Effect of positive pressure on venous return in volume-loaded cardiac surgical patients.

The hemodynamic effects of increases in airway pressure (Paw) are related in part to Paw-induced increases in right atrial pressure (Pra), the downstream pressure for venous return, thus decreasing the pressure gradient for venous return. However, numerous animal and clinical studies have shown that venous return is often sustained during ventilation with positive end-expiratory pressure (PEEP). Potentially, PEEP-induced diaphragmatic descent increases abdominal pressure (Pabd). We hypothesized that an increase in Paw induced by PEEP would minimally alter venous return because the associated increase in Pra would be partially offset by a concomitant increase in Pabd. Thus we studied the acute effects of graded increases of Paw on Pra, Pabd, and cardiac output by application of inspiratory-hold maneuvers in sedated and paralyzed humans. Forty-two patients were studied in the intensive care unit after coronary artery bypass surgery during hemodynamically stable, fluid-resuscitated conditions. Paw was progressively increased in steps of 2 to 4 cmH(2)O from 0 to 20 cmH(2)O in sequential 25-s inspiratory-hold maneuvers. Right ventricular (RV) cardiac output (CO(td)) and RV ejection fraction (EF(rv)) were measured at 5 s into the inspiratory-hold maneuver by the thermodilution technique. RV end-diastolic volume and stroke volume were calculated from EF(rv) and heart rate data, and Pra was measured from the pulmonary artery catheter. Pabd was estimated as bladder pressure. We found that, although increasing Paw progressively increased Pra, neither CO(td) nor RV end-diastolic volume changed. The ratio of change (Delta) in Paw to Delta Pra was 0.32 +/- 0.20. The ratio of Delta Pra to Delta CO(td) was 0.05 +/- 00.15 l x min(-1) x mmHg(-1). However, Pabd increased such that the ratio of Delta Pra to Delta Pabd was 0.73 +/- 0.36, meaning that most of the increase in Pra was reflected in increases in Pabd. We conclude that, in hemodynamically stable fluid-resuscitated postoperative surgical patients, inspiratory-hold maneuvers with increases in Paw of up to 20 cmH(2)O have minimal effects on cardiac output, primarily because of an in-phase-associated pressurization of the abdominal compartment associated with compression of the liver and squeezing of the lungs.     

Effects of positive end-expiratory pressure ventilation on cerebral venous pressure with head elevation in dogs.

Mechanical ventilation with positive end-expiratory pressure (PEEP) may prevent venous air embolism in the sitting position because cerebral venous pressure (Pcev) could be increased by the PEEP-induced increase in right atrial pressure (Pra). Whereas it is clear that there is a linear transmission of the PEEP-induced increase in Pra to Pcev while the dog is in the prone position, the mechanism of the transmission with the dog in the head-elevated position is unclear. We tested the hypothesis that a Starling resistor-type mechanism exists in the jugular veins when the head is elevated. In one group of dogs, increasing PEEP linearly increased Pcev with the dog in the prone position (head at heart level, slope = 0.851) but did not increase Pcev when the head was elevated. In another group of dogs, an external chest binder was used to produce a larger PEEP-induced increase in Pra. Further increasing Pra increased Pcev only after Pra exceeded a pressure of 19 mmHg (break pressure). This sharp inflection in the upstream (Pcev)-downstream (Pra) relationship suggests that this may be caused by a Starling resistor-type mechanism. We conclude that jugular venous collapse serves as a significant resistance in the transmission of Pra to Pcev in the head-elevated position.     

Theoretical analysis of the noncardiac limits to maximum exercise

When right atrial pressure (Pra) is greater than zero (atmospheric pressure), cardiac output is determined by the intersection of two functions, cardiac function and return function, which is used here to mean the determinants of venous return. When Pra < or = 0, flow is only determined by circuit function. The objective of this analysis was to determine the potential changes in return function that need to occur to allow the maximum cardiac output during exercise when Pra < or = 0 or is constant. The analysis expands on the model of Green and Jackman and includes the effects of changes in circuit parameters, including venous resistance, changes in capacitance, and muscle contractions. The analysis is based on the model of the circulation proposed by Permutt and co-workers, which assumes that the systemic circulation has two lumped compliant regions in parallel with independent inflow and outflow resistances. Changes in total flow in this model can come about by changes in the distribution of flow between the regions, recruitment of unstressed vascular volume, and changes in the regional venous resistances. The data for the analysis are from previous animal studies and are normalized to a 70-kg man. The major conclusions are that, to achieve the high cardiac output that occurs at peak exercise, there need to be marked changes in the distribution of blood flow, recruitment of unstressed volume, and the venous resistance draining vascular beds. A consequence of the increase in peripheral flow is a marked increase in pressure in the veins of the working muscle. Muscle contractions are potentially a very important mechanism for transiently decreasing this pressure and preventing excessive filtration of plasma during exercise.     

Diversion of blood flow from noncompliant to compliant vasculature in awake dogs: mechanical impact on right atrial pressure

The distribution of cardiac output between compliant vasculature (e.g., splanchnic organs and skin) and noncompliant vasculature (e.g., skeletal muscle) is proposed to constitute an important determinant of the amount of blood available to the heart (central blood volume and pressure). The aim here was to directly test the hypothesis that diversion of blood flow from a relatively noncompliant vasculature (muscle) to compliant vasculature (splanchnic organs and skin) acts to reduce right atrial pressure. The approach was to inflate an occluder cuff on the terminal aorta for 30 s in one of two modes of ventricular pacing in five awake dogs with atrioventricular block and autonomic blockade. In one trial, cardiac output was maintained constant, meaning cuff inflation caused a portion of terminal aortic flow (a noncompliant circulation) to be diverted to the splanchnic and skin circulations (compliant circulations). In the other trial, arterial pressure was maintained constant, meaning blood flow to these other regions did not change. The response of right atrial pressure (corrected for differences in arterial pressure between the two trials) fit our hypothesis, being lower when blood flow was diverted to compliant regions. We conclude that a small (4% of cardiac output) diversion of blood flow from a noncompliant region to a compliant region reduces right atrial pressure by 0.7 mmHg.     

Influence of positive airway pressure on the pressure gradient for venous return in humans.

To study the effect of positive airway pressure (Paw) on the pressure gradient for venous return [the difference between mean systemic filling pressure (Pms) and right atrial pressure (Pra)], we investigated 10 patients during general anesthesia for implantation of defibrillator devices. Paw was varied under apnea from 0 to 15 cmH(2)O, which increased Pra from 7.3 +/- 3.1 to 10.0 +/- 2.3 mmHg and decreased left ventricular stroke volume by 23 +/- 22%. Episodes of ventricular fibrillation, induced for defibrillator testing, were performed during 0- and 15-cmH(2)O Paw to measure Pms (value of Pra 7.5 s after onset of circulatory arrest). Positive Paw increased Pms from 10.2 +/- 3.5 to 12.7 +/- 3.2 mmHg, and thus the pressure gradient for venous return (Pms - Pra) remained unchanged. Echocardiography did not reveal signs of vascular collapse of the inferior and superior vena cava due to lung expansion. In conclusion, we demonstrated that positive Paw equally increases Pra and Pms in humans and alters venous return without changes in the pressure gradient (Pms - Pra).     

Comparative effects of vasodilator drugs on flow distribution and venous return

Systemic vascular effects of hydralazine, prazosin, captopril, and nifedipine were studied in 115 anesthetized dogs. Blood flow (Q) and right atrial pressure (Pra) were independently controlled by a right heart bypass. Transient changes in central blood volume after an acute reduction in Pra at a constant Q showed that blood was draining from two vascular compartments with different time constants, one fast and the other slow. At three dose levels producing comparable reductions in systemic arterial pressure (30-40% at the highest dose), these drugs had different effects on flow distribution and venous return. Hydralazine and prazosin had parallel and balanced effects on arterial resistance of the two vascular compartments, and flow distribution was unaltered. Captopril preferentially reduced arterial resistance of the compartment with a slow time constant for venous return (-26 +/- 6%, -30 +/- 6%, -50 +/- 5% at 0.02, 0.10, and 0.50 mg X kg-1 X h-1, respectively; means +/- SEM) without altering arterial resistance of the fast time-constant compartment. Blood flow to the slow time-constant compartment was increased 43 +/- 14% at the highest dose, and central blood volume was reduced 108 +/- 15 mL. In contrast, nifedipine had a balanced effect on arterial resistance with the lowest dose (0.025 mg/kg) but caused a preferential reduction in arterial resistance of the fast time-constant compartment at higher doses (-38 +/- 4% and -55 +/- 2% at 0.05 and 0.10 mg/kg, respectively). Blood flow to the slow time-constant compartment was reduced 36 +/- 5% at the highest dose of nifedipine, and central blood volume was increased 66 +/- 12 mL. Total systemic venous compliance was unaltered or slightly reduced by each of the four drugs. These results add further evidence to the hypothesis that peripheral blood flow distribution is a major determinant of venous return to the heart.     

Power dissipation associated with surgical operations' hemodynamics: critical issues and application to the total cavopulmonary connection

The issue of the correct determination of the mechanical power dissipated by the blood flow in the circulatory system is very important. This parameter is particularly critical when the patient's circulation has to overcome structural impairments, such as, e.g., in the case of only one functional ventricle. The surgical palliation of such a condition, which is a relatively common form of congenital heart disease, calls for an optimization of the new connection's hydrodynamics. Starting from the general formulation of the energy dissipation rate in a given control volume, this paper discusses the critical assumptions of the formula usually employed to assess the power dissipation in complex connections, such as the total cavopulmonary connection (TCPC). A new formula is derived, in which the mean elevation of the outlet and inlet sections is shown to be relevant, through the use of the piezometric pressure. Moreover, the flow profile at the boundary of the control volume is also important, since the usual approach implicitly assumes that the flow is perfectly flat: this assumption is doubtful, especially in the venous return (as in the TCPC). In the experimental part of the study, the power dissipation was measured in a physical model of the TCPC, and a large difference was found between the usual method and the proposed one, especially at low regime (85% relative difference, at 1.5 l/min total cardiac output). The proposed approach should be adopted in order to improve the accuracy of the hydrodynamical performance's assessment of surgical connections (e.g., TCPC) or implantable devices (e.g., valved conduit).     

Influence of increased abdominal pressure on steady-state cardiac performance.

The effect of steady-state increases in abdominal pressure (Pab) on cardiac performance was studied in seven acutely instrumented swine with pneumoperitoneum (PP). The animal was placed on volume-preset ventilation, and PP was created by air insufflation. Cardiac output (CO), right atrial (Pra), left atrial (Pla), pericardial (Ppe), and abdominal inferior vena cava pressures (Pivc) were measured while Pab was increased from baseline to 7.5, 15, and 30 mmHg (PP7.5, PP15, and PP30, respectively). Cardiac function curves of the right and left ventricle (RV and LV, respectively) were compared between baseline and PP30. CO presented biphasic changes, with an inital slight increase at PP7.5 followed by a fall at PP30. A significant discrepancy was observed between Pra and Pivc at PP15 and PP30, consistent with development of a "vascular waterfall." Transmural Pla (Pla - Ppe) showed parallel changes with CO, whereas transmural Pra (Pra - Ppe) exhibited a sustained increase. The RV cardiac-function curve was more depressed than was that of the LV at PP30; this suggests an increased RV afterload produced by the elevated airway pressure. These results support the hypothesis that our previously proposed concept of abdominal vascular zone conditions (M. Takata, R. A. Wise, and J. L. Robotham. J. Appl. Physiol. 69: 1961-1972, 1990) is also applicable to steady-state hemodynamic analyses. The abdominal zones appear to play an important role in determining CO, with increases in Pab, by modulating systemic venous return and the LV preload. Simultaneous measurements of Pra and Pivc may provide useful information in the hemodynamic care of patients with elevated Pab.     

Characteristics of adaptation and maladaptation of human cardiovascular system under space flight conditions

The goal of this study was to analyze and generalize hemodynamic data collected over 20 years from 26 cosmonauts, who had flown from 8 to 438 days aboard orbital stations Salut-7 and Mir. This paper describes the results of ultrasonographic studies of the heart and arterial and venous peripheral vessels in different parts of human body as well as the study of venous capacity by occlusion aeroplethysmography. It was established that, at rest, the key hemodynamic parameters (the pumping function of the heart and blood supply of the brain) and integral parameters (blood pressure and heart rate) were best “protected” and remained stable throughout long exposure in microgravity. In the absence of gravitational stimulation, arterial resistance decreased in almost all vascular regions below the heart level; i.e., the antigravity distribution of the vascular tone was gradually lost as unneeded in microgravity. Venous hemodynamics was found to be most sensitive to microgravity: changes in it were expressed earlier and were more pronounced than in the arterial part of the vasculature. The changes included deceleration of venous return, a decrease in the vascular resistance in the lower body, and an increase in the leg’s venous network capacity. The functional test with the lower body’s negative pressure revealed a deterioration of gravity-dependent responses, which increased with an increase in the duration of the space flight. Cardiovascular deconditioning clearly manifested itself after the return to the Earth’s gravity as a decreased g-tolerance during reentry and orthostatic instability in the post-flight period. The results of this study confirmed the multifactorial genesis of orthostatic instability during space flights including blood redistribution, changes in the regulation of vascular tone of arterial and venous vessels in legs, and hypovolemia.     

The venous circulation: a piscine perspective.

Vascular capacitance describes the pressure-volume relationship of the circulatory system. The venous vasculature, which is the main capacitive region in the circulation, is actively controlled by various neurohumoral systems. In terrestrial animals, vascular capacitance control is crucial to prevent orthostatic blood pooling in dependent limbs, while in aquatic animals like fish, the effects of gravity are cancelled out by hydrostatic forces making orthostatic blood pooling an unlikely concern for these animals. Nevertheless, changes in venous capacitance have important implications on cardiovascular homeostasis in fish since it affects venous return and cardiac filling pressure (i.e. central venous blood pressure), which in turn may affect cardiac output. The mean circulatory filling pressure is used to estimate vascular capacitance. In unanaesthetized animals, it is measured as the central venous plateau pressure during a transient stoppage of cardiac output. So far, most studies of venous function in fish have addressed the situation in teleosts (notably the rainbow trout, Oncorhynchus mykiss), while any information on elasmobranchs, cyclostomes and air-breathing fishes is more limited. This review describes venous haemodynamic concepts and neurohumoral control systems in fish. Particular emphasis is placed on venous responses to natural cardiovascular challenges such as exercise, environmental hypoxia and temperature changes.     

Effects of abdominal pressure on venous return: abdominal vascular zone conditions

The effects of changes in abdominal pressure (Pab) on inferior vena cava (IVC) venous return were analyzed using a model of the IVC circulation based on a concept of abdominal vascular zone conditions analogous to pulmonary vascular zone conditions. We hypothesized that an increase in Pab would increase IVC venous return when the IVC pressure at the level of the diaphragm (Pivc) exceeds the sum of Pab and the critical closing transmural pressure (Pc), i.e., zone 3 conditions, but reduce IVC venous return when Pivc is below the sum of Pab and Pc, i.e., zone 2 conditions. The validity of the model was tested in 12 canine experiments with an open-chest IVC bypass. An increase in Pab produced by phrenic stimulation increased the IVC venous return when Pivc-Pab was positive but decreased the IVC venous return when Pivc - Pab was negative. The value of Pivc - Pab that separated net increases from decreases in venous return was 1.00 +/- 0.72 (SE) mmHg (n = 6). An increase in Pivc did not influence the femoral venous pressure when Pivc was lower than the sum of Pab and a constant, 0.96 +/- 0.70 mmHg (n = 6), consistent with presence of a waterfall. These results agreed closely with the predictions of the model and its computer simulation. The abdominal venous compartment appears to function with changes in Pab either as a capacitor in zone 3 conditions or as a collapsible Starling resistor with little wall tone in zone 2 conditions.     

The venous circulation: a piscine perspective

Vascular capacitance describes the pressure–volume relationship of the circulatory system. The venous vasculature, which is the main capacitive region in the circulation, is actively controlled by various neurohumoral systems. In terrestrial animals, vascular capacitance control is crucial to prevent orthostatic blood pooling in dependent limbs, while in aquatic animals like fish, the effects of gravity are cancelled out by hydrostatic forces making orthostatic blood pooling an unlikely concern for these animals. Nevertheless, changes in venous capacitance have important implications on cardiovascular homeostasis in fish since it affects venous return and cardiac filling pressure (i.e. central venous blood pressure), which in turn may affect cardiac output. The mean circulatory filling pressure is used to estimate vascular capacitance. In unanaesthetized animals, it is measured as the central venous plateau pressure during a transient stoppage of cardiac output. So far, most studies of venous function in fish have addressed the situation in teleosts (notably the rainbow trout, Oncorhynchus mykiss), while any information on elasmobranchs, cyclostomes and air-breathing fishes is more limited. This review describes venous haemodynamic concepts and neurohumoral control systems in fish. Particular emphasis is placed on venous responses to natural cardiovascular challenges such as exercise, environmental hypoxia and temperature changes.     

Understanding Guyton's venous return curves

Based on observations that as cardiac output (as determined by an artificial pump) was experimentally increased the right atrial pressure decreased, Arthur Guyton and coworkers proposed an interpretation that right atrial pressure represents a back pressure restricting venous return (equal to cardiac output in steady state). The idea that right atrial pressure is a back pressure limiting cardiac output and the associated idea that "venous recoil" does work to produce flow have confused physiologists and clinicians for decades because Guyton's interpretation interchanges independent and dependent variables. Here Guyton's model and data are reanalyzed to clarify the role of arterial and right atrial pressures and cardiac output and to clearly delineate that cardiac output is the independent (causal) variable in the experiments. Guyton's original mathematical model is used with his data to show that a simultaneous increase in arterial pressure and decrease in right atrial pressure with increasing cardiac output is due to a blood volume shift into the systemic arterial circulation from the systemic venous circulation. This is because Guyton's model assumes a constant blood volume in the systemic circulation. The increase in right atrial pressure observed when cardiac output decreases in a closed circulation with constant resistance and capacitance is due to the redistribution of blood volume and not because right atrial pressure limits venous return. Because Guyton's venous return curves have generated much confusion and little clarity, we suggest that the concept and previous interpretations of venous return be removed from educational materials.     

Adrenergic control of venous capacitance during moderate hypoxia in the rainbow trout (Oncorhynchus mykiss): role of neural and circulating catecholamines

Central venous blood pressure (P(ven)) increases in response to hypoxia in rainbow trout (Oncorhynchus mykiss), but details on the control mechanisms of the venous vasculature during hypoxia have not been studied in fish. Basic cardiovascular variables including P(ven), dorsal aortic blood pressure, cardiac output, and heart rate were monitored in vivo during normoxia and moderate hypoxia (P(W)O(2) = approximately 9 kPa), where P(W)O(2) is water oxygen partial pressure. Venous capacitance curves for normoxia and hypoxia were constructed at 80-100, 90-110, and 100-120% of total blood volume by transiently (8 s) occluding the ventral aorta and measure P(ven) during circulatory arrest to estimate the mean circulatory filling pressure (MCFP). This allowed for estimates of hypoxia-induced changes in unstressed blood volume (USBV) and venous compliance. MCFP increased due to a decreased USBV at all blood volumes during hypoxia. These venous responses were blocked by alpha-adrenoceptor blockade with prazosin (1 mg/kg body mass). MCFP still increased during hypoxia after pretreatment with the adrenergic nerve-blocking agent bretylium (10 mg/kg body mass), but the decrease in USBV only persisted at 80-100% blood volume, whereas vascular capacitance decreased significantly at 90-110% blood volume. In all treatments, hypoxia typically reduced heart rate while cardiac output was maintained through a compensatory increase in stroke volume. Despite the markedly reduced response in venous capacitance after adrenergic blockade, P(ven) always increased in response to hypoxia. This study reveals that venous capacitance in rainbow trout is actively modulated in response to hypoxia by an alpha-adrenergic mechanism with both humoral and neural components.     

Relations between changes of the pulmonary and systemic hemodynamics following neurogenic stimuli

The character and values of changes of the pulmonary and systemic hemodynamics following neurogenic stimuli application on the cardiovascular system were studied in acute experiments on the anesthetized cats. Vagus nerve stimulation reduced the heart rate and decreased myocardial contractility in result, right and left atrial pressure increased, whereas pulmonary pressure and flow, venous return, cardiac output and venous return decreased. Pulmonary pressure reached maximal level and returned to the initial value earlier than the pulmonary flow. On the contrary, pulmonary pressure, following neurogenic pressor stimuli, reached maximal level and returned to the initial value later than the pulmonary flow; the sign of the changes of the pulmonary pressure could be positive or negative, whereas pulmonary flow were always increased. The venous return did not change, and for this reason it could not cause the increasing of pulmonary flow which was elevated following increasing of the heart rate and myocardial contractility. The shifts of the pulmonary pressure were correlated with the pulmonary resistance those, which were increased after the stellate ganglion stimulation and decreased following carotid reflex; they did not change in case of sciatic nerve stimulation. The shifts of the pulmonary pressure did not depended on the decreased right and left atrial pressures. When the pulmonary flow was always increased, the cardiac output following electrical stimulation of the stellate ganglion and sciatic nerve was elevated, and it was decreased following carotid reflex, i. e. linear correlation between these parameters were not found. Pulmonary and systemic arterial pressure changes were more obvious in case of direct neurogenic stimuli application comparing with reflectory ones; in both cases, the positive chrono- and inotropic cardiac effects were similar.     

Lower body positive pressure vs. dopamine during PEEP in humans

The application of lower body positive pressure (LBPP) of approximately 40 Torr was used to increase cardiac index (CI) in eight patients with acute respiratory failure (ARF) during positive end-expiratory pressure (PEEP) ventilation. The effects of LBPP on hemodynamics and gas exchange were compared with those of dopamine at the same level of CI without blood volume expansion. LBPP increased CI via an increase in stroke index without associated tachycardia, whereas dopamine combined both effects. A positive linear relationship (r = 0.82) was evidenced between CI and right atrial pressure (Pra) during application of LBPP according to the Frank-Starling mechanism, whereas dopamine did not increase Pra. The increase in CI with dopamine was associated with a significant rise in venous admixture (r = 0.84, P less than 0.001), whereas no such effect was observed with LBPP (r = 0.088). Changes in venous admixture were directly related to changes in mixed venous O2 pressure (PVO2) in both situations (r = 0.733, P less than 0.01), but the increase in PVO2 was more pronounced with dopamine than with LBPP (P less than 0.04). We conclude that LBPP can effectively counterbalance peripheral venous blood pooling during PEEP ventilation in humans with ARF and that changes in PVO2 appear as a major determinant of venous admixture in this setting.     

Biaxial mechanical properties of bovine jugular venous valve leaflet tissues

Venous valve incompetence has been implicated in diseases ranging from chronic venous insufficiency (CVI) to intracranial venous hypertension. However, while the mechanical properties of venous valve leaflet tissues are central to CVI biomechanics and mechanobiology, neither stress–strain curves nor tangent moduli have been reported. Here, equibiaxial tensile mechanical tests were conducted to assess the tangent modulus, strength and anisotropy of venous valve leaflet tissues from bovine jugular veins. Valvular tissues were stretched to 60% strain in both the circumferential and radial directions, and leaflet tissue stress–strain curves were generated for proximal and distal valves (i.e., valves closest and furthest from the right heart, respectively). Toward linking mechanical properties to leaflet microstructure and composition, Masson’s trichrome and Verhoeff–Van Gieson staining and collagen assays were conducted. Results showed: (1) Proximal bovine jugular vein venous valves tended to be bicuspid (i.e., have two leaflets), while distal valves tended to be tricuspid; (2) leaflet tissues from proximal valves exhibited approximately threefold higher peak tangent moduli in the circumferential direction than in the orthogonal radial direction (i.e., proximal valve leaflet tissues were anisotropic; \(p<0.01\)); (3) individual leaflets excised from the same valve apparatus appeared to exhibit different mechanical properties (i.e., intra-valve variability); and (4) leaflets from distal valves exhibited a trend of higher soluble collagen concentrations than proximal ones (i.e., inter-valve variability). To the best of the authors’ knowledge, this is the first study reporting biaxial mechanical properties of venous valve leaflet tissues. These results provide a baseline for studying venous valve incompetence at the tissue level and a quantitative basis for prosthetic venous valve design.     

Venous return in systemic haemodynamics

The paper generalizes unclear problems of venous return to the heart under different conditions. Data are presented on the venous return/cardiac output ratio, general peripheral resistance, arterial pressure and vascular bed capacity. A concept of double wave nature of formation of the circulation pressor systemic responses is advanced.     

Systematic nocturnal atrial demand pacing results in high-output heart failure.

Beat-to-beat parameters of heart rate (HR), intra-arterial blood pressure (BP), central venous pressure, and derived indexes of cardiac output and total peripheral resistance were recorded 18 h/day (from 1800 to 1200 h the following day) in four monkeys (Macaca mulatta) during 20 control days followed by 20 days of atrial demand pacing. The pacing rate was set at approximately 10 beats/min above the fastest hourly average HR recorded during the control period, i.e., sufficient to prevent the normal nocturnal fall in HR. Nocturnal pacing resulted in progressive weekly increases in central venous BP and arterial BP. Analyses of levels and diurnal trends in hemodynamic parameters and cardiac function curves across consecutive 5-day periods of nocturnal pacing revealed a hemodynamic pattern characteristic of high-output heart failure, which progressively increased (week by week) during the early morning hours (0500-0700). Sustained elevated left ventricular work resulting from the prevention of a nocturnal fall in HR may have been responsible for the reduction in cardiac function seen in this experimental model.     

Computational locality in morphological maps

This paper presents a computational investigation of a range of morphological operations. These operations are first represented as morphological maps, or functions that take a stem as input and return an output with the operation applied (e.g., the ing-suffixation map takes the input ‘d???k’ and returns ‘d???k+??’). Given such representations, each operation can be classified in terms of the computational complexity needed to map a given input to its correct output. The set of operations analyzed includes various types of affixation, reduplication, and non-concatenative morphology. The results indicate that many of these operations require less than the power of regular relations (i.e., they are subregular functions), the exception being total reduplication. A comparison of the maps that fall into different complexity classes raises important questions for our overall understanding of the computational nature of phonology, morphology, and the morpho-phonological interface.