Abstract:
:Intracellular calcium ([Ca]i) overload on reperfusion may be one of the mechanisms responsible for ischemia-induced regional myocardial dysfunction. Because inhibiting the Na-H exchanger (NHE) limits intracellular sodium ([Na]i) and subsequent [Ca]i accumulation, we hypothesized that NHE inhibition would attenuate regional dysfunction in response to 25 cycles of ischemia (I, 2-min) and reperfusion (R, 8-min) of the left circumflex coronary artery (LCx) in conscious swine. Six animals were instrumented to measure arterial pressure, regional myocardial blood flow (colored microspheres), systolic wall thickening (WTh) in the normally perfused (left anterior descending, LAD) and LCx regions (sonomicrometry), LCx blood flow velocity (Doppler), and to reversibly occlude the LCx (hydraulic occluder). Each animal completed three protocols separated by 7 days: ISC, 25 I/R cycles; CAR, 25 I/R cycles + NHE inhibition (cariporide); and VEH, vehicle administration for 4.2 h. Regional myocardial blood flow was measured during LCx occlusion in the first protocol and 10 min after I/R 25 in all protocols. Systemic hemodynamics were similar among and within each protocol. Blood flow measured during LCx occlusion confirmed that perfusion was reduced (p < 0.05) to this compared with the LAD region. During ISC, LCx WTh was reduced (p < 0.05) after five IR cycles, and a stable reduction (approximately 55% of baseline; p < 0.05) was present after 20 I/R cycles. During CAR, LCx systolic WTh was reduced (p < 0.05) only after 15 and 25 I/R cycles (approximately 80 and 72%, respectively). The decrease in LCx WTh was greater in ISC than in CAR (p < 0.05). LCx WTh was not altered during VEH, while LAD WTh was similar within and among all protocols. Regional blood flow measured after 25 I/R cycles was not different among protocols. Our results indicate that NHE inhibition delays the onset and limits the degree of regional dysfunction in response to repeated bouts of ischemia and reperfusion.
journal_name
J Cardiovasc Pharmacoljournal_title
Journal of cardiovascular pharmacologyauthors
Symons JD,Correa SD,Schaefer Sdoi
10.1097/00005344-199812000-00001subject
Has Abstractpub_date
1998-12-01 00:00:00pages
853-62issue
6eissn
0160-2446issn
1533-4023journal_volume
32pub_type
杂志文章abstract::We have evaluated the effects of indoramin, an alpha-adrenoreceptor blocking drug, used as sole therapy in a group of 27 patients with essential hypertension. Blood pressure and heart rate were measured continuously over prolonged ambulatory periods using an established invasive technique before and after six weeks of...
journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00005344-198305000-00001
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/00005344-199109000-00003
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
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更新日期:1990-01-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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journal_title:Journal of cardiovascular pharmacology
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更新日期:1994-03-01 00:00:00
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
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journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章
doi:10.1097/FJC.0b013e318236e380
更新日期:2012-01-01 00:00:00
abstract::The combination of a beta-adrenoceptor-blocking drug with the dihydropyridine calcium channel antagonist, nitrendipine, has particular therapeutic advantages in the management of hypertension. The beta-blocker reduces any reflex increases in sympathetic nervous system and renin-angiotensin system activity that result ...
journal_title:Journal of cardiovascular pharmacology
pub_type: 杂志文章,评审
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