The role of fatty acids in ischemic tissue injury: difference between oleic and palmitic acid

Abstract

Guinea pig hearts were subjected to low-flow perfusion (0.3 ml/g fresh weight/min) with an oxygen depleted perfusate. Fatty acids (palmitic or oleic acid), added to the perfusate, accelerated in a dose-dependent manner the anoxic decay of creatine phosphate and ATP, impaired lactate production and augmented enzyme release (lactate dehydrogenase, malate dehydrogenase). Palmitic and oleic acid, however, differed distinctly in their deleterious effect, this being greater for oleic acid. After 60 min anoxic low-flow perfusion with 11 mM glucose and 0.2 mM of either fatty acid, complexed in 5:1 molar relationship to albumin, the creatine phosphate content with palmitate is 39% greater than with oleate, the ATP content 23%, lactate production 15% greater, and release of malate dehydrogenase 24% lower, but the elevated contents of long-chain acyl CoA and acyl carnitine are not significantly different for the two fatty acids. These results accord with earlier experiences on subcellular systems showing that the physicochemical effects of the oleyl residue are more harmful than those of the palmityl residue.

Efectos del ayuno y del precondicionamiento hipóxico en bandas de ventrículo del corazón de rata expuestas a hipoxia-reoxigenación

“…The marked increase of the LCCoA and LCCa tissue-contents after the sustained hypoxic period agree with previous papers describing the effects of hypoxia on the rat heart (22,24,30,35). The increase of the LCCa content probably resulted from the activation of carnitine palmitoyltransferase I already described in the oxygen-deprived rat heart (21), while the concomitant depletion of freecarnitine most likely resulted from the trapping of carnitine as fatty acyl-esters due to the hypoxic accumulation of LCCa.…”

Amphiphile‐induced heart muscle‐cell (Myocyte) injury: Effects of intracellular fatty acid overload

“…Elevated plasma NEFA levels in myocardial ischemia patients (Kurien and Oliver, 1966) provided early support for a hypothesis that NEFA toxicity contributes to cardiac ischemic damage. Some (e.g., Piper and Das, 1986), but not all (e.g., Ichihara and Neely, 1985), subsequent studies are consistent with a pathophysicological role for NEFA as contributor to m y w e injury. Reduction of arterial NEFA levels or myocardial fatty acid production can decrease myocardial ischemic and reperfusion damage (Oliver et al, 1976;Vik-Mo et al, 1986).…”

“…Likewise, although the cellular effects of NEFAs and other amphiphiles are not completely understood, NEFAs have the potential to damage cells as membrane "anesthetics" (Seeman, 1972), enzyme inhibitors (Sandermann, 19781, and mitochondrial decouplers (Rottenberg and Hashimoto, 1986). As recently noted (Piper and Das, 1986;Vik-Mo et al, 1986) Myocyte isolation and culture Buffered balanced salt solution ("saline A") consisted NaH2P04, 5.0 mM glucose, and 20.0 mM Hepes, pH 7.4. Tissue digestion solution was prepared by dissolving pancreatin (60.0 mg) and collagenase (30.0 mg) in 100.0 ml saline A. Phosphate-buffered saline (PBS) consisted of In view of the constant energy demand of the myocar-137.0 mM NaC1, 2*7 mM KC1, 8*o mM Na2HP049 and dium, the influence of NEFAs on mitochondria1 fundion 1.0 mM KH2P04, PH 7.4.…”

Biochemical Basis of Ischemic Heart Injury and of Cardioprotective Interventions

“…[67][68][69][70][71][72]. Long-chain fatty acids released during ischemia may contribute to tissue injury [73][74][75][76][77][78][79][80]. In particular, they increase the open probability of sarcolemmal or intracellular Ca 2+ channels, by acting directly on the channel protein or by modifying the protein/lipid interface, contributing to cytotoxic Ca 2+ overload (See Section 3.3) [81].…”