JOURNAL OF SURGICAL RESEARCH 18, 163-167 (1975)

The Effects of Experimental Hypercholesterolemia

on Transposed Arterial and Venous Autografts’

JACK CURTIS, M.D., DAVID M. CONKLE, M.D., W. TYREE FINCH, M.D., VERNE C. LANIER, JR., M.D., RACHEL K. YOUNGER, B.A., AND

H. WILLIAM SCOTT, JR., M.D., F.A.C.S.

S. R. Light Laboratory for Surgical Research, Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee 37232.

Received November 8,1974

In both clinical and experimental hyper- lipidemic states, veins do not develop ather- osclerosis. While lipid concentration in both the venous and arterial systems are identical, marked structural and hemody- namic differences exist. Despite considerable clinical and laboratory investigation, the relative contribution of these anatomic and hemodynamic differences to the de- velopment of atherosclerosis is not com- pletely understood [2-81. This study evaluates the effects of experimental hyper- cholesterolemia on autogenous venous seg- ments transplanted into the arterial system and arterial autografts placed in the venous system.

MATERIALS AND METHODS Twenty-two mongrel dogs weighing 16-28

kg were used. All animals had arterial- venous segment transposition as follows: a left cervical incision was made, the carotid artery exposed and a 4-cm segment of jug- ular vein excised and placed in a bath containing 1000 units heparin in 250 ml saline. The femoral artery was then exposed via a left inguinal incision. A left thoractomy was then performed and a segment of the descending thoracic aorta isolated. An extracorporeal shunt between the left ca- rotid and femoral arteries was established to prevent ischemia of abdominal viscera, the thoracic aorta cross clamped, and a 2-cm segment excised and placed in heparinized saline solution. The 4-cm segment of jugular vein was then anastamosed to the thoracic

‘Supported in part by USPHC Grant HE 011192 and GM01742-07.

aorta end to end. The carotid-femoral external shunt was then discontinued, and the left chest was closed. A right thoractomy was then performed, the supe- rior vena cava (SVC) exposed and tran- sected, and the previously acquired aortic segment interposed in the SVC.

After full recovery from the operation, the animals were divided into two groups. Group 1 consisted of 18 animals made hypothyroid by 13’1 administration, 0.5 mCi/kg [9]. These animals were placed on a standardized atherogenic diet consisting of cooking oil 73 g, cholesterol 20 g, cholic acid 5 g, and thiouracil 2 g mixed with the dogs’ daily ration of l-2 lb of canned dog food. Group 2 consisted of four animals which received a regular diet of canned dog food and served as operated controls. Monthly serum cho- lesterol determinations were made after the method of Block [ 11.

At 3 mo, a superior venocavagram was performed to ensure patency of the trans- posed aortic segment (Fig. 1). At 12 mo all animals were sacrificed, the heart and great vessels removed, fixed in buffered formalin, and stained with Sudan IV. Gross atherosclerotic lesions were graded based on an estimate of the extent of intimal surface involvement (Fig. 2). Samples of the trans- posed arterial and venous segments and their parent vessels were obtained for microscopic inspection.

RESULTS The 18 dogs on an atherogenic diet (group

1) had a mean serum cholesterol of 939 mg/ 100 ml compared to 166 mg/lOO ml in the

163 Copyright o 1975 by Academic Press, Inc. All rights of reproduction in any form reserved.

164 JOURNAL OF SURGICAL RESEARCH VOL. 18, NO. 2, FEBRUARY 1975

FIG. 1. Superior venacavagram showing patent transposed aortic segment. Occlusion was found in 1 of 22 ani- mals.

Negative 0 Trace tr Minimal (S-10%) + Moderate (20-40%) ++ Moderately severe (SO-75%) +++ Severe (>75%) ++I-+

FIG. 2. Gross inspection grading system. Grading scale of intimal surface area involved by atheromatous lesions.

control groups (Fig. 3). The arterial system in the animals in group 1 had atherosclerotic lesions graded 1 + to 2+ while the animals in group 2 had no atheroma. All grafts were patent except one aortic segment interposed in the SVC of an animal in group 1. The degree of atherosclerotic involvement in the transposed vessel segments is shown in Fig. 4. Animals on a control diet developed no

Group

I II

Mean serum cholesterol

(mg/l 00 ml)

939 (311)” 166 ( 22)

Coronary

1+ 0

Severity of atheroma

Thoracic Renals aorta

2+ 1+ 0 0

Abdominal aorta

2+ 0

‘Standard deviation of the mean.

FIG. 3. Mean serum cholesterol and extent of atherosclerotic involvement of parent arterial vessels.

CURTIS ET AL: EFFECTS OF EXPERIMENTAL HYPERCHOLESTEROLEMIA 165

- FIG. 4. Degree of atherosclerotic involvement of transposed vessel segments.

atheroma in the transposed artery or vein (Fig. 5). Eleven of 17 patent aortic segments segments. Fifteen of 18 animals in group 1 transposed to the venous circulation in had severe atherosclerotic involvement of group 1 developed no or trace atheroma. the transposed vein segment in the thoracic Only two transposed aortic segments de- aorta. The severity of atherosclerotic in- veloped gross atheroma over 20% of the in- volvement of the transposed vein segment timal surface area and these were distributed was greater than the thoracic aorta itself near the suture lines.

FIG. 5. Gross appearance of transposed artery and vein segments. Note the absence of atheroma on the trans- posed arterial segment (upper) and the severity of atherosclerotic involvement of the vein segment exposed to arterial pressures (lower).

FIG. 6. Microscopic section of transposed vein to the aorta in gioup 1. Marked increase in vein wall thickness over controls was noted with the thickening occurring primarily in the media. Note the suhintimal clear spaces, evi- dence of lipid deposition in the vein segment now vacated by fixing techniques.

FIG. 7. Microscopic section of aortic segment transposed to the SVC. Note absence of atheroma in the aortic wall but greater than 50% occlusion of the vaso vasorum.

166

CURTIS ET AL: EFFECTS OF EXPERIMENTAL HYPERCHOLESTEROLEMIA 167

Microscopic findings correlated well with gross appearance of the transposed artery and vein segments and the parent vessels (Fig. 6). Of specific interest were the findings on histologic sections of the aortic segments transposed to the venous circulation in group 1 (Fig. 7). While the aorta per se did not develop atherosclerosis, the vaso vasorum of the aorta were severely involved.

REFERENCES 1. Block, W. A., Jarrett, K. J., Jr., and Levine, J. B. ,4n

improved automated determination of serum total cholesterol with a color reagent. Clin. Chem. 12:681 (1966).

2. Fisher, E. R., and Geller, J. H. Effect of cholesterol atherosclerosis, hypertension and cortisone on aortic oxygen consumption in the rabbit. Circ. Rex W20 (1960).

3. Heath, D., Wood, E. H., DuShane, J. W., and Edwards, J. E. The relation of age and blood

pressure to atheroma in the pulmonary arteries and thoracic aorta in congenital heart disease. Lab. fn- vest. 9:259 (1960).

4. Heptinstal, R. H., Barkley, H., and Porter, K. A. The relative roles of blood cholesterol level and blood pressure in the production of experimental aortic atheroma in rabbits. Angiology9:84 (1958).

5. Katz, L. N., Stamler, J., and Pick, R. Nutrition and Atherosclerosis. Lea & Febiger, Philadelphia, (1958).

6. Scott, H. W., Jr., Morgan, C. V., Balasny, B.‘L., Lanier, V. C., Younger, R. K., and Butts, W. H. Ex- perimental atherosclerosis in autogenous venous grafts. Arch. Surg. 101:677 (1970).

7. Sako, Y. Effects of turbulent blood flow and hypertension on experimental atherosclerosis. JAMA 179:36(1962).

8. Wilens, S. L. The experimental production of lipid deposition in excised arteries. Science 114:389 (1951).

9. Younger, R. K., Stephenson, S. E., Jr., Scott, H. William, Jr. Effects of radioactive iodine-induced hypothyroidism on experimental atherosclerosis. Surg. Forum, 18:351 (1962).