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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/
Bmp Signaling Controls Pasmc Kv Channel Expression In Vitro And In Vivo
Interesting research demonstrating that the loss of BMPR2 signaling, an established fundamental mechanism underlying PAH, is mediated by downregulation of K+ channels of the voltage regulated family. This implies that K+ downregulation may be a cause of pulmonary vasoconstriction and that K+ channel activators may be a promising treatment.
Citation
Young KA, Ivester C, West J, Carr M, Rodman DM. BMP signaling controls PASMC KV channel expression in vitro and in vivo. Am J Physiol Lung Cell Mol Physiol. 2006 May;290(5):L841-8.Source: https://pubmed.ncbi.nlm.nih.gov/16339782/
Oral Levosimendan Improves Filling Pressure and Systolic Function During Long-term Treatment
This was a small randomized clinical trial of oral levosimendan for HFrEF as an add-on medication for a 6-month period. The primary assessment was determined by echocardiography which included estimates of PCWP and tissue Doppler velocities. Both parameters improved in the levosimendan treated group compared to control.
Citation
Jalanko M, Kivikko M, Harjola VP, Nieminen MS, Laine M. Oral levosimendan improves filling pressure and systolic function during long-term treatment. Scand Cardiovasc J. 2011 Apr;45(2):91-7.Source: https://pubmed.ncbi.nlm.nih.gov/21348810/
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.
