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 myocardial long-chain fatty acid uptake has been clinically demonstrated in some patients with hypertrophic cardiomyopathy. However, the site where long-chain fatty acid metabolism is affected in cardiomyopathy remains unclear. Although cardiac hypertrophy is reported to be induced in rats by a fat-free diet, little is known of the consequences of depressed myocardial long-chain fatty acid uptake. Sulfo-N-succinimidyl derivatives of long-chain fatty acids have been shown to irreversibly inhibit long-chain fatty acid transport. To investigate the possible linkage 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 intraperitoneally administered to rats for 12 weeks, and its effects on physiological parameters, and cardiac morphology were studied. SSP treatment (20 mg/kg) 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±0.10 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, and serum hormones (insulin and triiodothyronine) between the control and SSP-treated groups. An increase of the serum glucose level (1.25±0.17 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 m m in controls v 4.00±0.38 m m after SSP) and triglycerides (97.5±13.0 mg/l in controls v 82.5±13.0 mg/l after SSP) were also observed. Light microscopy demonstrated that the transverse diameter of the myocardial cells was increased by SSP administration (14.83±0.41 μ m in controls v 18.31±0.65 μ m after SSP), although their morphology was not otherwise altered. The cardiac hypertrophy provoked by SSP, which depresses myocardial long-chain fatty acid uptake, seems to be associated with 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.