Zinc improves postischemic recovery of isolated rat hearts through inhibition of oxidative stress.

Abstract

We studied the cardiac protective qualities of zinc in the postischemic isolated rat heart. Hearts, perfused with Krebs-Henseleit buffer with or without zinc-bis-histidinate, were subjected to 20 min of "no-flow" normothermic global ischemia. Pre- and postischemic treatment with 0, 10, 20, or 30 microM zinc resulted in concentration-dependent enhancement of postischemic function as evidenced by decreased end-diastolic pressure (37 +/- 3, 25 +/- 5, 17 +/- 5, and 8 +/- 2 mmHg, respectively) and increased recovery of developed systolic pressure (41 +/- 6, 59 +/- 17, 76 +/- 18, and 87 +/- 16 mmHg, respectively) and maximum rate of rise in pressure (+dP/dtmax; 823 +/- 141, 1,413 +/- 396, 1,700 +/- 450, and 2,157 +/- 407 mmHg/s, respectively) as well as decreased lactate dehydrogenase efflux from the hearts (peak: 1,002%, 840%, 580%, and 440%, respectively). Only preischemic treatment resulted in an intermediate protective effect, whereas treatment starting at reperfusion worsened postischemic damage. In hearts perfused with zinc throughout the experiment, prolongation of the preischemic treatment interval further enhanced postischemic recovery. With the use of salicylate as a trap for .OH, it was determined that zinc virtually eliminated the early postischemic "burst" of this species normally observed in this preparation. Atomic absorption studies demonstrated that hearts treated with 30 microM zinc contained 27% less copper than control hearts by the end of the reperfusion period. In control hearts, electron microscopy revealed swollen mitochondria with marked loss of inner matrix density, whereas morphology of postischemic zinc-treated hearts was essentially normal. These studies indicate that zinc possesses cardiac cytoprotective qualities and support the concept that this metal can decrease .OH formation by affecting copper reactivity.

• Authors: S R Powell, D Hall, L Aiuto, R A Wapnir, S Teichberg, A J Tortolani
• Journal: The American journal of physiology (Am J Physiol) Vol. 266 Issue 6 Pt 2 Pg. H2497-507 (Jun 1994) ISSN: 0002-9513 [Print] United States
• PMID: 8024011 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Ions
• Metals
• Organometallic Compounds
• zinc bis(histidinate)
• Hydroxyl Radical
• Histidine
• L-Lactate Dehydrogenase
• Zinc

Topics

• Animals
• Heart (physiopathology)
• Histidine (analogs & derivatives, pharmacology)
• Hydroxyl Radical (metabolism)
• In Vitro Techniques
• Ions
• L-Lactate Dehydrogenase (metabolism)
• Male
• Metals (metabolism)
• Microscopy, Electron
• Myocardial Ischemia (pathology, physiopathology)
• Myocardial Reperfusion
• Myocardial Reperfusion Injury (prevention & control)
• Myocardium (metabolism, ultrastructure)
• Organometallic Compounds (pharmacology)
• Oxidation-Reduction (drug effects)
• Rats
• Rats, Sprague-Dawley
• Zinc (pharmacology)