Richard D. Rucker

Clinical angiographic regression of atherosclerosis after partial ileal bypass

Clinical documentation of atherosclerotic plaque regression has been difficult to obtain. This is a report of a patient with severe and early atherosclerotic cardiovascular disease with regression of at least three major atherosclerotic lesions demonstrated by coronary arteriography 10 years after partial ileal bypass operation. The patients total plasma cholesterol was reduced over these 10 years, ranging from 40% to 23%, from the preoperative level of 757 mg/dl. Sequential arteriograms were assessed independently by several arteriographers and blindly by the Arteriography Review Panel of the Program on Surgical Control of the Hyperlipidemias (POSCH). The readings were analyzed by 4 grading methods. Unanimously, marked regression was read in the proximal left circumflex artery (70% leads to 20%), middle segment of the right coronary artery (45% leads to 20%), and in the distal right coronary artery (80% leads to 50%). Thus, by any and all of the methods used, there was significant regression of arteriographically demonstrated atherosclerotic lesions.

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.

Changes in Atherosclerotic Lesions Following Surgical Cholesterol Reduction

Surgical procedures specifically employed to lower the plasma cholesterol concentration include partial ileal bypass, portacaval shunt, and various biliary drainage operations. These operations have all been used clinically and in the animal laboratory to assess changes in atherosclerotic plaque lesions induced by marked cholesterol reduction. Interesting and promising data have been derived from these studies.

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.