Document Detail

Mechanism of myocardial protective action of dilazep during ischaemia and reperfusion.
MedLine Citation:
PMID:  3628458     Owner:  NLM     Status:  MEDLINE    
The aim of this study was to investigate if dilazep is able to reduce with a direct protective action on the myocardium the deleterious effects caused by ischaemia and reperfusion. For this purpose we used an isolated rabbit heart preparation. The hearts were either perfused aerobically or made totally ischaemic for 60 min (by abolishing coronary flow) or made ischaemic for 60 min and then reperfused for 30 min. Ischaemic and reperfusion damage was measured in terms of alteration in mechanical function, lactate and CPK release, mitochondrial function and tissue content of Adenosine Triphosphate (ATP), Creatine Phosphate (CP) and calcium. Dilazep (10(-5) M) was administered in the perfusate either 20 minutes before ischaemia or only during post-ischaemic reperfusion. Ischaemia induced a decline of the endogenous stores of ATP and CP, followed by an alteration of calcium homeostasis with increase of diastolic pressure, mitochondria calcium overload and impairment of the oxidative phosphorylating capacities. On reperfusion, tissue and mitochondrial calcium increase the capacity of the mitochondria to use O2 for state III respiration was further impaired and the ATP-generating capacity reduced. Diastolic pressure increased and there was only a small recovery of active tension generation associated with massive CPK release. Administration of dilazep before ischaemia induced a negative inotropic effect which, in turn, resulted in a slowing of the rate of CP and ATP depletion during ischaemia. This protected the hearts against the ischemic, and reperfusion-induced decline in the ATP-generating and O2-utilizing capacities of the mitochondria. In addition, there was a less marked increase in tissue and mitochondrial Ca++, CPK and lactate release were reduced and the recovery of developed pressure on reperfusion was significantly increased. Administration of dilazep during reperfusion failed to modify the exacerbation of ischaemic damage caused by the readmission of coronary flow. These data suggest that dilazep benefits the ischaemic myocardium via an ATP sparing action.
A Cargnoni; E Condorelli; C Ceconi; S Curello; A Albertini; R Ferrari
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Pharmacological research communications     Volume:  19     ISSN:  0031-6989     ISO Abbreviation:  Pharmacol Res Commun     Publication Date:  1987 May 
Date Detail:
Created Date:  1987-10-14     Completed Date:  1987-10-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0236354     Medline TA:  Pharmacol Res Commun     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  341-57     Citation Subset:  IM    
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MeSH Terms
Adenosine Triphosphate / biosynthesis
Azepines / therapeutic use*
Calcium / metabolism
Coronary Circulation / drug effects
Coronary Disease / drug therapy*,  physiopathology
Dilazep / therapeutic use*
Mitochondria, Heart / metabolism
Myocardial Contraction / drug effects
Myocardium / metabolism
Oxygen Consumption / drug effects
Phosphocreatine / metabolism
Reg. No./Substance:
0/Azepines; 35898-87-4/Dilazep; 56-65-5/Adenosine Triphosphate; 67-07-2/Phosphocreatine; 7440-70-2/Calcium

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

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