scholarly journals Pathophysiologic Principles in the Management of Severe PAH

2015 ◽  
Vol 13 (4) ◽  
pp. 179-184
Author(s):  
John Granton
Keyword(s):  
Treatment Options ◽  
Volume Overload ◽  
Right Heart Failure ◽  
Progressive Increase ◽  
Left Ventricular ◽  
Pulmonary Vasculature ◽  
Cross Sectional ◽  
Ventricular Afterload ◽  
The Face ◽  
The Right

In the face of tremendous advances in our understanding of the pathophysiology and new treatment options, for many patients, pulmonary arterial hypertension (PAH) remains a progressive condition. The often-relentless reduction in the cross-sectional area of the pulmonary vasculature leads to progressive increase in right ventricular (RV) afterload. Although the right ventricle can adapt to an increase in afterload, progression of the pulmonary vasculopathy in PAH causes many patients to develop progressive RV failure.1 Alternately, for those with other forms of pulmonary hypertension, worsening lung disease or cardiac disease may destabilize the RV function. Acute RV decompensation may be triggered by disorders that lead to either an acute increase in cardiac demand (such as sepsis, surgery, or pregnancy), or an increase in ventricular afterload (such as an interruption in medical therapy or pulmonary embolism), or destabilization of a compensated RV (such as arrhythmia or volume overload). The poor reserve of the RV, RV ischemia, and adverse RV influence on left ventricular filling may lead to a global reduction in oxygen delivery and multi-organ failure.2 The goals of this article are to provide an approach to right heart failure in the context of an increase in its afterload. This article will focus on pathophysiologic principles on which to build an approach to medical therapies. Mechanical and surgical strategies will be the focus in the accompanying article by Dr de Perrot.

scholarly journals Jobb kamrai adaptáció pulmonalis artériás hypertoniában

2021 ◽  
Vol 162 (37) ◽  
pp. 1485-1493
Author(s):  
Györgyi Csósza ◽  
Zsófia Lázár ◽  
Zsolt Rozgonyi ◽  
Hajnalka Vágó ◽  
György Losonczy ◽  
...  
Keyword(s):  
Heart Failure ◽  
Pulmonary Hypertension ◽  
Right Ventricular Dysfunction ◽  
Right Heart Failure ◽  
Progressive Increase ◽  
Right Heart ◽  
Cardiac Adaptation ◽  
The Face ◽  
Pulmonary Arterial ◽  
The Right

Összefoglaló. Pulmonalis artériás hypertoniában (PAH) a tüdőartériák falának átépülése az elsődleges patofiziológiai eltérés, amely a pulmonalis vascularis rezisztencia (PVR) és a pulmonalis nyomás progresszív emelkedéséhez vezet. Ez a nyomásemelkedés a jobb szívfélben az afterload fokozódásához vezet, ami hosszú távon jobbkamra-diszfunkciót és jobbszívfél-elégtelenséget okoz. Az egyre növekvő PVR mellett kialakuló cardialis adaptáció pontos patomechanizmusa nem ismert, de egyes betegek esetén nagyon eltérő lehet az adaptáció mértéke és kialakulásának üteme. A kialakuló myocardium-hypertrophia és -dilatáció mértéke nagyban függ a PAH etiológiájától, de emellett egyéb tényezők – mint az életkor, a neurohumoralis aktiváció mértéke, genetikai és epigenetikai faktorok – is jelentősen befolyásolják. Minél kevésbé képes a jobb kamra megtartani funkcióját az egyre növekvő ellenállással szemben, annál gyorsabban alakul ki a jobbszívfél-elégtelenség, és annál rosszabbak a beteg életkilátásai. Ezen folyamatok jobb megismerése klinikai jelentőséggel bír, mivel a jobb kamrai adaptáció elősegítése javíthatja a betegség kimenetelét. Orv Hetil. 2021; 162(37): 1485–1493. Summary. Remodeling of the pulmonary artery wall is the primary pathophysiological abnormality in pulmonary arterial hypertension leading to a progressive increase in pulmonary vascular resistance (PVR) and pulmonary arterial pressure. The elevation of pressure increases the afterload in the right heart, causing right ventricular dysfunction and right heart failure in the long term. The exact pathomechanism of cardiac adaptation with increasing PVR is unknown, but the degree and rate of adaptation may be very different in patients suffering from pulmonary hypertension. The development of myocardial hypertrophy and dilatation is highly dependent on the etiology of pulmonary hypertension, but is also significantly influenced by other factors such as age, degree of neurohumoral activation, and genetic and epigenetic factors. Right heart failure develops and life expectancy shortens if the right ventricle is unable to maintain its function in the face of increasing resistance. Orv Hetil. 2021; 162(37): 1485–1493.

Pulmonary Vascular Versus Right Ventricular Function Changes During Targeted Therapies of Pulmonary Hypertension – An Argument for Upfront Combination Therapy?

2012 ◽  
Vol 8 (3) ◽  
pp. 209
Author(s):  
Wouter Jacobs ◽  
Anton Vonk-Noordegraaf ◽  
◽  
Keyword(s):  
Combination Therapy ◽  
Right Ventricle ◽  
Right Ventricular ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Meta Analysis ◽  
Right Heart Failure ◽  
Functional Class ◽  
Pulmonary Vasculature ◽  
The Right

Pulmonary arterial hypertension is a progressive disease of the pulmonary vasculature, ultimately leading to right heart failure and death. Current treatment is aimed at targeting three different pathways: the prostacyclin, endothelin and nitric oxide pathways. These therapies improve functional class, increase exercise capacity and improve haemodynamics. In addition, data from a meta-analysis provide compelling evidence of improved survival. Despite these treatments, the outcome is still grim and the cause of death is inevitable – right ventricular failure. One explanation for this paradox of haemodynamic benefit and still worse outcome is that the right ventricle does not benefit from a modest reduction in pulmonary vascular resistance. This article describes the physiological concepts that might underlie this paradox. Based on these concepts, we argue that not only a significant reduction in pulmonary vascular resistance, but also a significant reduction in pulmonary artery pressure is required to save the right ventricle. Haemodynamic data from clinical trials hold the promise that these haemodynamic requirements might be met if upfront combination therapy is used.

scholarly journals Pulmonary Hypertension in Acute and Chronic High Altitude Maladaptation Disorders

2021 ◽  
Vol 18 (4) ◽  
pp. 1692
Author(s):  
Akylbek Sydykov ◽  
Argen Mamazhakypov ◽  
Abdirashit Maripov ◽  
Djuro Kosanovic ◽  
Norbert Weissmann ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
High Altitude ◽  
Clinical Experience ◽  
Current Knowledge ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Treatment Options ◽  
Right Heart Failure ◽  
Channel Blockers ◽  
The Right ◽  
Extensive Clinical Experience

Alveolar hypoxia is the most prominent feature of high altitude environment with well-known consequences for the cardio-pulmonary system, including development of pulmonary hypertension. Pulmonary hypertension due to an exaggerated hypoxic pulmonary vasoconstriction contributes to high altitude pulmonary edema (HAPE), a life-threatening disorder, occurring at high altitudes in non-acclimatized healthy individuals. Despite a strong physiologic rationale for using vasodilators for prevention and treatment of HAPE, no systematic studies of their efficacy have been conducted to date. Calcium-channel blockers are currently recommended for drug prophylaxis in high-risk individuals with a clear history of recurrent HAPE based on the extensive clinical experience with nifedipine in HAPE prevention in susceptible individuals. Chronic exposure to hypoxia induces pulmonary vascular remodeling and development of pulmonary hypertension, which places an increased pressure load on the right ventricle leading to right heart failure. Further, pulmonary hypertension along with excessive erythrocytosis may complicate chronic mountain sickness, another high altitude maladaptation disorder. Importantly, other causes than hypoxia may potentially underlie and/or contribute to pulmonary hypertension at high altitude, such as chronic heart and lung diseases, thrombotic or embolic diseases. Extensive clinical experience with drugs in patients with pulmonary arterial hypertension suggests their potential for treatment of high altitude pulmonary hypertension. Small studies have demonstrated their efficacy in reducing pulmonary artery pressure in high altitude residents. However, no drugs have been approved to date for the therapy of chronic high altitude pulmonary hypertension. This work provides a literature review on the role of pulmonary hypertension in the pathogenesis of acute and chronic high altitude maladaptation disorders and summarizes current knowledge regarding potential treatment options.

Cardiac adjustments to left-side inotropic stimulation of in situ pig hearts

1987 ◽  
Vol 252 (6) ◽  
pp. H1164-H1174
Author(s):  
O. A. Vengen ◽  
K. Lande ◽  
O. Ellingsen ◽  
A. Ilebekk
Keyword(s):  
Right Ventricular ◽  
Systemic Circulation ◽  
Left Ventricular ◽  
Segment Length ◽  
Ventricular Afterload ◽  
Computer Based ◽  
The Right ◽  
Isoproterenol Infusion ◽  
Inotropic Stimulation ◽  
Stimulation Of

Cardiac adjustments to inotropic stimulation of the left side of the heart by continuous infusions of isoproterenol (0.6-0.8 microgram/min) and calcium chloride (240 mumol/min) into the left coronary artery were examined in open-chest pigs (17-36 kg) anesthetized with pentobarbital sodium. Both agents caused a reduction in the left ventricular (LV) preload and preejection segment length (PESL). Stroke volume (SV) rose by only 1.2 ml from 15.9 ml (P less than 0.01) during isoproterenol infusion, but when the reduction in LV PESL of 3.2% (P less than 0.01) was restored by saline infusion, SV increased by 27%. The LV PESL reduction was less at hypervolemia than at normovolemia. A computer-based model of the circulation predicted most of these changes and suggested redistribution of blood from the pulmonary to the systemic circulation. During isoproterenol infusion, the pulmonary arterial pressure fell, and the right ventricular end-ejection segment length declined. Reduced right ventricular afterload thus appears to be an important mechanism by which right ventricular output is increased during a selective increase in LV inotropy.

Echocardiographic assessment of LV mass in rabbits: models of pressure and volume overload hypertrophy

1993 ◽  
Vol 265 (6) ◽  
pp. H2066-H2072 ◽  
Author(s):  
J. F. Plehn ◽  
E. Foster ◽  
W. N. Grice ◽  
M. Huntington-Coats ◽  
C. S. Apstein
Keyword(s):  
Pressure Overload ◽  
Volume Overload ◽  
Accurate Method ◽  
Aortic Insufficiency ◽  
Left Ventricular ◽  
Cross Sectional ◽  
Group I ◽  
Lv Mass ◽  
Wet Weight ◽  
Group Ii

We describe a method for the noninvasive measurement of left ventricular mass in small animals using two-dimensionally guided M-mode echocardiography. We compared echocardiographic cross-sectional area (CSA) and cubed-based volumetric indexes of left ventricular (LV) mass with postmortem wet weight in renovascular hypertension-induced pressure overload (group I) and acute aortic insufficiency-induced volume overload (group II) models of ventricular hypertrophy. CSA and cubed echocardiographic indexes correlated well with wet weight from a combination of group I and II animals and their controls (r = 0.89, P < 0.001 for both groups). Separate analyses of groups I and II also demonstrated significant relationships between mass indexes and wet weight using CSA and cubed formulas, respectively, in both pressure (r = 0.57, P = 0.01 and r = 0.71, P < 0.001) and volume (r = 0.90 and r = 0.89, P < 0.001) overload models. Echocardiographically predicted LV mass derived from cubed and CSA regression formulas was 89 and 56% sensitive for pressure overload hypertrophy in group I and 100% sensitive (both cubed and CSA methods) for volume overload hypertrophy in group II. Cubed and CSA mass regression formulas were 60 and 80% specific for hypertrophy in group I and 100 and 90% specific in group II. Normalization of predicted LV mass for body weight added little to the overall technique accuracy with measured sensitivities of 83 and 75% and specificities of 92 and 77%, respectively, for cubed and CSA methods. Two-dimensionally guided M-mode echocardiography provides a reasonably accurate method of LV mass determination in rabbits with pressure- or volume-overloaded ventricles.

Cardiac interstitial bradykinin and mast cells modulate pattern of LV remodeling in volume overload in rats

2003 ◽  
Vol 285 (2) ◽  
pp. H784-H792 ◽  
Author(s):  
Chih-Chang Wei ◽  
Pamela A. Lucchesi ◽  
Jose Tallaj ◽  
Wayne E. Bradley ◽  
Pamela C. Powell ◽  
...  
Keyword(s):  
Mast Cells ◽  
Enzyme Inhibitor ◽  
Weight Ratio ◽  
Volume Overload ◽  
Left Ventricular ◽  
Ang Ii ◽  
Cross Sectional ◽  
Important Interaction ◽  
Lv Remodeling ◽  
Hoe 140

In the current study, interstitial fluid (ISF), bradykinin (BK), and angiotensin II (ANG II) levels were measured using cardiac microdialysis in conscious, nonsedated rats at baseline and at 48 h and 5 days after each of the following: sham surgery (sham, n = 6), sham + administration of ANG-converting enzyme inhibitor ramipril (R, n = 6), creation of aortocaval fistula (ACF, n = 6), ACF + R ( n = 6), and ACF + R + BK2 receptor antagonist (HOE-140) administration ( n = 6). At 5 days, both ISF ANG II and BK increased in ACF rats ( P < 0.05); however, in ACF + R rats, ISF ANG II did not differ from basal levels and ISF BK increased greater than threefold above baseline at 2 and 5 days ( P < 0.05). Five days after ACF, the left ventricular (LV) weight-to-body weight ratio increased 30% ( P < 0.05) in ACF but did not differ from sham in ACF + R and ACF + R + HOE-140 rats despite similar systemic arterial pressures across all ACF groups. However, ACF + R + HOE-140 rats had greater postmortem wall thickness-to-diameter ratio and smaller cross-sectional diameter compared with ACF + R rats. There was a significant increase in mast cell density in ACF and ACF + R rats that decreased below sham in ACF + R + HOE-140 rats. These results suggest a potentially important interaction of mast cells and BK in the cardiac interstitium that modulates the pattern of LV remodeling in the acute phase of volume overload.

scholarly journals Epigenetics, inflammation and metabolism in right heart failure associated with pulmonary hypertension

2017 ◽  
Vol 7 (3) ◽  
pp. 572-587 ◽  
Author(s):  
Nolwenn Samson ◽  
Roxane Paulin
Keyword(s):  
Left Ventricle ◽  
Right Ventricle ◽  
Right Ventricular ◽  
Pressure Overload ◽  
Right Heart Failure ◽  
Left Ventricular ◽  
Ventricular Failure ◽  
Pulmonary Arterial ◽  
Ventricle Hypertrophy ◽  
The Right

Right ventricular failure (RVF) is the most important prognostic factor for both morbidity and mortality in pulmonary arterial hypertension (PAH), but also occurs in numerous other common diseases and conditions, including left ventricle dysfunction. RVF remains understudied compared with left ventricular failure (LVF). However, right and left ventricles have many differences at the morphological level or the embryologic origin, and respond differently to pressure overload. Therefore, knowledge from the left ventricle cannot be extrapolated to the right ventricle. Few studies have focused on the right ventricle and have permitted to increase our knowledge on the right ventricular-specific mechanisms driving decompensation. Here we review basic principles such as mechanisms accounting for right ventricle hypertrophy, dysfunction, and transition toward failure, with a focus on epigenetics, inflammatory, and metabolic processes.

Portopulmonary Hypertension

2017 ◽  
Vol 38 (05) ◽  
pp. 651-661 ◽  
Author(s):  
Jason Watherald ◽  
Olivier Sitbon ◽  
Laurent Savale
Keyword(s):  
Heart Failure ◽  
Portal Hypertension ◽  
Right Heart Failure ◽  
Pulmonary Vasculature ◽  
Heart Catheterization ◽  
Portopulmonary Hypertension ◽  
Right Heart ◽  
Pulmonary Hemodynamics ◽  
Ventricular Afterload ◽  
The Impact

AbstractPortal hypertension may have major consequences on the pulmonary vasculature due to complex pathophysiological interactions between liver and lungs. Portopulmonary hypertension (PoPH) is characterized by the association of portal hypertension and pulmonary arterial hypertension (PAH). As progressive elevation of right ventricular afterload can lead to right heart failure, PoPH is a serious complication of portal hypertension, affecting functional status and prognosis of patients. Early detection by transthoracic echocardiography must be performed in symptomatic patients and in candidates for liver transplantation (LT). Right heart catheterization remains mandatory to confirm the diagnosis and exclude all other causes of elevated pulmonary pressures. The management of PoPH includes PAH-targeted therapies although few studies have evaluated these medications in this specific indication. The impact of LT on PoPH outcome remains complex and must be specified by future collaborative investigation. Although uncontrolled PoPH is associated with higher risk of postoperative right heart failure and death, stabilization, improvement, or normalization of pulmonary hemodynamics after LT seem to be achievable goals in selected patients with PoPH.

scholarly journals The Basic Science of Metabolism in Pulmonary Arterial Hypertension

2018 ◽  
Vol 17 (3) ◽  
pp. 95-102 ◽  
Author(s):  
Andrea L. Frump ◽  
Tim Lahm
Keyword(s):  
Skeletal Muscle ◽  
Right Heart Failure ◽  
Inflammatory Cells ◽  
Therapeutic Interventions ◽  
Pulmonary Vasculature ◽  
Metabolic Theory ◽  
Metabolic Defects ◽  
Metabolic Remodeling ◽  
Common Etiology ◽  
The Right

Pulmonary hypertension (PH) encompasses a group of progressive and incurable cardiopulmonary disorders characterized by pulmonary vascular remodeling and increased mean pulmonary artery pressure leading to right heart failure. Emerging data suggest a common etiology for the reported diverse molecular and physiological abnormalities observed in the pulmonary vasculature: the metabolic theory of PH. This theory proposes that aberrations in metabolism and mitochondrial function are a major underlying cause for the cellular and organ level PH phenotype. Additionally, the metabolic theory of PH provides a rationale for the observed metabolic defects in other organs and systems outside of the pulmonary vasculature, including the right ventricle (RV), immune system, and skeletal muscle. However, whether these metabolic changes are driving disease and the timing and extent of these aberrations are still unknown. This review highlights: 1) key examples of metabolic alterations in the pulmonary vasculature, RV, inflammatory cells, and skeletal muscle; 2) examples of promising therapeutic interventions directly modifying metabolism; and 3) key remaining questions about the role of metabolic remodeling in PH.

scholarly journals Smouldering fire or conflagration? An illustrated update on the concept of inflammation in pulmonary arterial hypertension

2021 ◽  
Vol 30 (162) ◽  
pp. 210161
Author(s):  
Frédéric Perros ◽  
Marc Humbert ◽  
Peter Dorfmüller
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Rare Condition ◽  
Progressive Increase ◽  
Pulmonary Vasculature ◽  
Ventricular Failure ◽  
Myocardial Remodelling ◽  
Pulmonary Arterial ◽  
The Right

Pulmonary arterial hypertension (PAH) is a rare condition that is characterised by a progressive increase of pulmonary vascular resistances that leads to right ventricular failure and death, if untreated. The underlying narrowing of the pulmonary vasculature relies on several independent and interdependent biological pathways, such as genetic predisposition and epigenetic changes, imbalance of vasodilating and vasoconstrictive mediators, as well as dysimmunity and inflammation that will trigger endothelial dysfunction, smooth muscle cell proliferation, fibroblast activation and collagen deposition. Progressive constriction of the pulmonary vasculature, in turn, initiates and sustains hypertrophic and maladaptive myocardial remodelling of the right ventricle. In this review, we focus on the role of inflammation and dysimmunity in PAH which is generally accepted today, although existing PAH-specific medical therapies still lack targeted immune-modulating approaches.

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