The venous circulation

Some aspects of the circulation through the veins remain unexplained. The pressure gradient which ordinarily exists across a large vein, for example, is much greater than that necessary to maintain the same flow through a rigid tube of identical diameter (Brecher, 1956; Starling and Evans, 1962). During inspiration, blood flow through the thoracic portion of the inferior vena cava increases markedly, while that through the distal abdominal portion does not change. Furthermore, an active source of pressure drop in the chest is necessary to maintain venous flow. For the open chest the pressure drop occurs mainly during ventricular contraction, while in the closed chest it is produced chiefly by inspiration. The present study indicates that the high distensibility of the veins accounts in significant degree for the behavior characteristic of the venous circulation.     

Intravascular pressure profiles in elephant seals: hypotheses on the caval sphincter, extradural vein and venous return to the heart

In order to evaluate hemodynamics in the complex vascular system of phocid seals, intravascular pressure profiles were measured during periods of rest-associated apnea in young elephant seals (Mirounga angustirostris). There were no significant differences between apneic and eupneic mean arterial pressures. During apnea, venous pressure profiles (pulmonary artery, thoracic portion of the vena cava (thoracic vena cava), extradural vein, and hepatic sinus) demonstrated only minor, transient fluctuations. During eupnea, all venous pressure profiles were dominated by respiratory fluctuations. During inspiration, pressures in the thoracic vena cava and extradural vein decreased -9 to -21 mm Hg, and -9 to -17 mm Hg, respectively. In contrast, hepatic sinus pressure increased 2-6 mm Hg during inspiration. Nearly constant hepatic sinus and intrathoracic vascular pressure profiles during the breath-hold period are consistent with incomplete constriction of the caval sphincter during these rest-associated apneas. During eupnea, negative inspiratory intravascular pressures in the chest ("the respiratory pump") should augment venous return via both the venae cavae and the extradural vein. It is hypothesized that, in addition to the venae cavae, the prominent para-caval venous system of phocid seals (i.e., the extradural vein) is necessary to allow adequate venous return for maintenance of high cardiac outputs and blood pressure during eupnea.     

The dynamic of breathing biomechanics and intrathoracic hemodynamics parameters during microgravity modeling

In ground-based model of the hemodynamics effects of weightlessness, the intersystem relation of breathing and circulation was investigated during inspiration and expiration separately in anesthetized catz. It's shown that the dynamics of central venous pressure, esophageal pressure and filling pressure of the heart during inspiration in supine and head-down tilt position has obvious similarity to those which hypothetically can be present in microgravity. The results suggest that intrathoracic hemodynamics during inspiration in supine and head-down position may be an adequate ground model for investigation of weightlessness influences on intrathoracic circulation.     

Coronary venous pressure and flow: effects of vagal stimulation, aortic occlusion, and vasodilators

Coronary venous pressure and coronary sinus flow in the canine heart were compared with intramyocardial, intraventricular, aortic, and coronary artery pressures. Stimulation of the thoracic vagus augmented coronary venous pressure, mean venous flow per systole, and coronary venous systolic resistance, but decreased the mean venous flow. Partial occlusion of the aorta augmented coronary venous pressure and coronary venous flow, while systolic coronary venous resistance remained unchanged. Adenosine increased peripheral and central coronary venous pressure and venous flow; it reduced peripheral coronary artery pressure. Adenosine augmented flow per systole and reduced venous resistance more than the other interventions. Dipyridamole decreased left ventricular, aortic, and central coronary artery systolic pressures and systolic venous resistance. It increased the venous flow, mean flow per systole, and coronary venous pressure, even though intramyocardial pressure remained unchanged. Nitroglycerine elevated coronary venous pressure and flow, as well as venous flow per systole, even though it decreased left ventricular, aortic, and central coronary artery pressures. Nitroglycerine significantly decreased coronary venous resistance. It is concluded that coronary venous resistance may be an important resistive component to consider when the total coronary circulation is studied.     

Arterial and venous circulation of the leg after intermittent venous occlusion

We study the arterial and venous circulation of the normal leg by strain gauge plethysmography and venous occlusion (thigh tourniquet). We propose the application of a simplified linear physical model of the venous circulation. It helps to analyse the plethysmographic data recorded during and after the congestion. It ignores the arterial inflow and consider the post-occlusive venous volume decay in function of time as being monoexponential. The venous compliance (C) is measured when the volume has reached a steady-state level during the congestion (known pressure). The time-constant (T) characterizes the volume decay in function of time when the occlusion is released. The tourniquet is successively inflated with two levels of pressure (30 and 60 mm Hg) in order to check if the system is actually linear as predicted by the model. The venous outflow is not strictly monoexponential and the model is only suitable to describe the beginning of the curve. The compliance does not behave linearly, the values measured at 30 mm Hg, being higher than at 60 mm Hg ($ 26%). The time-constant T is slightly influenced by the level of pressures. The calculated resistance is therefore lower at low pressure. We also study the arterial inflow before and after the venous congestion (3 min, 60 mm Hg). We observe a post-venous occlusion hyperaemia (mean rest flow: 5.2%/min, mean hyperemic flow: 12.1%/min) followed by a drop of the inflow (mean minimal flow: 3.4%/min). We evaluate the quantitative influence of neglecting the arterial inflow on the computing of the venous properties. The simplification appears acceptable.     

Measurement of alveolar pressure in closed-chest dogs during flow interruption

We have developed a technique for installing alveolar capsules in dogs with intact chest wall, by exposing a region of parietal pleura between a pair of ribs and gluing the parietal and visceral pleura together around a small region of lung. This allows the direct measurement of alveolar pressure during spontaneous breathing. We measured alveolar pressure in normal dogs using this technique while suddenly interrupting flow at the trachea during passive expiration. Tracheal pressure exhibited a very rapid rise immediately on interruption that we showed to be composed of two distinct and roughly equal parts: one was the resistive pressure drop across the airways, and the other was a resistive pressure drop across tissues. By simultaneously measuring pleural pressure we showed that the tissues responsible were only in the chest wall and not in the lungs.     

Influence of connection geometry and SVC-IVC flow rate ratio on flow structures within the total cavopulmonary connection: a numerical study

The total cavopulmonary connection (TCPC) is a palliative cardiothoracic surgical procedure used in patients with one functioning ventricle that excludes the heart from the systemic venous to pulmonary artery pathway. Blood in the superior and inferior vena cavae (SVC, IVC) is diverted directly to the pulmonary arteries. Since only one ventricle is left in the circulation, minimizing pressure drop by optimizing connection geometry becomes crucial. Although there have been numerical and in-vitro studies documenting the effect of connection geometry on overall pressure drop, there is little published data examining the effect of SVC-IVC flow rate ratio on detailed fluid mechanical structures within the various connection geometries. We present here results from a numerical study of the TCPC connection, configured with various connections and SVC:IVC flow ratios. The role of major flow parameters: shear stress, secondary flow, recirculation regions, flow stagnation regions, and flow separation, was examined. Results show a complex interplay among connection geometry, flow rate ratio and the types and effects of the various flow parameters described above. Significant changes in flow structures affected local distribution of pressure, which in turn changed overall pressure drop. Likewise, changes in local flow structure also produced changes in maximum shear stress values; this may have consequences for platelet activation and thrombus formation in the clinical situation. This study sheds light on the local flow structures created by the various connections andflow configurations and as such, provides an additional step toward understanding the detailed fluid mechanical behavior of the more complex physiological configurations seen clinically.     

Liquid drainage through the peritoneal diaphragmatic surface

In 14 spontaneously breathing anesthetized rabbits, we used cyanoacrylate to glue a hollow capsule, at end expiration or at end inspiration, to the peritoneal surface of the tendinous portion of the diaphragm. The capsule was connected to a pressure transducer and a pipette calibrated in microliters. We filled the system with fluid and measured flow into the diaphragmatic surface facing the capsule (Fcap, microliter/cm2), from liquid displacement in the pipette at different hydraulic pressures in the system (Pcap). Pleural liquid pressure was simultaneously measured in the supraphrenic region (Psup). Fcap was positively correlated to transdiaphragmatic pressure gradient (Psup-Pcap) and breathing frequency but was unaffected by protein concentration of capsular fluid. For a breathing frequency of 30 cycles/min and a Psup - Pcap = -2 cmH2O, Fcap was 0.54 microliter.min-1.cm-2 for capsules applied at end expiration and 10-fold greater for capsules applied at end inspiration. Data indicate that the diaphragmatic tendinous portion in rabbits is a draining site for peritoneal fluid and that the conductance of the draining pathways (lymphatic stomata) is related to diaphragmatic tension. In the intact rabbit the average peritoneal fluid drainage through the tendinous portion of the diaphragm (approximately 16 cm2) was estimated at 43 microliters/min.     

Zone 2 and zone 3 pulmonary blood flow

In the West model of zonal distribution of pulmonary blood flow, increases in flow down zone 2 are attributed to an increase in driving pressure and a decrease in resistance resulting from recruitment and distension. The increase in flow down zone 3 is attributed to a decrease in resistance only. Recent studies indicate that, besides the pressure required to maintain flow through a vessel, there is an added pressure cost that must be overcome in order to initiate flow. These additional pressure costs are designated critical pressures (Pcrit). Because Pcrit exceed alveolar pressure, the distinction between zones in the West model becomes less secure, and the explanation for the increase in flow even in West zone 3 requires reexamination. We used two methods to test the hypothesis that the Pcrit is the pertinent backpressure to flow even in zone 3, when the pulmonary venous pressure (Ppv) exceeds alveolar pressure (PA) but is less than Pcrit in the isolated canine left caudal lobe. First, PA was maintained at 5 cmH2O, and pressure flow (P-Q) characteristics were obtained in zone 2 and zone 3. Next, with PA still at 5 cmH2O, we maintained a constant flow and measured the change in pulmonary arterial pressure as Ppv was varied. Both techniques indicated that the pertinent backpressure to flow was the greater of either Pcrit or Ppv and that PA was never the pertinent backpressure to flow. Also, our results indicate no significant change in the geometry of the flow channels between zone 2 and zone 3. These findings refine the zonal model of the pulmonary circulation.     

Lung microvascular pressure profile measured by micropuncture in anesthetized dogs

We have micropunctured the lung in the open thorax of 17 anesthetized dogs to measure microvascular pressure. After intravenous pentobarbital sodium (25 mg/kg), we exposed the left lung through a wide left thoracotomy, which required rib excision. Through a double-lumen endotracheal tube, we ventilated the right lung to maintain normal blood gases and pH while we held the left lung motionless at an inflation pressure of 5 cmH2O. To reduce motion on the surface of the left lower lobe, we resected the left upper lobe, placed a Plexiglas baffle between the lobe and the heart, and held the lobe surface in a suction ring. In accordance with procedures we have previously described, we micropunctured subpleural vessels to measure microvascular pressure. At base line when alveolar pressure exceeded left atrial pressure (zone 2 conditions), 21, 38, and 41% of the total pressure drop occurred, respectively, in the arterial, microvascular, and venous segments. When we raised left atrial pressure above alveolar pressure (zone 3 conditions), the corresponding pressure drops were 30, 55, and 20% of total. The blood flow in the superficial layer of the lung averaged 15% less than the flow in the deeper layers as measured by distribution of 99mTc-albumin macroaggregates. We conclude that the intact and the isolated lung preparations in dog exhibit similar distributions of subpleural microvascular pressure.     

The constant level of the right atrial pressure and its role in the venous return characteristics]

Dynamics of the central venous pressure, superior and inferior v. cava flow and venous return following action of pressor stimuli were studied in acute experiments on anaesthetised mongrel cats with artificial lung ventilation and opened chest. The central venous pressure returned to the initial level faster as compared with the dynamics of superior and inferior v. cava flow and venous return. The superior v. cava blood flow increased more than that of inferior v. cava. The data suggest that the central venous pressure is controlled near the lower constant level.     

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.     

Effects of augmented respiratory muscle pressure production on locomotor limb venous return during calf contraction exercise.

We determined effects of augmented inspiratory and expiratory intrathoracic pressure or abdominal pressure (Pab) excursions on within-breath changes in steady-state femoral venous blood flow (Qfv) and net Qfv during tightly controlled (total breath time = 4 s, duty cycle = 0.5) accessory muscle/"rib cage" (DeltaPab <2 cmH2O) or diaphragmatic (DeltaPab >5 cmH2O) breathing. Selectively augmenting inspiratory intrathoracic pressure excursion during rib cage breathing augmented inspiratory facilitation of Qfv from the resting limb (69% and 89% of all flow occurred during nonloaded and loaded inspiration, respectively); however, net Qfv in the steady state was not altered because of slight reductions in femoral venous return during the ensuing expiratory phase of the breath. Selectively augmenting inspiratory esophageal pressure excursion during a predominantly diaphragmatic breath at rest did not alter within-breath changes in Qfv relative to nonloaded conditions (net retrograde flow = -9 +/- 12% and -4 +/- 9% during nonloaded and loaded inspiration, respectively), supporting the notion that the inferior vena cava is completely collapsed by relatively small increases in gastric pressure. Addition of inspiratory + expiratory loading to diaphragmatic breathing at rest resulted in reversal of within-breath changes in Qfv, such that >90% of all anterograde Qfv occurred during inspiration. Inspiratory + expiratory loading also reduced steady-state Qfv during mild- and moderate-intensity calf contractions compared with inspiratory loading alone. We conclude that 1) exaggerated inspiratory pressure excursions may augment within-breath changes in femoral venous return but do not increase net Qfv in the steady state and 2) active expiration during diaphragmatic breathing reduces the steady-state hyperemic response to dynamic exercise by mechanically impeding venous return from the locomotor limb, which may contribute to exercise limitation in health and disease.     

Systemic circulatory effects of pentagastrin

Effects of pentagastrin on systemic circulation were studied in anesthetized cats. Systemic arterial, central venous and portal pressure were monitored with electromanometers and blood flow through the superior mesenteric artery, common carotid artery, femoral artery and ascending aorta were measured with an electromagnetic blood flow meter. Pentagastrin injected intravenously at a doses of 2.0, 4.0 and 8.0 micrograms/kg induced a dose-dependent fall in arterial pressure, heart rate and cardiac output, increased mesenteric blood flow, decreased common carotid artery blood flow, did not change femoral artery blood flow and slightly rose central venous pressure. Atropine blocked observed effects. After repeated injections of the peptide, tachyphylaxis quickly developed. The obtained results indicate that pentagastrin influences general hemodynamics probably via interaction with cholinergic receptors.     

Mathematical modeling of gravitational effects on the circulation: importance of the time course of venous pooling and blood volume changes in the lungs

A dip in blood pressure (BP) in response to head-up tilt (HUT) or active standing might be due to rapid pooling in the veins below the heart (preload) or muscle activation-induced drop in systemic vascular resistance (afterload). We hypothesized that, in the cardiovascular response to passive HUT, where, in contrast to active standing, little BP dip is observed, features affecting the preload play a key role. We developed a baroreflex model combined with a lumped-parameter model of the circulation, including viscoelastic stress-relaxation of the systemic veins. Cardiac contraction is modeled using the varying-elastance concept. Gravity affects not only the systemic, but also the pulmonary, circulation. In accordance with the experimental results, model simulations do not show a BP dip on HUT; the tilt-back response is also realistic. If it is assumed that venous capacities are steady-state values, the introduction of stress-relaxation initially reduces venous pooling. The resulting time course of venous pooling is comparable to measured impedance changes. When venous pressure-volume dynamics are neglected, rapid (completed within 30 s) venous pooling leads to a drop in BP. The direct effect of gravity on the pulmonary circulation influences the BP response in the first approximately 5 s after HUT and tilt back. In conclusion, the initial BP response to HUT is mainly determined by the response of the venous system. The time course of lower body pooling is essential in understanding the response to passive HUT.     

Experimental analysis of pulsatile flow through elastic collapsible tubes: application to cardiac assist device

This study presents a simulated analysis of Phased Compression Cardiac Assist Device (PCCAD) and evaluation of its applicability as a non-invasive temporary assist for a failing heart. The new technique is based on the chest pump mechanism for blood flow augmentation during external massage by phased compression of the abdominal and thoracic cavities. A semi-closed hydraulic system to simulate the systemic circulation was constructed; the system includes a left ventricle which functions according to the Starling principle and a pneumatic system which controls the pressures applied to the thoracic and abdominal cavities, in complete synchronization with the beating normal or failing heart. The possibility of manipulating the three pumps in series (venous, heart, and arterial) has been checked, and the principal parameters which effect the efficiency of the PCCAD were evaluated. This in vitro analysis shows the high potential of a non-invasive temporary cardiac assist device. It points to the necessary measures one has to take in order to achieve good synchronization and to interfere externally with the augmentation of cardiac output or with the augmentation of root aortic pressure.     

Pulmonary mechanics during rapid mechanical ventilation in rabbits with saline-lavaged lungs

Infants with respiratory failure are frequently mechanically ventilated at rates exceeding 60 breaths/min. We analyzed the effect of ventilatory rates of 30, 60, and 90 breaths/min (inspiratory times of 0.6, 0.3, and 0.2 s, respectively) on the pressure-flow relationships of the lungs of anesthetized paralyzed rabbits after saline lavage. Tidal volume and functional residual capacity were maintained constant. We computed effective inspiratory and expiratory resistance and compliance of the lungs by dividing changes in transpulmonary pressure into resistive and elastic components with a multiple linear regression. We found that mean pulmonary resistance was lower at higher ventilatory rates, while pulmonary compliance was independent of ventilatory rate. The transpulmonary pressure developed by the ventilator during inspiration approximated a linear ramp. Gas flow became constant and the pressure-volume relationship linear during the last portion of inspiration. Even at a ventilatory rate of 90 breaths/min, 28-56% of the tidal volume was delivered with a constant inspiratory flow. Our findings are consistent with the model of Bates et al. (J. Appl. Physiol. 58: 1840-1848, 1985), wherein the distribution of gas flow within the lungs depends predominantly on resistive factors while inspiratory flow is increasing, and on elastic factors while inspiratory flow is constant. This dynamic behavior of the surfactant-depleted lungs suggests that, even with very short inspiratory times, distribution of gas flow within the lungs is in large part determined by elastic factors. Unless the inspiratory time is further shortened, gas flow may be directed to areas of increased resistance, resulting in hyperinflation and barotrauma.     

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.     

Pulsatile pressure and flow in the skeletal muscle microcirculation

Although blood flow in the microcirculation of the rat skeletal muscle has negligible inertia forces with very low Reynolds number and Womersley parameter, time-dependent pressure and flow variations can be observed. Such phenomena include, for example, arterial flow overshoot following a step arterial pressure, a gradual arterial pressure reduction for a step flow, or hysteresis between pressure and flow when a pulsatile pressure is applied. Arterial and venous flows do not follow the same time course during such transients. A theoretical analysis is presented for these phenomena using a microvessel with distensible viscoelastic walls and purely viscous flow subject to time variant arterial pressures. The results indicate that the vessel distensibility plays an important role in such time-dependent microvascular flow and the effects are of central physiological importance during normal muscle perfusion. In-vivo whole organ pressure-flow data in the dilated rat gracilis muscle agree in the time course with the theoretical predictions. Hemodynamic impedances of the skeletal muscle microcirculation are investigated for small arterial and venous pressure amplitudes superimposed on an initial steady flow and pressure drop along the vessel.     

Analysis of the behavior of the respiratory system with constant inspiratory flow

For a respiratory system with constant compliance and resistance a constant flow can occur during part or all of inspiration in two situations: when the flow is constrained to be constant throughout inspiration, such as is the case with some mechanical ventilators, and when the applied pressure is a ramp (i.e., increasing constantly with time), which may occur during mechanical ventilation and spontaneous breathing. After initial transients in pressure and flow, respectively, have decayed away both situations result in linear volume-time and pressure-time relationships. The slope of the corresponding pressure-volume line then yields an estimate of the total compliance of the respiratory system, and the intercept, divided by the constant flow, provides the total resistance. We have shown theoretically that, for a model composed of two compartments in parallel, the total compliance is the same as the static compliance and equals the sum of the compliances of the two compartments. Furthermore, this compliance is independent of the breathing frequency. However, the total resistance is, in general, a function of both the resistances and the compliances. When the time constants of the two compartments are equal the total resistance assumes its minimum value and becomes independent of the compliances. This minimum value of resistance can be obtained, regardless of the time constants, by dividing the immediate drop in airway opening pressure, obtained after occluding during steady state inspiration, by the inspiratory flow.