Generation Of Negative Intrathoracic Pressure Research Articles

Mechanisms of inspiration that modulate cardiovascular control: the other side of breathing.

The objective of this minireview is to describe the physiology and potential clinical benefits derived from inspiration. Recent animal and clinical studies demonstrate that one of the body's natural mechanisms associated with inspiration is to harness the respiratory pump to enhance circulation to vital organs. There is evidence that large reductions in intrathoracic pressure (>20 cmH2O) caused by some inspiration maneuvers (e.g., Mueller maneuver) or pathophysiology (e.g., heart failure, chronic obstructive lung disease) can result in adverse hemodynamic effects. However, the respiratory pump can improve cardiovascular functions when a "sweet spot" for generation of negative intrathoracic pressure during inspiration can be maintained at or less than 10 cmH2O below normal inspiration. These beneficial physiological effects include greater cardiac filling and output, lower intracranial pressure, cardiac baroreflex resetting, greater cerebral blood flow oscillatory patterns, increased vascular pressure gradients, and promoting sustained feedback between sympathetic nerve activity and arterial pressure. In addition to promoting gas exchange, data obtained from numerous animal and human experiments have provided new insights into "the other side of breathing": the modulation of circulation by reduced intrathoracic pressure generated during inspiration. The translation of these physiological relationships form the basis for the development and application of technologies designed to optimize the intrathoracic pump for treatment of clinical conditions associated with hypovolemia including cardiac arrest, orthostatic hypotension, hemorrhagic shock, and traumatic brain injury. Harnessing these fundamental mechanisms that control cardiopulmonary physiology provides opportunities to use inspiration as a potential tool to help treat significant and often life-threatening circulatory disorders.

Cardiac rhythm disorders in obstructive sleep apnea.

Obstructive sleep apnea (OSA) is common among patients with cardiac rhythm disorders. OSA may contribute to arrhythmias due to acute mechanisms, such as generation of negative intrathoracic pressure during futile efforts to breath, intermittent hypoxia, and surges in sympathetic activity. In addition, OSA may lead to heart remodeling and increases arrhythmia susceptibility. Atrial distension and remodeling, that has been shown to be associated with OSA, is a well-known anatomical substrate for atrial fibrillation (AF). AF is the arrhythmia most commonly described in patients with OSA. Several observational studies have shown that the treatment of OSA with continuous positive airway pressure (CPAP) reduces recurrence of AF after electrical cardioversion and catheter ablation. There is also evidence that nocturnal hypoxemia, a hallmark of OSA, predicts sudden cardiac death (SCD) independently of well-established cardiovascular risk factors. Among patients with an implantable cardiac defibrillator, those with OSA have a higher risk of receiving treatment for life-threatening arrhythmias. Nocturnal hypoxemia may also increase vagal tone, which increases susceptibility to bradycardic and conduction rhythm disorders that have also been described in patients with OSA. In conclusion, there are several biological pathways linking OSA and increased cardiac arrhythmogenesis propensity. However, the independent association is derived from observational studies and the direction of the association still needs clarification due to the lack of large clinical trials. This review focuses on the current scientific evidence linking OSA to cardiac rhythm disorders and point out future directions.

Hiccups and amniotic fluid regulation in early pregnancy

Hiccups are an unexplained phenomenon and a subject of medical curiosity. They arise through a reflex arc with central control at the level of the medulla, and their primary physiological effect is the generation of negative intra-thoracic pressure. This paper presents the hypothesis that hiccups serve a purpose during the first half of gestation, when they are most prevalent; namely, that they promote amniotic fluid influx to the primitive gut, allowing fluid to be transferred to the foetal and then maternal vasculature. Furthermore, hiccups could be provoked by increasing amniotic fluid volume and pressure, and act in a regulatory capacity. This hypothesis could be tested by studying foetal movements in the first half of gestation, and assessing whether there is correlation with amniotic fluid flux in the developing gut. Ascertaining whether hiccups increase in frequency with increasing amniotic fluid volume would provide evidence for or against a regulatory function.

Overnight Effects of Obstructive Sleep Apnea and Its Treatment on Stroke Volume in Patients With Heart Failure

BackgroundWe previously showed in heart failure (HF) patients that obstructive respiratory events during sleep and generation of negative intrathoracic pressure during Mueller manoeuvres, mimicking obstructive apneas, acutely reduced stroke volume (SV). We also showed that treating obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) increased left ventricular ejection fraction over a 1-month period. We therefore hypothesized that, in HF patients, those with OSA would have greater overnight declines in SV and cardiac output (CO) than in those without sleep apnea, and that therapy of OSA using CPAP would prevent these declines. MethodsWe examined overnight percent change in SV and CO in 32 HF patients with and 28 without OSA using digital photoplethysmography. Among patients with OSA, we also examined changes in SV and CO during a CPAP titration study. ResultsDuring the baseline polysomnogram SV and CO decreased more overnight in those with OSA than in those without sleep apnea (−12.6 ± 7.7% vs −3.2 ± 6.8%; P < 0.001 and −16.2 ± 9.9% vs −3.7 ± 8.3%; P < 0.001, respectively). Overnight changes in SV and CO correlated inversely with total apnea-hypopnea index (r = −0.551; P < 0.001 and r = −0.522; P < 0.001, respectively). In 21 patients with OSA, CPAP reduced the total apnea-hypopnea index from 37.7 ± 21.4 to 15.0 ± 16.0 (P < 0.001) in association with attenuation of the overnight reduction of SV (from −14.0 ± 7.9% to −3.4 ± 9.8%; P = 0.002) and CO (from −17.2 ± 9.0% to −9.7 ± 10.7%; P = 0.042). ConclusionsIn patients with HF, coexisting OSA causes overnight declines in SV and CO that are prevented through reversal of OSA by CPAP.

Amélioration de la perfusion des organes vitaux par la valve d’impédance inspiratoire et le concept de pompe respiratoire : rationnel physiologique et application clinique

ObjectiveIn this article, we review the effects of the respiratory pump to improve vital organ perfusion by the use of an inspiratory threshold device. Data sourcesMedline and MeSH database. Study selectionAll papers with a level of proof of I to III have been used. Data extractionThe analysis of the papers has focused on the physiological modifications induced by intrathoracic pressure regulation. Data synthesisPrimary function of breathing is to provide gas exchange. Studies of the mechanisms involved in animals and humans provide the physiological underpinnings for “the other side of breathing”: to increase circulation to the heart and brain. We describe studies that focus on the fundamental relationship between the generation of negative intrathoracic pressure during inspiration through a low-level of resistance created by an impedance threshold device and the physiologic effects of a respiratory pump. A decrease in intrathoracic pressure during inspiration through a fixed resistance resulting in an intrathoracic pressure of −7 cmH2O has multiple physiological benefits including: enhanced venous return, cardiac stroke volume and aortic blood pressure; lower intracranial pressure; resetting of the cardiac baroreflex; elevated cerebral blood flow oscillations and increased tissue blood flow/pressure gradient. ConclusionThe clinical and animal studies support the use of the intrathoracic pump to treat different clinical conditions: hemorrhagic shock, orthostatic hypotension, septic shock, and cardiac arrest.

Improved cerebral perfusion pressures and 24-hr neurological survival in a porcine model of cardiac arrest with active compression-decompression cardiopulmonary resuscitation and augmentation of negative intrathoracic pressure*

Generation of negative intrathoracic pressure during the decompression phase of cardiopulmonary resuscitation enhances the refilling of the heart. We tested the hypothesis that when compared with closed-chest manual compressions at 80 chest compressions per min, treatment with active compression-decompression cardiopulmonary resuscitation at 80 chest compressions/min combined with augmentation of negative intrathoracic pressure would lower intracranial pressure and increase cerebral perfusion, thereby improving neurologically intact survival rates following prolonged untreated cardiac arrest. Prospective, randomized animal study. Animal laboratory facilities. A total of 26 female farm pigs in two different protocols (n = 17 and n = 9). Seventeen pigs were subjected to 8.5 mins of untreated ventricular fibrillation and prospectively randomized to cardiopulmonary resuscitation at 80 chest compressions/min or active compression-decompression cardiopulmonary resuscitation at 80 chest compressions/min plus an impedance threshold device. Coronary perfusion pressures (29.5 ± 2.7 mm Hg vs. 22.4 ± 1.6 mm Hg, p = .03), carotid blood flow (44.0 ± 12.2 vs. 30.9 ± 10.4, p = .03), and 24-hr neurological survival (88% vs. 22%, p = .015) were higher with active compression-decompression cardiopulmonary resuscitation + an impedance threshold device. Cerebral perfusion pressures, measured in nine additional pigs, were improved with active compression-decompression cardiopulmonary resuscitation + an impedance threshold device (21.9 ± 1.2 mm Hg vs. 8.9 ± 0.8 mm Hg, p < .0001). With active compression-decompression cardiopulmonary resuscitation + impedance threshold device, mean diastolic intracranial pressure during decompression was lower (12.2 ± 0.2 mm Hg vs. 16.6 ± 1.2 mm Hg, p = .02) and the downward slope of the decompression phase intracranial pressure curve was steeper (-60.3 ± 12.9 mm Hg vs. -46.7 ± 11.1 mm Hg/sec, p < .001). Active compression-decompression cardiopulmonary resuscitation + an impedance threshold device increased cerebral perfusion pressures and lowered diastolic intracranial pressure and intracranial pressure rate during the decompression phase. These mechanisms may underlie the observed increase in cerebral perfusion pressure, carotid blood flow, and survival rates with favorable neurologic outcomes in this pig model of cardiac arrest.

Optimizing the Respiratory Pump: Harnessing Inspiratory Resistance to Treat Systemic Hypotension

We review the physiology and affects of inspiration through a low level of added resistance for the treatment of hypotension. Recent animal and clinical studies demonstrated that one of the body's natural response mechanisms to hypotension is to harness the respiratory pump to increase circulation. That finding is consistent with observations, in the 1960s, about the effect of lowering intrathoracic pressure on key physiological and hemodynamic variables. We describe studies that focused on the fundamental relationship between the generation of negative intrathoracic pressure during inspiration through a low level of resistance created by an impedance threshold device and the physiologic sequelae of a respiratory pump. A decrease in intrathoracic pressure during inspiration through a fixed resistance resulting in a pressure difference of 7 cm H(2)O has multiple physiological benefits, including: enhanced venous return and cardiac stroke volume, lower intracranial pressure, resetting of the cardiac baroreflex, elevated cerebral blood flow oscillations, increased tissue blood flow/pressure gradient, and maintenance of the integrity of the baroreflex-mediated coherence between arterial pressure and sympathetic nerve activity. While breathing has traditionally been thought primarily to provide gas exchange, studies of the mechanisms involved in animals and humans provide the physiological underpinnings for "the other side of breathing": to increase circulation to the heart and brain, especially in the setting of physiological stress. The existing results support the use of the intrathoracic pump to treat clinical conditions associated with hypotension, including orthostatic hypotension, hypotension during and after hemodialysis, hemorrhagic shock, heat stroke, septic shock, and cardiac arrest. Harnessing these fundamental mechanisms that control cardiopulmonary physiology provides new opportunities for respiratory therapists and others who have traditionally focused on ventilation to also help treat serious and often life-threatening circulatory disorders.

Heavy Snoring and Carotid Atherosclerosis: Is There More Than an Association?

THERE IS GROWING EVIDENCE SUGGESTING THAT OBSTRUCTIVE SLEEP APNEA (OSA) PROMOTES VASCULAR ENDOTHELIAL DYSFUNCTION AND atherosclerosis.1 OSA stimulates several intermediate pathways that are harmful to the cardiovascular system and includes sympathetic activation, increased production of reactive oxygen species, inflammatory mediators and lipid metabolism. The primary mechanisms by which OSA triggers cardiovascular disease include intermittent hypoxia, generation of negative intrathoracic pressure during occluded breaths and arousals from sleep.2 All these disturbances are entangled, and it is difficult to isolate the relative importance of each factor. In this context, we read with much interest the recent work by Lee et al. that provided evidence that snoring should be also regarded as a primary mechanism for the genesis of carotid atherosclerosis.3 The rationale is that the vibration during snoring is transmitted through the surrounding tissues to the carotid artery wall triggering an inflammatory cascade leading to early changes of atherosclerosis. This concept may to some extent parallel the vascular lesions observed in subjects submitted to prolonged exposure to hand-transmitted vibration.4 Lee et al. studied 110 participants, with 107 community volunteers and 3 patients undergoing diagnostic polysomnography for suspected OSA.3 The authors found that heavy snoring was significantly associated with carotid atherosclerosis but not with femoral atherosclerosis even after adjustments for potential confounding factors. Although there are important strengths in the Lee study, including the objective measurement of snoring during polysomnography and the evaluation of vascular parameters in the femoral bed (therefore a distant site from the upper airway), we were particularly concerned with the overinterpretation of the data as suggested by the title: “snoring causes carotid atherosclerosis.” First, the study is a cross-sectional design, which makes it impossible to establish a cause-effect relationship between heavy snoring and atherosclerosis. Although there is biological plausibility and a dose-response relationship, it will be necessary to demonstrate that the elimination of snoring reverses carotid atherosclerosis. Second, this study did not involve patients with primary snoring. Instead, there were several patients with OSA (particularly in patients with heavy snoring), and the relative importance of sleep parameters such as apnea-hypopnea index and other hypoxic parameters are not clear in the multivariate logistic regression (Table 2). Third, as acknowledged by the authors, the sample was neither representative of the general population nor of an OSA population, and therefore the results should be interpreted with caution. Finally, the relative impact of snoring on cardiovascular outcomes remains to be established. For instance, in the Spanish cohort study, Marin et al. found no increase risk of fatal and non-fatal cardiovascular events in the subset of 377 patients with primary snoring.5 In conclusion, the current relationship between heavy snoring and carotid atherosclerosis is an exciting new area of research. However, the conclusion so far is that there is an independent association between snoring and carotid atherosclerosis. Future treatment studies focusing on patients with primary snoring and the impact of snoring treatment on atherosclerosis of the carotid arteries should be performed in order to clarify this relationship.

Effects of incomplete chest wall decompression during cardiopulmonary resuscitation on coronary and cerebral perfusion pressures in a porcine model of cardiac arrest

Introduction: Recent data suggest that generation of negative intrathoracic pressure during the decompression phase of CPR improves hemodynamics, organ perfusion and survival. Hypothesis: Incomplete chest wall recoil during the decompression phase of standard CPR increases intrathoracic pressure and right atrial pressure, impedes venous return, decreases compression-induced aortic pressures and results in a decrease of mean arterial pressure, coronary and cerebral perfusion pressure. Methods: Nine pigs in ventricular fibrillation (VF) for 6 min, were treated with an automated compression/decompression device with a compression rate of 100 min −1, a depth of 25% of the anterior–posterior diameter, and a compression to ventilation ratio of 15:2 with 100% decompression (standard CPR) for 3 min. Compression was then reduced to 75% of complete decompression for 1 min of CPR and then restored for another 1 min of CPR to 100% full decompression. Coronary perfusion pressure (CPP) was calculated as the diastolic (aortic (Ao)–right atrial (RA) pressure). Cerebral perfusion pressure (CerPP) was calculated multiple ways: (1) the positive area (in mmHg s) between aortic pressure and intracranial pressure (ICP) waveforms, (2) the coincident difference in systolic and diastolic aortic and intracranial pressures (mmHg), and (3) CerPP = MAP − ICP. ANOVA was used for statistical analysis and all values were expressed as mean ± S.E.M. The power of the study for an alpha level of significance set at 0.05 was >0.90. Results: With CPR performed with 100%–75%–100% of complete chest wall recoil, respectively, the CPP was 23.3 ± 1.9, 15.1 ± 1.6, 16.6 ± 1.9, p = 0.003; CerPP was: (1) area: 313.8 ± 104, 89.2 ± 39, 170.5 ± 42.9, p = 0.03, (2) systolic aortic minus intracranial pressure difference: 22.8 ± 3.6, 16.5 ± 4, 23.7 ± 4.5, p = n.s., and diastolic pressure difference: 5.7 ± 3, −2.4 ± 2.4, 3.2 ± 2.5, p = 0.04 and (3) mean: 14.3 ± 3, 7 ± 2.9, 12.4 ± 2.9, p = 0.03, diastolic aortic pressure was 28.1 ± 2.5, 20.7 ± 1.9, 20.9 ± 2.1, p = 0.0125; ICP during decompression was 22.8 ± 1.7, 23 ± 1.5, 19.7 ± 1.7, p = n.s. and mean ICP was 37.1 ± 2.3, 35.5 ± 2.2, 35.2 ± 2.4, p = n.s.; RA diastolic pressure 4.8 ± 1.3, 5.6 ± 1.2, 4.3 ± 1.2 p = 0.1; MAP was 52 ± 2.9, 43.3 ± 3, 48.3 ± 2.9, p = 0.04; decompression endotracheal pressure, −0.7 ± 0.1, −0.3 ± 0.1, −0.75 ± 0.1, p = 0.045. Conclusions: Incomplete chest wall recoil during the decompression phase of CPR increases endotracheal pressure, impedes venous return and decreases mean arterial pressure, and coronary and cerebral perfusion pressures.

Hemodynamic Effects of Simulated Obstructive Apneas in Humans With and Without Heart Failure

To determine whether generation of negative intrathoracic pressure during apnea would cause more pronounced and sustained reductions in cardiac output in patients with congestive heart failure (CHF) than in healthy subjects. Physiologic intervention study. Cardiorespiratory physiology laboratory. Nine patients with CHF and nine healthy control subjects matched for age and sex. Patients with CHF and healthy subjects generated - 30 cm H(2)O of intrathoracic pressure during 15-s Mueller maneuvers (MMs) to simulate the acute hemodynamic effects and aftereffects of obstructive apneas. In both groups, MMs caused an immediate rise in left ventricular transmural pressure during systole (LVPtmsys) [p < 0.05], but in CHF patients, this immediate increase was followed by a significant drop in LVPtmsys (p < 0.05), associated with significantly greater reductions in systolic BP and cardiac index than in healthy subjects (- 25 +/- 3 mm Hg vs - 11 +/- 2 mm Hg [p < 0.05] and - 0.53 +/- 0.11 L/min/m(2) vs - 0.15 +/- 0.11 L/min/m(2) [p < 0.05], respectively). Healthy subjects recovered promptly, but in CHF patients, these adverse hemodynamic effects were sustained following release of the MM. CHF patients experience more pronounced and sustained reductions in BP and cardiac output both during and following the MM than do healthy subjects. These findings suggest the potential for adverse hemodynamic effects and aftereffects of negative intrathoracic pressure generation during obstructive sleep apnea in patients with CHF.

Magnitude and time course of hemodynamic responses to Mueller maneuvers in patients with congestive heart failure.

To simulate the immediate hemodynamic effect of negative intrathoracic pressure during obstructive apneas in congestive heart failure (CHF), without inducing confounding factors such as hypoxia and arousals from sleep, eight awake patients performed, at random, 15-s Mueller maneuvers (MM) at target intrathoracic pressures of -20 (MM -20) and -40 cmH2O (MM -40), confirmed by esophageal pressure, and 15-s breath holds, as apneic time controls. Compared with quiet breathing, at baseline, before these interventions, the immediate effects [first 5 cardiac cycles (SD), P values refer to MM -40 compared with breath holds] of apnea, MM -20, and MM -40 were, for left ventricular (LV) systolic transmural pressure (Ptm), 1.0 +/- 1. 9, 7.2 +/- 3.5, and 11.3 +/- 6.8 mmHg (P < 0.01); for systolic blood pressure (SBP), 2.9 +/- 2.6, -5.5 +/- 3.4, and -12.1 +/- 6.8 mmHg (P < 0.01); and for stroke volume (SV) index, 0.4 +/- 2.8, -4.1 +/- 2.8, and -6.9 +/- 2.3 ml/m2 (P < 0.001), respectively. Corresponding values over the last five cardiac cycles were for LVPtm 6.4 +/- 4.4, 5.4 +/- 6.6, and -4.5 +/- 9.1 mmHg (P < 0.01); for SBP 6.9 +/- 4.2, -8.2 +/- 7.7, and -24.2 +/- 6.9 mmHg (P < 0.01); and for SV index -0. 4 +/- 2.1, -5.2 +/- 2.8, and -9.2 +/- 4.8 ml/m2 (P < 0.001), respectively. Thus, in CHF patients, the initial hemodynamic response to the generation of negative intrathoracic pressure includes an immediate increase in LV afterload and an abrupt fall in SV. The magnitude of response is proportional to the intensity of the MM stimulus. By the end of a 15-s MM -40, LVPtm falls below baseline values, yet SV and SBP do not recover. Thus, when -40 cmH2O intrathoracic pressure is sustained, additional mechanisms, such as a drop in LV preload due to ventricular interaction, are engaged, further reducing SV. The net effect of MM -40 was a 33% reduction in SV index (from 27 to 18 ml/min2), and a 21% reduction in SBP (from 121 to 96 mmHg). Obstructive apneas can have adverse effects on systemic and, possibly, coronary perfusion in CHF through dynamic mechanisms that are both stimulus and time dependent.

Effects of changes in central venous pressure on upper airway size in patients with obstructive sleep apnea.

Intraluminal airway pressure and pharyngeal muscle activity are widely recognized as major determinants of the size and collapsibility of the upper airway. In addition, changes in the volume or pressure of tissue surrounding the pharyngeal airway may significantly influence its size. The present study used fast computed tomography (CT) to determine the effects of changes in central venous pressure (CVP) on upper airway size. Ten awake male patients with obstructive sleep apnea (OSA) were studied. Scans were performed at functional residual capacity (FRC) and at the end of a tidal inspiration (VTei) under three conditions of CVP: (1) at baseline (CVP nl) with patients lying supine; (2) at decreased CVP (CVP-) by inflating blood pressure cuffs to 40 mm Hg on both legs; and (3) at increased CVP (CVP+) by elevating both legs to 33 degrees. At FRC, changes in CVP had no significant effect on either mean or minimum cross-sectional area (CSA) of the upper airway. In contrast, an analysis of variance (ANOVA) indicated that alterations in CVP were associated with changes in mean CSA (p = 0.03) and to a lesser extent in minimum CSA (p = 0.07) at VTei. With the legs elevated (CVP+), neither mean nor minimum CSA showed any significant change with tidal breathing. However, after leg-cuff inflation (CVP-), highly significant increases in both mean (163 +/- 22 to 218 +/- 19 mm2, p = 0.001) and minimum (48 +/- 8 to 85 +/- 12 mm2, p = 0.02) CSA were detected. Changes in mean and minimum CSA with tidal breathing at baseline (CVP nl) were intermediate. These results indicate that changes in CVP significantly alter the response of the upper airway to tidal breathing. They further suggest that increases in upper airway size with tidal breathing may be related to reduction in venous blood volume in pharyngeal and neck tissues as the generation of negative intrathoracic pressure during inspiration increases venous return to the chest.