Pentoxifylline protects the small intestine after severe ischemia and reperfusion.

OBJECTIVES: Pentoxifylline, a methylxanthine derivative with significant hemorheologic properties, is used for claudication in patients with peripheral vascular disease, and experimentally for ischemic injury to organs because of its antioxidant and antiinflammatory effects. We used a rat model of severe small intestinal ischemia and reperfusion to determine the ability of pentoxifylline in improving survival, molecular response, and pathological protection. MATERIALS AND METHODS: We used 6 groups of male Wistar rats (n=25 each). The superior mesenteric artery was occluded for 120 minutes. Laboratory and tissue studies were done on 5 animals, 1 hour after reperfusion, and animal survival was assessed at 7 days. There were 2 control groups that received normal saline, either before ischemia or during reperfusion. The 4 treated groups received pentoxifylline 1 or 10 mg/kg at the same times mentioned above. Laboratory studies included measuring serum lactic acid dehydrogenase, tumor necrosis factor-α, interleukin-1ß, and interleukin-6.Intestinal tissue malondialdehyde and myeloperoxidase in small intestine tissue also were measured. Histology and laser vascular blood flow at baseline and reperfusion were obtained, and survival was determined 7 days after ischemia. RESULTS: A significant survival benefit in the animals treated with 10 mg/kg of pentoxifylline at reperfusion was noted. This coincided with a reduction in biochemical markers of cell damage - specifically, serum lactic acid dehydrogenase, and tissue malondialdehyde, ischemia, and reperfusion. Additionally, we saw decreased levels of tumor necrosis factor-α, interleukin-1ß, and interleukin-6. Improved postreperfusion blood flow shown by laser Doppler technology also was seen in the treated groups. Histologically, we observed less neutrophil infiltration in the intestine of ischemic-treated rats. Also seen in the control animals were increased necrotic lesions in the microvilli with a higher presence of lysozyme in the Paneth cells. Survival was significantly better at 7 days (70% vs 40%) when we compared the pentoxifylline group treated at reperfusion (10 mg/kg) to the ischemic controls. CONCLUSIONS: Pentoxifylline had a significant protective effect on severely ischemic bowel when administered during reperfusion at a dosage of 10 mg/kg. Better survival, improved histology, and molecular response should urge consideration of the consideration of applying these findings in some general surgery and transplant conditions.

John Collins Warren: Master educator and pioneer surgeon of ether fame.

John Collins Warren (1778-1856) represented the apex of surgery and medicine of the first half of nineteenth century Boston. Educated at Harvard College where he obtained a Bachelor of Arts in 1797, he contemplated the idea of a business career prior to setting sail for a traditional medical education at Europe's finest universities. From 1799 to 1802, he attended prestigious medical and surgical lectures in London, Edinburgh, and Paris. Warren received an honorary MD from Scotland's St. Andrews University in 1802. He then returned to Boston and joined his father's practice. In 1815, he followed his accomplished father as the Hersey Professor of Anatomy and Surgery at Harvard Medical School. He held this position with great distinction until 1847 when he retired as professor emeritus. From 1816 to 1819 he served as Harvard Medical School dean and received an honorary medical degree at the end of his term.John Collins Warren had numerous surgical accomplishments during his illustrious career. Clinically, he was active and varied in his practice, operating on strangulated hernias, tumors, and cataracts, in addition to performing vascular surgery and amputations. He published many articles and books of widespread circulation. Professor Warren also performed the first reported case of ether anesthesia administered by William T. Morton on October 16, 1846. Outside the operating theatre, Doctor Warren and his colleagues were revered for founding the Massachusetts General Hospital in 1821, and years before, in 1812, Warren and his associates established the New England Journal of Medicine and Surgery. In light of his varied contributions, John Collins Warren is remembered as a dedicated and innovative surgeon, as well as a committed medical educator, able administrator and effective leader.

1954.

1954 marked the most important year for modern transplantation. It represented the date in which the first successful live kidney transplant was performed by the devoted group of Joseph Murray, Hartwell Harrison, and their Peter Bent Brigham associates in Boston. Intense preparation and careful analysis was required for a long time to arrive at the resounding success manifested in the case of the Herrick twin brothers. Years later, only the discovery of chemical immunosuppression such as azathioprine and the use of radiation therapy permitted occasional good results in kidney transplantation. Great contributors of this period included Elion and Hitchings, Calne and Zukowski, Woodruff, Goodwin, and many others. In a few more years, the use of steroids and an antilymphocyte preparation by the committed team of Tom Starzl from Colorado improved the opportunities for patient outcome. The latter part of the 1960s witnessed the maturation of the Minnesota program with the arrival of John Najarian from California. The 1970s introduced different morbidity and mortality associated with immunosuppressive treatment, and required adjustments in patient management were necessary. New advances were to come in years ahead.