Hemodynamic effects of incremental lung hyperinflation.

Dynamic hyperinflation (DH) is common in chronic obstructive pulmonary disease and is associated with dyspnea and exercise intolerance. DH also has adverse cardiac effects, although the magnitude of DH and the mechanisms responsible for the hemodynamic impairment remain unclear. We hypothesized that incrementally increasing DH would systematically reduce left ventricular (LV) end-diastolic volume (LVEDV) and LV stroke volume (LVSV) because of direct ventricular interaction. Twenty-three healthy subjects (22 ± 2 yr) were exposed to varying degrees of expiratory loading to induce DH such that inspiratory capacity was decreased by 25%, 50%, 75%, and 100% (100% DH = inspiratory capacity of resting tidal volume plus inspiratory reserve volume ≈ 0.5 l). LV volumes, LV geometry, inferior vena cava collapsibility, and LV end-systolic wall stress were assessed by triplane echocardiography. 25% DH reduced LVEDV (-6 ± 5%) and LVSV (-9 ± 8%). 50% DH elicited a similar response in LVEDV (-6 ± 7%) and LVSV (-11 ± 10%) and was associated with significant septal flattening [31 ± 32% increase in the radius of septal curvature at end diastole (RSC-ED)]. 75% DH caused a larger reduction in LVEDV and LVSV (-9 ± 7% and -16 ± 10%, respectively) and RSC-ED (49 ± 70%). 100% DH caused the largest reduction in LVEDV and LVSV (-13 ± 9% and -18 ± 9%) and an increase in RSC-ED (56 ± 63%). Inferior vena cava collapsibility and LV afterload (LV end-systolic wall stress) were unchanged at all levels of DH. Modest DH (-0.6 ± 0.2 l inspiratory reserve volume) reduced LVSV because of reduced LVEDV, likely because of increased pulmonary vascular resistance. At higher levels of DH, direct ventricular interaction may be the primary cause of attenuated LVSV, as indicated by septal flattening because of a greater relative increase in right ventricular pressure and/or mediastinal constraint. NEW & NOTEWORTHY By systematically reducing inspiratory capacity during spontaneous breathing, we demonstrate that dynamic hyperinflation (DH) progressively reduces left ventricular (LV) end diastolic volume and LV stroke volume. Evidence of significant septal flattening suggests that direct ventricular interaction may be primarily responsible for the reduced LV stroke volume during DH. Hemodynamic impairment appears to occur at relatively lower levels of DH and may have important clinical implications for patients with chronic obstructive pulmonary disease.

The haemodynamic response to incremental increases in negative intrathoracic pressure in healthy humans.

NEW FINDINGS: What is the central question of this study? The haemodynamic response to incremental increases in negative intrathoracic pressure (nITP) during spontaneous breathing and the mechanisms of cardiac impairment at these levels of nITP remain unclear. What is the main finding and its importance? nITP of -20 cmH2 O or greater reduces stroke volume in healthy, spontaneously breathing supine humans due to direct ventricular interaction and increased left ventricular afterload. ABSTRACT: Negative intrathoracic pressure (nITP) generally augments venous return and left ventricular (LV) stroke volume (LVSV), though large increases in nITP, commonly seen in respiratory disease, attenuate LVSV. Despite this consistent finding, the degree of nITP required to reduce LVSV and the contributions of series and direct ventricular interaction (DVI) in mediating this response remain unclear. We hypothesized that nITP ≤-15 cmH2 O would augment LVSV, while nITP ≥-20 cmH2 O would reduce LVSV via DVI and increased afterload. Twenty-three healthy subjects were randomly given inspiratory loads during spontaneous breathing to generate -5, -10, -15, -20 and -25 cmH2 O. LV volumes, LV geometry, inferior vena cava collapsibility (cIVC) and LV end-systolic meridional wall-stress (LVESMWS) were assessed in the supine position using tri-plane echocardiography. LVSV remained unchanged up to -15 cmH2 O, but was significantly reduced at nITP ≥-20 cmH2 O (-12 ± 8% and -15 ± 11% at -20 and -25 cmH2 O, respectively, P < 0.05) due to significant reductions in LV end-diastolic volume (LVEDV), while LV end-systolic volume was unchanged. cIVC on inspiration was significantly increased at all levels of nITP, while LVESMWS only increased at -25 cmH2 O (P < 0.05). DVI, as indicated by a significant increase in the radius of septal curvature, occurred at nITP ≥-10 cmH2 O. In supine healthy humans, nITP ≤-15 cmH2 O does not significantly affect LV function, despite increased DVI. In contrast, nITP ≥-20 cmH2 O causes significant reductions in LVSV and LVEDV, which appear to be mediated by DVI and increased afterload at -25 cmH2 O. The impact of cIVC during nITP remains unclear.

Cardiopulmonary physiology: why the heart and lungs are inextricably linked.

Because the heart and lungs are confined within the thoracic cavity, understanding their interactions is integral for studying each system. Such interactions include changes in external constraint to the heart, blood volume redistribution (venous return), direct ventricular interaction (DVI), and left ventricular (LV) afterload. During mechanical ventilation, these interactions can be amplified and result in reduced cardiac output. For example, increased intrathoracic pressure associated with mechanical ventilation can increase external constraint and limit ventricular diastolic filling and, therefore, output. Similarly, high intrathoracic pressures can alter blood volume distribution and limit diastolic filling of both ventricles while concomitantly increasing pulmonary vascular resistance, leading to increased DVI, which may further limit LV filling. While LV afterload is generally considered to decrease with increased intrathoracic pressure, the question arises if the reduced LV afterload is primarily a consequence of a reduced LV preload. A thorough understanding of the interaction between the heart and lungs can be complicated but is essential for clinicians and health science students alike. In this teaching review, we have attempted to highlight the present understanding of certain salient aspects of cardiopulmonary physiology and pathophysiology, as well as provide a resource for multidisciplined health science educators and students.

Heart-lung interaction in a model of COPD: importance of lung volume and direct ventricular interaction.

Chronic obstructive pulmonary disease (COPD) is associated with dynamic lung hyperinflation (DH), increased pulmonary vascular resistance (PVR), and large increases in negative intrathoracic pressure (nITP). The individual and interactive effect of these stressors on left ventricular (LV) filling, emptying, and geometry and the role of direct ventricular interaction (DVI) in mediating these interactions have not been fully elucidated. Twenty healthy subjects were exposed to the following stressors alone and in combination: 1) inspiratory resistive loading of -20 cmH2O (nITP), 2) expiratory resistive loading to cause dynamic hyperinflation (DH), and 3) normobaric-hypoxia to increase PVR (hPVR). LV volumes and geometry were assessed using triplane echocardiography. LV stroke volume (LVSV) was reduced during nITP by 7 ± 7% (mean ± SD; P < 0.001) through a 4 ± 5% reduction in LV end-diastolic volume (LVEDV) (P = 0.002), while DH reduced LVSV by 12 ± 13% (P = 0.001) due to a 9 ± 10% reduction in LVEDV (P < 0.001). The combination of nITP and DH (nITP+DH) caused larger reductions in LVSV (16 ± 16%, P < 0.001) and LVEDV (12 ± 10%, P < 0.001) than nITP alone (P < 0.05). The addition of hPVR to nITP+DH did not further reduce LV volumes. Significant septal flattening (indicating DVI) occurred in all conditions, with a significantly greater leftward septal shift occurring with nITP+DH than either condition alone (P < 0.05). In summary, the interaction of nITP and DH reduces LV filling through DVI. However, DH may be more detrimental to LV hemodynamics than nITP, likely due to mediastinal constraint of the heart amplifying DVI.

Mechanical cardiopulmonary interactions during exercise in health and disease.

The heart and lungs are anatomically coupled through the pulmonary circulation and coexist within the sealed thoracic cavity, making the function of these systems highly interdependent. Understanding of the complex mechanical interactions between cardiac and pulmonary systems has evolved over the last century to appreciate that changes in respiratory mechanics significantly impact pulmonary hemodynamics and ventricular filling and ejection. Furthermore, given that the left and right heart share a common septum and are surrounded by the nondistensible pericardium, direct ventricular interaction is an important mediator of both diastolic and systolic performance. Although it is generally considered that cardiopulmonary interaction in healthy individuals at rest minimally affects hemodynamics, the significance during exercise is less clear. Adverse heart-lung interaction in respiratory disease is of growing interest as it may contribute to the pathogenesis of comorbid cardiovascular dysfunction and exercise intolerance in these patients. Similarly, heart failure represents a pathological uncoupling of the cardiovascular and pulmonary systems, whereby cardiac function may be impaired by the normal ventilatory response to exercise. Despite significant research contributions to this complex area, the mechanisms of cardiopulmonary interaction in the intact human and the clinical consequences of adverse interactions in common respiratory and cardiovascular diseases, particularly during exercise, remain incompletely understood. The purpose of this review is to present the key physiological principles of cardiopulmonary interaction as they pertain to resting and exercising hemodynamics in healthy humans and the clinical implications of adverse cardiopulmonary interaction during exercise in chronic obstructive pulmonary disease (COPD), pulmonary hypertension, and heart failure.

Acute volume loading exacerbates direct ventricular interaction in a model of COPD.

Volume loading increases left ventricular (LV) stroke volume (LVSV) through series interaction, but may paradoxically reduce LVSV in the presence of large increases in right ventricular (RV) afterload because of direct ventricular interaction (DVI). RV afterload is often increased in chronic obstructive pulmonary disease (COPD) as a result of pathological changes to respiratory mechanics, namely increased negative intrathoracic pressure (nITP), dynamic lung hyperinflation (DH), and increased pulmonary vascular resistance (PVR). These hallmarks of COPD negatively impact LV hemodynamics in normovolemia. However, it is unknown how these heart-lung interactions are impacted by acute volume loading. Twenty healthy subjects (23 ± 2 yr) completed the study protocol, involving acute volume loading via 20° head-down tilt (HDT) in isolation and with 1) inspiratory resistance of -20 cmH2O (HDT+nITP) and 2) nITP, expiratory resistance to induce DH and hypoxic-mediated increases in PVR (HDT+COPD model). LV volumes and geometry were assessed using triplane echocardiography. HDT significantly increased LVSV by 10 ± 10% through an 8 ± 6% increase in LV end-diastolic volume (LVEDV). HDT+nITP paradoxically decreased LVSV by 11 ± 12% and LVEDV by 6 ± 9% from supine baseline, or -14 ± 10% LVSV and -15 ± 13% LVEDV from HDT (P < 0.001). HDT+COPD model decreased LVSV (21 ± 10% and 28 ± 11%) and LVEDV (16 ± 10% and 22 ± 10%) from both supine and HDT, respectively (P < 0.001). Under all conditions, significant septal flattening (increased radius of septal curvature) occurred, indicating DVI. Thus, when RV afterload is increased and/or an external constraint to ventricular filling exists, acute volume loading appears to paradoxically reduce LVSV. These findings have important implications for understanding how volume status impacts cardiopulmonary interactions in COPD.NEW & NOTEWORTHY Volume loading may exacerbate adverse cardiopulmonary interaction in COPD; however, the mechanisms remain unclear. We found that when negative intrathoracic pressure is increased, acute volume loading paradoxically reduces stroke volume. This reduction in stroke volume is considerably greater in a model of COPD, owing to the effects of lung hyperinflation.