Immediate effects of lung transplantation on right ventricular morphology and function in patients with variable degrees of pulmonary hypertension

Katz, William E.; Gasior, Thomas A.; Quinlan, Joseph J.; Lazar, Jason; Firestone, Leonard L.; Griffith, Bartley P.; Gorcsan, John

doi:10.1016/0735-1097(95)00502-1

Cited by 89 publications

(46 citation statements)

References 37 publications

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“…Reversal of RV function and remodeling in patients with PH after LTx has been reported. [12][13][14][15] Because ill patients are currently treated with combination therapy of PAH-targeted drugs, LTx should be reserved for patients whose RV function deteriorates despite such therapy. However, reverse RV remodeling after LTx in patients with end-stage PAH despite combination therapy of PAH-targeted drugs has not been fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

Reverse Right Ventricular Remodeling After Lung Transplantation in Patients With Pulmonary Arterial Hypertension Under Combination Therapy of Targeted Medical Drugs

Sarashina

Nakamura

Akagi

et al. 2017

Circ J

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Section: Discussionmentioning

confidence: 99%

Reverse Right Ventricular Remodeling After Lung Transplantation in Patients With Pulmonary Arterial Hypertension Under Combination Therapy of Targeted Medical Drugs

Sarashina

Nakamura

Akagi

et al. 2017

Circ J

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“…However, it is well documented that pathological RV remodeling in PAH can be reversed with lung transplantation or with pulmonary thromboendarterectomy in chronic thromboembolic pulmonary hypertension (CTEPH). [2][3][4][5][6][7][8][9] The molecular mechanisms that mediate the transition from adaptive RV compensation to failure or that can promote reversible RV remodeling are presently unknown. Recently, our group and others have found evidence indicating that intracellular lipid accumulation and decreased fatty acid oxidation (FAO) may be features of RV failure related to PAH.…”

mentioning

confidence: 99%

Fatty Acid Metabolism in Pulmonary Arterial Hypertension: Role in Right Ventricular Dysfunction and Hypertrophy

Talati

Hemnes

2015

Pulm. circ.

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Pulmonary arterial hypertension (PAH) is a complex, multifactorial disease in which an increase in pulmonary vascular resistance leads to increased afterload on the right ventricle (RV), causing right heart failure and death. Our understanding of the pathophysiology of RV dysfunction in PAH is limited but is constantly improving. Increasing evidence suggests that in PAH RV dysfunction is associated with various components of metabolic syndrome, such as insulin resistance, hyperglycemia, and dyslipidemia. The relationship between RV dysfunction and fatty acid/glucose metabolites is multifaceted, and in PAH it is characterized by a shift in utilization of energy sources toward increased glucose utilization and reduced fatty acid consumption. RV dysfunction may be caused by maladaptive fatty acid metabolism resulting from an increase in fatty acid uptake by fatty acid transporter molecule CD36 and an imbalance between glucose and fatty acid oxidation in mitochondria. This leads to lipid accumulation in the form of triglycerides, diacylglycerol, and ceramides in the cytoplasm, hallmarks of lipotoxicity. Current interventions in animal models focus on improving RV dysfunction through altering fatty acid oxidation rates and limiting lipid accumulation, but more specific and effective therapies may be available in the coming years based on current research. In conclusion, a deeper understanding of the complex mechanisms of the metabolic remodeling of the RV will aid in the development of targeted treatments for RV failure in PAH.Keywords: pulmonary arterial hypertension, metabolic syndrome, fatty acid oxidation, glucose oxidation, right ventricle, fatty acid transporter (CD36), glucose transporters, insulin resistance, right ventricular lipotoxicity, lipotoxic cardiomyopathy. Pulmonary arterial hypertension (PAH) is a devastating disease characterized by progressive obliteration of the pulmonary vasculature, right heart failure, and death. The pathobiology of PAH is complex, and presently there is no curative treatment. Although PAH is classically thought to be a disease of the lungs, the role played by right ventricular (RV) hypertrophy and dysfunction that ultimately results in right heart failure and death is understudied. RV failure is the most common cause of death in PAH, 1 yet there are no specific therapies aimed at improving RV adaptation or function. However, it is well documented that pathological RV remodeling in PAH can be reversed with lung transplantation or with pulmonary thromboendarterectomy in chronic thromboembolic pulmonary hypertension (CTEPH). 2-9 The molecular mechanisms that mediate the transition from adaptive RV compensation to failure or that can promote reversible RV remodeling are presently unknown. Recently, our group and others have found evidence indicating that intracellular lipid accumulation and decreased fatty acid oxidation (FAO) may be features of RV failure related to PAH. [10][11][12][13] This raises a question: In PAH, can accumulation of fatty acids promote RV dysfun...

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“…One study of resting LVEF and RVEF before and after SLTx and BLTx showed that the RVEF recovers with the substantial reduction in afterload following transplantation (48). Katz et al have shown these changes occur almost immediately posttransplant in most, but in those patients whose RV function does not immediately improve, mortality is high (141). However, these studies did not adequately study the cardiac response to exercise.…”

Section: Posttransplant Factors In Hltx Sltx and Bltxmentioning

confidence: 91%

Exercise Limitation Following Transplantation

Williams

McKenna

2012

Comprehensive Physiology

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Organ transplantation is one of the medical miracles or the 20th century. It has the capacity to substantially improve exercise performance and quality of life in patients who are severely limited with chronic organ failure. We focus on the most commonly performed solid‐organ transplants and describe peak exercise performance following recovery from transplantation. Across all of the common transplants, evaluated significant reduction in o 2 peak is seen (typically renal and liver 65%‐80% with heart and/or lung 50%‐60% of predicted). Those with the lowest o 2 peak pretransplant have the lowest o 2 peak posttransplant. Overall very few patients have a o 2 peak in the normal range. Investigation of the cause of the reduction of o 2 peak has identified many factors pre‐ and posttransplant that may contribute. These include organ‐specific factors in the otherwise well‐functioning allograft (e.g., chronotropic incompetence in heart transplantation) as well as allograft dysfunction itself (e.g., chronic lung allograft dysfunction). However, looking across all transplants, a pattern emerges. A low muscle mass with qualitative change in large exercising skeletal muscle groups is seen pretransplant. Many factor posttransplant aggravate these changes or prevent them recovering, especially calcineurin antagonist drugs which are key immunosuppressing agents. This results in the reduction of o 2 peak despite restoration of near normal function of the initially failing organ system. As such organ transplantation has provided an experiment of nature that has focused our attention on an important confounder of chronic organ failure‐skeletal muscle dysfunction. © 2012 American Physiological Society. Compr Physiol 2:1937‐1979, 2012.

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Immediate effects of lung transplantation on right ventricular morphology and function in patients with variable degrees of pulmonary hypertension

Cited by 89 publications

References 37 publications

Reverse Right Ventricular Remodeling After Lung Transplantation in Patients With Pulmonary Arterial Hypertension Under Combination Therapy of Targeted Medical Drugs

Reverse Right Ventricular Remodeling After Lung Transplantation in Patients With Pulmonary Arterial Hypertension Under Combination Therapy of Targeted Medical Drugs

Fatty Acid Metabolism in Pulmonary Arterial Hypertension: Role in Right Ventricular Dysfunction and Hypertrophy

Exercise Limitation Following Transplantation

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