The role of the pericardium in cardiac function in the dogfish, Squalus acanthias

Opening the pericardium to the ambient bathing fluid surrounding the in situ perfused dogfish ( Squalus acanthias ) heart caused a precipitous fall in cardiac output. Cardiac output fell by 55% despite the rise of mean input pressure from subambient, to near zero levels. Lower cardiac output caused a fall in mean output pressure but not diastolic pressure as this was set by the experimenters. With the pericardium intact, the heart was filled by suction. With an open pericardium the magnitude of negative input pressures was severely reduced. None the less, far short periods within the cardiac cycle, the heart was still able to generate subambient pressures in the atrium and so draw fluid from the central veins.     

Axial stretch: A novel mechanism of the lower esophageal sphincter relaxation

Swallow and esophageal distension-induced relaxations of the lower esophageal sphincter (LES) are associated with an orad movement of the LES because of a concurrent esophageal longitudinal muscle contraction. We hypothesized that the esophageal longitudinal muscle contraction induces a cranially directed mechanical stretch on the LES and therefore studied the effects of a mechanical stretch on the LES pressure. In adult opossums, a silicon tube was placed via mouth into the esophagus and laparotomy was performed. Two needles with silk sutures were passed, 90 degrees apart, through the esophageal walls and silicon tube, 2 cm above the LES. The tube was withdrawn, and one end of each of the four sutures was anchored to the esophageal wall and the other end exited through the mouth to exert graded cranially directed stretch on the LES by using pulley and weights. A cranially directed stretch caused LES relaxation, and with the cessation of stretch there was recovery of the LES pressure. The degree an d duration of LES relaxation increased with the weight and the duration of stretch, respectively. The mean LES relaxation in all animals was 77.7 +/- 4.7%. The required weight to induce maximal LES relaxation differed in animals (714 +/- 348 g). N(G)-nitro-L-arginine, a nitric oxide inhibitor, blocked the axial stretch-induced LES relaxation almost completely (from 78 to 19%). Our data support the presence of an axial stretch-activated inhibitory mechanism in the LES. The role of axial stretch in the LES relaxation induced by swallow and esophageal distension requires further investigation.     

Hypothesis; overdistention of the neural tube may cause anomalies of non-neural organs

This hypothesis is offered by a neurological surgeon interested in anomalies of the central nervous system. It is based on accumulating evidence indicating that some neural tube defects result not from failure of the tube to close but from its rupture after closure. The central nervous system, serving all organs, is the first to develop and its maldevelopment may cause damage to other emerging structures. The neural tube closes during the fourth week and is immediately distended by a proteinaceous neural tube fluid (NTF) secreted by its lining cells at a pressure four to five times that of the surrounding amniotic fluid. This NTF has been miscalled "cerebrospinal fluid." The choroid plexus does not begin to secrete true cerebrospinal fluid (CSF) until 2 weeks later. If oversecretion of NTF should occur during this 2-week interval, the resulting overexpansion of the neural tube may spread apart the developing somite, eventuating in a combination of anterior and posterior spina bifida that constitutes bilateral hemivertebrae. If the distending neural tube ruptures beneath intact cutaneous ectoderm, the escaping NTF will infiltrate mesoderm. The resulting dislocation of cells and their possible injury by the extraneous protein may damage the as yet unidentifiable anlagen of mesodermal organs. If neural tube overdistention splits the underlying notochord and damages primitive gut, anomalies of entodermal organs may result. The neuroenteric cyst is one such anomaly that the neurosurgeon is called upon to treat. He finds it accompanied by hemivertebrae and hydromyelia. A preliminary report on this hypothesis has been published (Gardner and Breuer, '80).     

Passive pericardial constraint protects against stretch-induced vulnerability to atrial fibrillation in rabbits

Atrial fibrillation is more common in conditions with elevated atrial pressure and can be induced experimentally with acute increases in atrial pressure. We examined the effect of increased atrial pressure with and without pericardial constraint to better separate the effects of increased pressure and atrial stretch. In Langendorff-perfused rabbit hearts with intact pericardium, after ligating the pulmonary and caval veins, intra-atrial pressures were increased in a stepwise manner by adjusting the pulmonary outflow cannula. Rapid burst pacing was applied to induce atrial fibrillation at increasing intra-atrial pressures from 0 to 24 cmH(2)O. The atrial refractory period was recorded at each pressure using a single extra stimulus. The protocol was repeated after the pericardium was removed. When the pericardium was intact, atrial stretch was limited by passive constraint, and sustained atrial fibrillation could not be induced despite atrial pressures in excess of 20 cmH(2)O. In contrast, when the pericardium was removed, atrial fibrillation could be reliably induced when atrial pressure exceeded 15 cmH(2)O. This suggests that the electrophysiological effects of acute atrial volume loading rely on atrial stretch rather than increased atrial pressure alone.     

Relaxation-induced contraction of smooth muscle surrounding hamster ovarian follicles

Changes in intrafollicular pressure and follicular diameter resulting from injecting or withdrawing fluid from the antrum were measured in preovulatory follicles and used as an assay for changes in tension in the follicular wall by applying the Laplace relationship for thin-walled spheres. Passive length-tension curves were constructed from pressure-volume measurements to establish baseline wall stiffness. Any subsequent change in pressure could then be compared to the length-tension curves to evaluate whether it arose from active tension development or from passive stretch. When intact follicles (1-2h before ovulation) were subjected to release of passive stretch, they exhibited a contractile response that lasted 15 sec-2 min and was characterized by cyclic increases and decreases in tension, with a period of 1 cycle every 2-3 sec. The probability of activating a response in the tissue was most strongly correlated with the rate of release of passive stretch. Intrafollicular pressures generated during active contractile responses sometimes reached 80 mmHg (10.64 mPa), corresponding to a wall tension of 5332 dynes/cm (5.332 N/m) (for a 1 mm follicle) and were clearly well above the passive length-tension curves. Passive stretching of the follicular wall during a contractile response to 5-hydroxytryptamine stimulation resulted in large reductions in active wall tension for the duration of the stretch. These results are consistent with a stretch-activated inhibition of contractile events.     

The effects of feeding on heart activity in the terrestrial slug,Limax maximus: central and peripheral control

Summary The role of the central nervous system (CNS) in the modulation of heart activity induced by feeding was investigated in the terrestrial slug,Limax maximus. Intact slugs and semi-intact preparations were used to examine the effects of food, non-nutritive bulk, digestive tract distension, and the concentration of hemolymph glucose on the control of heart activity. The heart rate of intact slugs increased following ingestion of food or nonnutritive bulk and in response to injections of glucose. The heart rate of semi-intact preparations increased in response to gradual crop inflation and to perfusion of the heart with a glucose solution for longer than 30 min. The present results indicate that the increase in heart rate observed in intact slugs following a meal is mediated in part by the CNS and in part is a direct response of the heart musculature. The CNS mediates an immediate response to proprioceptive input from stretch of the crop while the heart musculature responds directly to increased hemolymph glucose concentration following ingestion of food.     

Fluid Dynamics of Ventricular Filling in the Embryonic Heart

The vertebrate embryonic heart first forms as a valveless tube that pumps blood using waves of contraction. As the heart develops, the atrium and ventricle bulge out from the heart tube, and valves begin to form through the expansion of the endocardial cushions. As a result of changes in geometry, conduction velocities, and material properties of the heart wall, the fluid dynamics and resulting spatial patterns of shear stress and transmural pressure change dramatically. Recent work suggests that these transitions are significant because fluid forces acting on the cardiac walls, as well as the activity of myocardial cells that drive the flow, are necessary for correct chamber and valve morphogenesis. In this article, computational fluid dynamics was used to explore how spatial distributions of the normal forces acting on the heart wall change as the endocardial cushions grow and as the cardiac wall increases in stiffness. The immersed boundary method was used to simulate the fluid-moving boundary problem of the cardiac wall driving the motion of the blood in a simplified model of a two-dimensional heart. The normal forces acting on the heart walls increased during the period of one atrial contraction because inertial forces are negligible and the ventricular walls must be stretched during filling. Furthermore, the force required to fill the ventricle increased as the stiffness of the ventricular wall was increased. Increased endocardial cushion height also drastically increased the force necessary to contract the ventricle. Finally, flow in the moving boundary model was compared to flow through immobile rigid chambers, and the forces acting normal to the walls were substantially different.     

Effect of cyclic axial stretch of rat arteries on endothelial cytoskeletal morphology and vascular reactivity

Pulsatile fluid shear stress and circumferential stretch are responsible for the axial alignment of vascular endothelial cells and their actin stress fibers in vivo. We studied the effect of cyclic alterations in axial stretch independent of flow on endothelial cytoskeletal organization in intact arteries and determined if functional alterations accompanied morphologic alterations. Rat renal arteries were axially stretched (20%, 0.5 Hz) around their in vivo lengths, for up to 4h. Actin stress fibers were examined by immunofluorescent staining. We found that cyclic axial stretching of intact vessels under normal transmural pressure in the absence of shear stress induces within a few hours realignment of endothelial actin stress fibers toward the circumferential direction. Concomitant with this morphologic alteration, the sensitivity (log(EC(50))) to the endothelium-dependent vasodilator (acetylcholine) was significantly decreased in the stretched vessels (after stretching -5.15+/-0.79 and before stretching -6.71+/-0.78, resp.), while there was no difference in sodium nitroprusside (SNP) sensitivity. There was no difference in sensitivity to both acetylcholine and SNP in time control vessels. Similar to cultured cells, endothelial cells in intact vessels subjected to cyclic stretching reorganize their actin filaments almost perpendicular to the stretching direction. Accompanying this morphological alteration is a loss of endothelium-dependent vasodilation but not of smooth muscle responsiveness.     

Effects of cyclic mechanical stimulation of the cellular components of the heart: In vitro

Summary The response of the cellular components of the heart to cyclic mechanical stimulation is of particular importance because these cells are continually subjected to mechanical forces as a result of changes in blood volume and pressure. To directly investigate how mechanical tension affects these cellular components of the heart, an in vitro system that exposes the particular cell type (cardiac myocytes, endothelial cells, or fibroblasts) to a calibrated increase in cyclical linear stretch was developed. Cells were grown on silastic membranes coated with laminin and subjected to a 10% cyclical distention 10 times a minute for 72 h. Within 24 h of being exposed to the mechanical stretch, the cells became elongated and oriented perpendicular to the direction of the stretch. These results indicate that cyclical mechanical stimulation directly influences the cellular organization of the heart cells in vitro. This work was supported in part by grants HL 33656 and HL 24935 from the National Institutes of Health, Bethesda, MD.     

The velocity of the arterial pulse wave: a viscous-fluid shock wave in an elastic tube

Background

The arterial pulse is a viscous-fluid shock wave that is initiated by blood ejected from the heart. This wave travels away from the heart at a speed termed the pulse wave velocity (PWV). The PWV increases during the course of a number of diseases, and this increase is often attributed to arterial stiffness. As the pulse wave approaches a point in an artery, the pressure rises as does the pressure gradient. This pressure gradient increases the rate of blood flow ahead of the wave. The rate of blood flow ahead of the wave decreases with distance because the pressure gradient also decreases with distance ahead of the wave. Consequently, the amount of blood per unit length in a segment of an artery increases ahead of the wave, and this increase stretches the wall of the artery. As a result, the tension in the wall increases, and this results in an increase in the pressure of blood in the artery.

Methods

An expression for the PWV is derived from an equation describing the flow-pressure coupling (FPC) for a pulse wave in an incompressible, viscous fluid in an elastic tube. The initial increase in force of the fluid in the tube is described by an increasing exponential function of time. The relationship between force gradient and fluid flow is approximated by an expression known to hold for a rigid tube.

Results

For large arteries, the PWV derived by this method agrees with the Korteweg-Moens equation for the PWV in a non-viscous fluid. For small arteries, the PWV is approximately proportional to the Korteweg-Moens velocity divided by the radius of the artery. The PWV in small arteries is also predicted to increase when the specific rate of increase in pressure as a function of time decreases. This rate decreases with increasing myocardial ischemia, suggesting an explanation for the observation that an increase in the PWV is a predictor of future myocardial infarction. The derivation of the equation for the PWV that has been used for more than fifty years is analyzed and shown to yield predictions that do not appear to be correct.

Conclusion

Contrary to the theory used for more than fifty years to predict the PWV, it speeds up as arteries become smaller and smaller. Furthermore, an increase in the PWV in some cases may be due to decreasing force of myocardial contraction rather than arterial stiffness.     

Sympathetic outflow enhances the stretch reflex response in the relaxed soleus muscle in humans.

Animal experiments suggest that an increase in sympathetic outflow can depress muscle spindle sensitivity and thus modulate the stretch reflex response. The results are, however, controversial, and human studies have failed to demonstrate a direct influence of the sympathetic nervous system on the sensitivity of muscle spindles. We studied the effect of increased sympathetic outflow on the short-latency stretch reflex in the soleus muscle evoked by tapping the Achilles tendon. Nine subjects performed three maneuvers causing a sustained activation of sympathetic outflow to the leg: 3 min of static handgrip exercise at 30% of maximal voluntary contraction, followed by 3 min of posthandgrip ischemia, and finally during a 3-min mental arithmetic task. Electromyography was measured from the soleus muscle with bipolar surface electrodes during the Achilles tendon tapping, and beat-to-beat changes in heart rate and mean arterial blood pressure were monitored continuously. Mean arterial pressure was significantly elevated during all three maneuvers, whereas heart rate was significantly elevated during static handgrip exercise and mental arithmetic but not during posthandgrip ischemia. The peak-to-peak amplitude of the short-latency stretch reflex was significantly increased during mental arithmetic (P < 0.05), static handgrip exercise (P < 0.001), and posthandgrip ischemia (P < 0.005). When expressed in percent change from rest, the mean peak-to-peak amplitude increased by 111 (SD 100)% during mental arithmetic, by 160 (SD 103)% during static handgrip exercise, and by 90 (SD 67)% during posthandgrip ischemia. The study clearly indicates a facilitation of the short-latency stretch reflex during increased sympathetic outflow. We note that the enhanced stretch reflex responses observed in relaxed muscles in the absence of skeletomotor activity support the idea that the sympathetic nervous system can exert a direct influence on the human muscle spindles.     

Muscle mechanosensitive receptors close to the myotendinous junction of the Achilles tendon elicit a pressor reflex.

Feedback regulation by activation of mechanosensitive afferents in the exercising muscle causes the cardiovascular and sympathetic nerve responses, which follow tension development and are almost identical between static contraction and passive stretch. The precise location of the mechanoreceptors contributing to the exercise pressor reflex, however, remained unknown. To test the hypothesis that the mechanoreceptors will be located around the myotendinous junction to monitor a change in muscle tension than a change in muscle length, we examined the reflex cardiovascular responses to passive stretch of the triceps surae muscle in anesthetized rats with three interventions; systemic injection of gadolinium, cutting the Achilles tendon, and local injection of lidocaine into the myotendinous junction. Gadolinium (42 micromol/kg iv) blunted the increases in heart rate and mean arterial blood pressure during passive stretch by 36 and 22-26%, respectively, suggesting that the reflex cardiovascular responses were evoked by stimulation of muscle mechanosensitive receptors. The cardiovascular responses to passive stretch were not different between the cut Achilles tendon and the intact tendon in the same rats, suggesting that any mechanoreceptors, terminated in the more distal part of the tendon, did not contribute to the reflex cardiovascular responses. Lidocaine (volume, 0.04-0.1 ml) injected into the myotendinous junction blunted the stretch-induced increases in heart rate and mean arterial blood pressure by 37-49 and 27-34%, respectively. We conclude that the muscle mechanosensitive receptors evoking the reflex cardiovascular responses at least partly locate at or close to the myotendinous junction of the Achilles tendon.     

Pulse waves in prestressed arteries

In order to better understand the effect of initial stress in blood flow in arteries, a theoretical analysis of wave propagation in an initially inflated and axially stretched cylindrical thick shell is investigated. For simplicity in the mathematical analysis, the blood is assumed to be an incompressible inviscid fluid while the arterial wall is taken to be an isotropic, homogeneous and incompressible elastic material. Employing the theory of small deformations superimposed on a large initial field the governing differential equations of perturbed solid motions are obtained in cylindrical polar coordinates. Considering the difficulty in obtaining a closed form solution for the field equations, an approximate power series method is utilized. The dispersion relations for the most general case of this approximation and for the thin tube case are thoroughly discussed. The speeds of waves propagating in an unstressed tube are obtained as a special case of our general treatment. It is observed that the speeds of both waves increase with increasing inner pressure and axial stretch.     

Wave Propagation in a Viscous Fluid Contained in an Orthotropic Elastic Tube

The problem of pressure wave propagation through a viscous fluid contained in an orthotropic elastic tube is considered in connection with arterial blood flow. Solutions to the fluid flow and elasticity equations are obtained for the presence of a reflected wave. Numerical results are presented for both isotropic and orthotropic elastic tubes. In particular, the pressure pulse, flow rate, axial fluid velocity, and wall displacements are plotted vs. time at various stations along the ascending aorta of man. The results indicate an increase in the peak value of the pressure pulse and a decrease in the flow rate as the pulse propagates away from the heart. Finally, the velocity of wave propagation depends mainly on the tangential modulus of elasticity of the arterial wall, and anisotropy of the wall accounts in part for the reduction of longitudinal movements and an increase in the hydraulic resistance.     

The effect of shear stress on solitary waves in arteries

In the present work, we study the propagation of solitary waves in a prestressed thick walled elastic tube filled with an incompressible inviscid fluid. In order to include the geometric dispersion in the analysis the wall inertia and shear deformation effects are taken into account for the inner pressure-cross-sectional area relation. Using the reductive perturbation technique, the propagation of weakly non-linear waves in the long-wave approximation is examined. It is shown that, contrary to thin tube theories, the present approach makes it possible to have solitary waves even for a Mooney-Rivlin (M-R) material. Due to dependence of the coefficients of the governing Korteweg-deVries equation on initial deformation, the solution profile changes with inner pressure and the axial stretch. The variation of wave profiles for a class of elastic materals are depicted in graphical forms. As might be seen from these illustrations, with increasing thickness ratio, the profile of solitary wave is steepened for a M-R material but it is broadened for biological tissues.     

Penetrating chest wound: a case report.

An unusual penetrating chest injury was caused by a ball-point pen. Because of apparent penetration of the heart, preparations were made for an emergency open-heart procedure before emergency thoracotomy was undertaken, with the pen still in situ. The pen had bruised the epicardium but had not penetrated the pericardial sac. After removal of the pen, the wound was closed and a chest tube left in place. Recovery, apart from minor degrees of basal atelectasis, pleural effusion and wound infection, was uneventful. The outcome was consistent with that associated with current aggressive management of penetrating chest injuries. Management is based on three approaches. The primary one is intercostal thoracostomy tube drainage and fluid and blood replacement. In cases of massive hemorrhage or air leak, thoracotomy is necessary. The third approach is to prevent post-traumatic pulmonary insufficiency by using fine, high-efficiency filters during blood transfusion, avoiding excessive administration of intravenous fluids, performing tracheostomy after prolonged endotracheal intubation, and using a volume respirator with positive end-expiratory pressure. The average mortality for penetrating wounds of the heart is 25%.     

Stretch and radial compression studies on relaxed skinned muscle fibers of the frog.

The influence of stretch and radial compression on the width of mechanically skinned fibers from the semitendinosus muscle of the frog (R. pipiens) was examined in relaxing solutions with high-power light microscopy. Fibers were skinned under mineral oil. We find that, after correcting for water uptake in the oil, fiber width increased by an average of 28% upon transfer from oil to relaxing medium, with some tendency for greater swelling at longer sarcomere lengths. Subsequently, fibers were compressed by addition of the long-chain polymer polyvinylpyrrolidone (PVP-40, number average molecular weight 40,000) to relaxing solutions. Sarcomere length does not appear to be affected by addition of PVP. At any PVP concentration, the inverse square of the fiber width increased smoothly and linearly with increasing stretch for sarcomere lengths between 2.10 and 4.60 micrometer. At any fixed sarcomere length, fiber width decreased linearly with the logarithm of the osmotic compressive pressure exerted by PVP (2-10% concentration). From this logarithmic relation we estimate that the swelling pressure of the intact fiber is 3.40 x 10(3) N/m2, between that of a 2 and a 3% PVP solution. The pressure giving rise to fiber swelling is not due to dilation of the sarcoplasmic reticulum (SR), since the experimental results above were not significantly different after treatment with 0.5% BRIJ-58, a nonionic detergent that disrupts the SR. Swelling may be due simply to elastic structures within the fiber that are constrained in the intact cell. Values of bulk moduli of fibers, calculated from the compression experiments, and preliminary measurements of Young's modulus from stretch experiments, are quantitatively consistent with the idea that skinned fibers behave as nonisotropic elastic bodies.     

A role for BMP signalling in heart looping morphogenesis in Xenopus

The heart develops from a linear tubular precursor, which loops to the right and undergoes terminal differentiation to form the multichambered heart. Heart looping is the earliest manifestation of left-right asymmetry and determines the eventual heart situs. The signalling processes that impart laterality to the unlooped heart tube and thus allow the developing organ to interpret the left-right axis of the embryo are poorly understood. Recent experiments in zebrafish led to the suggestion that bone morphogenetic protein 4 (BMP4) may impart laterality to the developing heart tube. Here we show that in Xenopus, as in zebrafish, BMP4 is expressed predominantly on the left of the linear heart tube. Furthermore we demonstrate that ectopic expression of Xenopus nodal-related protein 1 (Xnr1) RNA affects BMP4 expression in the heart, linking asymmetric BMP4 expression to the left-right axis. We show that transgenic embryos overexpressing BMP4 bilaterally in the heart tube tend towards a randomisation of heart situs in an otherwise intact left-right axis. Additionally, inhibition of BMP signalling by expressing noggin or a truncated, dominant negative BMP receptor prevents heart looping but allows the initial events of chamber specification and anteroposterior morphogenesis to occur. Thus in Xenopus asymmetric BMP4 expression links heart development to the left-right axis, by being both controlled by Xnr1 expression and necessary for heart looping morphogenesis.     

Parenchymal stress affects interstitial and pleural pressures in in situ lung.

After resecting the intercostal muscles and thinning the endothoracic fascia, we micropunctured the lung tissue through the intact pleural space at functional residual capacity (FRC) and at volumes above FRC to evaluate the effect of increasing parenchymal stresses on pulmonary interstitial pressure (Pip). Pip was measured at a depth of approximately 230 microns from the pleural surface, at 50% lung height, in 12 anesthetized paralyzed rabbits oxygenated via a tracheal tube with 50% humidified O2. Pip was -10 +/- 1.5 cmH2O at FRC. At alveolar pressure of 5 and 10 cmH2O, lung volume increased by 8.5 and 19 ml and Pip decreased to -12.4 +/- 1.6 and -12.3 +/- 5 cmH2O, respectively. For the same lung volumes held by decreasing pleural surface pressure to about -5 and -8.5 cmH2O, Pip decreased to -17.4 +/- 1.6 and -23.8 +/- 5 cmH2O, respectively. Because Pip is more negative than pleural pressure, the data suggest that in intact pulmonary interstitium the pressure of the liquid phase is primarily set by the mechanisms controlling interstitial fluid turnover.     

Mechanical anisotropy of inflated elastic tissue from the pig aorta

Uniaxial and biaxial mechanical properties of purified elastic tissue from the proximal thoracic aorta were studied to understand physiological load distributions within the arterial wall. Stress–strain behaviour was non-linear in uniaxial and inflation tests. Elastic tissue was 40% stiffer in the circumferential direction compared to axial in uniaxial tests and～100% stiffer in vessels at an axial stretch ratio of 1.2 or 1.3 and inflated to physiological pressure. Poisson’s ratio v_θz averaged 0.2 and v_zθ increased with circumferential stretch from ～0.2 to ～0.4. Axial stretch had little impact on circumferential behaviour. In intact (unpurified) vessels at constant length, axial forces decreased with pressure at low axial stretches but remained constant at higher stretches. Such a constant axial force is characteristic of incrementally isotropic arteries at their in vivo dimensions. In purified elastic tissue, force decreased with pressure at all axial strains, showing no trend towards isotropy. Analysis of the force–length–pressure data indicated a vessel with v_θz≈0.2 would stretch axially 2–4% with the cardiac pulse yet maintain constant axial force. We compared the ability of 4 mathematical models to predict the pressure-circumferential stretch behaviour of tethered, purified elastic tissue. Models that assumed isotropy could not predict the stretch at zero pressure. The neo-Hookean model overestimated the non-linearity of the response and two non-linear models underestimated it. A model incorporating contributions from orthogonal fibres captured the non-linearity but not the zero-pressure response. Models incorporating anisotropy and non-linearity should better predict the mechanical behaviour of elastic tissue of the proximal thoracic aorta.