Lidocaine Attenuates Mechanical and Metabolic Derangements Induced by Palmitoyl-L-Carnitine in the Isolated Perfused Rat Heart

Abstract

The effect of lidocaine on the palmitoyl-L-carnitine (PAL-CAR)-induced mechanical and metabolic derangements was studied in Langendorff rat hearts, perfused aerobically at a constant flow rate and paced electrically. PALCAR (5 µmol/l) increased the left ventricular end-diastolic pressure, decreased the left ventricular developed pressure (i.e., mechanical dysfunction), and decreased the tissue levels of adenosine triphosphate and creatine phosphate (i.e., metabolic change). These mechanical and metabolic alterations induced by PALCAR were concentration-dependently attenuated by lidocaine (20, 50 or 100 µmol/l). Nevertheless, lidocaine (20, 50 or 100 µmol/l) did not affect the mechanical function and energy metabolism of the normal (PALCAR-untreated) heart. These results indicate that lidocaine has a cardioprotective action against the PALCAR-induced mechanical and metabolic derangements.

The Late Na+ Current (INa) Inhibitor Ranolazine Attenuates Effects of Palmitoyl-L-Carnitine to Increase Late INa and Cause Ventricular Diastolic Dysfunction

“…The content of long-chain acyl carnitines (including PC) increases in myocytes during hypoxia (DaTorre et al, 1991), and these molecules are reported to accumulate in sarcolemmal membranes (Knabb et al, 1986). Although the concentration of PC in ischemic myocardial cells has not been reported to our knowledge and the effects of endogenously produced and exogenously applied PC may be different, the concentration of 4 M PC used in this study is similar to concentrations used in previous studies (Mészà ros and Pappano, 1990;Sato et al, 1992;Wu and Corr, 1992;Shen and Pappano, 1995;Arakawa et al, 1997;Arakawa and Hara, 1999;Netticadan et al, 1999;Maruyama et al, 2000), and the effects of an exogenous application of 4 M PC in this study are similar in magnitude to the effects of brief ischemia associated with a 4-to 5-fold elevation of long-chain acyl carnitine content in the heart (DaTorre et al, 1991). Thus, the results of the present study suggest that a pathologically enhanced, PC-induced late I Na may be a contributor to ischemia-induced dysfunction.…”

Effect of 5-(N,N-Dimethyl)-Amiloride, a Specific Inhibitor of Na⁺/H⁺ Exchanger, on the Palmitoyl-<i>L</i>-Carnitine-Induced Mechanical and Metabolic Derangements in the Isolated Perfused Rat Heart

“…Long-chain acylcarnitines are regarded as one of the important factors in producing irreversible damage in the ischemic heart [6,7], and therefore several studies have addressed the actions of substances that protect the myocardium from damage induced by long-chain acylcarnitine [10,[15][16][17][18]. We have shown that lidocaine [15], dilazep [16,17] and diltiazem [10] attenuate the PALCAR-induced mechanical and metabolic derangements in the isolated perfused heart.…”

“…We have shown that lidocaine [15], dilazep [16,17] and diltiazem [10] attenuate the PALCAR-induced mechanical and metabolic derangements in the isolated perfused heart. Kang and Leaf [18] have reported that free polyunsaturated fatty acids attenuate arrhythmia induced by PAL- CAR in cardiac myocytes.…”

“…Second, administration of 5 Ìmol/l PALCAR may inflict damage to the heart to an extent similar to that induced by ischemia in terms of tissue accumulation of long-chain acylcarnitines [19]. Last, 5 Ìmol/l PALCAR produces not only mechanical dysfunction and energy deficiency [10,15,16] but also membrane damage [10,19], and induces electrophysiological alterations [11,12,20] in the heart.…”

“…These facts indicate that inhibition of the Na + /H + exchanger with DMA protects the myocardium from the PALCAR-induced derangements. We have previously demonstrated that lidocaine [15] and tetrodotoxin [16], both of which have an inhibitory action on the Na + channel, attenuate the PALCAR-induced mechanical and metabolic derangements in the isolated perfused heart. Therefore, inhibitors of the Na + /H + exchanger or the Na + channel would attenuate the PALCAR-induced de-rangements, probably because of inhibition of Na + entry into the myocardial cell.…”