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Viscero-sympathetic reflex responses to mechanical stimulation of pelvic viscera in the cat.

Viscero-sympathetic reflex responses to mechanical stimulation of urinary bladder and colon were studied in cutaneous vasoconstrictor (CVC) neurones supplying hairy skin, in muscle vasoconstrictor (MVC) neurones supplying skeletal muscle and in sudomotor (SM) neurones supplying the sweat glands of the central paw pad of the cat hindlimb. The cats were anaesthetized, paralysed and artificially ventilated. The vasoconstrictor activity was recorded from the axons of the postganglionic fibres that were isolated in filaments from the respective peripheral hindlimb nerves. The activity in the sudomotor neurones was monitored by recording the fast skin potential changes occurring on the surface of the central paw pad. Afferents from the urinary bladder and from the colon were stimulated by isotonic distension and isovolumetric contraction of the organs. Most CVC neurones with ongoing activity were inhibited by these stimuli; only a few CVC neurones were excited. The MVC and SM neurones were generally excited by the visceral stimuli, yet the size of the evoked skin potential changes was variable. The reflex responses elicited in the sympathetic outflow to the cat hindlimb by stimulation of visceral afferents from the pelvic organs are uniform with respect to the different types of afferent input system but differentiated with respect to the efferent output systems. Graded stimulation of the visceral afferents from the urinary bladder by isotonic pressure steps elicited graded reflex responses in CVC (threshold less than 30 mmHg) and MVC neurones (threshold less than 20 mmHg) and a graded increase of the arterial blood pressure (threshold less than 20 mmHg). These graded reflex responses are closely related to the quantitative activation of sacral afferent neurones with thin myelinated axons innervating the urinary bladder that are also responsible for eliciting the micturition reflex, but not to the quantitative activation of sacral afferent neurones with unmyelinated axons. The latter have thresholds of 40-50 mmHg intravesical pressure at which the size of the vesico-sympathetic reflexes in the vasoconstrictor neurones was about 50% of maximal size. This does not exclude the fact that activation of unmyelinated vesical afferents contributes to the vesico-sympathetic reflexes.

Animals↗

Novel adaptation of a method to assess responsiveness of bronchial segments in vitro.

In vivo agonist delivery to the lungs is characterized by absorption through the mucosal layer followed by access to the smooth muscle. When agonists are applied to perfused bronchial segments, a difference in potency to agonists applied to the serosal (outside) or mucosal (inside) surface can be demonstrated. In order to elucidate this effect in canine bronchial segments, we adapted a method to assess responsiveness of agonists applied to the inside or outside surface of canine bronchial segments. A 2 cm "fluid-tight" length of bronchus was cannulated and mounted in a perfusion chamber. Auxotonic contraction of the bronchus displaced fluid inside the segment up a column and the change in height of fluid within the column (afterload) was measured as a change in hydrostatic pressure (volumetric). We assessed the optimal conditions for measuring bronchial responsiveness to acetylcholine. Neither stretching segments lengthways from 100 to 140% of resting length, nor altering the transmural pressure from 3 to 21 cmH2O had a significant effect on the potency of acetylcholine applied to the outside surface. Both acetylcholine (n=7) and methacholine (n=4) were approximately 10-fold more potent when applied to the outside surface than the inside surface of bronchial segments (p<0.0001). Furthermore, mechanical removal of the epithelium (n=6) led to a 67-fold increase in potency of acetylcholine applied to the inside surface compared with segments with epithelium. The advantages that this system has over previously reported methods include: 1) agonists can be injected at a low flow rate so as to minimize epithelial stress; 2) changes in luminal volume are measured under conditions of no flow; 3) after-load can be varied such that contraction is either practically isotonic or auxotonic; and 4) a "barrier effect" of the epithelium of canine bronchial segments can be demonstrated. This new adapted method will provide us with the means to assess the relationship between in vitro and in vivo responsiveness in human bronchi.

Acetylcholine↗

Mechanical properties of the rabbit iris smooth muscles.

The study focuses on obtaining the visco-elastic properties of the iris sphincter and dilator muscles. Two kinds of experiments were performed: the isometric contraction experiment and the isotonic quick release experiment. The length-tension relationship was obtained from the former experiment. This relationship clarified the contribution of each muscle in determining the statics of the pupil. The viscous and serial elastic properties were obtained from the latter experiment. The viscosity could be expressed by the expanded Hill's equation as a function of velocity and contractile tension. We argue that serial elasticity is independent of contractile tension. These properties provide insights into the pupillary mechanism.

Animals↗

Variation of muscle stiffness with force at increasing speeds of shortening.

Single frog skeletal muscle fibers were attached to a servo motor and force transducer by knotting the tendons to pieces of wire at the fiver insertions. Small amplitude, high frequency sinusoidal length changes were then applied during tetani while fibers contracted both isometrically and isotonically at various constant velocities. The amlitude of the resulting force oscillation provides a relative measure of muscle stiffness. It is shown from an analysis of the transient force responses observed after sudden changes in muscle length applied both at full and reduced overlap and during the rising phase of short tetani that these responses can be explained on the basis of varying numbers of cross bridges attached at the time of the length step. Therefore, the stiffness measured by the high frequency legth oscillation method is taken to be directly proportional to the number of cross bridges attached to thin filament sittes. It is found that muscle stiffness measured in this way falls with increasing shortening velocity, but not as rapidly as the force. The results suggest that at the maximum velocity of shortening, when the external force is zero, muscle stiffness is still substantial. The findings are interpreted in terms of a specific model for muscle contraction in which the maximum velocity of shortening under zero external load arises when a force balance is attained between attached cross bridges somr interpretations of these results are also discussed.

Animals↗

Effects of dantrolene on rat diaphragm muscle during postnatal maturation.

BACKGROUND: Dantrolene is the only known effective treatment for malignant hyperthermia. However, its effects on diaphragm muscle during postnatal maturation remain unknown. METHODS: The effects of dantrolene (10(-8) to 10(-4) M) were investigated in vitro on diaphragm muscle strips in adult rats and in postnatal rats aged 3, 10, and 17 days, and compared with those of ryanodine (10(-8) to 10(-6) M). The authors studied contraction and relaxation under isotonic and isometric conditions (29 degrees C, Krebs-Henseleit solution, tetanic stimulation at 50 Hz). Data are mean +/- SD. RESULTS: During postnatal maturation, the authors observed a progressive increase in active force developed per cross-sectional area (from 34 +/- 25 to 69 +/- 32 mN/mm2; P < 0.05) and maximum shortening velocity (from 2.9 +/- 0.5 to 4.9 +/- 1.4 Lmax/s; P < 0.05). Dantrolene induced a negative inotropic effect in diaphragm muscles in isotonic and isometric conditions in all groups, but this effect was significantly less marked in the 3-day-old rats compared with older rats. Dantrolene did not induce significant lusitropic effects during postnatal maturation. Developmental changes in the pharmacologic response to dantrolene were more rapid than those of ryanodine. CONCLUSION: Dantrolene induced less pronounced negative inotropic effects on the diaphragm in neonatal rats as compared with adult rats. Our study suggests that developmental changes in the pharmacologic response to dantrolene are more rapid than those of ryanodine.

Aging↗

Physiological effects in vitro of calcitonin gene-related peptide on gubernacular contractility with or without denervation.

The gubernaculum in neonatal rats has been shown previously by direct observation to contract rhythmically in response to exogenous calcitonin gene-related peptide (CGRP), but the physiological properties of these contractions were unknown. In the first study the authors investigated gubernacular contractility in vitro using a strain gauge to see if there were characteristics of skeletal or smooth muscle. Both the frequency and the amplitude of contractions were significantly enhanced by CGRP, and isotonic tension of the gubernaculum and the duration of contractions were also increased after CGRP. The effect of CGRP on gubernacular contractions appeared several minutes after adding CGRP, and it was independent of the acetylcholine action, which induced only a single twitch response of the gubernaculum. In the second study the authors investigated the effect on gubernacular contractility of prior transection of the genitofemoral nerve (GFN), which contains CGRP. Vigorous contractions occurred in 85% of denervated gubernacular compared with 46% of controls (P < .01). These data provide the first quantitative evidence of rhythmic gubernacular contractions, and suggest that CGRP enhances gubernacular contractility by a direct effect independent of acetylcholine. Further, the contractile properties resemble those of differentiated cardiac muscle or primitive embryonic skeletal muscle. GFN transection enhances the gubernacular contractile response to exogenous CGRP, which is consistent with the GFN being the normal source of CGRP for the gubernaculum in vivo.

Animals↗

Mechanics of the isolated ventricular myocardium of rats conditioned by physical training.

Force-velocity relations from after-loaded contractions, from isometric and isotonic QR experiments, resting-tension curves and biochemical analyses were conducted on sixteen trabecular muscles (SH) from hearts of rats conditioned by eight weeks of swimming training (increase in heart weight 8%), and compared to a control (CH) of eighteen trabecular muscles. (SH) showed increased tension development (p less than 0.01), whereas the diastolic properties remained almost unchanged. Analysis of the amount of hydroxyproline did not prove any variation. Vmax of (SH) was only slightly increase when there was a singificnat rise in actomyosin and myosin ATPase activity, while PO of the force-velocity relations of (SH) on the x axis (tension) shifted clearly to the right (p less than 0.01). Consequently, the maximum instantaneous power of (SH), expressed by the maximum rectangular plane under the force-velocity curve, increased considerably (p less than 0.01) in comparison with (CH). The experiments show that haemodynamic load induced by training does not alter the passive properties of the myocardium, but does bring about an increase in the contractile capabiltiy.

Actomyosin↗

Dissociation of the ascending excitatory reflex from peristalsis in the guinea-pig small intestine.

Localized distension of the intestine evokes an ascending excitatory reflex and a descending inhibitory reflex in the circular muscle layer. The sequential activation of these two reflexes is believed to underlie the motor pattern of peristalsis, which is responsible for the co-ordinated propulsion of intestinal contents. In this study we have shown that the initiation of peristalsis involves mechanisms additional to those mediating the ascending excitatory reflex. A short length of guinea-pig small intestine was mounted in a partitioned organ bath so that the lumen was occluded by the partition, but neuronal continuity was maintained. The anal segment was distended by intraluminal fluid infusion to evoke a peristalsis; in the oral segment, an isotonic transducer was used to record circular muscle contractions due to ascending excitatory reflexes. Stepwise distension of the anal segment with 5 microliters increments at 10 s intervals, or with a large, single-step infusion, elicited both the ascending excitatory reflex and peristalsis, when carried out at 3 min intervals. The threshold volume for the ascending excitatory reflex was smaller than the threshold for peristalsis with either incremental or single-step distensions. The ascending excitatory reflex appeared with a shorter delay than peristalsis. Tetrodotoxin (0.6 microM) or hexamethonium (100 microM) added to the oral compartment abolished the ascending excitatory reflex but not peristalsis. These drugs abolished both the ascending excitatory reflex and peristalsis when added to the anal compartment. When stimuli were delivered at 1 min intervals, peristalsis failed completely after the first trial, but the ascending excitatory reflex persisted, at a slightly reduced amplitude. When the anal segment was distended to just-subthreshold volume, electrical field stimulation (0.25-0.5 ms, 1-5 Hz for 1 s), delivered at 3 min intervals, evoked ascending excitatory responses but not peristalsis. Higher frequency stimulation (10 Hz) consistently evoked both peristalsis and the ascending excitatory responses. When trains of electrical stimulation were repeated at 1 min intervals, peristalsis quickly failed, but the ascending excitatory response persisted, although reduced in amplitude. The initiation of peristalsis can be dissociated from the ascending excitatory reflex by its threshold volume, by the duration of distension or the intensity of electrical stimulation required, and by its susceptibility to fatigue with repeated mechanical or electrical stimuli. This suggests that the ascending excitatory reflex may be part of the mechanism underlying the initiation of peristalsis, but that additional mechanisms must also be involved. Peristalsis should not be regarded as a reflex response but rather as an all-or-nothing motor pattern, triggered by mechanical stimulation, similar to other co-ordinated motor patterns in vertebrates and invertebrates.

Animals↗

Differences in detrusor contractile function in women with neuropathic and idiopathic detrusor instability.

OBJECTIVE: To compare urodynamic indices of isometric and isotonic detrusor contractile function between patients with idiopathic detrusor instability and patients with multiple sclerosis (MS) and detrusor hyper-reflexia and thus determine whether the different types of detrusor instability share a common pathophysiological pathway. PATIENTS AND METHODS: Two groups of women were studied; 1139 neurologically normal patients with detrusor instability (mean age 55 years, SD 17) and 141 with multiple sclerosis (MS) and detrusor hyper-reflexia (mean age 45 years, SD 11). Patients were assessed using static water cystometry, examining storage function, isometric and isotonic detrusor contractile function and voiding outflow function. RESULTS: Bladder capacities were lower in the MS group, with a median of 357 mL, 95% confidence interval (CI) 305-400 mL, compared with the neurologically normal patients (median 450 mL, 95% CI 425-450, P < 0.001, Mann-Whitney U-test). Voiding was incomplete in the MS group, with a median (95% CI) residual volume of 100 (100-125) mL, but complete in the normal group, at 10 (10-10) mL. Higher median (95% CI) detrusor pressures at urethral opening (P(det open)) and closing (P(det close)) were recorded in the MS group than in the neurologically normal group, at 35.5 (33.2-46.6) cmH2O and 30 (27.6-31.6) cmH2O for P(det open), respectively (P = 0.003), and 25.3 (20.9-31.6)cmH2O and 16.6 (15.0-18.1) for P(det close), respectively, (P = 0.001). In the MS group, the median (95% CI) isometric unstable contractions were less well maintained, but were more powerful, at 17.6 (15.6-18.9) N, compared to the neurologically intact group at 14.4 (14.0-14.9) N (P = 0.002). In the MS group, contractions frequently did not relax back to baseline, whereas in the group with detrusor instability, full relaxation after contraction was more usual. There was no significant difference in the maximum speed of detrusor shortening (isotonic activity), measured by the velocity constant Q*, between the groups (median for both groups 20 mL/s, 95% CI 17-23). CONCLUSION: These results show differences in storage function, isometric detrusor contractile function and voiding outflow function between detrusor instability and detrusor hyper-reflexia, indicating that the two conditions may not share a common pathophysiological pathway.

Adult↗

Comparison of vastus medialis obliquus: vastus lateralis muscle integrated electromyographic ratios between healthy subjects and patients with patellofemoral pain.

The purpose of this study was to compare vastus medialis obliquus:vastus lateralis muscle (VMO:VL) integrated electromyographic (IEMG) ratios of healthy subjects and patients with unilateral patellofemoral pain (PFP) under isotonic and isometric quadriceps femoris muscle contraction conditions. Subjects ranging in age from 18 to 35 years (mean = 28.06, SD = 5.97) were assigned to one of three groups on the basis of type of knee condition. In group 1, which consisted of seven healthy control subjects with no history of knee pathology, both knees were tested. In group 2, which consisted of nine patients with unilateral PFP, only the painful knee was tested. In group 3, which consisted of the same nine patients who comprised group 2, only the nonpainful knee was tested. Nonnormalized and normalized VMO:VL IEMG ratios were computed for ascending stairs, descending stairs, submaximal isometric contraction, and maximal isometric contraction (nonnormalized only). A two-way analysis of variance for repeated measures indicated VMO:VL ratios for isotonic stair-climbing activities were significantly greater than VMO:VL ratios for isometric contractions. Nonnormalized VMO:VL ratios in group 1 were significantly greater than nonnormalized VMO:VL ratios in the other two groups. Patients with PFP may have abnormal VMO:VL activation patterns, and isotonic quadriceps femoris muscle exercise may elicit more favorable muscle activation patterns than isometric exercise for patients with PFP.

Adult↗

Postoperative hypophosphataemia and muscle function.

Muscle function tests of the triceps brachii muscle were performed before operation and on the third postoperative day in ten patients undergoing elective cholecystectomy. Electromyograms (EMGs) were recorded by surface electrodes during sustained isotonic and isometric muscle contraction with a constant force of 20 per cent of the preoperative maximal voluntary contraction. Root-mean-square of the EMG was calculated together with the neuromuscular efficiency and measures of the fatiguability. These parameters were compared with changes in the simultaneously measured serum phosphate concentrations. Mean (s.e.m.) neuromuscular efficiency measured after 32-40 s of muscle contraction decreased 14(5) per cent after operation (P less than 0.01), whereas the mean fatiguability of the muscle was unchanged. Mean serum phosphate concentration was 0.87(0.06) mmol/l before operation and 0.79(0.06) mmol/l 3 days after the operation (P greater than 0.05). Two patients developed severe postoperative hypophosphataemia (serum phosphate concentration less than 0.50 mmol/l). Postoperative muscle function deterioration was not associated with changes in the serum phosphate level (P greater than 0.10; r = 0.03). We conclude that patients undergoing cholecystectomy develop postoperative deterioration in skeletal muscle function, which is not associated with serum phosphate concentration.

Adult↗

Energetics of anaerobic glycolysis in dog gastrocnemius.

Thermally isolated gastrocnemii were stimulated to exhaustion, by rhythmic isotonic (70 N) tetanic contractions, during complete occlusion of blood flow. Enthalpy change (h = work + heat) and work output (w) (kJ/kg) were obtained from records of deep muscle temperature and shortening. The lactate produced (LA, mol/kg) was measured in the outflow after reestablishement of blood flow. The following relationships were obtained: h = 76LA + 1.2, and w = 19.8LA + 0.30. As the energy liberated at exhaustion by alactic energy sources (approximately P and O2 stores) is constant, deltah/deltaLA = 76 (+/- 10.5; S.E.) kJ/mol is the enthalpy change for lactate formation (delta HLA). The neutralization heat was estimated on muscle homogenates at 12kJ/mol, leaving approximately 64 kJ/MOL for deltaH of LA formation proper. The mechanical efficiencies of work related to LA formation (ELA) and of that not related to LA formation (EnonLA) were practically identical (0.25). From these values and from deltaHLA, the enthalpy change of approximately P splitting was estimated in the range of 52--62kJ/mol, depending on the value of the ratio delta approximately P/deltaLA assumed in the calculation.

Adenosine Triphosphate↗

Effects of increasing osmolality on rat ileal smooth muscle.

The effects of changing bathing medium osmolality on tension generation in smooth muscle were studied on potassium-depolarized segments of rat ileum. Increasing the tonicity of the medium evokes a transient relaxation of the smooth muscle; restoration of isotonicity evokes a transient contraction of similar amplitude and time course. While immersed in hypertonic media of less than 1.3 times normal tonicity, the smooth muscle slowly increases its isometric tension; in media of nearly twice normal tonicity, the smooth muscle loses tension. All of these effects occur whether the medium is made hypertonic with added NaCl or sucrose.

Animals↗

The effects of a calcium dependent protease on the ultrastructure and contractile mechanics of skinned uterine smooth muscle.

In situ substrates for a vascular smooth muscle calcium-dependent protease (CDP) were investigated using a chemically skinned uterine smooth muscle preparation. Treatment of skinned smooth muscles with CDP had no effect on the total content of actin and myosin. Electron microscopical observations demonstrated that membrane plaques, cytoplasmic dense bodies, and intermediate filaments were all degraded by CDP. In addition, CDP reduced both isometric force and isotonic shortening velocity of contracted muscles in a concentration and time-dependent manner. Treatment of contracting muscles with CDP resulted in a condensation of myofilaments away from the plasma membrane concurrent with the loss of contractility. The condensation of myofilaments was ATP-dependent and could be inhibited by removal of ATP prior to proteolysis. The effects of proteolysis on smooth muscle ultrastructure and contractility support previously proposed models which assign a role to cytoskeletal elements in coordinating the molecular interaction of actomyosin to produce muscle contraction. The loss of cytoskeletal structures following protease treatment suggests that one of the functions of CDP in smooth muscle may be the disassembly of the cell cytoskeleton.

Actins↗

[Dynamics of left ventricular hypertrophy and function in spontaneous hypertension of rats (author's transl)].

Left ventricular dynamics and papillary muscle mechanics were examined in 44 spontaneously hypertensive rats (SHR) (Okamoto, 9-21 weeks old), in 38 normotensive Wistar Kyoto inbred rats and in 31 control rats. In spite of marked pressure overload, SHR had normal peak systolic wall stress and reduced (21%) diastolic wall stress due to an increased proportion between left ventricular wall thickness and radius. Left ventricular function was normal (isovolumic contractility indices before and after aortic clamping) or augmented (pressure development per gramm of left ventricular weight before and after clamping). Papillary muscle mechanics showed decreases of contraction velocities (isometric and isotonic), whereas shortening and maximum tension development were nearly unaffected. Left ventricular hypertrophy in proportion to pressure overload, the increase in wall thickness/radius ratio and hence the normalisation or decrease of wall stress, provides normal left ventricular function even at extreme pressure overload.

Animals↗

Effects of the BKCa channel activator, NS1619, on rat cerebral artery smooth muscle.

1. We have investigated the actions of NS1619, a putative activator of large conductance calcium-activated potassium channels (BKCa) by use of the patch-clamp technique on smooth muscle cells enzymatically isolated from the rat basilar artery. 2. Using whole cell current-clamp to measure membrane potential, addition of 30 microM NS1619 produced cellular hyperpolarization, moving the membrane potential towards the calculated equilibrium potential for potassium. This hyperpolarization was rapidly reversed by IbTX (100 nM), a selective inhibitor of BKCa. 3. In whole cell recordings made from cells voltage-clamped at 0 mV using the perforated-patch technique, addition of NS1619 (10-30 microM) activated an outward current, which reversed following washout of NS1619. 4. This outward current was unaffected by application of either glibenclamide (5 microM), an inhibitor of ATP-sensitive potassium channels, or apamin (100 nM), an inhibitor of small-conductance calcium-activated potassium channels. However, this current was almost completely abolished by iberiotoxin (IbTX; 50-100nM). 5. Depolarizing voltage steps activated small outward currents from cells held at -15 mV. Application of NS1619 (10-30 microM) increased the size of these currents, producing a shift to the left of the current-voltage (I-V) relationship. These currents were largely inhibited by IbTX (100 nM). 6. Measurements of the unitary amplitude of the single channels activated by NS1619 which could be resolved in whole cell recordings yielded a value of 5.6 +/- 0.14 pA at 0 mV. 7. NS1619 (10-30 microM) directly activated single channels contained in excised inside-out and outside-out membrane patches. In both configurations NS1619 (10-30 microM) rapidly increased the open probability of a large conductance calcium-dependent channel. The activation produced by NS1619 was calcium-dependent and inhibited by external IbTX (100 nM). The unitary current amplitude was unaffected by NS1619. 8. By use of conventional whole cell recording methods and conditions that suppressed BKCa openings, outward potassium currents were activated by depolarizing potentials positive to -35 mV from a holding potential of -65 mV. NS1619 (10-30 microM) inhibited this current in a concentration-dependent manner. This inhibition was reversed following washout of NS1619, recovering to 60-90% of control values within 2 min. 9. Ba2+ currents, measured by conventional whole cell recording, were activated by depolarizing voltage steps from negative holding potentials. NS1619 (1-30 microM) inhibited the evoked current in a concentration-dependent manner, yielding an IC50 value of 7 microM with a Hill coefficient approaching unity. This inhibition was reversible, with the currents recovering to 65-100% of control values after washout of NS1619 for 2 min. 10. NS1619 (0.3-100 microM) induced concentration-dependent relaxation of basilar artery segments contracted with histamine/5-HT (IC50 = 12.5 +/- 2.0 microM; n = 4). This relaxation curve was shifted to the right, but not abolished, when the tissue was treated with a blocker of BKCa channels (IbTX; 100nM). Additionally, NS1619 produced concentration-dependent relaxation of basilar artery contracted with a depolarizing, isotonic salt solution containing 80 mM K+. 11. Thus NS1619 produces hyperpolarization of basilar artery myocytes through direct activation of BKCa and also directly inhibits Ca2+ currents and voltage-activated K+ channels. We discuss the implications of these results for its vasorelaxant actions.

Animals↗

Receptive properties of myelinated primary afferents innervating the inflamed urinary bladder of the cat.

1. The present study has investigated the receptive properties of myelinated mechanoreceptive primary afferents innervating the inflamed urinary bladder of the cat. In 15 experiments, 20 units were recorded from the dorsal and 3 from the ventral root S2. Before inflammation the afferents had no resting activity and responded consistently to increases of intravesical pressure evoked by isotonic distension or isovolumetric contractions. All units were studied before and after the onset of an acute inflammation induced by intraluminal injection of mustard (1-2.5%) or turpentine oil (50%), which are known to induce an acute cystitis. 2. Eleven out of 14 units tested with mustard oil and 5/9 units tested with turpentine oil were activated at short latency. The response could not be explained by a concomitant increase of intraluminal pressure resulting from the intravesical injection of the irritant. This suggests that a large proportion of mechanosensitive afferents has an additional chemosensitivity. 3. After removal of the irritants and with empty bladder, all afferent units exhibited irregular ongoing activity with intermittent high-frequency bursts. Such ongoing activity was entirely absent in myelinated afferents supplying the noninflamed bladder. The median rate of ongoing activity was significantly higher after mustard oil (1.65 imp/s) than after turpentine oil treatment (0.05 imp/s) 1 h after chemical stimulation. Post-hoc analysis revealed that afferents that developed high levels of ongoing activity had steeper stimulus response functions to changes of intravesical pressure before inflammation. 4. The stimulus-response function of vesical afferents changed characteristically in the inflamed bladder. Within 30 min of mustard oil treatment, the responses of some units to bladder filling was transiently enhanced, but later the units desensitized to this stimulus. However, there was no significant change of the stimulus-response function of six afferents studied before and for 2 h after induction of the inflammation. By contrast, the afferents exhibited significant increases of their mechanosensitivity after turpentine treatment. 5. In conclusion, sacral myelinated mechanoreceptive afferents supplying the urinary bladder are chemosensitive. Their receptive properties change rather uniformly when the tissue becomes inflamed, and, on the basis of these changes, it is not possible to differentiate subpopulations of primary afferents. The induction of ongoing activity and the increased responses to intravesical pressure stimuli in the inflamed organ, together with central changes that may occur under these conditions, are probably responsible for changes of bladder motility and sensations that arise during cystitis.

Animals↗

Effects of damaging the endocardial surface on the mechanical performance of isolated cardiac muscle.

The mechanical properties of mammalian ventricular cardiac muscle have been studied in the presence and in the absence of an intact endocardial surface. Isotonic and isometric twitch contractions were obtained from papillary muscles of the right ventricle of cat at 29 degrees and 37 degrees C, at different extracellular calcium concentrations ([Ca2+]o), and at different initial muscle lengths. The endocardial surface was damaged by gentle abrasion of the muscle surface with a plastic blade or by brief immersion for 1 second with 1% Triton X-100. Although there was no evidence of damage to myocardial cells, damaging the endocardial surface resulted in an immediate and irreversible abbreviation of the twitch contractions with, except at the highest ([Ca2+]o, a decrease in peak isometric twitch tension. These changes induced 1) an asymmetrical shift of the tension-[Ca2+]o relation towards increasing [Ca2+]o but with no effect at the highest [Ca2+]o, and 2) a rightward and downward shift of the length-tension relation. Both shifts were significantly more pronounced at 37 degrees C than at 29 degrees C; they were not accompanied by significant changes in Vmax. The asymmetrical shift of the tension-[Ca2+]o relation suggests that the endocardium-mediated chain of events may be mediated by changes in the sensitivity of the contractile proteins to Ca2+. This hypothesis is also supported by the similar pattern of changes (i.e., modulation of the onset of early tension decline) induced by decreasing length at each [Ca2+]o and by the removal of a functional endocardium. Accordingly, the endocardium may help to control the performance of the heart by modulating peak contractile performance and relaxation of the underlying myocardium.

Adenosine Triphosphate↗