Nonuniform behavior of intravenous anesthetics on postischemic adhesion of neutrophils in the guinea pig heart.
Adhesion of polymorphonuclear neutrophils (PMN) to the coronary endothelium is a crucial step in the development of ischemic myocardial injury. We tested the possible effects of six widely used IV anesthetics on non- and postischemic coronary adhesion of PMN in isolated perfused guinea pig hearts. Hearts (n = 5-11/group) were perfused under conditions of constant coronary flow. After 15 min global warm ischemia, PMN (10(6)) were infused in the second minute of reperfusion. The number of cells reemerging in the coronary effluent within 2 min was expressed as a percentage of the total number of administered PMN. Anesthetics were given 20 min before ischemia and during reperfusion. In addition, the ability of the drugs to influence the oxidative burst reaction of PMN was assessed by measuring luminol-enhanced chemiluminescence in response to 0.1 microM N-formyl-L-methionyl-L-leucyl-L-phenylalanine. Under nonischemic conditions, 26.3% +/- 0.5% of the injected PMN did not acutely reemerge from the coronary system. Subjecting the hearts to ischemia augmented retention to 40.0% +/- 1.6% (P < 0.05). This postischemic stimulation of adhesion was fully prevented by ketamine (10 microM: 22.8% +/- 1.6%, 20 microM: 26.6% +/- 0.7%), thiopental (25 microM: 24.0% +/- 1.7%, 50 microM: 24.0% +/- 1.4%), and midazolam (1.5 microM: 29.0% +/- 0.9%, 3 microM: 26.4% +/- 1.4%). Propofol also inhibited the augmented postischemic retention at 25 microM (28.7% +/- 2.4%). However, 50 microM propofol, etomidate (0.5 and 1 microM), and fentanyl (1 microM) all had no effect. Only thiopental reduced the nonischemic adhesion value (14.0% +/- 3.7%). This may be linked to the direct antioxidative action of thiopental (50% reduction in oxidative burst activity). Whereas ketamine, midazolam, and propofol did not significantly influence oxidant production by PMN, etomidate and the lipid solvent Intralipid enhanced the burst reaction. This activating effect of the lipid component could explain the biphasic behavior of propofol emulsion. Despite some possible differences in efficacy, several IV anesthetics may protect the heart from PMN-mediated reperfusion injury.


CONCLUSIONS
Ketamine, thiopental, and midazolam, but not etomodate or fentanyl, reduce postischemic adhesion of neutrophils in the coronary system of isolated perfused guinea pig hearts, suggesting a role in mitigating myocardial reperfusion injury.
Szekely
A
A
Institutes of Anesthesiology and Physiology, University of Munich, Munich, Germany.
Heindl
B
B
Zahler
S
S
Conzen
P F
PF
Becker
B F
BF
D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects*; D003326:Coronary Circulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D008163:Luminescent Measurements; D008165:Luminol; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000473:pathology; D009206:Myocardium / Q000166:cytology*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects
D018686:Anesthetics, Intravenous; D000975:Antioxidants; D007202:Indicators and Reagents; D008165:Luminol