Free radical-mediated damage during myocardial ischemia and reperfusion and protection by carnitine esters.
Ischemic injury may be exacerbated by readmission of oxygen into the myocardium, probably due to the formation of free radicals and their interaction with membrane lipids. We tested the hypothesis that ischemic myocardial damage is potentiated during reperfusion with excess free fatty acids in the globally ischemic rat heart, and in parallel studies, we investigated the protective effects of carnitine derivatives. Intermittent ischemia, i.e. three 20 min periods of ischemia followed by 10 min reperfusion each, was induced in isolated working rat hearts perfused with either glucose (11 mM) alone or glucose with palmitate (11 mM and 1.2 mM). The ischemic coronary flow was reduced to 1.1 ml/min in a low-flow group and equalled 0 ml/min in a no-flow group. Loss of functional recovery in the low-flow and no-flow group was more pronounced when palmitate was present in the perfusate. This was associated with increased levels of long-chain acyl-CoA esters in the palmitate perfused hearts. Malondialdehyde, an indicator of free radical formation, was elevated in both low-flow and no-flow groups when either substrate was used. We therefore suggest that free radical formation contributes to myocardial injury in intermittent ischemia. The mechanism of free radical formation and their sites of action have not yet been completely elucidated - the peroxidation of membrane lipids is probably involved, particularly in the presence of high palmitate. The protective effect of the carnitine derivatives D-propionylcarnitine, L-propionylcarnitine and propionylcarnitine taurine amide was studied in the no-flow hearts (Table 2).(ABSTRACT TRUNCATED AT 250 WORDS)
Pathology Department, University of Wisconsin, Madison.
R
R
Subramanian
S
S
Plehn
J
J
Noonan
M
M
Schmidt
A L
AL
Shug
D000818:Animals; D002264:Carboxylic Acids / Q000502:physiology*; D002331:Carnitine / Q000031:analogs & derivatives / Q000502:physiology*; D003326:Coronary Circulation; D003327:Coronary Disease / Q000473:pathology / Q000503:physiopathology*; D004952:Esters / Q000502:physiology*; D005609:Free Radicals; D008297:Male; D010100:Oxygen / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D002264:Carboxylic Acids; D004952:Esters; D005609:Free Radicals; D002331:Carnitine; D010100:Oxygen