Faculty Collaboration Database

Isoflurane-enhanced recovery of canine stunned myocardium: role for protein kinase C? Anesthesiology 1999 Sep;91(3):713-22

Date

09/15/1999

Pubmed ID

10485783

DOI

10.1097/00000542-199909000-00024

Scopus ID

2-s2.0-0032842470 (requires institutional sign-in at Scopus site)   73 Citations

Abstract

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.

Author List

Toller WG, Montgomery MW, Pagel PS, Hettrick DA, Warltier DC, Kersten JR

MESH terms used to index this publication - Major topics in bold

Anesthetics, Inhalation
Animals
Coronary Circulation
Dogs
Dose-Response Relationship, Drug
Female
Heart
Hemodynamics
Indoles
Ischemic Preconditioning
Isoflurane
Male
Maleimides
Myocardial Contraction
Myocardial Stunning
Protein Kinase C
Signal Transduction