J Thorac Cardiovasc Surg 1994;108:789-790
© 1994 Mosby, Inc.
Potential uses of prostaglandin E1analog for cardiovascular disease
Harvey I. Pass, MD,
Helen W. Pogrebniak, MD
Surgery Branch
National Cancer Institute
National Institutes of Health
Building 10, Room 2B07
Bethesda, MD 20892
To the Editor:
We read with interest two recent reports in the JOURNALregarding the therapeutic efficacy of prostaglandin E1 (PGE1) for improved preservation of ultrastructure in heart-lung transplantation 
1 and amelioration of pulmonary function in patients with heart and lung failure after cardiotomy 2. PGE1 analogs, specifically misoprostol (Cytotec), are already in use for inhibition of acid secretion in patients with peptic ulceration. These analogs differ from PGE1 and PGE2 in that there is a methylydroxyl group at position 16 and the absence of the cisdouble bond at position 5. These analogs, moreover, are associated with a longer survival for cardiac allografts in murine models 3 and prevention of acute renal graft rejection inhuman beings. 4 Such immunologicaly based mechanisms, we hypothesized, may be related to downregulation of cytokine production by effector cells such as macrophages. To test this hypothesis, we treated peritoneal exudative cells from mice (which are predominantly macrophages) with lipopolysaccharide, an endotoxin known to activate these cells and cause them to produce tumor necrosis factor, interferon gamma, and interleukin-1 and interleukin-6, in the presence or absence of a PGE1 analog (provided by Searle Pharmaceutical, Chicago, Ill.). As seen in Table I, a dose-dependent decrease in cytokine production occurred with the addition of the analog. Furthermore, in other experiments, the misoprostol protected tumor necrosis factor–sensitive cells from that cytokine.
We theorize that some of the effects seen with the amelioration of lung function in the transplant situation, as well as after cardiotomy, may be due to downregulation of these potentially toxic cytokines. The PGE1 would prevent activated alveolar macrophages from producing harmful levels of these substances, which are associated with endothelial injury, edema, and eventually fibrosis. If the commercially available analog works in the same manner as the PGE1, it could be potentially useful not only in future trials of organ preservation, but as a potential additive to cardioplegic solutions to prevent cytokine ampli fication associated with free radical–based reperfusion injuries.
References
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Higgins RS, Letsou GV, Sanchez JA, et al. Improved ultrastructural lung preservation with prostaglandin E1 as donor pretreatment in a primate model of heart-lung transplantation. J THORAC CARDIOVASC SURG 1993;105:965-71.[Abstract]
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Mayumi H, Tokunaga K. Prostaglandin E1 for patients who have both heart and lung failure after cardiotomy. J THORAC CARDIOVASC SURG 1993;05:1120-1.
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Wiederkehr JC, Dumble L, Pollak R, Moran M. Immunosuppressive effect of misoprostol: a new synthetic prostaglandin E1 analogue. Aust N Z Surg 1990;60:121-4.
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Moran M, Mozes MF, Maddus MS, et al. Prevention of acute graft rejection by the prostaglandin E1 analogue misoprostol in renal-transplant recipients treated with cycolsporine and prednisone. N Engl J Med 1990;322:1183-8.[Abstract]
