EFFECT OF SULFO-N-SUCCINIMIDYL PALMITATE ON THE RAT-HEART - MYOCARDIAL LONG-CHAIN FATTY-ACID UPTAKE AND CARDIAC-HYPERTROPHY

Abnormal long-chain fatty acid metabolism has been suggested as having a role in the genesis of certain cardiac diseases, and depressed myoc ardial long-chain fatty acid uptake has been clinically demonstrated i n some patients with hypertrophic cardiomyopathy. However, the site wh ere long-chain fatty acid metabolism is affected in cardiomyopathy rem ains unclear. Although cardiac hypertrophy is reported to be induced i n rats by a fat-free diet, little is known of the consequences of depr essed myocardial long-chain fatty acid uptake, Sulfo-N-succinimidyl de rivatives of long-chain fatty acids have been shown to irreversibly in hibit long-chain fatty acid transport. To investigate the possible lin kage of abnormal long-chain fatty acid uptake with cardiac hypertrophy , myocardial long-chain fatty acid uptake was blocked in rats using a sulfo-N-succinimidyl derivative of palmitate (SSP). SSP was intraperit oneally administered to rats for 12 weeks, and its effects on physiolo gical parameters, and cardiac morphology were studied. SSP treatment ( 20 mg/Lg) caused a 12% increase in heart weight (663.7 +/- 33.6 mg in controls v 741.2 +/- 26.5 mg after SSP treatment) and an 11% increase in the heart weight to body weight ratio (2.46 +/- in controls v 2.72 +/- 0.17 after SSP) without any significant change of body weight, No significant differences were observed in blood pressure, heart rate, a nd serum hormones (insulin and triiodothyronine) between the control a nd SSP-treated groups. An increase of the serum glucose level (1.25 +/ - 0.1 7 g/l in controls v 1.90 +/- 0.10 g/l after SSP) and a decrease of serum non-esterified fatty acids (5.69 +/- 0.59 mM in controls v 4. 00 +/- 0.38 mM after SSP) and triglycerides (97.5 +/- 13.0 mg/l in con trols v 82.5 +/- 13.0 mg/l after SSP) were also observed. Light micros copy demonstrated that the transverse diameter of the myocardial cells was increased by SSP administration (14.83 +/- 0.41 mu m in controls v 18.31 +/- 0.65 mu m after SSP), although their morphology was not ot herwise altered. The cardiac hypertrophy provoked by SSP, which depres ses myocardial long-chain fatty acid uptake, seems to be associated wi th metabolic changes in the absence of any significant hemodynamic or hormonal effects. Some types of cardiac hypertrophy may be related to altered myocardial long-chain fatty acid uptake. (C) 1995 Academic Pre ss Limited.