Compensatory enlargement of Ossabaw miniature swine coronary arteries in diffuse atherosclerosis

Abstract

Studies in human and non-human primates have confirmed the compensatory enlargement or positive remodeling (Glagov phenomenon) of coronary vessels in the presence of focal stenosis. To our knowledge, this is the first study to document arterial enlargement in a metabolic syndrome animal model with diffuse coronary artery disease (DCAD) in the absence of severe focal stenosis. Two different groups of Ossabaw miniature pigs were fed a high fat atherogenic diet for 4 months (Group I) and 12 months (Group II), respectively. Group I (6 pigs) underwent contrast enhanced computed tomographic angiography (CCTA) and intravascular ultrasound (IVUS) at baseline and after 4 months of high fat diet, whereas Group II (7 pigs) underwent only IVUS at 12 months of high fat diet. IVUS measurements of the left anterior descending (LAD), left circumflex (LCX) and right coronary (RCA) arteries in Group I showed an average increase in their lumen cross-sectional areas (CSA) of 25.8%, 11.4%, and 43.4%, respectively, as compared to baseline. The lumen CSA values of LAD in Group II were found to be between the baseline and 4 months values in Group I. IVUS and CCTA measurements showed a similar trend and positive correlation. Fractional flow reserve (FFR) was 0.91±0.07 at baseline and 0.93±0.05 at 4 months with only 2.2%, 1.6% and 1% stenosis in the LAD, LCX and RCA, respectively. The relation between percent stenosis and lumen CSA shows a classical Glagov phenomenon in this animal model of DCAD.

The Ossabaw Pig Is a Suitable Translational Model to Evaluate Dietary Patterns and Coronary Artery Disease Risk

“…syrup, and 43-45%E from fat sources including hydrogenated coconut oil, soybean oil, or lard, with supplementation of cholesterol at 2% wt:wt) in caloric excess relative to a low-fat "control" diet (18%E from protein, 71%E from carbohydrate, and 11%E from fat) results in obesity and the manifestation of several pathologic aspects of the metabolic syndrome, as well as insulin resistance and atherosclerosis (19)(20)(21)(22)(38)(39)(40)(41)(42)(43)(44). Compared with the atherogenic diet, the WD used in our study had a lower proportion of fat, carbohydrate, and cholesterol.…”

Pre-arterialization of coronary veins prior to retroperfusion of ischemic myocardium: percutaneous closure device

“…Furthermore, this chronic model of ischemia is accepted as representative of the pathophysiologic process of human coronary stenosis. Future studies should be performed in swine with both focal and diffuse disease ( 26 ). Additionally, vein occlusion should be performed once ischemia is established to mimic the clinical scenario.…”

Swine Disease Models for Optimal Vascular Engineering

“…The ideal age to initiate MetS development in normal, healthy pigs is ∼6 months because that is when body weight starts to plateau (Figure 3). The relatively steady body weight and health status facilitate baseline physiological measures, tissue biopsies, glucose tolerance tests, assessment of coronary atherosclerosis with intravascular ultrasound, and so forth (30,110). The 6-month starting age represents a compromise between cost and desire for robust effects of the MetS diet on metabolic and coronary artery disease.…”

“…Specifically, the development of more robust T2D and more complex coronary artery atherosclerosis almost certainly requires longer durations of study. Alternatively, screening pigs for robust insulin resistance (92) and coronary disease with serial intravascular ultrasound (110) would facilitate selection of optimally diseased subjects. A compromise that combines some natural models with targeted gene editing may facilitate disease severity.…”