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Acute Administration of PPARγ Agonist Rosiglitazone in Isolated Hearts Differentially Aggravates Cardiac Ischemia Reperfusion Injury in a Consomic Rat Model
Author(s) -
Cheng Qunli,
Elorbany Reem,
Stowe David,
Camara Amadou,
Weihrauch Dorothee,
Riess Matthias
Publication year - 2013
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.27.1_supplement.917.4
Subject(s) - rosiglitazone , agonist , thiazolidinedione , medicine , reperfusion injury , cardiac function curve , ischemia , cardioprotection , cardiac output , peroxisome proliferator activated receptor , contractility , pharmacology , cardiology , endocrinology , receptor , hemodynamics , diabetes mellitus , heart failure , type 2 diabetes
The effect of peroxisome proliferator‐activated receptor‐gamma (PPARγ) agonist rosiglitazone (RGZ), a thiazolidinedione (TZL), on cardiac ischemia/reperfusion (IR) injury is controversial. We tested effects of RGZ on post‐IR function and infarction in a consomic rat model that exhibits genetically determined cardioprotection. 15 min after 2 × 5‐min boluses of 50 μM RGZ or vehicle (Con), isolated hearts from Brown Norway (BN), Dahl Salt Sensitive (SS), and consomic (SS‐6BN) rats underwent 30 min global I and 120 min R. Systolic and developed left‐ventricular pressure (LVP), contractility, and coronary flow at 120 min R were decreased while diastolic LVP and infarct size increased in all Con groups, more so in SS than in BN or SS‐6BN hearts. RGZ enhanced IR injury more in SS‐6BN than in SS or BN hearts. Concurrent fluorescent redox state measurements suggested incomplete washout of RGZ and mitochondrial uncoupling before IR. These data confirm prior reports of deleterious effects of TZL on cardiac IR injury that appear to vary by species, dose, timing and route of administration, model used and PPARγ‐independent actions. These results also suggest genetic predisposition plays a role in the adverse response to TZLs. If translated clinically, PPARγ agonists may adversely enhance cardiac IR injury in genetically susceptible patients. Research supported by Department of Veterans Affairs (MR: CARA‐026–10F) and NIH.