Isoflurane applied during ischemia enhances intracellular calcium accumulation in ventricular myocytes in part by reactive oxygen species.

Abstract

BACKGROUND:

Isoflurane applied before myocardial ischemia has a beneficial preconditioning effect which involves generation of reactive oxygen species (ROS); ROS, however, have been implicated in critical cytosolic calcium ([Ca2+]i) overload during ischemia. We therefore investigated isoflurane's effects on intracellular Ca2+ handling in ischemic ventricular myocytes and the association with ROS.

METHODS:

Simulated ischemia was induced in electrically stimulated rat ventricular myocytes for 30 min (ischemia). Isoflurane-treated cells were additionally exposed to 1MAC of isoflurane (ischemia + iso). To determine the contribution of ROS to Ca2+ homeostasis during ischemia in both groups, the intracellular ROS scavenger, N-mercaptopropionylglycine (MPG), was added to the superfusion buffer. The fluorescent ratiometric Ca2+ dye fura-2 was employed to determine [Ca2+]i.

RESULTS:

Resting and peak [Ca2+]i increased in the ischemia and the ischemia + iso group. However, Ca2+ accumulation was most prominent in isoflurane-treated cardiomyocytes (P < 0.05) and could be mitigated by MPG in both groups (P < 0.001). Isoflurane also decreased the rate constant of the Ca2+ transient decline but did not further diminish the amplitude of the transient during ischemia.

CONCLUSION:

Isoflurane when applied during ischemia appears to worsen [Ca2+]i overload, which is caused by impeding Ca2+ clearance. As MPG mitigated the increase in [Ca2+]i, isoflurane seems to enhance ROS-mediated effects on intracellular Ca2+ handling in cellular ischemia.

• Authors: M Dworschak, D Breukelmann, J D Hannon
• Journal: Acta anaesthesiologica Scandinavica (Acta Anaesthesiol Scand) Vol. 48 Issue 6 Pg. 716-21 (Jul 2004) ISSN: 0001-5172 [Print] England
• PMID: 15196104 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2004 Acta Anaesthesiologica Scandinavica

Chemical References

• Anesthetics, Inhalation
• Fluorescent Dyes
• Reactive Oxygen Species
• fura-2-am
• Isoflurane
• Calcium
• Fura-2

Topics

• Analysis of Variance
• Anesthetics, Inhalation (administration & dosage, pharmacology)
• Animals
• Calcium (metabolism)
• Disease Models, Animal
• Fluorescent Dyes (administration & dosage)
• Fura-2 (administration & dosage, analogs & derivatives)
• Heart (drug effects)
• Intracellular Fluid (metabolism)
• Isoflurane (administration & dosage, pharmacology)
• Male
• Myocardial Ischemia (drug therapy)
• Myocytes, Cardiac (drug effects, metabolism)
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Time Factors