Ignacio J. Guzman

Arteriography Changes after Partial Ileal Bypass

This paper on atherosclerosis progression and regression will confine itself to the role of the partial ileal bypass operation and arteriographic assessment. Specifically, we will report a prospective study of serial coronary arteriograms in a cohort of our hyperlipidemia patients who have undergone partial ileal bypass operation.

Long-term hypolipidemic effect of portacaval transposition and distal intestinal resection without change in liver function tests☆

Partial ileal bypass and end-to-side portacaval shunt (PCS) have significantly reduced serum cholesterol levels in clinical use. PCS can cause deterioration of liver function. Portacaval transposition (PCT) may induce plasma cholesterol lowering equivalent to PCS without deleterious side effects. We have followed four dogs with PCT, two with 50% distal ileal resection (IR), and five with PCT + IR for 3 years, as well as four control animals for 1 year, and have measured their hepatic cholesterol synthesis, hepatic lipid concentration, and cholesterol turnover rates. The dogs at 3 years postoperatively are in good health without deterioration of liver function tests (BSP retention, bilirubin, GGT, SGOT, alkaline phosphatase) and BUN. Dogs with IR had 25% reduction of plasma cholesterol and 58% reduction of triglycerides; dogs with PCT had 36% reduction of plasma cholesterol (P < 0.01) and 39% reduction of triglycerides (P < 0.01); those with PCT + IR had 43% reduction of plasma cholesterol (P < 0.01) and 68% reduction of triglycerides (P < 0.001). Compared to normal dogs, IR dogs have increased cholesterol turnover rate (P < 0.05), hepatic total lipid (P < 0.02), free cholesterol (P < 0.01), and cholesterol esters (P < 0.01). PCT + IR dogs have increased hepatic cholesterol synthesis (P < 0.05), increased cholesterol turnover (P < 0.001), and increased hepatic free cholesterol (P < 0.05), and cholesterol ester (P < 0.05). Neither PCT nor IR alone affected the cholesterol-exchangeable pool sizes. However, the PCT + IR dogs, compared to normal dogs, have larger slowly (P < 0.05) and rapidly (P < 0.01) exchangeable cholesterol pool sizes. The rapidly exchangeable cholesterol pool size of PCT + IR was also larger than that after PCT alone (P < 0.01). In summary, there is significant and lasting 35+% reduction of plasma cholesterol and triglyceride for 36+ months after either PCT or PCT + IR without deterioration of liver function parameters. Combining the IR and PCT in euthyroid dogs does not significantly improve the cholesterol lowering and causes increased cholesterol pool sizes and hepatic cholesterol content. PCT dogs remained in good health, without deterioration of liver function, for 3 years. It is suggested that PCT may be an attractive clinical alternative to PCS, at least for lipid reduction.

Sterol dynamics following portacaval shunt

Abstract This study reports lipid studies on dogs up to 44 weeks following portacaval shunt. We have shown portacaval shunt to be associated with significant decreases in plasma cholesterol and triglyceride levels in the dog. Cholesterol synthesis and absorption appear to be unchanged following operation when compared to control animals. Two-hour postprandial serum bile acids are fortyfold greater in shunted animals than in control dogs. Further studies of the interrelationship of bile acid and cholesterol metabolism following portacaval shunt are suggested.

Increased hepatic cholesterol synthesis in normal rats by cross-circulation with ileal bypassed partners

Aortic cross-circulation between Holtzman rat littermates was employed to investigate the possible role of a blood-borne factor from the small intestine in the regulation of hepatic cholesterol synthesis. Experimental pairs, consisting of a normal rat and a distal 50% small bowel excluded partner, demonstrated significantly increased combined hepatic cholesterol synthesis when compared to control pairs, consisting of two normal rats, both at 3 and 5 days following parabiosis. This difference was accounted for by increased hepatic cholesterol synthesis in the normal rat in each experimental pair. Neither weight loss nor differences in dietary intake contributed to this effect. Whole blood cholesterol in the common circulation of both experimental and control pairs was lowered; while hepatic cholesterol content was transiently increased, at 3 but not 5 days following parabiosis. Thus, the intestinal bypassed rat stimulates, or releases inhibition of, hepatic cholesterol synthesis in a non-bypassed parabiotic partner. The mechanism for this phenomenon has yet to be defined.

Surgical Management of Hyperlipidemia

At the present time, there are three clinical surgical procedures that have been demonstrated to lower the circulating lipids: jejunoileal by-pass for management of morbid obesity, end-to-side portacaval shunt, and partial ileal by-pass. The primary purpose of jejunoileal by-pass is to achieve a caloric absorptive defect and subsequent weight reduction; an accompanying effect is plasma cholesterol and triglyceride lowering. Systemic diversion of the portal blood stream, long employed in the treatment of portal hypertension and esophageal varices, has been suggested as a therapeutic approach in the treatment of type IIa homozygous hyperlipoproteinemia in children. The partial ileal by-pass was designed specifically as a means to achieve cholesterol lowering.