Author + information
- Yuri Dmitriev,
- Sarkis Minasian,
- Valentina Bayrasheva,
- Elena Demchenko and
- Michael Galagudza
Background: We investigated the effect of novel highly active necroptosis inhibitors, necrosulfonamide (NSA) and necrostatin-1s (Nec-1s), on myocardial tolerance to ischemia-reperfusion injury (IRI).
Methods: The isolated Langendorff-perfused rat hearts were subjected to 35-min global ischemia followed by 120-min reperfusion. The hearts were randomized into one of the 4 groups: 1) Control (CON, n = 5); 2) Dimethyl sulfoxide (DMSO, n = 5); 3) Necrosulfonamide (NSA, n = 8); 4) Necrostatin-1s (Nec-1s, n = 5). Both NSA and Nec-1s in DMSO were administered by intraperitoneal injection in a dose 1.65 mg/kg. Infarct size (IS) was determined histochemically.
Results: NSA significantly reduced IS compared with CON and DMSO (32 ± 14.0%, p = 0.016 and p = 0.038, respectively). Nec-1s was equally protective (36 ± 10.2 %, p=0.02 vs. both Con and DMSO). Left ventricular end diastolic pressure and left ventricular developed pressure, as well as rate – pressure product were significantly higher in NSA and Nec-1s groups as compared with DMSO and CON groups (p < 0.01 vs. both Con and DMSO). Coronary flow was also higher in NSA and Nec-1s groups in comparison with CON and DMSO (p < 0.01 vs. both Con and DMSO).
Conclusions: This study first demonstrated cardioprotective effects of novel necroptosis inhibitors NSA and Nec-1s. Both NSA and Nec-1s ameliorated postischemic cardiac function and reduced infarct size, which provides the rationale for further (pre)clinical studies.
This work was supported by the RFBR[project15-04-08138].
Poster Hall, Hall C
Saturday, March 18, 2017, 9:45 a.m.-10:30 a.m.
Session Title: Cutting Edge Vascular Medicine
Abstract Category: 38. Vascular Medicine: Basic
Presentation Number: 1205-353
- 2017 American College of Cardiology Foundation