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Found Posts: 66
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Uncovered Contribution of Kv7 Channels to Pulmonary Vascular Tone in Pulmonary Arterial Hypertension
This is a report of preclinical research that studied the role of K+(V.7) channels in PAH. Unlike other K+ channels that appear to be downregulated in PAH, the Kv7 channel function was preserved whereas the KCNE4 subunit was upregulated. This research highlights the complexities behind K+ channel control over the pulmonary circulation and the impact of their actions.
Citation
Mondéjar-Parreño G, Barreira B, Callejo M, Morales-Cano D, Barrese V, Esquivel-Ruiz S, Olivencia MA, Macías M, Moreno L, Greenwood IA, Perez-Vizcaino F, Cogolludo A. Uncovered Contribution of Kv7 Channels to Pulmonary Vascular Tone in Pulmonary Arterial Hypertension. Hypertension. 2020 Oct;76(4):1134-1146Source: https://pubmed.ncbi.nlm.nih.gov/32829658/
The Role of ATP-sensitive Potassium Channels in Cellular Function and Protection in the Cardiovascular System
This review covers the role of K+ATP channels in cardiovascular disease and links cellular metabolism to clinical disease states. This suggests that the exploitation of K+ATP channel activators may prove useful as a treatment for many facets of cardiovascular disease.
Citation
Tinker A, Aziz Q, Thomas A. The role of ATP-sensitive potassium channels in cellular function and protection in the cardiovascular system. Br J Pharmacol. 2014 Jan;171(1):12-23.Source: https://pubmed.ncbi.nlm.nih.gov/24102106/
Role Of K+ Channels In Pulmonary Hypertension
This authoritative review from a leading authority in the field explains the complex pathophysiology behind the development of pulmonary hypertension which may apply to all of the 5 groups of clinical pulmonary hypertension.
Citation
Mandegar M, Yuan JX. Role of K+ channels in pulmonary hypertension. Vascul Pharmacol. 2002 Jan;38(1):25-33.Source: https://pubmed.ncbi.nlm.nih.gov/12378819/
Atp-dependent Potassium Channels As A Key Target For The Treatment Of Myocardial And Vascular Dysfunction
This is a review of the role of K+ATP channels in the cardiovascular system, and the potential of K+ channel opener drugs. Included in the review is the finding that myocardial ischemia may be prevented from K+ATP channel activators, including levosimendan, via effects on cardiac mitochondria.
Citation
Pollesello P, Mebazaa A. ATP-dependent potassium channels as a key target for the treatment of myocardial and vascular dysfunction. Curr Opin Crit Care. 2004 Dec;10(6):436-41.Source: https://pubmed.ncbi.nlm.nih.gov/15616383/
The Neurohormonal Basis of Pulmonary Hypertension in Heart Failure with Preserved Ejection Fraction
This important review highlights the data showing a strong neurohormonal maladaptive basis underlying PH-HFpEF. These data provide a compelling argument for developing novel treatments that target these abnormalities to improve outcomes.
Citation
Obokata M, Kane GC, Reddy YNV, Melenovsky V, Olson TP, Jarolim P, Borlaug BA. The neurohormonal basis of pulmonary hypertension in heart failure with preserved ejection fraction. Eur Heart J. 2019 Dec 1;40(45):3707-3717.Source: https://pubmed.ncbi.nlm.nih.gov/31513270/
Potassium Channel Diversity in the Pulmonary Arteries and Pulmonary Veins: Implications for Regulation of the Pulmonary Vasculature in Health and During Pulmonary Hypertension
This authoritative review from eminent translational researchers in this field demonstrates the diversity of K+ channels which regulates the pulmonary arterial and venous circulations. It raises the question as to why there has not been the development of K+ channel activator drugs as a treatment, as there appears to be an extraordinary opportunity and need for such therapies.
Citation
Bonnet S, Archer SL. Potassium channel diversity in the pulmonary arteries and pulmonary veins: implications for regulation of the pulmonary vasculature in health and during pulmonary hypertension. Pharmacol Ther. 2007 Jul;115(1):56-69.Source: https://pubmed.ncbi.nlm.nih.gov/17583356/
Levosimendan Beyond Inotropy and Acute Heart Failure: Evidence of Pleiotropic Effects on the Heart and Other Organs: An Expert Panel Position Paper
Levosimendan has been used in Europe for the past 20 years as an intravenous inotropic treatment of acute decompensated heart failure. This expert panel with firsthand experience in its clinical efficacy summarizes this experience and the many unexplored potential uses in various conditions. Levosimendan is a pleotropic drug with multiple mechanisms of action.
Citation
Farmakis D, Alvarez J, Gal TB, Brito D, Fedele F, Fonseca C, Gordon AC, Gotsman I, Grossini E, Guarracino F, Harjola VP, Hellman Y, Heunks L, Ivancan V, Karavidas A, Kivikko M, Lomivorotov V, Longrois D, Masip J, Metra M, Morelli A, Nikolaou M, Papp Z, Parkhomenko A, Poelzl G, Pollesello P, Ravn HB, Rex S, Riha H, Ricksten SE, Schwinger RHG, Vrtovec B, Yilmaz MB, Zielinska M, Parissis J. Levosimendan beyond inotropy and acute heart failure: Evidence of pleiotropic effects on the heart and other organs: An expert panel position paper. Int J Cardiol. 2016 Nov 1;222:303-312.Source: https://pubmed.ncbi.nlm.nih.gov/27498374/
Comparison of The Vasorelaxing Effect of Cromakalim and the New Inodilator, Levosimendan, In Human Isolated Portal Vein
Levosimendan is a K+ATP channel activator, and via this mechanism has the potential for dilating both arterial and venous blood vessels. This experiment focused on human portal veins, and compared it to another K+ATP channel activator drug cromakalim. The in vitro preparation employed pre-treating the veins with norepinephrine to simulate the physiologic environment in heart failure syndromes.
Citation
Pataricza J, Hõhn J, Petri A, Balogh A, Papp JG. Comparison of the vasorelaxing effect of cromakalim and the new inodilator, levosimendan, in human isolated portal vein. J Pharm Pharmacol. 2000 Feb;52(2):213-7Source: https://pubmed.ncbi.nlm.nih.gov/10714952/
Left Ventricular Dysfunction with Pulmonary Hypertension: Part 1: Epidemiology, Pathophysiology, And Definitions
This is the first part of an extraordinary 2-part review of the complexity of pulmonary hypertension in LV dysfunction. One particularly enlightening focus is on the difference between the reversible elevations in pulmonary pressure vs. irreversible elevations which explain why persistent pulmonary hypertension occurs in many of these patients.
Citation
Georgiopoulou VV, Kalogeropoulos AP, Borlaug BA, Gheorghiade M, Butler J. Left ventricular dysfunction with pulmonary hypertension: Part 1: epidemiology, pathophysiology, and definitions. Circ Heart Fail. 2013 Mar;6(2):344-54.Source: https://pubmed.ncbi.nlm.nih.gov/23513049/
The Pathophysiology of Heart Failure with Preserved Ejection Fraction
Comprehensive review of the pathophysiology of HFpEF by a worldwide leader in the field. This paper explains why the term diastolic dysfunction does not adequately explain the very complex and diverse pathophysiology that underlies the abnormal compliance of the LV in HFpEF.
