title: Protection of ischemic hearts perfused with an anion exchange inhibitor, DIDS, is associated with beneficial changes in substrate metabolism.
abstract: OBJECTIVE
  Metabolic interventions that promote glucose use during ischemia have been shown to protect the myocardium and improve functional recovery on reperfusion. In this study we evaluated if cardioprotection can be accomplished by inhibiting fatty acid uptake, which would be expected to increase glycolytic metabolism.
  
  
  METHODS
  Diisothiocyanostilbene sulfonic acid (DIDS), commonly used to inhibit Band-3 mediated anion exchanger, and has also been demonstrated to inhibit fatty acid transport in adipocytes, was used to inhibit fatty acid uptake prior to ischemia. Isolated rat hearts were perfused with buffer containing 5 mM glucose, 70 mU/l insulin, 0.4 mM palmitate, and 0.4 mM albumin, paced at 300 beats/min, and subjected to 50 min of low-flow ischemia followed by 60 min of reperfusion.
  
  
  RESULTS
  Ischemic injury, as assessed by creatine kinase release, was diminished in hearts perfused with DIDS (334+/-72 in DIDS vs. 565+/-314 IU/g dry wt in controls, P<0.04). Increases in LVEDP during ischemia were attenuated (8+/-3 mmHg in DIDS vs. 15+/-18 mmHg in controls, P<0.03) and the % recovery of LV function with reperfusion was enhanced in DIDS-treated hearts (78+/-10% of baseline in DIDS vs. 62+/-19% of baseline in controls, P<0.04). These beneficial effects of DIDS were associated with increased glucose metabolism and ATP content during ischemia and reperfusion. Furthermore, treatment with DIDS lowered the accumulation of long chain acyl carnitines.
  
  
  CONCLUSIONS
  This study demonstrates that DIDS protects ischemic myocardium, and is associated with inhibition of fatty acid uptake, improved glucose metabolism, and enhanced functional recovery on reperfusion. The data presented here suggest a potential role for therapeutic agents that lower fatty acid uptake as a metabolic adjunct in the treatment of myocardial ischemia.
authors.affiliation: Department of Medicine, PH 3-342, Division of Cardiology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, 10032, New York, NY, USA. rr260@columbia.edu
authors.forename: R
authors.initials: R
authors.lastname: Ramasamy
authors.forename: Y
authors.initials: Y
authors.lastname: Hwang
authors.forename: S
authors.initials: S
authors.lastname: Bakr
authors.forename: S R
authors.initials: SR
authors.lastname: Bergmann
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000627:therapeutic use*; D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000037:antagonists & inhibitors*; D002331:Carnitine / Q000031:analogs & derivatives* / Q000032:analysis; D005227:Fatty Acids / Q000032:analysis / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D010084:Oxidation-Reduction; D010477:Perfusion; D010725:Phosphocreatine / Q000032:analysis; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D005227:Fatty Acids; D010743:Phospholipids; D014280:Triglycerides; C116917:acylcarnitine; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D005947:Glucose; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D002331:Carnitine