title: Effects of sildenafil on nanostructural and nanomechanical changes in mitochondria in an ischaemia-reperfusion rat model.
abstract: Sildenafil exerts cardioprotective effects by activating the opening of mitochondrial ATP-sensitive potassium channels to attenuate ischaemia-reperfusion (IR) injury. In the present study, we used atomic force microscopy (AFM) to investigate changes in mitochondrial morphology and properties to assess sildenafil-mediated cardioprotection in a rat myocardial infarction model. To investigate the cardioprotective effects of sildenafil, we used an in vivo Sprague-Dawley rat model of IR. Rats were randomly divided into three groups: (i) sham-operated rats (control; n = 5); (ii) IR-injured rats treated with vehicle (normal saline; IR; n = 10); and (iii) IR-injured rats treated with 0.75 mg/kg, i.p., sildenafil (IR + Sil; n = 10). Morphological and mechanical changes to mitochondria were analysed by AFM. Infarct areas were significantly reduced in sildenafil-treated rats (7.8 ± 3.9% vs 20.4 ± 7.0% in the sildenafil-treated and untreated IR groups, respectively; relative reduction 62%; P < 0.001). Analysis of mitochondria by AFM showed that IR injury significantly increased the areas of isolated mitochondria compared with control (24 150 ± 18 289 vs 1495 ± 1139 nm(2) , respectively; P < 0.001), indicative of mitochondrial swelling. Pretreatment with sildenafil before IR injury reduced the mitochondrial areas (7428 ± 3682 nm(2) ; P < 0.001; relative reduction 69.2% compared with the IR group) and ameliorated the adhesion force of mitochondrial surfaces. Together, these results suggest that sildenafil has cardioprotective effects against IR injury in a rat model by improving the morphological and mechanical characteristics of mitochondria.
authors.affiliation: Cardiovascular Division, Department of Internal Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Kyung Hye
authors.initials: KH
authors.lastname: Lee
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Kwon
authors.forename: Jong-Shin
authors.initials: JS
authors.lastname: Woo
authors.forename: Gi-Ja
authors.initials: GJ
authors.lastname: Lee
authors.forename: So-Ra
authors.initials: SR
authors.lastname: Lee
authors.forename: Hyun-Hee
authors.initials: HH
authors.lastname: Jang
authors.forename: Hyun Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Jung Wook
authors.initials: JW
authors.lastname: Kim
authors.forename: Hun Kuk
authors.initials: HK
authors.lastname: Park
authors.forename: Kyu Seok
authors.initials: KS
authors.lastname: Cho
authors.forename: Weon
authors.initials: W
authors.lastname: Kim
mesh_terms: D000818:Animals; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure*; D008933:Mitochondrial Swelling / Q000187:drug effects; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure*; D010879:Piperazines / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D000068677:Sildenafil Citrate; D013449:Sulfonamides / Q000494:pharmacology*
chemical_list: D010879:Piperazines; D015221:Potassium Channels; D011687:Purines; D013449:Sulfonamides; D000068677:Sildenafil Citrate
keywords: atomic force microscopy; ischaemia-reperfusion injury; mitochondria; myocardial preconditioning; sildenafil