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Cardiovascular Research Aug 2023The contribution of the right ventricle (RV) to cardiac output is negligible in normal resting conditions when pressures in the pulmonary circulation are low. However,...
The contribution of the right ventricle (RV) to cardiac output is negligible in normal resting conditions when pressures in the pulmonary circulation are low. However, the RV becomes relevant in healthy subjects during exercise and definitely so in patients with increased pulmonary artery pressures both at rest and during exercise. The adaptation of RV function to loading rests basically on an increased contractility. This is assessed by RV end-systolic elastance (Ees) to match afterload assessed by arterial elastance (Ea). The system has reserve as the Ees/Ea ratio or its imaging surrogate ejection fraction has to decrease by more than half, before the RV undergoes an increase in dimensions with eventual increase in filling pressures and systemic congestion. RV-arterial uncoupling is accompanied by an increase in diastolic elastance. Measurements of RV systolic function but also of diastolic function predict outcome in any cause pulmonary hypertension and heart failure with or without preserved left ventricular ejection fraction. Pathobiological changes in the overloaded RV include a combination of myocardial fibre hypertrophy, fibrosis and capillary rarefaction, a titin phosphorylation-related displacement of myofibril tension-length relationships to higher pressures, a metabolic shift from mitochondrial free fatty acid oxidation to cytoplasmic glycolysis, toxic lipid accumulation, and activation of apoptotic and inflammatory signalling pathways. Treatment of RV failure rests on the relief of excessive loading.
Topics: Humans; Heart Ventricles; Stroke Volume; Ventricular Function, Left; Hypertension, Pulmonary; Pulmonary Circulation; Ventricular Function, Right; Ventricular Dysfunction, Right; Pulmonary Artery
PubMed: 37463510
DOI: 10.1093/cvr/cvad108 -
Comprehensive Physiology Sep 2021Pulmonary arterial hypertension (PAH) is a rare disease characterized by an obliterative vasculopathy of the distal pulmonary circulation that results in severe... (Review)
Review
Pulmonary arterial hypertension (PAH) is a rare disease characterized by an obliterative vasculopathy of the distal pulmonary circulation that results in severe elevation in pulmonary pressure and pulmonary vascular resistance. PAH is a progressive and devastating disease that usually results in right heart failure and death. Currently available medications have only moderate effects and none are curative. Thus, there is a pressing need for new pharmacologic approaches to this disease. In order to meaningfully advance the treatment of PAH, new agents must target the underlying cause of disease induction and progression. This review discusses the extensive work that has been done in the areas of altered glucose metabolism, tyrosine kinase inhibitions, signaling pathways associated with disease causing gene mutations such as the bone morphogenic protein receptor 2, and inflammation and immunomodulation including the effects of mesenchymal stem cells and the extracellular vesicles they secrete. Epigenetic modifications including the roles of micro RNAs, DNA methylation, histone acetylation and transcription factors that modulate pulmonary vascular remodeling are also reviewed. A brief background of each area of interest is provided with emphasis on those components that have potential to be exploited for the treatment of PAH. Significant findings of cell-based and animal studies and, where available, the results of early clinical trials, are presented to illustrate the potential of these novel therapeutic targets. Current challenges to the development of small peptides and biologicals for the treatment of PAH and direction for future studies are also briefly discussed. © 2021 American Physiological Society. Compr Physiol 11:1-53, 2021.
Topics: Animals; Heart Failure; Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Pulmonary Circulation; Vascular Resistance
PubMed: 34558669
DOI: 10.1002/cphy.c200015 -
Echocardiography (Mount Kisco, N.Y.) Jan 2015The right ventricle (RV) can be described in terms of 3 components: the inlet, the apex, and the infundibulum. In the normal adult, the RV shows an arrangement suited... (Review)
Review
The right ventricle (RV) can be described in terms of 3 components: the inlet, the apex, and the infundibulum. In the normal adult, the RV shows an arrangement suited for pumping blood against low resistance, with a mass about one sixth that of left ventricle (LV) mass, and a larger volume than the LV. The RV is able to manage a progressive increase in the afterload by increasing contractility and remodeling. The gold standard measurement of contractility is maximal elastance (Emax), or the ratio between end-systolic pressure (ESP) and end-systolic volume (ESV), and the best measurement of afterload is arterial elastance (Ea), or the ratio between ESP and stroke volume (SV). The ratio Emax/Ea defines RV-arterial coupling. The optimal energy transfer from the RV to the pulmonary circulation is measured at Emax/Ea ratios of 1.5-2. In the presence of pulmonary hypertension, the SV/ESV ratio may be an acceptable surrogate of Emax/Ea. The right atrium (RA) has 3 anatomical components: the appendage, the venous part, and the vestibule. It is a dynamic structure having different functions: reservoir, conduit, and booster pump function. In case of increased afterload, the RA is enlarged, denoting high RA pressure, as a consequence of elevated RV diastolic pressure. RA area is a strong predictor of adverse clinical outcome in pulmonary arterial hypertension. In patients with severe pulmonary hypertension, in several congenital heart diseases, and in Eisenmenger syndrome, symptoms and prognosis are greatly dependent on RV function and its ability to adapt to a chronic increase in afterload.
Topics: Adult; Female; Heart Atria; Heart Defects, Congenital; Heart Ventricles; Humans; Hypertension, Pulmonary; Male; Myocardial Contraction; Pulmonary Artery; Pulmonary Circulation; Role; Stroke Volume; Ventricular Function, Right; Ventricular Remodeling
PubMed: 25244348
DOI: 10.1111/echo.12227 -
Heart Failure Clinics Jan 2021Right heart and pulmonary circulation disorders are generally caused by right ventricle (RV) pressure overload, volume overload, and cardiomyopathy, and they are... (Review)
Review
Right heart and pulmonary circulation disorders are generally caused by right ventricle (RV) pressure overload, volume overload, and cardiomyopathy, and they are associated with distinct clinical courses and therapeutic approaches, although they often may coexist. Cardiac magnetic resonance (CMR) provides a noninvasive accurate and reproducible multiplanar anatomic and functional assessment, tissue characterization, and blood flow evaluation of the right heart and pulmonary circulation. This article reviews the current status of the CMR, the most recent techniques, the new parameters and their clinical utility in diagnosis, prognosis, and therapeutic management in the right heart and pulmonary circulation disorders.
Topics: Cardiomyopathies; Humans; Hypertension, Pulmonary; Magnetic Resonance Imaging, Cine; Magnetic Resonance Spectroscopy; Pulmonary Circulation; Ventricular Function, Right
PubMed: 33220887
DOI: 10.1016/j.hfc.2020.08.006 -
JAMA Cardiology Jan 2022The recognition of the pulmonary circulation is a complex evolution in medical history and draws on theories across eras and cultures. (Review)
Review
IMPORTANCE
The recognition of the pulmonary circulation is a complex evolution in medical history and draws on theories across eras and cultures.
OBSERVATIONS
This narrative review summarizes evidence suggesting that the recognition of pulmonary circulation is older than the time of Ibn Nafis. The theory of pulmonary circulation originated in ancient Persia (ad 224-637), was overshadowed by Greek theory from the 11th century, and reestablished by Ibn Nafis in the 13th century.
CONCLUSIONS AND RELEVANCE
The findings of this review may help contextualize the story of the discovery of pulmonary circulation in ancient Persian and Greek theories before Ibn Nafis.
Topics: Cardiology; Greece; History, 15th Century; History, 16th Century; History, 17th Century; History, 18th Century; History, 19th Century; History, 20th Century; History, Ancient; History, Medieval; Humans; Persia; Pulmonary Circulation
PubMed: 34550308
DOI: 10.1001/jamacardio.2021.3520 -
Pediatric Clinics of North America Feb 2021This review addresses how anomalous cardiovascular anatomy imparts consequences to the airway, respiratory system mechanics, pulmonary vascular system, and lymphatic... (Review)
Review
This review addresses how anomalous cardiovascular anatomy imparts consequences to the airway, respiratory system mechanics, pulmonary vascular system, and lymphatic system. Abnormal formation or enlargement of great vessels can compress airways and cause large and small airway obstructions. Alterations in pulmonary blood flow associated with congenital heart disease (CHD) can cause abnormalities in pulmonary mechanics and limitation of exercise. CHD can lead to pulmonary arterial hypertension. Lymphatic abnormalities associated with CHD can cause pulmonary edema, chylothorax, or plastic bronchitis. Understanding how the cardiovascular system has an impact on pulmonary growth and function can help determine options and timing of intervention.
Topics: Child; Heart Defects, Congenital; Humans; Lymphatic Abnormalities; Pulmonary Circulation; Respiratory Tract Diseases
PubMed: 33228936
DOI: 10.1016/j.pcl.2020.09.001 -
Heart Failure Clinics Jul 2018Pulmonary hypertension (PH) is a common hemodynamic evolution of heart failure (HF) with preserved or reduced ejection fraction, responsible for congestion, symptoms... (Review)
Review
Pulmonary hypertension (PH) is a common hemodynamic evolution of heart failure (HF) with preserved or reduced ejection fraction, responsible for congestion, symptoms worsening, exercise limitation, and negative outcome. In HF of any origin, PH develops in response to a passive backward pressure transmission as result of increased left atrial pressure. Sustained pressure injury and chronic venous congestion can trigger pulmonary vasoconstriction and vascular remodeling, leading to irreversible pulmonary vascular disease, right ventricular hypertrophy, and failure. In this article, the key determinants of this "dangerous liaison" are analyzed with some digressions on related "leitmotiv" at the horizon.
Topics: Heart Failure; Heart Ventricles; Hemodynamics; Humans; Hypertension, Pulmonary; Pulmonary Circulation
PubMed: 29966628
DOI: 10.1016/j.hfc.2018.02.006 -
Anesthesiology Apr 2015Hypoxic pulmonary vasoconstriction (HPV) represents a fundamental difference between the pulmonary and systemic circulations. HPV is active in utero, reducing pulmonary... (Review)
Review
Hypoxic pulmonary vasoconstriction (HPV) represents a fundamental difference between the pulmonary and systemic circulations. HPV is active in utero, reducing pulmonary blood flow, and in adults helps to match regional ventilation and perfusion although it has little effect in healthy lungs. Many factors affect HPV including pH or PCO2, cardiac output, and several drugs, including antihypertensives. In patients with lung pathology and any patient having one-lung ventilation, HPV contributes to maintaining oxygenation, so anesthesiologists should be aware of the effects of anesthesia on this protective reflex. Intravenous anesthetic drugs have little effect on HPV, but it is attenuated by inhaled anesthetics, although less so with newer agents. The reflex is biphasic, and once the second phase becomes active after about an hour of hypoxia, this pulmonary vasoconstriction takes hours to reverse when normoxia returns. This has significant clinical implications for repeated periods of one-lung ventilation.
Topics: Anesthetics, Inhalation; Animals; Humans; Hypoxia; Lung; Pulmonary Circulation; Vasoconstriction
PubMed: 25587641
DOI: 10.1097/ALN.0000000000000569 -
Circulation Research Apr 2022There is an increased appreciation for the importance of the right heart and pulmonary circulation in several disease states across the spectrum of pulmonary... (Review)
Review
There is an increased appreciation for the importance of the right heart and pulmonary circulation in several disease states across the spectrum of pulmonary hypertension and left heart failure. However, assessment of the structure and function of the right heart and pulmonary circulation can be challenging, due to the complex geometry of the right ventricle, comorbid pulmonary airways and parenchymal disease, and the overlap of hemodynamic abnormalities with left heart failure. Several new and evolving imaging modalities interrogate the right heart and pulmonary circulation with greater diagnostic precision. Echocardiographic approaches such as speckle-tracking and 3-dimensional imaging provide detailed assessments of regional systolic and diastolic function and volumetric assessments. Magnetic resonance approaches can provide high-resolution views of cardiac structure/function, tissue characterization, and perfusion through the pulmonary vasculature. Molecular imaging with positron emission tomography allows an assessment of specific pathobiologically relevant targets in the right heart and pulmonary circulation. Machine learning analysis of high-resolution computed tomographic lung scans permits quantitative morphometry of the lung circulation without intravenous contrast. Inhaled magnetic resonance imaging probes, such as hyperpolarized 129Xe magnetic resonance imaging, report on pulmonary gas exchange and pulmonary capillary hemodynamics. These approaches provide important information on right ventricular structure and function along with perfusion through the pulmonary circulation. At this time, the majority of these developing technologies have yet to be clinically validated, with few studies demonstrating the utility of these imaging biomarkers for diagnosis or monitoring disease. These technologies hold promise for earlier diagnosis and noninvasive monitoring of right heart failure and pulmonary hypertension that will aid in preclinical studies, enhance patient selection and provide surrogate end points in clinical trials, and ultimately improve bedside care.
Topics: Heart Failure; Humans; Hypertension, Pulmonary; Pulmonary Circulation; Xenon Isotopes
PubMed: 35482838
DOI: 10.1161/CIRCRESAHA.121.319990 -
Biomolecules Sep 2021A variety of cell types in pulmonary arteries (endothelial cells, fibroblasts, and smooth muscle cells) are continuously exposed to mechanical stimulations such as shear... (Review)
Review
A variety of cell types in pulmonary arteries (endothelial cells, fibroblasts, and smooth muscle cells) are continuously exposed to mechanical stimulations such as shear stress and pulsatile blood pressure, which are altered under conditions of pulmonary hypertension (PH). Most functions of such vascular cells (e.g., contraction, migration, proliferation, production of extracellular matrix proteins, etc.) depend on a key event, i.e., the increase in intracellular calcium concentration ([Ca]) which results from an influx of extracellular Ca and/or a release of intracellular stored Ca. Calcium entry from the extracellular space is a major step in the elevation of [Ca], involving a variety of plasmalemmal Ca channels including the superfamily of stretch-activated channels (SAC). A common characteristic of SAC is that their gating depends on membrane stretch. In general, SAC are non-selective Ca-permeable cation channels, including proteins of the TRP (Transient Receptor Potential) and Piezo channel superfamily. As membrane mechano-transducers, SAC convert physical forces into biological signals and hence into a cell response. Consequently, SAC play a major role in pulmonary arterial calcium homeostasis and, thus, appear as potential novel drug targets for a better management of PH.
Topics: Animals; Biomechanical Phenomena; Biophysical Phenomena; Calcium Channels; Humans; Hypertension, Pulmonary; Models, Biological; Pulmonary Circulation
PubMed: 34572602
DOI: 10.3390/biom11091389