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PubMed2000

Cerebral activation during micturition in normal men.

Specific cerebral lesions have shown the crucial role of the brain in the control of micturition. The precise identification of the anatomical cerebral structures involved in micturition can contribute to a better understanding of the control of micturition and the development of therapeutic models. Various neuropathological and animal studies have referred to the medulla oblongata, pons, limbic system, superior frontal lobe and premotor cortical regions as areas implicated in micturition control. The aim of this study was to investigate whether the activity of these areas during micturition can be confirmed by PET in normal men. The distribution of the regional cerebral blood flow after bolus injection of (15)O water was used as an indirect measure of cerebral activation. PET scans were performed during the following three conditions: (i) at rest with the bladder empty; (ii) during simulated micturition after instillation of isotonic saline into the urinary bladder; and (iii) the withholding of urine (saline). Normal micturition using this model was achieved in eight out of 12 right-handed normal subjects. The changes in bladder contraction, bladder pressure and intra-abdominal pressure were monitored on-line during the whole scanning session by a cystometry device. The images were analysed using statistical parametric mapping at a significance threshold of P < 0.05 with correction for multiple independent comparisons. Micturition versus rest was associated with bilateral activation of areas close to the postcentral gyrus, inferior frontal gyrus, globus pallidus, cortex cerebelli, vermis and midbrain. On the left side, activation of the middle frontal gyrus, superior frontal gyrus, superior precentral gyrus, thalamus and the caudal part of the anterior cingulate gyrus was seen, while on the right side we found activation in the supramarginal gyrus, mesencephalon and insula. When the threshold value was lowered to P < 0.001 (Z > 3.09) without correction for multiple comparisons, we found additional activation in the medial pontine tegmentum, mesencephalon, right thalamus, right middle frontal gyrus and left insula. When urine- withholding was compared with rest, the left insula showed a tendency to activate. We conclude from this study, in which urinary bladder contraction was verified cystometrically, that the onset and maintenance of micturition in normal men is associated with a vast network of cortical and subcortical regions, confirming observations from clinical and animal studies.

Adult↗

PubMedDate not supplied

Autonomic stimulation, osmolarity and prostaglandin effects in the Eustachian tube.

Stimulation of the vidian nerve in the dog induced an apparent vasodilation in the mucosa of the Eustachian tube. It is presumed that these parasympathetic fibers course from the greater petrosal nerve through the vidian to the sphenopalatine ganglion. The pharyngeal nerve arises from the ganglion and innervates the mucosa of the tube. Perfusion of the dog's Eustachian tube with solutions of various osmolarities caused a shrinking or swelling of the tube mucosa. Ten percent alterations in the concentration of saline, Ringer's or isotonic KCl produced a hypo- or hypertonic effect. Systemic administration of osmotic diuretics was shown to remove water from normal and edematous tubal mucosa. An agent in human middle ear effusions was found to contract smooth muscle. The behavior of this agent in pharmacological tests suggested the presence of prostaglandins (PG). The effusions were tested for the presence of other inflammatory mediators such as bradykinin, acetylcholine and histamine. These were felt to be absent or present in small amounts. A radioimmune assay of pooled samples of middle ear effusions revealed the presence of several PG, notably PGF2alpha and PGE2. There appeared to be a higher concentration of PG in mucoid effusions than serous effusions. The inflammatory capabilities of these agents are mentioned.

Animals↗

PubMed1990

A comparison in vitro of human and rabbit distal colonic muscle responses to inflammatory mediators.

The present study compared in vitro the motor responses of human and rabbit distal colonic longitudinal and circular muscle to acetylcholine, histamine, leukotrienes B4 and D4, and prostaglandins E2 and F2 alpha. The active and passive mechanical properties of these muscles were also evaluated. All muscle types were contracted by acetylcholine and histamine. Longitudinal muscle from both species was contracted by prostaglandin E2 and prostaglandin F2 alpha, although rabbit muscle was more sensitive. Prostaglandin E2 relaxed the majority of both human and rabbit circular muscle preparations that were studied. Prostaglandin F2 alpha first relaxed and then contracted circular muscle from both species. Leukotriene B4 had no effect on any tissue studied. Leukotriene D4 caused transient relaxations in a proportion of all muscle types, but the relaxations were not concentration-related. Contractile responses did not differ under isotonic recording conditions, but relaxations were much more clearly defined. Based on experiments using atropine, phentolamine and propranolol, and pyrilamine or tetrodotoxin, it was concluded that the responses of both human and rabbit distal colonic muscles to these inflammatory mediators have a similar pharmacological basis. All muscle types exhibited low passive tension and developed active tension in the range 0.8-1.2 Lo. These data strongly support the belief that after the onset of an induced colitis, the rabbit colon has value as a predictive model for the study of inflammatory mediator-induced colonic motility changes in humans.

Acetylcholine↗

PubMed1992

Movement-dependent after-effects in the firing of the spindle endings from the de-efferented muscles of the cat hindlimb.

The muscle spindle reactions evoked by the servo-controlled changes in the muscle length or external load were studied on the de-efferented muscles in experiments on cats under Nembutal anaesthesia. The activity of 39 primary and 10 secondary endings of the muscle spindles from four hindlimb extensor muscles: soleus, plantaris, lateral and medial heads of gastrocnemius has been recorded during servo-controlled changes in muscle length (L-control) or external load (P-control). Slow linear reciprocating (triangular) signals and their modification with fixation of the controlled parameter at the same level at forward and reverse phases were used as commands for the muscle stretcher. The steady firing rates in primary and secondary endings during fixation of muscle length or external load were shown to be strongly dependent on the direction of previous changes in these parameters. The firing rates were always higher after preceding lengthening (loading) and lower after shortening (unloading). These rate uncertainties in the steady firing of spindle endings at the same level of controlled parameter could be as much as 15-20 p.p.s. The revealed dependence of the spindle ending firing on the past history of the muscle movement was denoted as movement-dependent after-effects. Two kinds of movement-dependent after-effects in the firing of the spindle endings can be observed: (1) the movement-dependent ones being studied in the present work, and (2) those connected with the conditioning fusimotor stimulation and described elsewhere. Their common origin is supposed to be connected with the hysterical (thixotropic) properties of the intrafusal muscle fibres. Similarity of the movement-dependent after-effects in L- and P-control conditions was shown to be connected with a resemblance of the length-firing rate [F(L)] and load-firing rate [F(P)] hysterical loops registered during reciprocating movements. Both kinds of loops were in a clock-wise direction, their comparison in normalized form showed that F(L) loops were always broader than F(P) ones. Isotonic and isometric uncertainty vectors were introduced to analyse quantitatively the hysterical effects in the spindle firing and their relation to the muscle hysteresis proper. Uncertainty vectors connect the points of equal load (isotonic uncertainty vectors) and equal length (isometric uncertainty vectors) on F(L) and F(P) loops correspondingly. The projections of both uncertainty vectors onto the Y-axis give the rate uncertainty coinciding in sign for both cases, whereas their projections onto the X-axis differ in sign, being positive for isometric uncertainty vectors (the tension uncertainty) and negative for isotonic uncertainty vectors (the length uncertainty).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1990

[Changes in contraction-relaxation coupling in experimental cardiac hypertrophy in the guinea pig].

Guinea pig myocardium resembles human myocardium with respect to the mechanisms which regulate contractility (enzymatic activity of myosine, functional activity of the sarcoplasmic reticulum). Guinea pig left ventricular hypertrophy (LVH) is therefore a good experimental model for the study of human LVH. The mechanical properties of 5 months old female guinea pigs' left ventricular papillary muscle, 3 weeks after constriction of the abdominal aorta (N = 10), were investigated. Ten papillary muscles of operated control animals and eight of normal guinea pigs submitted to 20 minutes hypoxia were also studied. The animals had no signs of cardiac failure after constriction of the abdominal aorta but the increase in the ratio of heart to body weight (p less than 0.001) confirmed the LVH. When compared with the operated controls, there was a decrease of the maximum velocity of contraction at zero load, of the velocity of contraction with preload alone (Vc), of the total isometric force normalized for the section of the muscle(s) and of the positive peak of the derivative of the isometric force normalized for section (+ dF/s) (p less than 0.001 for each parameter). The parameters of relaxation were also abnormal: decreased velocity of isotonic relaxation with preload only (Vr) and of the negative peak of the derivative of the isometric force normalized for section (- dF/s) (p less than 0.001 for each parameter), and an increase in the half relaxation time (t1/2) (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2006

Identification of key residues that cause differential gallbladder response to PACAP and VIP in the guinea pig.

Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) have opposite actions on the gallbladder; PACAP induces contraction, whereas VIP induces relaxation. Here, we have attempted to identify key residues responsible for their interactions with PACAP (PAC1) and VIP (VPAC) receptors in the guinea pig gallbladder. We synthesized PACAP-27/VIP hybrid peptides and compared their actions on isolated guinea pig gallbladder smooth muscle strips using isotonic transducers. [Ala4]- and [Val5]PACAP-27 were more potent than PACAP-27 in stimulating the gallbladder. In contrast, [Ala4, Val5]- and [Ala4, Val5, Asn9]PACAP-27 induced relaxation similarly to VIP. [Asn9]-, [Thr11]-, or [Leu13]PACAP-27 had 20-70% contractile activity of PACAP-27, whereas [Asn24,Ser25,Ile26]PACAP-27 showed no change in the activity. All VIP analogs, including [Gly4,Ile5,Ser9]VIP, induced relaxation. In the presence of a PAC1 receptor antagonist, PACAP(6-38), the contractile response to PACAP-27 was inhibited and relaxation became evident. RT-PCR analysis revealed abundant expressions of PAC1 receptor, "hop" splice variant, and VPAC1 and VPAC2 receptor mRNAs in the guinea pig gallbladder. In conclusion, PACAP-27 induces contraction of the gallbladder via PAC1/hop receptors. Gly4 and Ile5 are the key NH2-terminal residues of PACAP-27 that distinguish PAC1/hop receptors from VPAC1/VPAC2 receptors. However, both the NH2-terminal and alpha-helical regions of PACAP-27 are required for initiating gallbladder contraction.

Animals↗

PubMed1979

Experimental evaluation of myocardial preservation techniques: IV. Potassium cardioplegia.

To investigate whether potassium per se plays a significant role in cold potassium cardioplegia, isolated blood-perfused rabbit papillary muscle preparations were used to determine the recovery of myocardial contractility after normothermic anoxia. Cardioplegia was induced by infusing an isotonic electrolyte solution containing either 5 or 40 mEq/liter of potassium chloride. Anoxic periods of 30 minutes (9 experiments each) 45 minutes (10 experiments each), and 60 minutes (1 experiment each) were compared. Hearts stopped contracting in 45 seconds with infusion of a 40mEq/liter of potassium chloride solution compared to 5 minutes with a 5 mEq/liter solution. After 30 minutes of anoxia, myocardial recovery was 65.39 +/- 24.48 per cent with 5 mEq/liter of potassium chloride and 90.05 +/- 6.40 per cent with 40mEq/liter of potassium chloride. The difference was highly significant (p less than 0.01). After 45 minutes of anoxia the same trend as just described was noted, but the difference was statistically insignificant. After 60 minutes of anoxia, recovery was extremely poor regardless of the potassium concentration of the cardioplegic solution. Our conclusion was that a high potassium solution will arrest the heart rapidly and provide protection against anoxic injury of the myocardium. Its protective effect becomes less significant, however, as the anoxic time is prolonged.

Animals↗

PubMed1975

Isotonic relaxation in cardiac muscle.

The force-velocity-length determinants of isotonic relaxation were studied in 12 cat papillary muscles. Isotonic relaxation velocity (VL) was found to be a function of total load (preload + afterload), with peak VL increasing to a maximum at loads approximately .3 to .4 Po(L') (Po(L') defined as maximum isometric force developed during a twitch at the experimental length) and falling with increasing loads. Initial muscle length (ML) had no effect on the peak VL with constant load. Increasing the initial length at which isotonic relaxation occurred (LL) decreased peak VL but did not alter the unique length-velocity trajectory at constant load. This unique length-velocity trajectory occurred, despite a wide variation in time during the contraction when peak VL was measured. Increasing Ca++ from 2.5 to 7.5 mM increased peak VL (1.73 +/- .16 to 2.32 +/- .20 ML/s) and shifted the entire length-velocity trajectory toward higher velocities of lengthening. The addition of 10 mM caffeine increased peak VL also (1.67 +/- .18 to 2.54 +/- .20 ML/s) and had a similar effect on the length-velocity trajectory during lengthening as Ca++. Both increased Ca++ and caffeine (10 mM) augmented the maximum VL measured on addition of load.

Animals↗

PubMed1982

Developing a formulary for enteral nutrition products.

A formulary for enteral nutrition products was developed at a university hospital. Advice was solicited from clinical dietetics and the medical staff. Reported important product variables were osmolality, caloric density, protein content and source, fat content and source, freedom from lactose, and, for oral supplements, available flavors. Data were also obtained from manufacturers regarding the composition of their products. Products were categorized as follows: liquid supplemental feedings, high calorie supplemental feedings, isotonic tube feedings, high caloric/high nitrogen tube feedings, high nitrogen tube feedings, and blenderized tube feedings. Bids were solicited in April 1981 (and annually thereafter) from manufacturers of the classified enteral nutrition products, and a contract was signed with the manufacturer in each category submitting the lowest bid. In contrast with previous experience, there was no loss from outdated products during the first year of the formulary. Categorizing enteral nutrition products into therapeutic categories appears to be a workable method to limit the number of products used in a hospital, thereby potentially decreasing inventory, waste, and hospital costs. The descriptive category titles also may encourage rational use of these products without promoting allegiance to a particular company or product.

Electrolytes↗

PubMed1982

Energy cost and heart rate response to static and dynamic leg exercise.

The energy cost (VO2) and heart rate (HR) response to variable-load static (isometric) and dynamic (isotonic) leg exercise were determined in 5 young women who performed 5-minute bouts of leg extension while in a sitting position on a weight-loaded dynamometer using 4 loads for each type of contraction. Results indicated that VO2 and HR increased as apparently linear functions of workload for both types of exercise, although a difference in the amount of change was observed. When the 2 types of exercise were compared using the same resistance load, the dynamic bouts required a significantly greater net VO2 and HR. At a given VO2 level, HR was higher during static exercise. Net HR also appeared to increase more steeply as a function of VO2 during static than during dynamic exercise. It was concluded that bouts of static and dynamic exercise which employ equal loads for an equal period of time are not physiologically equal or directly comparable since the VO2 and HR response are not the same for the 2 types of exercise. For this reason, VO2 and HR response should not be used interchangeably for relating static to dynamic workloads, or when prescribing exercise for the purpose of patient conditioning or rehabilitation.

Adult↗

PubMed2003

The biophysics of asthmatic airway smooth muscle.

It is clear that significant advances have been made in the understanding of the physiology, biochemistry and molecular biology of airway smooth muscle (ASM) contraction and how the knowledge obtained from these approaches may be used to elucidate the pathogenesis of asthma. Not to belittle other theories of smooth muscle contraction extant in the field, perhaps the most outstanding development has been the formulation of plasticity theory. This may radically alter our understanding of smooth muscle contraction. Its message is that while shortening velocity and capacity are linear functions of length, active force is length independent. These changes are explained by the ability of thick filament protein to depolymerize at short lengths and to increase numbers of contractile units in series at lengths greater than optimal length or L(ref). Other advances are represented by the report that the major part of ASM shortening is complete within the initial first 20% of contraction time, that the nature and history of loading determine the extent of shortening and that these findings can be explained by the finding that the crossbridges are cycling four times faster than in the remaining time. Another unexpected finding is that late in the course of isotonic relaxation the muscle undergoes spontaneous activation which delays relaxation and smoothes it out; speculatively this could minimize turbulence of airflow. On the applied front evidence now shows the shortening ability of bronchial smooth muscle of human subjects of asthma is significantly increased. Measurements also indicate that increased smooth muscle myosin light chain kinase content, via increased actomyosin ATPase activity could be responsible for the changes in contractility.

Adaptation, Physiological↗

PubMed2000

Controlled auxotonic twitch in papillary muscle: a new computer-based control approach.

Based on new advancements in digital technology, we developed a PC- and DSP-based measurement and control system for isolated papillary muscle experiments. High flexibility was obtained through a three level control. Length or force was controlled real-time with a sample frequency of 5000 Hz. Muscle length and up to three segment lengths were measured simultaneously and each of these lengths could be chosen as feedback variable. Individual algorithms were implemented for different twitch types. Batches of twitches were organized in experiment protocols. The system included a new twitch type, namely a controlled auxotonic twitch. In this twitch, the muscle acted against a virtual ideal spring, giving a proportional change in developed force and shortening. The value of the virtual spring constant could be set on-line or defined in the experiment protocol. An increasing virtual spring constant represented a smooth transition from isotonic to isometric conditions.

Algorithms↗

PubMed1984

The response of the isolated iris sphincter muscle of various mammalian species to substance P.

Contractile responses of the isolated iris sphincter muscle from the rabbit, cow, pig, cat, dog, baboon and man to substance P were compared under isotonic conditions using carbachol as a reference standard. Iris preparations from the rabbit, pig and cow showed strong and consistent responses to substance P whilst those from the cat, dog, baboon and human eyes did not contract.

Animals↗

PubMed1995

Effects of calmodulin and protein kinase C antagonists on muscle in the filariid, Acanthocheilonema viteae.

Drugs that act on calmodulin and protein kinase C (PKC) were investigated in the filariid Acanthocheilonema viteae. The filariid was slit open longitudinally and attached to an isotonic muscle transducer in a warmed (37 C) chamber containing physiologic solution bubbled with 95% N2-5% CO2. The calmodulin inhibitors, trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7), increased the spontaneous contractions of the parasite at low concentrations and induced a contraction followed by a flaccid paralysis at high concentrations. Trifluoperazine and W-7 also reduced the contractions from acetylcholine (ACh) and KCl in a concentration-dependent manner. The phorbol esters, phorbol 12-myristate 13-acetate and phorbol 12, 13-dibutyrate, which activate PKC, were either inactive or only weakly active at inducing contractions. Staurosporine (10(-6) M), a PKC inhibitor, enhanced and then blocked the spontaneous contractions of the filariid. Two other PKC inhibitors, H-7 (10(-4) M) and sphingosine (3 x 10(-5) M), induced much smaller increases in the spontaneous contractions and did not inhibit them. Staurosporine and sphingosine inhibited the ACh contractions; however, staurosporine only slightly reduced the maximal KCl contraction. These results support a role for calmodulin, but not for PKC, in filarial muscle contraction.

Acetylcholine↗

PubMed1997

Bee venom-induced shrinkage of erythrocyte ghosts.

When hemolysis of erythrocyte ghosts is induced by bee venom, their volume becomes significantly less than the initial volume of the cells. Treating isolated ghost membranes with bee venom has the same effect. An analogous phenomenon is caused by a mixture of purified melittin and phospholipase A2, but not by the separate action of these substances. The volume changes develop non-monotonously in time. A prolonged phase of spontaneous volume restoration follows the initial phase of shrinkage. Inhibitors of melittin-induced hemolysis (Mg2+, chlorpromazine) retarded the development of both shrinkage and restoration phases, but did not influence the extent of the volume changes. High concentrations of Ca2+ (10 mM) acted in a similar manner, but increased the extent of shrinkage at low concentration (0.1 mM). The extent of shrinkage was increased several-fold in isotonic nonelectrolyte solutions. Analysis of the data shows that bee venom-induced reduction in ghost volume is not due to osmotic effects or permeabilization and/or fragmentation of the membrane, but rather is attributed to membrane contraction, which presumably relates to the membrane cytoskeleton. In this respect venom-induced shrinkage resembles that of contractile events in non-muscle cells.

Bee Venoms↗

PubMed1979

Dynamic analysis of the structure and function of sarcomeres.

We attempted to analyze the relationships between the steric structure of the sarcomere and its physiological functions by the use of a sarcomere model of muscle contraction, which includes the geometric arrangement of the thick and thin filaments of the sarcomere, as well as of the cross-bridges and actin sites. Motions of both cross-bridges and myofilaments were considered in terms of our three-state model of the elementary cycle under constraints caused by the steric structure of the sarcomere proposed by Huxley and Brown. Each cross-bridge moves in a molecular potential of our three-state model under the influence of the sliding motions of myofilaments. The sarcomere model described well the tension-velocity relation and isotonic transient processes quantitatively and consistently. In addition, it allowed independence of the no-load shortening velocity upon the overlap of the thick and thin filaments, although the motions of cross-bridges were not independent. Effects of the helical periodicities of the thick and thin filaments and of the number of cross-bridges upon muscle contraction were studied, and the conditions for smooth and efficient contraction of muscle were obtained.

Animals↗

PubMed2004

Experimental muscle pain increases trapezius muscle activity during sustained isometric contractions of arm muscles.

OBJECTIVE: In the present study, the influence of experimental muscle pain on muscle co-ordination and fatigue development during sustained isometric elbow flexion was investigated. METHODS: Conventional surface electromyography (EMG) was recorded from the biceps brachii, brachioradialis, deltoideus and trapezius muscle during isometric elbow flexion at 40% maximum force. Single motor unit (MU) conduction velocity in the biceps brachii was assessed using a high spatial resolution surface EMG technique. Measurements were performed on 15 healthy subjects before, during and after (1) injection of hypertonic (pain condition) and (2) isotonic saline (control) into the biceps brachii. The pain intensity was assessed on a 10 cm visual analogue scale. RESULTS: The experimental results showed in both experimental sessions a fatigue-related increase of the root mean square value of EMG (222+/-164% of the baseline), and a decrease of the median frequency (118+/-16% of the baseline) in all investigated muscles. A maximum pain level of in average 3.2 cm on the visual analogue scale was reached after injection of hypertonic saline during contraction. Differences between painful and control condition were seen in an increased trapezius activity (230+/-141%) during pain. The global EMG activity of the brachioradialis and biceps brachii was unaffected by experimental muscle pain in line with unaffected single MU conduction velocity in the biceps brachii. Differences in endurance time (mean 89.3 and 102.3 s, pain and control, respectively) were not significant. CONCLUSIONS/SIGNIFICANCE: The findings suggest that upper extremity pain could be a possible source for overloading the trapezius muscle and as such is an important factor in occupational settings.

Adult↗

PubMed2006

Products of cyclooxygenase-2 depress duodenal function in rats subjected to abdominal surgery.

AIM: Abdominal surgery evokes powerful biological responses that affect gastrointestinal functions. Here we investigate the role of the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) isoforms in post-operative duodenal ileus. METHODS: Proximal duodenum of anesthetized rats was perfused in situ with isotonic or hypotonic (50 mM) NaCl. Mucosal bicarbonate secretion, motility, mucosal permeability and effluent osmolality were determined in the absence and presence of different COX inhibitors. RESULTS: The majority of control animals had no or few duodenal contractions and bicarbonate secretion averaged 10.9 +/- 1.4 micromol cm(-1) h(-1). These 'paralytic' controls responded to hypotonic NaCl with a small increase in mucosal permeability. In control animals exhibiting spontaneous duodenal contractions, the bicarbonate secretion was 50% higher and the hypotonicity-induced net increase in mucosal permeability sevenfold higher than in 'paralytic' controls. Treatment with the selective COX-2 inhibitors rofecoxib or parecoxib induced duodenal motility, increased bicarbonate secretion and potentiated the hypotonicity-induced increase in mucosal permeability. COX-2-inhibited animals had a twofold greater capacity to adjust luminal osmolality than 'paralytic' controls. The selective COX-1 inhibitor SC-560 only transiently stimulated motility and bicarbonate secretion and the hypotonicity-induced increase in mucosal permeability was smaller than in COX-2-inhibited animals. CONCLUSIONS: Abdominal surgery increases the synthesis of prostanoids, particularly via the COX-2 isoform. This compromises the ability of the duodenum to contract and to secrete HCO and to adjust luminal osmolality possibly via altered mucosal permeability. It is proposed that studies of gastrointestinal functions in animals subjected to abdominal surgery should include animals pre-treated with a COX-2 inhibitor.

Animals↗