Document Detail


Improved cardiac function after prolonged hypothermic ischemia with the Na+/H+ exchange inhibitor HOE 694.
MedLine Citation:
PMID:  8633949     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Na+/H+ exchange represents an important mechanism for pH regulation in the cardiac cell that, however, may paradoxically mediate tissue damage in the reperfused myocardium. We investigated whether inhibition of the exchanger can protect the heart against damage after prolonged hypothermic storage with the use of the selective inhibitor 3-methylsulfonyl-4-piperidinobenzoyl-guanidine methanesulfonate (HOE 694). METHODS: After equilibration, isolated rabbit hearts were arrested with a 3 minute infusion of modified St. Thomas' cardioplegic solution and subsequently maintained in ischemic arrest at 4 degrees C for 12 hours before reperfusion at 37 degrees C for 60 minutes. Left ventricular function and creatine kinase release were measured at intervals throughout reperfusion. High-energy phosphate and adenine nucleotide content were determined in hearts before cardioplegia, at the end of the 12-hour storage period, and at the end of reperfusion. HOE 694 (1 mumol/L) was administered either with cardioplegia and throughout reperfusion (study 1) or selectively with either cardioplegia or reperfusion only (study 2). RESULTS: In study 1, systolic function in untreated hearts recovered to less than 40% of preischemic values and was associated with a greater than 1,000% percent sustained elevation in left ventricular end-diastolic pressure. In contrast, systolic recovery in HOE 694-treated hearts was significantly accelerated and improved to approximately 80%, whereas left ventricular end-diastolic pressure increased to only 300% of baseline. Significant protection also occurred in those hearts in which HOE 694 was administered only at reperfusion while the drug was less effective if given only during cardioplegia. Creatine kinase release was not significantly affected except in study 2, where it was significantly lower after 60 minutes of reperfusion in hearts where HOE 694 was added at the time of reperfusion. Tissue metabolite content was not affected by drug treatment. CONCLUSIONS: This study shows a marked protective effect of the Na+/H+ exchange inhibitor HOE 694 in rabbit hearts subjected to 12 hours of hypothermic ischemia and strongly suggests that antiport inhibitors could play an effective role in myocardial preservation.
Authors:
M L Myers; M Karmazyn
Related Documents :
18437149 - Effect of pressure overload on cardioprotection of mitochondrial katp channels and gsk-...
9004149 - Is stunning an important component of preconditioning?
8569209 - Influence of indapamide and chlorthalidone on reperfusion-induced ventricular fibrillat...
6084769 - Direct effects of streptokinase on the isolated rat myocardium.
10471349 - Trace amounts of albumin protect against ischemia and reperfusion injury in isolated ra...
9309669 - Detection of early ischemic damage by analysis of mitochondrial function in skinned fib...
23021349 - Sibling composition during childhood and adult blood pressure among native amazonians i...
23844619 - Blood pressure rises more in pre-eclampsia than normal pregnancy when acral skin is loc...
324319 - Effects of ventilatory techniques during cardiopulmonary bypass on post-bypass and post...
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Annals of thoracic surgery     Volume:  61     ISSN:  0003-4975     ISO Abbreviation:  Ann. Thorac. Surg.     Publication Date:  1996 May 
Date Detail:
Created Date:  1996-07-02     Completed Date:  1996-07-02     Revised Date:  2010-03-24    
Medline Journal Info:
Nlm Unique ID:  15030100R     Medline TA:  Ann Thorac Surg     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1400-6     Citation Subset:  AIM; IM    
Affiliation:
Department of Cardiovascular Surgery, University of Western Ontario, London, Canada.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Cardioplegic Solutions*
Creatine Kinase / metabolism
Guanidines / pharmacology*
Heart / drug effects*,  physiology*
Heart Arrest, Induced
Hemodynamics / drug effects
Hypothermia, Induced
Male
Myocardial Reperfusion*
Myocardial Reperfusion Injury / physiopathology,  prevention & control
Rabbits
Sodium-Hydrogen Antiporter / antagonists & inhibitors*
Sulfones / pharmacology*
Time Factors
Ventricular Function, Left
Chemical
Reg. No./Substance:
0/Cardioplegic Solutions; 0/Guanidines; 0/Sodium-Hydrogen Antiporter; 0/Sulfones; 141923-47-9/3-methylsulfonyl-4-piperidinobenzoyl guanidine; EC 2.7.3.2/Creatine Kinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Hyperkalemia alters endothelium-dependent relaxation through non-nitric oxide and noncyclooxygenase ...
Next Document:  Kinetics of induction and protective effect of heat-shock proteins after cardioplegic arrest.