Substrate-induced changes in the lipid content of ischemic and reperfused myocardium. Its relation to hemodynamic recovery.

Abstract

To investigate the effect of lactate, pyruvate, and glucose on the endogenous levels of lipids in the normoxic, ischemic, and reperfused myocardium, isolated working rat hearts were exposed to various grades of ischemic insult (15, 30, or 45 minutes). Glucose was present as the basal substrate in the perfusion medium, and lactate (5 mM) or pyruvate (5 mM) was added as the cosubstrate. Lipid metabolism was evaluated by fatty acid accumulation, triacylglycerol turnover, and phospholipid homeostasis. Exogenous lactate significantly increased fatty acid content above preischemic levels after 45 minutes of ischemia. In glucose-perfused hearts, fatty acid levels were even slightly higher than in lactate-perfused hearts, whereas pyruvate-perfused hearts demonstrated less accumulation of fatty acids. By reperfusion, fatty acid levels in glucose-perfused hearts returned to control values. In lactate- and pyruvate-perfused hearts, fatty acid accumulation was further enhanced by reperfusion. When the fatty acid content exceeded 400 nmol/g dry wt during reperfusion, hemodynamic function was impaired, whereas fatty acid levels below 400 nmol/g dry wt did not correlate with hemodynamic recovery. The total triacylglycerol content did not change during ischemia and reperfusion. However, accumulation of glycerol was remarkable during the first 15 minutes of ischemia in all hearts, and release of glycerol by reperfusion was considerable in lactate-perfused hearts after 30 minutes of ischemia and in all groups of hearts after 45 minutes of ischemia. Release of glycerol in association with maintained levels of triacylglycerols suggests turnover of the triacylglycerol pool. The rate of triacylglycerol cycling correlated poorly with hemodynamic recovery. Accumulation of arachidonic acid revealed disturbances in phospholipid turnover. Arachidonic acid accumulation during reperfusion demonstrated a strong relation with impairment of cardiac function. Hence, derangements in phospholipid homeostasis during reperfusion might be involved in myocardial damage, which is influenced by the substrates available.

Long-chain fatty acids increase basal metabolism and depolarize mitochondria in cardiac muscle cells

“…During prolonged ischemia (Ͼ20 min) and after reperfusion, the intracellular concentration of LC fatty acids is known to increase significantly (6,33), probably because of lipase-catalyzed release of acyl groups from phospholipids and endogenous triacylglycerols. For example, in the glucose-perfused heart, tissue fatty acid content has been shown to increase from ϳ70 nmol/g dry wt (preischemia) to ϳ290 nmol/g dry wt after 30-min ischemia and to remain elevated during reperfusion (6).…”

“…For example, in the glucose-perfused heart, tissue fatty acid content has been shown to increase from ϳ70 nmol/g dry wt (preischemia) to ϳ290 nmol/g dry wt after 30-min ischemia and to remain elevated during reperfusion (6). When fatty acid content exceeded a threshold value of ϳ400 nmol/g dry wt, reperfused hearts did not recover any contractile function.…”

“…Whether this uncoupling action manifests in intact cardiac muscle is not known (14,35). This unresolved issue is important because LC fatty acids are the major metabolic substrates of the heart and, furthermore, they are known to accumulate in high concentrations during ischemia (6,33). The aims of the present study were to determine the effects of LC fatty acids on both resting heat rate and mitochondrial membrane potential (⌬⌿) of intact cardiac muscle.…”

Myocardial ischemia-reperfusion and cardioprotection: a study with microdialysis in a porcine model

“…However, at reperfusion after 45 min of ischemia, as compared to ischemia of shorter duration, there was a greater magnitude of glycerol release into the effluent than was expected when the accumulated concentration before reperfusion was considered (de Groot 1993). The prolonged release of glycerol after ischemia of longer duration coincided with prolonged lactate dehydrogenase release (de Groot 1993). This supports that increased severity or duration of ischemia may lead to increased glycerol release at reperfusion indicating further injury.…”

“…In isolated rat hearts, with ischemia of different durations from 15 min to 45 min, there was a glycerol accumulation in all hearts during ischemia (de Groot 1993). However, at reperfusion after 45 min of ischemia, as compared to ischemia of shorter duration, there was a greater magnitude of glycerol release into the effluent than was expected when the accumulated concentration before reperfusion was considered (de Groot 1993). The prolonged release of glycerol after ischemia of longer duration coincided with prolonged lactate dehydrogenase release (de Groot 1993).…”