Stimulation of soluble guanylate cyclase improves donor organ function in rat heart transplantation
Heart transplantation remains the definitive therapy of end-stage heart failure. Ischemia-reperfusion injury occurring during transplantation is a primary determinant of long-term outcome of heart transplantation and primary graft insufficiency. Modification of the nitric oxide/soluble guanylate cyclase/cyclic guanosine monophosphate signaling pathway appears to be one of the most promising among the pharmacological interventional options. We aimed at characterizing the cardio-protective effects of the soluble guanylate cyclase stimulator riociguat in a rat model of heterotopic heart transplantation. Donor Lewis rats were treated orally with either riociguat or placebo for two days (n = 9) in each transplanted group and (n = 7) in donor groups. Following explantation, hearts were heterotopically transplanted. After one hour reperfusion, left ventricular pressure-volume relations and coronary blood flow were recorded. Molecular biological measurements and histological examination were also completed. Left ventricular contractility (systolic pressure: 117 ± 13 vs. 48 ± 5 mmHg, p < 0.001; dP/dtmax: 2963 ± 221 vs. 1653 ± 159 mmHg/s, p < 0.001), active relaxation (dP/dtmin: -2014 ± 305 vs. -1063 ± 177 mmHg/s, p = 0.02; all at 120 µl of left ventricular volume), and alteration of coronary blood flow standardized to heart weight (2.55 ± 0.32 vs. 1.67 ± 0.22 ml/min/g, p = 0.03) were markedly increased following preconditioning with riociguat. Myocardial apoptosis markers were also significantly reduced in the riociguat pretreated group as well as the antioxidant markers were elevated. Pharmacological preconditioning with riociguat decreases ischemia-reperfusion injury and improves donor organ function in our animal model of heart transplantation. Therefore, riociguat might be a potential cardioprotective agent.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
|---|---|
| Enthalten in: |
Scientific reports - 10(2020), 1 vom: 24. März, Seite 5358 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Benke, Kálmán [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 18.12.2020 Date Revised 24.03.2021 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1038/s41598-020-62156-y |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM307962431 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM307962431 | ||
| 003 | DE-627 | ||
| 005 | 20231226201250.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1038/s41598-020-62156-y |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1026.xml |
| 035 | |a (DE-627)NLM307962431 | ||
| 035 | |a (NLM)32210293 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Benke, Kálmán |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Stimulation of soluble guanylate cyclase improves donor organ function in rat heart transplantation |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 18.12.2020 | ||
| 500 | |a Date Revised 24.03.2021 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Heart transplantation remains the definitive therapy of end-stage heart failure. Ischemia-reperfusion injury occurring during transplantation is a primary determinant of long-term outcome of heart transplantation and primary graft insufficiency. Modification of the nitric oxide/soluble guanylate cyclase/cyclic guanosine monophosphate signaling pathway appears to be one of the most promising among the pharmacological interventional options. We aimed at characterizing the cardio-protective effects of the soluble guanylate cyclase stimulator riociguat in a rat model of heterotopic heart transplantation. Donor Lewis rats were treated orally with either riociguat or placebo for two days (n = 9) in each transplanted group and (n = 7) in donor groups. Following explantation, hearts were heterotopically transplanted. After one hour reperfusion, left ventricular pressure-volume relations and coronary blood flow were recorded. Molecular biological measurements and histological examination were also completed. Left ventricular contractility (systolic pressure: 117 ± 13 vs. 48 ± 5 mmHg, p < 0.001; dP/dtmax: 2963 ± 221 vs. 1653 ± 159 mmHg/s, p < 0.001), active relaxation (dP/dtmin: -2014 ± 305 vs. -1063 ± 177 mmHg/s, p = 0.02; all at 120 µl of left ventricular volume), and alteration of coronary blood flow standardized to heart weight (2.55 ± 0.32 vs. 1.67 ± 0.22 ml/min/g, p = 0.03) were markedly increased following preconditioning with riociguat. Myocardial apoptosis markers were also significantly reduced in the riociguat pretreated group as well as the antioxidant markers were elevated. Pharmacological preconditioning with riociguat decreases ischemia-reperfusion injury and improves donor organ function in our animal model of heart transplantation. Therefore, riociguat might be a potential cardioprotective agent | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antioxidants |2 NLM | |
| 650 | 7 | |a Cardiotonic Agents |2 NLM | |
| 650 | 7 | |a Enzyme Activators |2 NLM | |
| 650 | 7 | |a Enzymes |2 NLM | |
| 650 | 7 | |a Pyrazoles |2 NLM | |
| 650 | 7 | |a Pyrimidines |2 NLM | |
| 650 | 7 | |a Nitric Oxide |2 NLM | |
| 650 | 7 | |a 31C4KY9ESH |2 NLM | |
| 650 | 7 | |a Cyclic GMP-Dependent Protein Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.11.12 |2 NLM | |
| 650 | 7 | |a Soluble Guanylyl Cyclase |2 NLM | |
| 650 | 7 | |a EC 4.6.1.2 |2 NLM | |
| 650 | 7 | |a Cyclic GMP |2 NLM | |
| 650 | 7 | |a H2D2X058MU |2 NLM | |
| 650 | 7 | |a riociguat |2 NLM | |
| 650 | 7 | |a RU3FE2Y4XI |2 NLM | |
| 700 | 1 | |a Németh, Balázs Tamás |e verfasserin |4 aut | |
| 700 | 1 | |a Sayour, Alex Ali |e verfasserin |4 aut | |
| 700 | 1 | |a Stark, Klára Aliz |e verfasserin |4 aut | |
| 700 | 1 | |a Oláh, Attila |e verfasserin |4 aut | |
| 700 | 1 | |a Ruppert, Mihály |e verfasserin |4 aut | |
| 700 | 1 | |a Szabó, Gábor |e verfasserin |4 aut | |
| 700 | 1 | |a Korkmaz-Icöz, Sevil |e verfasserin |4 aut | |
| 700 | 1 | |a Horváth, Eszter Mária |e verfasserin |4 aut | |
| 700 | 1 | |a Benkő, Rita |e verfasserin |4 aut | |
| 700 | 1 | |a Hartyánszky, István |e verfasserin |4 aut | |
| 700 | 1 | |a Szabolcs, Zoltán |e verfasserin |4 aut | |
| 700 | 1 | |a Merkely, Béla |e verfasserin |4 aut | |
| 700 | 1 | |a Radovits, Tamás |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Scientific reports |d 2011 |g 10(2020), 1 vom: 24. März, Seite 5358 |w (DE-627)NLM215703936 |x 2045-2322 |7 nnns |
| 773 | 1 | 8 | |g volume:10 |g year:2020 |g number:1 |g day:24 |g month:03 |g pages:5358 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1038/s41598-020-62156-y |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 10 |j 2020 |e 1 |b 24 |c 03 |h 5358 | ||