were determined by a linear regression computer program. Agreement between ATGE and ATLA was poor; the median intraclass correlation coefficient (ri) was 0.53. Among evaluators, ATLA agreement (median ri = 0.81) was better than ATGE agreement (median ri = 0.70). In general, the ability of any evaluator to choose similar values from duplicate plots for either ATGE (median ri = 0.97) or ATLA (median ri = 0.995) was good. There was better agreement between the mean ATLA of the evaluators and the computer ATLA (ComLA) (ri = 0.88) than between the mean ATGE of the evaluators and the computer ATGE (ComVE), (ri = 0.58). Agreement between ComVE and ComLA was poor (ri = 0.29). These results suggest that ATGE does not accurately predict ATLA and that different evaluators choose different thresholds from the same data. Further assessment of the validity and precision of ATGE based on breath-by-breath and minute-by-minute data is needed.

Vascular delay of the latissimus dorsi muscle: an essential component of cardiomyoplasty.

BACKGROUND: Cardiomyoplasty (CMP) uses the latissimus dorsi muscle (LDM) to assist the heart in cases of cardiac failure. Distal ischemia and necrosis of the LDM is a recognized complication of CMP that can reduce distal muscle function and the mechanical effectiveness of CMP. METHODS: Canine (n = 9) LDMs were subjected to a 10-day period of vascular delay followed by a simulated CMP. Two weeks after simulated CMP (corresponding to the healing delay between CMP and the onset of LDM stimulation used in the clinical setting), LDM perfusion was measured in the distal, middle, and proximal segments of the muscle, and circumferential (distal and middle squeezing muscle function) and longitudinal (proximal pulling muscle function) force generation and fatigue rates were measured. The results were compared with the contralateral nondelayed simulated CMP. RESULTS: Muscle perfusion was significantly (p < 0.05) greater in the distal and middle segments of vascular-delayed LDMs. Circumferential muscle force generation and fatigue rates were significantly (p < 0.05) improved in the vascular-delayed LDMs. CONCLUSIONS: Vascular delay can significantly improve LDM perfusion and function in a model that closely reflects clinical CMP, and the use of vascular delay may improve clinical outcomes in CMP.

The nucleus reticularis gigantocellularis modulates the cardiopulmonary responses to central and peripheral drives related to exercise.

It is known that muscle afferents and the hypothalamic locomotor region (HLR) both project to the nucleus reticularis gigantocellularis (NGC) and that the NGC is capable of influencing cardiovascular and respiratory variables. Therefore, the role of NGC in the cardiovascular and respiratory response to exercise-related signals was investigated in anesthetized cats. These signals were generated by stimulation of: (1) spinal ventral roots to induce hindlimb muscle contraction (MC) and (2) the HLR. Bilateral electrolytic lesion of the NGC at the pontomedullary border caused tidal volume, respiratory frequency and heart rate responses to HLR stimulation to be greater than the responses recorded prior to lesioning. Lesioning had no effect on the ventilatory or cardiovascular responses to MC but did decrease phrenic responsiveness; lesion had no effect on any resting values. In this preparation, the pontomedullary NGC acts as an inhibitory influence on tidal volume, breathing frequency and heart rate responses to the central command for exercise. In addition, NGC modulation of ventilation would appear to be selective for certain respiratory muscle groups.

Involvement of the raphe in the respiratory effects of gigantocellular area activation.

Previous reports indicate that the nucleus reticularis gigantocellularis (NGC) of the brainstem reticular formation is involved in inhibitory respiratory and cardiovascular reflexes. Stimulation of portions of the nearby bulbar raphe complex, specifically the raphe magnus (RM), have also been shown to suppress phrenic activity and to decrease blood pressure and heart rate. Since synaptic connectivity between the NGC and the RM has been demonstrated, we hypothesized that the RM may be involved in the cardiopulmonary effects of NGC stimulation. This study found that electrolytic lesions in the raphe magnus attenuated the inhibitory respiratory effects but not the cardiovascular suppression due to NGC stimulation. Lesions in the raphe magnus also lowered resting blood pressure and resting breath frequency. We conclude that the RM may mediate part of the NGC-mediated respiratory effects.

Occlusion of pressor responses to posterior diencephalic stimulation and muscular contraction.

Although neural occlusion has been suggested to occur between the central and reflex mechanisms increasing arterial pressure, evidence consistent with this phenomenon is lacking. To assess the possibility of neural occlusion we recorded, in chloralose-anesthetized cats, the pressor responses to statically contracting the hindlimb muscles and to electrically stimulating histologically confirmed sites in the posterior hypothalamus and subthalamus. We also recorded the pressor responses to topical application of capsaicin onto the intestine and to stimulation of these diencephalic sites. The pressor responses to simultaneous static contraction and diencephalic stimulation were significantly smaller than the algebraic sum of the pressor responses to contraction and diencephalic stimulation evoked separately. Likewise, the pressor responses to simultaneous capsaicin application and diencephalic stimulation were significantly smaller than the algebraic sum of the responses evoked separately. High intensity stimulation of the L7 dorsal root or the diencephalic sites evoked pressor responses similar in magnitude to the algebraic sum of the two responses evoked separately; thus, the inability of the simultaneous maneuvers to evoke pressor responses that summed algebraically was not due to the fact that they caused a maximal effect. Our findings are consistent with the hypothesis that neural occlusion occurs during stimulation of the posterior diencephalon and static muscular contraction.

Cardiorespiratory responses to stimulation of the nucleus reticularis gigantocellularis.

The nucleus reticularis gigantocellularis (NGC) has been shown to be involved in somatosensory and somatomotor functions. The purpose of the present study was to determine, in anesthetized cats, the modulatory influence of the portion of the NGC at the ponto-medullary border on respiratory and cardiovascular control. Electrical stimulation (25-100 microA 70 Hz, and 1.0-msec pulse duration) significantly depressed mean arterial pressure, heart rate, breathing frequency, tidal volume and phrenic amplitude. Chemical stimulation of NGC cell bodies (1.0 M L-glutamate or 10(-3) M kainic acid) elicited similar decreases in ventilation, arterial pressure and heart rate. These results show that selective activation of cell bodies in the ponto-medullary NGC can depress, in parallel, respiratory and cardiovascular activity and suggests that the influence of diverse sensory information within this region of the reticular formation must be inhibitory to respiratory and cardiovascular output.

Hypothalamic GABAergic influences on treadmill exercise responses in rats.

Microinjection of GABAergic antagonists in the posterior hypothalamus (PH) produces exercise-like adjustments in cardiovascular function. To test the hypothesis that a hypothalamic GABAergic mechanism within the PH modulates the cardiovascular adjustments to dynamic exercise in conscious animals, Sprague-Dawley rats (n = 10) were instrumented with bilateral guide cannula directed at the pH, an arterial cannula, and Doppler flow probes on the iliac and mesenteric arteries. Saline (100 nl) or the GABAA receptor agonist muscimol (125 ng.100 nl-1) was bilaterally injected into the PH during treadmill exercise (20 m.min-1). Microinjection of saline had no effect on mean arterial pressure (MAP), heart rate (HR), mesenteric vascular resistance (MR), or iliac vascular resistance (IR) during exercise. Microinjection of muscimol during exercise produced no significant changes in MAP (mean change +/- SE; +0 +/- 1 mmHg), HR (+17 +/- 12 b.min-1), or MR (+7 +/- 13%). However, microinjection of muscimol produced a significant increase in IR during exercise (16 +/- 6%). In addition, muscimol significantly decreased treadmill run time (saline = 19.6 +/- 0.4 min; muscimol = 17.8 +/- 0.6 min) and produced behavioral effects (including mild sedation) that were most evident after exercise. The results of these experiments suggest that while the posterior hypothalamic GABAergic system may modulate iliac blood flow during exercise in rats, this system does not modulate HR and MR responses to dynamic exercise.

Evaluation of stimulation parameters on aortomyoplasty, using Latissimus Dorsi muscle in a goat model: an acute study.

OBJECTIVE: Dynamic aortomyoplasty using Latissimus Dorsi muscle (LDM) has been shown to improve myocardial function. However, systematic examination of the effects of stimulation parameters on aortic wrap function has not been done. Thus, the present study measures the direct effect of stimulation voltage, pulse train duration, frequency of the pulses, and the duration of the stimulation delay from R wave on the aortic wrap function. METHODS: In eight female goats, the left LDM was wrapped around the descending aorta. The muscle was then subjected to electrical stimulation, altering frequency of stimulation pulses (16.6, 20, 25, 33 and 50 Hz), amplitude (2, 4, 6, 8 and 10 V), and number of pulses (2, 4, 6, 8 and 10 pulses) in a train stimulation. Left ventricular, aortic pressure, and pressure generated by LDM on aorta (wrap pressure) was measured. The changes in hemodynamic parameters mentioned above were calculated and compared for different stimulation parameters during unassisted and assisted cardiac cycles. RESULTS: Aortomyoplasty counterpulsation using LDM provided significant improvement in wrap pressure (78 mmHg +/- 2), aortic diastolic pressure, and changes in aortic diastolic pressure from 2 to 4 V (P < 0.05). Further increase in amplitude did not make any significant improvements of the above mentioned parameters. Significant augmentation of wrap pressure (82 mmHg +/- 2), aortic diastolic pressure (79 mmHg +/- 3) and changes in aortic diastolic pressure (12 mmHg +/- 1) occurred at 6 pulses (P < 0.05). Other changes in number of pulses did not show any significant improvements. Significant improvement of wrap pressure (80 mmHg +/- 2), aortic diastolic pressure (73 mmHg +/- 3) and changes in aortic diastolic pressure (12 mmHg +/- 1) was observed with a frequency of 33 Hz. To examine a wide range of delays from the onset of the QRS complex to LDM stimulation, stimulation was delivered randomly. The exact delay was determined from the ECG signal and superimposed LDM stimulation pulses. CONCLUSIONS: In this study we present a new measurement, wrap pressure. We also present that in aortomyoplasty using LDM, the most significant improvement in wrap pressure, aortic diastolic pressure and changes in aortic diastolic pressure occurs when the stimulation consists of an amplitude of 4 V, a frequency of 33 Hz and a train stimulation of 6 pulses.

Vascular delay improves latissimus dorsi muscle perfusion and muscle function for use in cardiomyoplasty.

Ischemia of the distal portion of the latissimus dorsi muscle occurs in muscle transfer for cardiomyoplasty and reduces distal muscle contractility and thus the mechanical effectiveness of cardiomyoplasty. We hypothesized that muscle function would be improved by a vascular delay procedure that increases distal muscle perfusion of the latissimus dorsi muscle. The latissimus dorsi muscles of 10 adult mongrel dogs were subjected to a vascular delay procedure on one side and a sham procedure on the other. Following 10 days of vascular delay, muscle perfusion was measured with a laser-Doppler perfusion imager before and after elevation of the muscles as flaps based only on their thoracodorsal neurovascular pedicles. The muscles were wrapped and sutured around silicone chambers (simulating cardiomyoplasty), a stimulating electrode was placed around each thoracodorsal nerve, and the muscles were stimulated to contract in both rhythmic and tetanic fashion. Circumferential (distal and middle latissimus dorsi muscle function) force generation and fatigue rates were measured independently. Circumferential muscle force, circumferential and longitudinal fatigue rate, and distal, middle, and overall perfusion were significantly (p < 0.05) improved in delayed muscle compared with nondelayed muscle. We found that a vascular delay procedure and a 10-day delay adaptation period significantly improve latissimus dorsi muscle flap perfusion and function, particularly in the distal and middle portions of the muscle. Delay should be considered as a means of improving the clinical outcome in cardiomyoplasty.

Vascular delay and administration of basic fibroblast growth factor augment latissimus dorsi muscle flap perfusion and function.

Ischemia of the distal latissimus dorsi muscle flap occurs when the entire muscle is acutely elevated. Although this level of ischemia may not be critical if the muscle is to be used as a conventional muscle flap, the ischemia causes decreased distal muscle function if it is used for dynamic muscle flap transfer. This experiment was designed to determine whether or not the administration of exogenous basic fibroblast growth factor (bFGF), combined with a sublethal ischemic insult (i.e., vascular delay), would further augment muscle perfusion and function. Both latissimus dorsi muscles of nine canines were subjected to a bipedicle vascular delay procedure immediately followed by thoracodorsal intraarterial injection of 100 microg of bFGF on one side and by intraarterial injection of vehicle on the other. Ten days later, both latissimus dorsi muscles were raised as thoracodorsally based island flaps, with perfusion determined by laser-Doppler fluximetry. The muscles were wrapped around silicone chambers, simulating cardiomyoplasty, and stimulating electrodes were placed around each thoracodorsal nerve. The muscles were then subjected to an experimental protocol to determine muscle contractile function. At the end of the experiment, latissimus dorsi muscle biopsies were obtained for measurement of bFGF expression. The results demonstrated that the administration of 100 microg of bFGF immediately after the vascular delay procedure increases expression of native bFGF. In the distal and middle muscle segments, it also significantly increased muscle perfusion by approximately 20 percent and fatigue resistance by approximately 300 percent. The administration of growth factors may serve as an important adjuvant to surgical procedures using dynamic muscle flap transfers.

Use of the rectus abdominis muscle for abdominal stoma sphincter construction: an anatomical feasibility study.

Permanent fecal abdominal stomas significantly decrease quality of life. Previous attempts to create continent stomas by using dynamic myoplasty procedures have resulted in disappointing outcomes, primarily owing to denervation atrophy of the muscle flap that was used in the creation of the sphincter and because of muscle fatigue resulting from continuous electrical stimulation that is received by the flap to force contraction. On the basis of these problems, we designed two separate studies: an anatomical study addressing flap denervation and a functional study addressing muscle fatigue. The present study addresses the first topic and was designed to develop a rectus abdominis muscle flap into a sphincter that was anatomically situated to create a stoma while preserving as much innervation as possible. In 24 rectus abdominis muscles of human cadavers, the neurovascular anatomy was defined, then the anatomical feasibility of two different muscle flap configurations was considered. The flaps investigated were the peninsula flap and island flap designs, with both using the most caudal segment of the rectus abdominis muscle in construction of the sphincter. Neither flap design required the killing of a nerve for stoma sphincter creation, resulting in minimal muscle denervation. The conclusion of our comparison was that the above, in conjunction with other features of the island flap design, such as muscle overlap after sphincter formation and abdominal wall positioning of the sphincter, made the island flap design better suited to stoma sphincter construction.

Sequential segmental neuromuscular stimulation: an effective approach to enhance fatigue resistance.

Electrical stimulation of skeletal muscle flaps is used clinically in applications that require contraction of muscle and force generation at the recipient site, for example, to assist a failing myocardium (cardiomyoplasty) or to reestablish urinary or fecal continence as a neo-sphincter (dynamic graciloplasty). A major problem in these applications (muscle fatigue) results from the nonphysiologic manner in which most of the fibers within the muscle are recruited in a single burst-like contraction. To circumvent this problem, current protocols call for the muscle to be put through a rigorous training regimen to transform it from a fatigue-prone to a fatigue-resistant state. This process takes several weeks during which, aside from becoming fatigue-resistant, the muscle loses power and contraction speed. This study tested the feasibility of electrically stimulating a muscle flap in a more physiologic way; namely, by stimulating different anatomical parts of the muscle sequentially rather than the entire muscle all at once. Sequential segmental neuromuscular stimulation (SSNS) allows parts of the muscle to rest while other parts are contracting. In a paired designed study in dogs (n = 7), the effects of SSNS on muscle fatigability and muscle blood perfusion in gracilis muscles were compared with conventional stimulation: SSNS on one side and whole muscle stimulation on the other. In SSNS, electrodes were implanted in the muscles in such a way that four separate segments of each muscle could be stimulated separately. Then, each segment was stimulated so that part of the muscle was always contracted while part was always resting. This type of stimulation permitted sequential yet continuous force generation. Muscles in both groups maintained an equal amount of continuous force. In SSNS muscles, separate segments were stimulated so that the duty cycle for any one segment was 25, 50, 75, or 100 percent, thus varying the amount of work and rest that any segment experienced at any one time. With duty cycles of 25, 50, and 75 percent, SSNS produced significantly (p < 0.01) enhanced resistance to fatigue. In addition, muscle perfusion was significantly (p < 0.01) increased in these sequentially stimulated muscles compared with the controls receiving whole muscle stimulation. It was concluded that SSNS reduces muscle fatigue and enhances muscle blood flow during stimulation. These findings suggest that using SSNS in clinical myoplasty procedures could obviate the need for prolonged training protocols and minimize problems associated with muscle training.

Dynamic rectus abdominis muscle sphincter for stoma continence: an acute functional study in a dog model.

Fecal stomal incontinence is a problem that continues to defy surgical treatment. Previous attempts to create continent stomas using dynamic myoplasty have had limited success due to denervation atrophy of the muscle flap used in the creation of the sphincter and because of muscle fatigue resulting from continuous electrical stimulation. To address the problem of denervation atrophy, a stomal sphincter was designed using the most caudal segment of the rectus abdominis muscle, preserving its intercostal innervation as well as its vascular supply. The purpose of the present study was to determine whether this rectus abdominis muscle island flap sphincter design could maintain stomal continence acutely. In this experiment, six dogs were used to create eight rectus abdominis island flap stoma sphincters around a segment of distal ileum. Initially, the intraluminal stomal pressures generated by the sphincter using different stimulation frequencies were determined. The ability of this stomal sphincter to generate continence at different intraluminal bowel pressures was then assessed. In all cases, the rectus abdominis muscle sphincter generated peak pressures well above those needed to maintain stomal continence (60 mmHg). In addition, each sphincter was able to maintain stomal continence at all intraluminal bowel pressures tested.

Electrically stimulated free-flap graciloplasty for urinary sphincter reconstruction: a new surgical procedure.

In electrically stimulated (dynamic) graciloplasty for urinary incontinence, the gracilis muscle is transposed into the pelvis, and the distal part is used to reconstruct a neosphincter. Clinical outcomes using this technique have been disappointing due to stricture of the urethra caused by ischemia in the distal part of the gracilis and limited gracilis length available for neosphincter construction. Furthermore, the urethra is twisted by the contracting gracilis, rather than circumferentially squeezed. The purpose of the present study was to test the anatomical and functional feasibility of a new surgical approach to reconstruct a urinary sphincter, using the gracilis muscle as a free flap. In 12 human cadavers, the anatomical feasibility for creating a neosphincter by using the gracilis free flap was determined. In all cases, transfer of the gracilis muscle into the pelvis as a free flap (with the nerve intact) was feasible, and ample muscle was available to construct a neosphincter around the bladder neck. Gracilis neosphincter function was studied in seven dogs. The left gracilis muscle was subjected to transfer into the pelvis as an innervated free flap to create a neosphincter around the urethra. The right (control) gracilis muscle was lifted as a single pedicle flap, remained in situ, and was wrapped around a stent to mimic the urethra. Function (expressed as peak pressure generation and fatigue rate) and surface perfusion were determined for all gracilis muscles. In each dog, both sides were compared using the paired Student's t test for statistical analysis, and no significant difference was measured for the two groups. In conclusion, an innervated gracilis free flap can be used to create a neosphincter around the bladder neck. In an acute study in dogs, function and perfusion of the innervated gracilis free flap are not compromised.

A computer analysis of reflex eyelid motion in normal subjects and in facial neuropathy.

OBJECTIVE: To demonstrate how computerized eyelid motion analysis can quantify the human reflex blink. DESIGN: Seventeen normal subjects and 10 patients with unilateral facial nerve paralysis were analyzed. BACKGROUND: Eyelid closure is currently evaluated by systems primarily designed to assess lower/midfacial movements. The methods are subjective, difficult to reproduce, and measure only volitional closure. Reflex closure is responsible for eye hydration, and its evaluation demands dynamic analysis. METHODS: A 60Hz video camera incorporated into a helmet was used to analyze blinking. Reflective markers on the forehead and eyelids allowed for the dynamic measurement of the reflex blink. Eyelid displacement, velocity and acceleration were calculated. The degree of synchrony between bilateral blinks was also determined. RESULTS: This study demonstrates that video motion analysis can describe normal and altered eyelid motions in a quantifiable manner. CONCLUSIONS: To our knowledge, this is the first study to measure dynamic reflex blinks. Eyelid closure may now be evaluated in kinematic terms. This technique could increase understanding of eyelid motion and permit more accurate evaluation of eyelid function. Dynamic eyelid evaluation has immediate applications in the treatment of facial palsy affecting the reflex blink. Relevance No method has been developed that objectively quantifies dynamic eyelid closure. Methods currently in use evaluate only volitional eyelid closure, and are based on direct and indirect observer assessments. These methods are subjective and are incapable of analyzing dynamic eyelid movements, which are critical to maintenance of corneal hydration and comfort. A system that quantifies eyelid kinematics can provide a functional analysis of blink disorders and an objective evaluation of their treatment(s).

Cardiorespiratory responses to exercise after bed rest in men and women.

The purpose of this study was to compare cardiorespiratory responses of men and women to submaximal and maximal workloads before and after bed rest (BR). Fifteen male college students (19-23 yr) and 8 female nurses (23-34 yr) underwent 14 d and 17 d, respectively of bed rest. The maximal work capacity test was performed in the supine position on a bicycle ergometer just before and immediately after bed rest. The women's maximal O2 uptake (maximal VO2) was 41% lower (P<0.05) than the men's before bed rest and 42% lower (P<0.05) after bed rest. During bed rest the women's maximal VO2 decreased from 2.06 to 1.86 liter/min (-9.7%, P<0.05), and that of the men decreased from 3.52 to 3.20 liter/min (-9.1%, P<0.05). Compared with pre-BR values, after bed rest the maximal ventilatory volume was essentially unchanged in the men (+1.8%) and women (+ 2.3%), but maximal heart rate was elevated from 185 to 193 b/min (+ 4.3%, P<0.05) in the men and from 181 to 187 b/min (3.3%, P<0.05) in the women. Submaximal VO2 was unchanged after bed rest in the men but was significantly reduced in the women; the women's Hct and RBC levels were lower (P<0.05) than comparable male data. Mean corpuscular volume was unchanged in both groups pre- and post-bed rest. It is concluded that the proportional deterioration in maximal VO2 following prolonged bed rest was essentially the same in young men and women.