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A quarter of the world's population experience wheezing. These sounds have been used for diagnosis since the time of the Ebers Papyrus ( ca 1500 BC). We know that wheezing is a result of the oscillations of the airways that make up the lung. However, the physical mechanisms for the onset of wheezing remain poorly understood, and we do not have a quantitative model to predict when wheezing occurs. We address these issues in this paper. We model the airways of the lungs by a modified Starling resistor in which airflow is driven through thin, stretched elastic tubes. By completing systematic experiments, we find a generalized ‘tube law’ that describes how the cross-sectional area of the tubes change in response to the transmural pressure difference across them. We find the necessary conditions for the onset of oscillations that represent wheezing and propose a flutter-like instability model for it about a heavily deformed state of the tube. Our findings allow for a predictive tool for wheezing in lungs, which could lead to better diagnosis and treatment of lung diseases.

Available evidences suggest that a number of known assumption on idiopathic intracranial hypertension (IIH) with or without papilledema might be discussed. These include (1) the primary pathogenetic role of an excessive dural sinus collapsibility in IIH, allowing a new relatively stable intracranial fluids pressure balance at higher values; (2) the non-mandatory role of papilledema for a definite diagnosis; (3) the possibly much higher prevalence of IIH without papilledema than currently considered; (4) the crucial role of the cerebral compliance exhaustion that precede the raise in intracranial pressure and that may already be pathologic in cases showing a moderately elevated opening pressure; (5) the role as “intracranial pressure sensor” played by the trigeminovascular innervation of dural sinuses and cortical bridge veins, which could represent a major source of CGRP and may explain the high comorbidity and the emerging causative link between IIHWOP and chronic migraine (CM). Accordingly, the control of intracranial pressure is to be considered a promising new therapeutic target in CM.

We developed electrical circuit based model for the different components of the cerebral circulation, what allowed us to simulate cerebral blood flow in a variety of cerebrovascular disorders. This approach allowed us to derive a set of equations by which relative maximum, or fractional flow reserve, can be defined and calculated in three relevant sites: the stenotic artery, in the veins related to the stenotic artery, and in the collateral circulation of the affected region of the brain. Our results create theoretical basis for the entirely new approach to cerebrovascular disorders that currently emphasise anatomical identification of the disease to guide the treatment, such as the degree of arterial luminal stenosis obtained from various imaging modalities. In doing so, we directly address an urgent need for stroke experts to advance the care of their patients, since current approach of stroke treatment has not been meaningfully successful. DOI: http://dx.doi.org/10.5755/j01.eee.20.10.8877

Beard & Feigl's call for the removal of Guyton's venous return curve from teaching materials (referred to here as the Guyton–Levy venous pressure curve, VPC), is not based on any deficiency of the VPC itself but purely on Guyton's own conceptual misinterpretations thereof (Beard & Feigl, 2013). Levy resolved these misinterpretations in 1979 (Levy, 1979) and there is today no valid remaining misinterpretation. Yet Beard & Feigl, evidently unaware of the full power of the VPC when combined with the Frank-Starling cardiac output (CO) curve to form Guyton's Graphical Analysis (GGA; Guyton et al. 1973), to this day unsurpassed in its ability to model the central haemodynamics of any circulatory state, would have the baby (GGA) thrown out with the bathwater (Guyton's misinterpretations). Hoping not to put too fine a point on the matter, Beard & Feigl assert that in Guyton's original VPC experiment (Guyton et al. 1957) the artificial pump was the independent variable. In fact, the pump was downstream to the Starling resistor (SR) thus rendering pump output dependent on the hydrostatic height of the SR relative to the canine surrogate mid right atrium. The pump was adjusted manually simply to insure quantitative transfer to the canine left heart of whatever flow emerged through the SR; how much flow was entirely dependent on the throttling effect of the SR. Accordingly, the SR, not the pump, was the true independent variable governing the experiment. This in no way alters the reality that CO was the independent variable controlling right atrial pressure (RAP). As cited (Beard & Feigl, 2013), Grodins and Levy used preparations essentially identical to Guyton's (the SR was excluded) and they varied CO by simply changing the pump rate. Their VPC was similar. This not only supported the validity of Guyton's experiment and the VPC itself, but it also helped disprove Guyton's backpressure premise – if the VPC is the same with or without a SR (which is a simulated tricuspid stenosis intuitively implying backpressure), then RAP must vary due to something other than backpressure. Beard & Feigl imply the VPC and GGA are deficient for their failure to model peripheral tissue–organ haemodynamics. The VPC/GGA are models of the central circulation. Irrespective of the sundry nuances of peripheral perfusion, spent blood is presented back to the heart by the vasculature in aggregate, not in particular, and this is faithfully represented by the VPC/GGA. GGA, properly understood, exposes clinical decision making based on considerations of ‘venous return’ as the conceptual distraction it is. GGA accurately provides all the central circulatory information needed to optimally comprehend and manage clinical cardiovascular disorders. There is no clinical circumstance compelling considerations of venous return in lieu of venous pressure as all changes in venous return translate into proportionate changes in venous pressure.

Clinical evidence suggests that increased amniotic fluid volume due to polyhydrarnnios increases placental vascular resistance. We have sought to model the possible effects of an increased amniotic fluid volume oil the net fetofetal transfusion in monochorionic twin pregnancies. We wanted to compare these effects with the results of previous simulations, which aimed to explain why the twin-twin transfusion syndrome (TTTS) placentas more often include bidirectional arteriovenous (AV) rather than AV plus arterioarterial (AA) anastomoses. We extended our mathematical model of TTTS by simulating two different mechanisms that increase the placental vascular resistance as a consequence of polyhydramnios. First, there is an increase in the placental capillary resistance and hence in deep AV and opposite AV (denoted as VA) resistances due to polyhydramnios. Second, there is an increase in the resistance of chorionic veins due to polyhydramnios, assuming that these veins act as Starling resistors. We then simulated the effects of polyhydramnios on different placental anastomotic patterns. The results were as follows. In the first mechanism (polyhydramnios affects AV-VA resistances), an increased amniotic fluid volume hardly affected bidirectional AV, but slightly decreased fetofetal transfusion in AV plus AA anastomoses. However, for these effects to change the natural development of the pregnancy, polyhydramnios needed to persist for approximately 4 weeks, and by comparing the effects of polyhydramnios with the effects of amnioreduction, amnioreduction was more beneficial for normalizing the donor amniotic fluid volume. Therefore, these beneficial effects due to polyhydramnios have no practical clinical significance. In the second mechanism (Starling resistor for chorionic veins), polyhydramnios slightly increased fetofetal transfusion and hence slightly increased TTTS severity in bidirectional AV and AV plus VV, but did not affect AV plus AA anastomoses. In conclusion, we hypothesize that the simulated effects of polyhydramnios are not the primary cause of the fact that TTTS placentas more often include bidirectional AV than AV plus AA anastomoses. Rather, the more likely explanation is the previously identified larger range of AA than VA anastomotic diameters that adequately compensate for the effects of the AV

Retinal venous pressure was examined in six pigs using a balanced servo-nulling micropuncture technique. The mean transmural venous pressure was 0.95 mmHg (SD 1.50 mmHg). The transmural venous pressure was lower at the optic disc than away from the disc (0.32 +/- 1.46 mmHg vs 1.69 +/- 1.19 mmHg, P < 0.01). At the disc a transmural pressure of zero or less (0 to -0.5 mmHg) was demonstrated in 10/21 (48%) of the disc readings. Over an intraocular pressure range of 15-26 mmHg there was a strong correlation between intraocular pressure and retinal venous pressure (Pearson coefficient r = 0.92). The results are compatible with the Starling resistor theory of venous outflow from the eye.

Background: Brain arteriovenous malformations (AVMs) produce circulatory and functional disturbances in adjacent as well as in remote areas of the brain, but their physiological effect on the cerebrospinal fluid (CSF) pressure is not well known. Methods: The hypothesis of an intrinsic disease mechanism leading to increased CSF pressure in all patients with brain AVM is outlined, based on a theory of hemodynamic control of intracranial pressure that asserts that CSF pressure is a fraction of the systemic arterial pressure as predicted by a two-resistor series circuit hydraulic model. The resistors are the arteriolar resistance (that is regulated by vasomotor tonus), and the venous resistance (which is mechanically passive as a Starling resistor). This theory is discussed and compared with the knowledge accumulated by now on intravasal pressures and CSF pressure measured in patients with brain AVM. Results: The theory provides a basis for understanding the occurrence of pseudotumor cerebri syndrome in patients with nonhemorrhagic brain AVMs, for the occurrence of local mass effect and brain edema bordering unruptured AVMs, and for the development of hydrocephalus in patients with unruptured AVMs. The theory also contributes to a better appreciation of the pathophysiology of dural arteriovenous fistulas, of vein of Galen aneurismal malformation, and of autoregulation-related disorders in AVM patients. Conclusions: The hydraulic hypothesis provides a comprehensive frame to understand brain AVM hemodynamics and its effect on the CSF dynamics.

To further explore the mechanism of hypoxic pulmonary vasoconstriction, we studied the mean pulmonary arterial pressure (Ppa)/left atrial pressure (Pla) relationship at fixed cardiac index (Q) and the Ppa/Q relationship at several levels of fixed Pla in pentobarbital sodium-anesthetized dogs ventilated alternately in hyperoxia [fraction of inspired O2 (FIO2) 0.4 or 1.0] and in hypoxia (FIO2 0.1). In all experimental conditions, Ppa/Q plots were linear with extrapolated pressure intercepts (Pi) not significantly different from Pla. Hypoxia increased the slope of Ppa/Q plots and did not affect Pi. In hyperoxia, increasing Pla (3 to 26 mmHg) induced approximately equal increases in Ppa at fixed Q and shifted Ppa/Q plots toward higher pressures in a parallel manner. In hypoxia, increasing Pla (4 to 25 mmHg) did not affect Ppa at fixed Q until Pla exceeded 16 mmHg and shifted Ppa/Q plots toward higher pressures with a decrease in slope. Consequently, the hypoxia-induced increases in Ppa at constant Q and constant Pla were attenuated at higher Pla. Thus, in anesthetized dogs, hypoxia increases the slope of Ppa/Q plots without affecting Pi at fixed Pla, and an increase in Pla inhibits hypoxic pulmonary vasoconstriction. These results can be explained without invoking a hypoxia-induced Starling resistor mechanism in the pulmonary circulation.

This study was designed to investigate the effect of stenosis on wall motion and collapse in a latex tube model. Much work has been reported on the collapse of veins and other thin-walled tubes within Starling resistor chambers [1,2]. These papers identify critical controlling factors such as the transmural pressure, upstream and downstream pressure and longitudinal tension. Additionally, they report choking, the waterfall phenomenon, and dynamic behavior such as flutter. None of these articles specifically address the problem of wall excursion and collapse distal to a high grade stenosis. However, Elad et al [3] report on the increased likelihood of transition to supercritical flow with a local area constriction in a model of the pulmonary system which suggests that stenoses may cause collapse. In this article, we report theoretical and experimental physiologic conditions under which arterial wall collapse may occur distal to an atherosclerotic stenosis.

Since 1964, when Fishman and Richards published Circulation of the Blood: Men and Ideas, Guyton's model of the circulation, in which mean circulatory pressure serves as the upstream pressure for venous return, has been extended, and the concept of vascular smooth muscle tone acting like the pressure surrounding a Starling resistor has been postulated. According to this scheme, the positive zero flow intercepts of rapidly determined arterial pressure-flow curves are the effective downstream pressures for arterial flow to different tissues. The arterioles, like Starling resistors, determine the downstream pressures and are followed by abrupt pressure drops, or "waterfalls." Capillary pressures are closely linked to those of the venules into which they flow. Capillary-venular pressures are the upstream pressures for venous return. In exercising muscles, reduced arteriolar tone lowers arteriolar pressure and increases arterial flow. This, in turn, raises capillary-venular pressure and increases venous flow. The arteriolar-capillary waterfall is decreased or eliminated. Total blood flow is increased by diversion of blood from tissues with slow venous drainage to muscles with fast venous drainage (low resistance X compliance). The heart pumps away the increased venous return by shifting to a new ventricular function curve.

The application of the Starling resistor concept of the lungs during continuous positive pressure ventilation (CPPV) was evaluated. Ventilation and hemodynamics were studied in eight anesthetized and paralyzed dogs before and during the use of CPPV. CPPV resulted in an increase in transpulmonary pressure and functional residual capacity (FRC), and a decrease in arterial pH and mixed venous oxygen tension (PvO2). Cardica index decreased 32% (p less than 0.01) and stroke volume 51% (p less than 0.01). Neither right nor left transmural pressures changed but pulmonary vascular resistance increased 189% (p less than 0.01). This study supports the concept that the pulmonary vasculature behaves as a Starling resistor during the use of CPPV. The increase in pulmonary vascular resistance must be considered when transpulmonary pressure is raised by CPPV.

One of the major aims of treatment for intracranial hypertension is the prevention of plateau waves. Our investigation of this phenomenon supposes an inherent nonlinear reversible physiological mechanism as the cause of the abrupt onset and resolution of these waves. We hypothesise that under certain conditions, the cerebral bridging veins exhibit a characteristic Starling resistor behavior sufficient to explain the increase in cerebral blood volume and the simultaneous decrease in blood flow associated with the onset of a plateau wave and that a modest reduction of CSF pressure due to CSF absorption causes a reversal of this process.

We investigated whether the Starling resistor model (Mitzner et al. J. Appl. Physiol. 51: 1065–1071, 1981) or a distensible vessel model (Haworth et al. J. Appl. Physiol. 70: 15–26, 1991) best describes pulmonary vascular pressure-flow (Q) relationships in embolic pulmonary hypertension. Mean pulmonary arterial pressure (Ppa)-Q plots at constant left atrial pressure (Pla) and Ppa-Pla plots at constant Q were investigated in seven dogs before and after 500-micron glass bead pulmonary embolism. Embolization to a mean angiographic obstruction of 78% increased the slope and extrapolated pressure intercept (P(i)) of Ppa-Q plots and increased the inflection point of Ppa-Pla plots, above which an increase in Pla is transmitted to Ppa in a ratio of approximately 1:1. The Starling resistor and the distensible vessel model provided a reasonably good fit to the Ppa-Q and Ppa-Pla coordinates before and after embolism. However, contrary to the prediction of the Starling resistor model, no correlation was found between the inflection point of Ppa-Pla plots and P(i). We therefore conclude that an increased closing pressure is unlikely to contribute to embolic pulmonary hypertension.

It is possible to separately measure two areas of resistance in the pulmonary circulation: proximal resistance (RP), or the resistance from a point at which pulmonary arterial pressure is measured to the vessels acting as Starling resistors, and distal resistance (RD), or the resistance from the Starling resistor vessels to a point at which pulmonary venous pressure is measured. A model has been set up in the near term fetal goat utilizing a Starling resistor concept of the pulmonary circulation and requires that the circulation to a portion of the left lung be isolated and perfused at a constant flow. Resistance in the different segments are calculated from figures derived in the experimental procedure previously reported in the Fed. Pro. 29:775-6, 1970. Previous work has demonstrated that the drop in resistance which occurs with expansion of the lung and with increased PaO2 occurs in both RP and RD. During hypoxia in the newborn both RP and RD increase. In the unventilated lung bradykinin infusion into the pulmonary artery (60–240 η.g./min.) produced a significant decrease in the RP to 52% of control values, no change in RD, and a decrease in the pressure tending to close the Starling resistor vessles (Ps). In the ventilated lung, there was a significant decrease in the RP (64% of control values) with no changes in either RD or Ps. These data indicate that bradykinin has an immediate and direct effect on the pulmonary vasculature and significantly reduces its resistance to flow. This effect is mediated through the resistance vessels proximal to the area of the Starling resistor.