Intrathoracic Pressure Variations Research Articles

Plethysmography variation index versus pulse pressure variation as an indicator of fluid responsiveness in colorectal surgeries during immediate postoperative period

ABSTRACT Background During major abdominal surgery, goal-directed fluid therapy may lessen postoperative morbidity. It has been demonstrated that the Plethysmography Variability Index (PVI), which is generated from the pulse oximeter waveform, can predict fluid responsiveness in a variety of surgical settings. Pulse pressure variation (PPV), one of the indicators of fluid responsiveness, has received the most research attention and clinical application of all the indicators. Through arterial cannulation, primarily the radial artery, pulse pressure fluctuation is recorded. The cyclic variations in intrathoracic pressure have less of an immediate impact on pulse pressure than they do on systolic pressure. In this study, sedated, intubated, mechanically ventilated patients admitted for postoperative resuscitation in our surgical ICU following colorectal surgeries had their fluid responsiveness assessed using the Plethysmography Variation Index (PVI) and the Pulse Pressure Variation (PPV) to compare their effectiveness and reliability.

Физиологические основы целенаправленной инфузионной терапии в кардиохирургии (обзор)

Goal-directed fluid therapy is a paradigm in perioperative medicine, which includes haemodynamic monitoring and individualized haemodynamic management in high-risk patients by means of fluid therapy. This approach has certain benefits compared with the traditional model of fluid therapy during the perioperative period of cardiac surgery. The required fluid volume can be hard to determine. Traditionally, fluid therapy was guided by static preload parameters, such as central venous pressure and pulmonary artery occlusion pressure, which failed to provide adequate precision. In opposition to static parameters, a number of dynamic indices and tests were developed to assess fluid responsiveness. The cornerstone of dynamic indices are cyclic preload changes due to intrathoracic pressure variations during mechanical ventilation. Dynamic tests are circulatory stress tests involving preload changes. The most frequently used tests are passive leg raise, fluid challenge test, and some others. However, in spite of their satisfactory predictive value, dynamic indices and tests have certain limitations, which must be taken into consideration. For instance, mechanical ventilation, sinus rhythm, intact thorax, and normal respiratory mechanics are obligatory conditions for applying dynamic indices. Thus, using dynamic indices can be difficult in cardiac surgery, making the search for new methods to overcome their limitations highly important.

Automated didactic prototype of pulmonary ventilation exhibits a simulation of intrathoracic pressure variations during diaphragmatic function

The movement of air from the environment to the alveoli is a vital and complex phenomenon that occurs due to variations in intrathoracic and airway pressures in relation to the atmosphere. The construction of didactic prototypes can minimize the abstraction required in these in vivo phenomena. In this study, we automated a didactic prototype of pulmonary ventilation already described in literature to simulate and exhibit variations in intrathoracic pressure during diaphragmatic function. A pulmonary ventilation (PV) prototype was produced with recyclable materials, and automated by adapting a pressure sensor in the system to generate pressure curves as a function of time during the simulation of diaphragmatic function. The automated plunger’s downward traction induced by the servomotor (such as diaphragmatic) reduced the pressure inside the bottle (intrathoracic), and this variation can be observed graphically on a computer interface while the balloon was expanded, and atmospheric air invaded its interior. Conclusion: The incorporation of technology into a simple PV prototype allowed a safe and simulated demonstration of how the diaphragm induces the variation of the intrathoracic pressure in relation to the atmosphere concomitantly with the pulmonary deformation that occurs during inspiration and exhalation.

A new physiological model for studying the effect of chest compression and ventilation during cardiopulmonary resuscitation: The Thiel cadaver

BackgroundStudying ventilation and intrathoracic pressure (ITP) induced by chest compressions (CC) during Cardio Pulmonary Resuscitation is challenging and important aspects such as airway closure have been mostly ignored. We hypothesized that Thiel Embalmed Cadavers could constitute an appropriate model. MethodsWe assessed respiratory mechanics and ITP during CC in 11 cadavers, and we compared it to measurements obtained in 9 out-of-hospital cardiac arrest patients and to predicted values from a bench model. An oesophageal catheter was inserted to assess chest wall compliance, and ITP variation (ΔITP). Airway pressure variation (ΔPaw) at airway opening and ΔITP generated by CC were measured at decremental positive end expiratory pressure (PEEP) to test its impact on flow and ΔPaw. The patient’s data were derived from flow and airway pressure captured via the ventilator during resuscitation. ResultsResistance and Compliance of the respiratory system were comparable to those of the out-of-hospital cardiac arrest patients (CRSTEC 42 ± 12 vs CRSPAT 37.3 ± 10.9 mL/cmH2O and ResTEC 17.5 ± 7.5 vs ResPAT 20.2 ± 5.3 cmH2O/L/sec), and remained stable over time. During CC, ΔITP varied from 32 ± 12 cmH2O to 69 ± 14 cmH2O with manual and automatic CC respectively. Transmission of ΔITP at the airway opening was significantly affected by PEEP, suggesting dynamic small airway closure at low lung volumes. This phenomenon was similarly observed in patients. ConclusionRespiratory mechanics and dynamic pressures during CC of cadavers behave as predicted by a theoretical model and similarly to patients. The Thiel model is a suitable to assess ITP variations induced by ventilation during CC.

Effects of septum and pericardium on heart-lung interactions in a cardiopulmonary simulation model.

Mechanical heart-lung interactions are often overlooked in clinical settings. However, their impact on cardiac function can be quite significant. Mechanistic physiology-based models can provide invaluable insights into such cardiorespiratory interactions, which occur not only under external mechanical ventilatory support but in normal physiology as well. In this work, we focus on the cardiac component of a previously developed mathematical model of the human cardiopulmonary system, aiming to improve the model's response to the intrathoracic pressure variations that are associated with the respiratory cycle. Interventricular septum and pericardial membrane are integrated into the existing model. Their effect on the overall cardiac response is explained by means of comparison against simulation results from the original model as well as experimental data from literature.

In Response.

We thank Jan Vos et al.1 for their interest in our study recently published in Anesthesia & Analgesia.2 It is important to understand the physiological differences between dynamic arterial elastance (Eadyn) and arterial elastance (Ea). Edyn is not arterial elastance but a functional parameter relating changes in pulse pressure variations (PPVs) to stroke volume variations (SVVs): PPV/SVV. Edyn has been reported as being able to predict changes in arterial pressure after a change in volume. Unlike Ea, Eadyn has a significant central component that is independently influenced by left ventricular dP/dt, because central vascular impedance is not linear. Thus, paradoxically vasopressors may decrease Eadyn and inodilators increase it. Eadyn is primarily a central parameter, whereas Ea is a lumped sum parameter of both central and peripheral tone.3 As these authors correctly pointed out, spontaneously breathing is a known limitation for assessing fluid responsiveness using the functional hemodynamic parameters of PPV or SVV.4 The impact of varying tidal volumes, ventricular interdependence, and the small changes in intrathoracic pressure during spontaneous breathing diminishes the usefulness of these parameters for assessing preload dependency.5,6 However, Eadyn is the instantaneous ratio between PPV and SVV, not the determinants of each; thus, the effects of nonuniform ventilation should have no effect on their ratio. Consequently, it is logical to assume that spontaneous breathing is not a limitation for Eadyn estimation. SVV is the main determinant of PPV. Because aortic impedance remains constant during a respiratory cycle, discrepancies between PPV and SVV should be primarily related to how left ventricular stroke volume dynamically interacts with the arterial system.7,8 It is noteworthy, however, that very low PPV and SVV values resulting from small variations in intrathoracic pressure, as seen during spontaneous breathing, could reduce the reliability of the Eadyn for defining the slope in the PPV–SVV relationship because the changes in both PPV and SVV would be small. Jan Vos et al.1 also point out a possible issue with mathematical coupling in the estimation of Eadyn. With this regard, it is important to differentiate how mathematical coupling can affect the calculation of PPV and SVV and how it can affect the ratio between the 2 (Eadyn). In the article by Cecconi et al.,2 PPV was measured by the Nexfin monitor (BMEYE, Amsterdam, The Netherlands) from the noninvasive assessment of arterial pressure using the Clamp method described by Penáz et al.,9 whereas SVV was computed using the Nexfin-CO algorithm.10 Still, both parameters were obtained from the same arterial pressure signal, and hence, some degree of mathematical coupling cannot be excluded. Importantly, García et al.11 previously confirmed the physiological assumptions and the clinical usefulness of Eadyn for predicting arterial pressure response to fluid administration and found a similar threshold value of <0.89 for the PPV/SVV, and they calculated SVV (esophageal Doppler) and PPV (obtained from an arterial line) independently. Regarding the second point about mathematical coupling, if the PPV/SVV ratio was mathematically coupled, it would not be expected to discriminate between responders and nonresponders. In practice, when using pulse pressure analysis, the reliability of Eadyn relies on the robustness of the algorithm to estimate stroke volume and its changes over a respiratory cycle.12 As long as this estimation is trustworthy enough, this assumption should allow the calculation of a valid Eadyn. This raises another issue regarding the external validity of studies performed with a specific monitor. Because Eadyn relies on the robustness of the algorithm, it is important to study and validate the reliability of Eadyn for different monitors. Finally, although the clinical applicability of Eadyn seems now purely limited by the technological boundaries, the impact of its implementation during hemodynamic resuscitation in a patient’s outcome has yet to be determined.12 Maurizio Cecconi, MD, FRCA, FFICM, MD St. George’s Healthcare NHS Trust and St. George’s University of London Tooting, London, United Kingdom [email protected] Manuel Ignacio Monge García, MD St. George’s Healthcare NHS Trust and St. George’s University of London Tooting, London, United Kingdom Servicio de Cuidados Intensivos y Urgencias Hospital SAS de Jerez Jerez de la Frontera, Spain Michael R. Pinsky, MD Department of Critical Care Medicine University of Pittsburgh Pittsburgh, Pennsylvania Andrew Rhodes, FRCP, FRCA, FFICM, MD St. George’s Healthcare NHS Trust and St. George’s University of London Tooting, London, United Kingdom

Respirophasic Forward Diastolic Flow through the Pulmonary Valve in Massive Right Ventricular Infarction

Mini‐AbstractWe report a case illustrating Fontan physiology in massive right ventricular infarction. The infarcted right ventricle acted as a passive conduit between the right atrium and the pulmonary artery, and the flow was largely driven by respiratory variations in intrathoracic pressure. During inspiration, the pulmonary valve remained open throughout the whole cardiac cycle and the right ventricular outflow was almost entirely antegrade both in systole and diastole.

Impact of dynamic airway collapse and continuous flow insufflation on initial and dynamic lung volume changes and intrathoracic pressure variation during automated cardiopulmonary resuscitation

Introduction: During CPR, chest compressions (CC) cause variations in intrathoracic pressure (PTH) that (1) allow blood circulation, (2) generates ventilation, (3) reduce lung volumes bellow the functional residual capacity (FRC). During the decompression phase, the negative PTH favors venous return but also promotes airways collapse. During compression phase, positive PTH favors the heart ejection.

Respiration Signals from Photoplethysmography

Pulse oximetry is based on the technique of photoplethysmography (PPG) wherein light transmitted through tissues is modulated by the pulse. In addition to variations in light modulation by the cardiac cycle, the PPG signal contains a respiratory modulation and variations associated with changing tissue blood volume of other origins. Cardiovascular, respiratory, and neural fluctuations in the PPG signal are of different frequencies and can all be characterized according to their sinusoidal components. PPG was described in 1937 to measure blood volume changes. The technique is today increasingly used, in part because of developments in semiconductor technology during recent decades that have resulted in considerable advances in PPG probe design. Artificial neural networks help to detect complex nonlinear relationships and are extensively used in electronic signal analysis, including PPG. Patient and/or probe-tissue movement artifacts are sources of signal interference. Physiologic variations such as vasoconstriction, a deep gasp, or yawn also affect the signal. Monitoring respiratory rates from PPG are often based on respiratory-induced intensity variations (RIIVs) contained in the baseline of the PPG signal. Qualitative RIIV signals may be used for monitoring purposes regardless of age, gender, anesthesia, and mode of ventilation. Detection of breaths in adult volunteers had a maximal error of 8%, and in infants the rates of overdetected and missed breaths using PPG were 1.5% and 2.7%, respectively. During central apnea, the rhythmic RIIV signals caused by variations in intrathoracic pressure disappear. PPG has been evaluated for detecting airway obstruction with a sensitivity of 75% and a specificity of 85%. The RIIV and the pulse synchronous PPG waveform are sensitive for detecting hypovolemia. The respiratory synchronous variation of the PPG pulse amplitude is an accurate predictor of fluid responsiveness. Pleth variability index is a continuous measure of the respiratory modulation of the pulse oximeter waveform and has been shown to predict fluid responsiveness in mechanically ventilated patients including infants. The pleth variability index value depends on the size of the tidal volume and on positive end-expiratory pressure. In conclusion, the respiration modulation of the PPG signal can be used to monitor respiratory rate. It is probable that improvements in neural network technology will increase sensitivity and specificity for detecting both central and obstructive apnea. The size of the PPG respiration variation can predict fluid responsiveness in mechanically ventilated patients.

Influence of ventilatory settings on static and functional haemodynamic parameters during experimental hypovolaemia

The influence of ventilatory settings on static and functional haemodynamic parameters during mechanical ventilation is not completely known. The purpose of this study was to evaluate the effect of positive end-expiratory pressure, tidal volume and inspiratory to expiratory time ratio variations on haemodynamic parameters during haemorrhage and after transfusion of shed blood. Ten anaesthetized pigs were instrumented and mechanically ventilated with a tidal volume of 8 mlkg(-1), a positive end-expiratory pressure of 5 cmH(2)O and an inspiratory to expiratory ratio of 1:2. Then, they were submitted in a random order to different ventilatory settings (tidal volume 16 mlkg(-1), positive end-expiratory pressure 15 cmH(2)O or inspiratory to expiratory time ratio 2:1). Functional and static haemodynamic parameters (central venous pressure, pulmonary artery occlusion pressure, right ventricular end-diastolic volume and pulse pressure variation) were evaluated at baseline, during hypovolaemia (withdrawal of 20% of estimated blood volume) and after an infusion of withdrawn blood (posttransfusion). During baseline, a positive end-expiratory pressure of 15 cmH(2)O significantly increased pulmonary artery occlusion pressure from 14.6 +/- 1.6 mmHg to 17.4 +/- 1.7 mmHg (P < 0.001) and pulse pressure variation from 15.8 +/- 8.5% to 25.3 +/- 9.5% (P < 0.001). High tidal volume increased pulse pressure variation from 15.8 +/- 8.5% to 31.6 +/- 10.4% (P < 0.001), and an inspiratory to expiratory time ratio of 2: 1 significantly increased only central venous pressure. During hypovolaemia, high positive end-expiratory pressure influenced all studied variables, and high tidal volume strongly increased pulse pressure variation (40.5 +/- 12.4% pre vs. 84.2 +/- 19.1% post, P < 0.001). The inversion of the inspiratory to expiratory time ratio only slightly increased filling pressures during hypovolaemia, without affecting pulse pressure variation or right ventricle end-diastolic volume. We concluded that pulse pressure variation measurement is influenced by cyclic variations in intrathoracic pressure, such as those caused by augmentations in tidal volume. The increase in mean airway pressure caused by positive end-expiratory pressure affects cardiac filling pressures and also pulse pressure variation, although to a lesser extent. Inversion of the inspiratory to expiratory time ratio does not induce significant changes in static and functional haemodynamic parameters.

High frequency oscillatory ventilation in children: an overview

The last 30 years, high frequency ventilation (HFV) has found its way from the neonatal to the paediatric and adult ICU. With its small tidal volumes, strict intrathoracic pressure variations and disengagement of ventilation from oxygenation, HFV fits in our insights nowadays in lung protective ventilation. This review provides you with an understanding of the different modes of HFV, gas exchange mechanisms during HFV which uses tidal volumes below dead space volume, and some information on nursing and weaning a child on HFV. Focus will be on the clinical use of high frequency oscillatory ventilation with a practical overview of the strategies used: the high-volume strategy designed to rapidly recruit and maintain optimal lung volume in diffuse alveolar disease and lung haemorrhage, the low volume strategy in airleak, and the open airway strategy in small airway disease where the continuous distending pressure is used to recruit and stent the airways.

Comment on: Tchoukalova Y, Koutsari C, Jensen M (2007) Committed subcutaneous preadipocytes are reduced in human obesity. Diabetologia 50:151–157

To the Editor: In their recent paper [1], Tchoukalova et al. provide very interesting data on preadipocyte availability according to the body fat distribution phenotype: preadipocytes of upper-body-obese women exhibited reduced differentiation and were more prone to apoptosis than preadipocytes isolated from adipose tissue of lower-bodyobese or lean women. Moreover, in obese women preadipocytes constituted a much lower percentage of adipose tissue stromovascular cells, fat cell size was higher and fat cell number per gram of tissue was lower than in lean women. We would like to propose an extended discussion of these results taking into account the fact that dimensions attained by adipocytes in obesity may lead, by purely physical and geometrical reasons, to their rupture [2], thus creating an inflammatory reaction. As we demonstrate in that paper [2], the higher the size of the adipocyte, the more prone it is to rupture upon exposure to common physical forces. Intra-abdominal and intra-thoracic acute pressure variations, for example with cough, physical exercise [2] and even with obstructive sleep apnoea [3], put visceral fat adipocytes at the highest risk, and may explain, in part, the special pathogenicity of visceral fat accumulation. As stated in those papers, description of macrophages around dead adipocytes in adipose tissue [4] has been seminal to our work on the hypothesis of adipocyte rupture. Our interpretation of the obesity–inflammation story may bring some help to the obesity health problem as, besides constituting a testable hypothesis, it suggests that the increase in the ratio of the number of adipocytes:volume of fat may decrease the inflammatory complications of obesity. This is where the results of Tchoukalova et al. on preadipocyte commitment cause us concern: they demonstrate a shortage of preadipocyte commitment exactly where they are more needed, i. e. in situations of upper-body obesity, where visceral fat proportion is higher. Interestingly, evidence for an inhibitory effect of cyclic mechanical stretching on preadipocyte differentiation has already been reported [5]. So, although the conclusion of Tchoukalova et al.—that body fat distribution may be regulated partly through differences in adipogenesis—is indisputably tenable, it could and would be more useful put the other way around: Is upper-body obesity exerting a negative influence on preadipocyte viability?

Interdépendance cœur–poumons chez le patient ventilé par pression positive

Heart-lung interactions during positive-pressure ventilation are characterized by an extreme sensibility to the patient's intravascular volume status. Indeed, a fall in cardiac output due to decreased ventricular preload can be observed when initiating positive-pressure ventilation. This phenomenon is due to the close anatomic-functional association between heart and lungs, and to the fact that pulmonary volume and intrathoracic pressure variations cyclically modify heart-lung interactions. The present review address the questions of the physiological and physiopathological effects of positive-pressure ventilation on the right and left venous returns, and on pulmonary and systemic vascular resistances.

Modeling in Cardiopulmonary Resuscitation: Pumping the Heart

Physiology offers insights into fundamental aspects of the circulation, even when the circulation is nonphysiological, as during cardiac arrest and cardiopulmonary resuscitation (CPR). Human and animal experiments offer only limited insights as they are susceptible to uncontrollable variables. Mathematical models offer quantitative results for flows, pressures and volumes under clearly defined conditions, chosen by the experimenters. This report describes the left ventricle and its immediate environment as the core of a larger mathematical model. The model works normally under physiological conditions, and is specifically designed to allow understanding of flow, pressure, and volume phenomena under CPR as an extreme pathophysiological scenario. Using impedance-defined flow, the importance of valves for both the contracting as well as the asystolic ventricle is quantified. It demonstrates the role of venous pressure, sloshing of blood and flow around the cardiovascular circuit. The flow of 8 mL/s, in a pathological situation is demonstrated to be due not to cardiac compression, but to venous pressure. The principal conclusions are that the model functions in the physiological situation and that in an asystolic left ventricle with competent valves, intrathoracic pressure can modestly replace contractile properties. In an asystolic ventricle without competent valves, intrathoracic pressure variations accomplish little. The cardiac pump theory in CPR has limited applicability.

Pulmonary haemodynamics in obstructive sleep apnoea.

In patients with obstructive sleep apnoea syndrome (OSAS), pulmonary haemodynamics can show both transient perturbations during sleep and permanent alterations. During sleep, repeated fluctuations in pulmonary artery pressure and pulmonary wedge pressure, coincident with apnoeas, can be observed. Calculation of transmural pressure values is preferable to intravascular pressures in OSAS, due to the marked swings in intrathoracic pressure associated with obstructive apnoeas. Pulmonary artery pressure may progressively increase during sleep, particularly in close sequences of highly desaturating apnoeas. Apnoea-induced hypoxia appears as the most important determinant of this pulmonary artery pressure behaviour. Stroke volume and cardiac output during obstructive apnoeas show changes mainly related to intrathoracic pressure variations. Permanent precapillary pulmonary hypertension at rest is observed in <50% OSAS patients, and is poorly reversible after OSAS treatment. It correlates best with diurnal respiratory function parameters. However, the finding of pulmonary hypertension in some patients with near normal diurnal lung function led to suggest that sleep respiratory disorders may contribute to permanent pulmonary haemodynamic impairment in predisposed subjects. Knowledge on right ventricle hypertrophy in OSAS is inconsistent. As to right ventricle failure, it is clinically evident in subjects with associated lung disease or morbid obesity, while it may be detected instrumentally in subjects without such alterations, presumably as effect of apnoeas themselves. Besides, it appears more fully reversible after long-term OSAS treatment than pulmonary hypertension.

The effect of esophageal pressure monitoring on nasal airway resistance.

Artificial obstruction of nasal airflow has been shown to increase the amount of apneas and arousals. An esophageal catheter inserted through the nasal cavity is used in sleep studies to show intrathoracic pressure variations as sign of obstructive apneas and increased respiratory resistance. This study evaluates the effect of transnasal esophageal catheter on nasal airflow. Fifty patients with problem snoring referred to our ENT clinic underwent overnight limited sleep study with an esophageal catheter. Nasal airway resistance was measured the following morning with active anterior rhinomanometry. After exclusion of 17 measurements, the results of 33 patients were compared with same parameters obtained earlier without nasal manipulation. The ipsilateral nasal resistance was clearly elevated when measured with a catheter used overnight compared with the control measurement (P < 0.05). However, the combined nasal resistance was not significantly increased in this material with patent nasal airways. In patients with already compromised nasal airflow, the possibility of clinically relevant changes in nasal airflow during catheter use should be taken in account.

Heart rate variability and hemodynamic alterations in canines with normal cardiac function during exposure to pressure support, continuous positive airway pressure, and a combination of pressure support and continuous positive airway pressure.

Variations in intrathoracic pressure generated by different ventilator weaning modes may significantly affect intrathoracic hemodynamics and cardiovascular stability. Although several investigators have attributed cardiovascular alterations during ventilator weaning to augmented sympathetic tone, there is limited investigation of changes in autonomic tone during ventilator weaning. Heart rate variability (HRV), the analysis of beat-to-beat changes in heart rate, is a noninvasive indicator of autonomic tone that might be useful in the identification of patients who are at risk for weaning difficulty due to underlying cardiac dysfunction. The authors describe HRV and hemodynamics in response to 3 ventilatory conditions: pressure support (PS) 10 cmH2O, continuous positive airway pressure (CPAP) 10 cmH2O, and a combination of PS 10 cmH2O and CPAP 10 cmH2O (PS + CPAP) in a group of canines with normal ventricular function. Six canines were studied in the laboratory. Continuous 3-lead electrocardiographic data were collected during baseline (controlled mechanical ventilation) and following transition to each of the ventilatory conditions (PS, CPAP, PS + CPAP) for analysis of HRV. HRV was evaluated using power spectral analysis to define the power under the curve in a very low frequency range (0.0033 to < 0.04 Hz, sympathetic tone), a low frequency range (0.04 to < 0.15 Hz, primarily sympathetic tone), and a high frequency range (0.15 to < 0.40 Hz, parasympathetic tone). A thermodilution pulmonary artery catheter measured cardiac output and right ventricular end-diastolic volume to describe global hemodynamics. There were significant increases in very low frequency power (sympathetic tone) with a concomitant significant reduction in high-frequency power (parasympathetic tone) with exposure to PS + CPAP. These alterations in HRV were associated with significantly increased heart rate and reduced right ventricular end-diastolic volume. Although there was a small but significant increase in cardiac output with exposure to PS, HRV was unchanged. These data indicate that there was a relative shift in autonomic balance to increased sympathetic and decreased parasympathetic tone with exposure to PS + CPAP. The increase in intrathoracic pressure reduced right ventricular end-diastolic volume (preload). This hemodynamic alteration generated a change in autonomic tone, so that cardiac output could be maintained. Individuals with autonomic and/or cardiovascular dysfunction may not be capable of this type of response and may fail to successfully wean from mechanical ventilation.

Cardiovascular responses to intrathoracic pressure variations in coronary disease patients: a computer simulation.

Several studies have suggested that the Valsalva maneuver may predispose potential lethal arrhythmias in patients with coronary artery disease, since this maneuver induces diminished coronary flow. On the other hand some studies have suggested that the Valsalva maneuver abruptly reduces determinants of cardiac oxygen demand, relieving angina pectoris. In order to study the variations of the myocardial oxygen supply-demand relation, during different applications of the maneuver, a mathematical model of the human cardiovascular system is presented. The model has been submitted to an evaluation process allowing the inclusion of a number of additional refinements to the mathematical model structures, and the obtaining of a reduced model in order to improve the computer time and parameter estimation of the simulation. The simulated output variables of the model correlate well with in vivo data obtained from ten patients with typical exertional angina pectoris studied during cardiac catheterization. The evaluation of the cardiac catheterization data has allowed the differentiation of two subsets of patients by the identification of two different coronary controllers. Computer simulation has permitted the analysis of the relative influences of the intrathoracic and intraabdominal pressure variations on the cardiovascular variables. Depending on the coronary control of the patients, the simulation results have shown that the myocardial oxygen supply-demand relation, calculated during the simulation of high intrathoracic pressures, long duration Valsalva maneuvers, or two consecutive maneuvers, gets values higher or lower than unity. These results suggest, respectively, beneficial or detrimental cardiac effects on the patients.

Model studies of the contribution of ventricular interdependence to the transient changes in ventricular function with respiratory efforts.

The effects of variations in intrathoracic pressure on left ventricular function were studied using a mathematical model of the circulation. The variations in intrathoracic pressure directly affect the left ventricular afterload, and indirectly alter left ventricular filling by changing the right ventricular volume. The decrease in intrathoracic pressure with sustained inspiratory efforts increased the left ventricular afterload and thus reduced the left ventricular stroke volume. Secondary to the reduction in stroke volume, the left ventricular end systolic and end diastolic volumes increased. Decreasing intrathoracic pressure also increased the systemic venous return, thereby increasing right ventricular volume. The model predicted that an enlarged right ventricular volume would, through diastolic ventricular interdependence, immediately reduce the left ventricular end diastolic volume (which in turn reduced the left ventricular stroke volume), while through systolic ventricular interdependence it would increase left ventricular stroke volume and reduce left ventricular end systolic volume. An increased right ventricular volume would also increase right ventricular stroke volume and after a delay of a few heart beats raise left ventricular end diastolic and stroke volumes. The net effect of respiratory variations in intrathoracic pressure on left ventricular function would be a combination of these effects. Thus on sustained inspiration the left ventricular stroke volume initially decreased (left ventricular afterload and diastolic interdependence secondary to the increase in right ventricular volume partly counteracted by the effects of systolic interdependence), followed by an increase as the increased venous return reached the left ventricle. The model indicated that the response to a forced expiratory effort was not simply the opposite of the inspiratory response, since the increase in intrathoracic pressure during a forced expiration is accompanied by increases in abdominal pressure. On sustained expiration the left ventricular stroke volume initially increased, with no significant initial change in end diastolic volume. The cardiovascular response to respiration is complex, and model studies can help to isolate and identify the various components involved.

Model studies of the effects of the thoracic pressure on the circulation.

Two models of the cardiovascular system subjected to changes in intrathoracic pressure (ITP) are used to simulate the response to normal and positive pressure ventilation and the Mueller maneuver. The first model, based on our earlier model for cardiopulmonary resuscitation and cardiac assist by ITP variations, is based on lumped parameter representation of the cardiovascular system with two ventricles which function based on the time-varying elastance concept using their transmural pressures as the load. The ITP is assumed to be equally distributed in the thoracic cavity and equally affecting all cardiovascular structures within the chest. The model shows that a decrease in ITP is associated with an initial decrease in aortic pressure and flow and an increase in left ventricular end-diastolic and end-systolic volumes. A transient decrease in left ventricular volume which was suggested to occur by a few studies cannot be predicted based on this model. Such a decrease in left ventricular volume can be only predicted when a pericardial constraint is included, as done in the second model. Positive pressure interventions are associated with decreased heart volumes and cardiac output which is primarily a "preload" effect. In general the model reasonably predicts the hemodynamics as a function of the ITP changes and may be used as a tool to investigate the response of the cardiovascular system to various ITP interventions.