Premium
Postconditioning Effect of PDE5 inhibitor, Sildenafil in Normal and Diabetic Rabbits following Myocardial Ischemia/Reperfusion injury.
Author(s) -
Ockaili Ramzi,
Samidurai Arun,
Filippone Scott M.,
Cain Chad K.,
Das Anindita,
Kukreja Rakesh C.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.580.16
Subject(s) - sildenafil , medicine , alloxan , myocardial infarction , ischemia , troponin i , cardioprotection , cardiology , cgmp specific phosphodiesterase type 5 , reperfusion injury , hemodynamics , diabetes mellitus , saline , anesthesia , endocrinology
Background Several studies have demonstrated cardioprotective effects of the phosphodiesterase 5 inhibitor, sildenafil (SILD), in the setting of myocardial ischemia and reperfusion (MI/R) in mice and rabbits. However, it is unclear whether sildenafil exerts postconditioning effect in normal and diabetic rabbits. Methods and Results To induce diabetes, alloxan monohydrate (125 mg/kg, i.v.) was administered in New Zealand white male rabbits (n=10; ~3 kg, 4 months old). Blood glucose level increased to 342±21 mg/dL following 2 weeks of alloxan administration. Balloon occluders were implanted on the top of the coronary artery and 7 days later, conscious rabbits were subjected to 45‐min ischemia (I) and 3 days of reperfusion (R) by inflating/deflating the balloon. Saline (as control) or Sildenafil (0.71 or 1.4 mg/kg; i.v.) was infused for 60 min starting 5 min before reperfusion. Myocardial infarct size was determined by triphenyltetrazolium chloride staining and troponin I (cTnI) was measured using ELISA method in the plasma. The result showed that sildenafil (both concentrations) significantly reduced myocardial infarct size (Figure A) and peak plasma levels of cardiac troponin I. Similarly, sildenafil reduced infarct size in diabetic rabbits (DM) following MI/R (Figure C). There were no differences in hemodynamics during MI/R or myocardial area‐at‐risk (AAR) (Figure B and D). Conclusion Sildenafil exerts significant postconditioning effect in normal and diabetic rabbits of conscious I/R model that is potentially is free of confounding factors associated with open‐chest preparations. Support or Funding Information NIHRO1HL134366 (AD & RCK), RO1HL118808 (RCK), RO1HL133167 (RCK) This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .