Document Detail

Isoflurane-enhanced recovery of canine stunned myocardium: role for protein kinase C?
MedLine Citation:
PMID:  10485783     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Isoflurane enhances the functional recovery of postischemic, reperfused myocardium by activating adenosine A1 receptors and adenosine triphosphate-regulated potassium channels. Whether protein kinase C is involved in this process is unknown. The authors tested the hypothesis that inhibition of protein kinase C, using the selective antagonist bisindolylmaleimide, attenuates isoflurane-enhanced recovery of stunned myocardium in dogs. METHODS: Fifty dogs were randomly assigned to receive intracoronary vehicle or bisindolylmaleimide (2 or 8 microg/min) in the presence or absence of isoflurane (1 minimum alveolar concentration). Five brief (5 min) coronary artery occlusions interspersed with 5-min reperfusion periods followed by 180 min of final reperfusion were used to produce myocardial stunning. Hemodynamics, regional segment shortening, and myocardial blood flow (radioactive microspheres) were measured at selected intervals. RESULTS: There were no differences in baseline hemodynamics, segment shortening, or coronary collateral blood flow between groups. Isoflurane significantly (P<0.05) decreased heart rate, mean arterial pressure, rate pressure product, and the maximum rate of increase of left ventricular pressure (+dP/dt(max)) in the presence or absence of bisindolylmaleimide. Sustained contractile dysfunction was observed in dogs that received vehicle (recovery of segment shortening to 12+/-8% of baseline), in contrast to those that received isoflurane (75+/-7% recovery). Bisindolylmaleimide at a dose of 2 microg/min alone enhanced recovery of segment shortening (50+/-7% of baseline) compared with vehicle-pretreated dogs, and isoflurane in the presence of 2 microg/min bisindolylmaleimide further enhanced recovery of contractile function (79+/-8% of baseline). In contrast, 8 microg/min bisindolylmaleimide alone (32+/-12%) or combined with isoflurane (37+/-17%) did not enhance recovery of segment shortening compared with vehicle-pretreated dogs. CONCLUSIONS: The results indicate that protein kinase C inhibition using low doses of bisindolylmaleimide alone produces cardioprotection, and isoflurane further enhances this protection. In contrast, high doses of bisindolylmaleimide are not cardioprotective in the presence or absence of isoflurane. A role for protein kinase C during isoflurane-induced recovery of the stunned myocardium cannot be excluded.
W G Toller; M W Montgomery; P S Pagel; D A Hettrick; D C Warltier; J R Kersten
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Anesthesiology     Volume:  91     ISSN:  0003-3022     ISO Abbreviation:  Anesthesiology     Publication Date:  1999 Sep 
Date Detail:
Created Date:  1999-09-23     Completed Date:  1999-09-23     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  1300217     Medline TA:  Anesthesiology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  713-22     Citation Subset:  AIM; IM    
Department of Anesthesiology, Medical College of Wisconsin and the Zablocki VA Medical Center, Milwaukee 53226, USA.
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MeSH Terms
Anesthetics, Inhalation / pharmacology*
Coronary Circulation / drug effects
Dose-Response Relationship, Drug
Heart / drug effects*
Hemodynamics / drug effects
Indoles / pharmacology
Ischemic Preconditioning
Isoflurane / pharmacology*
Maleimides / pharmacology
Myocardial Contraction / drug effects
Myocardial Stunning / drug therapy*,  physiopathology
Protein Kinase C / antagonists & inhibitors,  physiology*
Signal Transduction / drug effects
Grant Support
Reg. No./Substance:
0/Anesthetics, Inhalation; 0/Indoles; 0/Maleimides; 119139-23-0/bisindolylmaleimide; 26675-46-7/Isoflurane; EC Kinase C

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

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