In:
Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 84, No. 7 ( 1999-04-16), p. 763-775
Abstract:
Abstract —The objective of this study was to examine the role of chloride (Cl – ) channels in the myocardial protection of ischemic preconditioning (IP). Isolated rabbit ventricular myocytes were preconditioned with 10-minute simulated ischemia (SI) and 20-minute simulated reperfusion (SR) or not preconditioned (control). The myocytes then received 180-minute SI or 45-minute SI/120-minute SR. Indanyloxyacetic acid 94 (IAA-94, 10 μmol/L) or 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB, 1 μmol/L) was administered before IP or before SI or SI/SR to inhibit Cl – channels. Electrophysiological studies indicate that these drugs, at the concentrations used, selectively abolished Cl – currents activated under hypo-osmotic conditions (215 versus 290 mOsm). IP significantly ( P 〈 0.001) reduced the percentage of dead myocytes after 60-minute (30.8±1.3%, mean±SEM), 90-minute (35.3±1.3%), and 120-minute (39.2±1.7%) SI compared with controls (44.7±1.6%, 54.5±1.3%, and 58.9±1.8%, respectively) and after 45-minute SI/120-minute SR (36.3±0.6%) compared with control (56.6±2.2%). Hypo-osmotic stress also produced protection similar to IP. IAA-94 or NPPB abolished the protection of both IP and hypo-osmotic stress. In buffer-perfused rabbit hearts preconditioned with three 5-minute ischemia/10-minute reperfusion cycles given before the 40-minute long ischemia and 60-minute reperfusion, IP significantly (P 〈 0.0001) reduced infarct size (IP+vehicle, 4.7±0.9%, versus control+vehicle, 26.6±3.3%; mean±SEM). Again, IAA-94 or NPPB abolished the protection of IP. Our results implicate Cl – channels in the IP protection of the myocardium against ischemic/reperfusion injury and demonstrate that hypo-osmotic stress is capable of preconditioning cardiomyocytes.
Type of Medium:
Online Resource
ISSN:
0009-7330
,
1524-4571
DOI:
10.1161/01.RES.84.7.763
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
1999
detail.hit.zdb_id:
1467838-X
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