Adenosine triphosphate infusion increases liver energy status in advanced lung cancer patients: An in vivo 31P magnetic resonance spectroscopy study

Abstract

We recently observed inhibition of weight loss in patients with advanced nonsmall-cell lung cancer after intravenous infusion of ATP. Because liver ATP levels were found to be decreased in lung cancer patients with weight loss, the present 31 P magnetic resonance spectroscopy (MRS) study was aimed at investigating whether ATP infusion restores liver energy status in these patients. Nine patients with advanced nonsmall-cell lung cancer (stage IIIB/ IV) were studied 1 week before (baseline) and at 22 to 24 hours of continuous ATP infusion (37-75 g/kg/min). Localized hepatic 31 P MR spectra (repetition time 15 seconds), obtained in the overnight-fasted state, were analyzed for ATP and P i content. Ten healthy subjects (without ATP infusion) served as control. Liver ATP levels in lung cancer patients increased from 8.8 ؎ 0.7% (relative to total MR-detectable phosphate; mean ؎ SE) at baseline to 12.2 ؎ 0.9% during ATP infusion (P < .05), i.e., a level similar to that in healthy subjects (11.9 ؎ .9%). The increase in ATP level during ATP infusion was most prominent in patients with >5% weight loss (baseline: 7.9 ؎ 0.7%, during ATP infusion: 12.8 ؎ 1.0%, P < .01). In conclusion, ATP infusion restores hepatic energy levels in patients with advanced lung cancer, especially in weight-losing patients. These changes may contribute to the previously reported beneficial effects of ATP infusion on the nutritional status of lung cancer patients. (HEPATOLOGY 2002;35:421-424.) W eight loss is a common phenomenon in lung cancer patients and contributes significantly to the high morbidity and mortality in this disease. 1,2 Alterations in intermediary host metabolism have been frequently described, including elevated protein turnover, 3,4 glucose production, 5,6 and Cori cycle activity. 7 In an in vitro study, gluconeogenesis in isolated hepatocytes from sarcoma-bearing rats was increased during incubation with lactate, resulting in a 42% decrease in adenosine triphosphate (ATP) levels, as compared with hepatocytes from healthy rats (no change in ATP). 8 This suggests that elevated rates of gluconeogenesis in the cancer-bearing host put an increased demand on the energy stores and contribute to weight loss.Alterations in hepatic energy status have been well documented in animal models of various tumors. Decreased liver phosphorylation status, as observed by increased P i /ATP ratios, was detected in rats bearing prostate tumors 9 or sarcomas 10-12 and was correlated with increasing tumor burden. 10 Increased P i /ATP ratios may indicate a decreased energy-regenerating capacity within the hepatocytes of the cancer-bearing host. 8 It is noteworthy that these alterations in liver energy status were already detected before the development of weight loss. 13 Decreased liver ATP levels as detected by 31 P magnetic resonance spectroscopy (MRS) were reported in patients with various tumor types. 14 Recently, we reported decreased hepatic ATP and phosphorylation status in weight-losing lung cancer patients, when compared with weight-stabl...

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