Pharmacological preconditioning with gemfibrozil preserves cardiac function after heart transplantation View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-10-27

AUTHORS

Kálmán Benke, Csaba Mátyás, Alex Ali Sayour, Attila Oláh, Balázs Tamás Németh, Mihály Ruppert, Gábor Szabó, Gábor Kökény, Eszter Mária Horváth, István Hartyánszky, Zoltán Szabolcs, Béla Merkely, Tamás Radovits

ABSTRACT

While heart transplantation (HTX) is the definitive therapy of heart failure, donor shortage is emerging. Pharmacological activation of soluble guanylate cyclase (sGC) and increased cGMP-signalling have been reported to have cardioprotective properties. Gemfibrozil has recently been shown to exert sGC activating effects in vitro. We aimed to investigate whether pharmacological preconditioning of donor hearts with gemfibrozil could protect against ischemia/reperfusion injury and preserve myocardial function in a heterotopic rat HTX model. Donor Lewis rats received p.o. gemfibrozil (150 mg/kg body weight) or vehicle for 2 days. The hearts were explanted, stored for 1 h in cold preservation solution, and heterotopically transplanted. 1 h after starting reperfusion, left ventricular (LV) pressure-volume relations and coronary blood flow (CBF) were assessed to evaluate early post-transplant graft function. After 1 h reperfusion, LV contractility, active relaxation and CBF were significantly (p < 0.05) improved in the gemfibrozil pretreated hearts compared to that of controls. Additionally, gemfibrozil treatment reduced nitro-oxidative stress and apoptosis, and improved cGMP-signalling in HTX. Pharmacological preconditioning with gemfibrozil reduces ischemia/reperfusion injury and preserves graft function in a rat HTX model, which could be the consequence of enhanced myocardial cGMP-signalling. Gemfibrozil might represent a useful tool for cardioprotection in the clinical setting of HTX surgery soon. More... »

PAGES

14232

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-017-14587-3

DOI

http://dx.doi.org/10.1038/s41598-017-14587-3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1092371221

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29079777


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29 schema:description While heart transplantation (HTX) is the definitive therapy of heart failure, donor shortage is emerging. Pharmacological activation of soluble guanylate cyclase (sGC) and increased cGMP-signalling have been reported to have cardioprotective properties. Gemfibrozil has recently been shown to exert sGC activating effects in vitro. We aimed to investigate whether pharmacological preconditioning of donor hearts with gemfibrozil could protect against ischemia/reperfusion injury and preserve myocardial function in a heterotopic rat HTX model. Donor Lewis rats received p.o. gemfibrozil (150 mg/kg body weight) or vehicle for 2 days. The hearts were explanted, stored for 1 h in cold preservation solution, and heterotopically transplanted. 1 h after starting reperfusion, left ventricular (LV) pressure-volume relations and coronary blood flow (CBF) were assessed to evaluate early post-transplant graft function. After 1 h reperfusion, LV contractility, active relaxation and CBF were significantly (p < 0.05) improved in the gemfibrozil pretreated hearts compared to that of controls. Additionally, gemfibrozil treatment reduced nitro-oxidative stress and apoptosis, and improved cGMP-signalling in HTX. Pharmacological preconditioning with gemfibrozil reduces ischemia/reperfusion injury and preserves graft function in a rat HTX model, which could be the consequence of enhanced myocardial cGMP-signalling. Gemfibrozil might represent a useful tool for cardioprotection in the clinical setting of HTX surgery soon.
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37 HTX surgery
38 HTx
39 LV contractility
40 Lewis rats
41 activation
42 active relaxation
43 apoptosis
44 blood flow
45 cGMP
46 cGMP signaling
47 cardiac function
48 cardioprotection
49 cardioprotective properties
50 clinical setting
51 cold preservation solution
52 consequences
53 contractility
54 control
55 coronary blood flow
56 cyclase
57 days
58 definitive therapy
59 donor Lewis rats
60 donor hearts
61 donor shortage
62 early post-transplant graft function
63 effect
64 exert sGC
65 failure
66 flow
67 function
68 gemfibrozil
69 gemfibrozil preserves cardiac function
70 gemfibrozil treatment
71 graft function
72 guanylate cyclase
73 heart
74 heart failure
75 heart transplantation
76 heterotopic rat HTX model
77 injury
78 ischemia/reperfusion injury
79 model
80 myocardial cGMP-signalling
81 myocardial function
82 nitro-oxidative stress
83 pharmacological activation
84 pharmacological preconditioning
85 post-transplant graft function
86 preconditioning
87 preservation solution
88 preserves cardiac function
89 preserves graft function
90 pressure-volume relation
91 properties
92 rat HTX model
93 rats
94 relation
95 relaxation
96 reperfusion
97 reperfusion injury
98 setting
99 shortage
100 soluble guanylate cyclase
101 solution
102 stress
103 surgery
104 therapy
105 tool
106 transplantation
107 treatment
108 useful tool
109 vehicles
110 ventricular pressure-volume relations
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