Acute exposure to a high cholesterol diet attenuates myocardial ischemia-reperfusion injury in cholesteryl ester transfer protein mice

Background Previous experiments have demonstrated that acute exposure to a high-cholesterol diet (HCD) increases the severity of myocardial infarction in animals, Recent results suggest that the process is modulated by multip le genes and their interactions with circulating cholesterol. Design In the present study cholesteryl-ester-transfer-protein (CETP) trans genic mice were generated and fed a normal rodent-chow diet, HCD for 1 week , or a HCD for 6 weeks in order to define the role of CETP in myocardial in farction after acute exposure to a HCD. Methods Cholesterol levels in mice of all groups were measured. Separate gr oups of mice were exposed to 30 min of in-vivo occlusion of coronary artery and 2 h of reperfusion. We assessed the sizes of the ischemic zone and inf arct using Evans blue and 2,3,5-triphenyltetrazolium chloride. Results The extent of infarction (percentage infarct/area at risk) was sign ificantly less (P < 0.05) after 1 week of a HCD (18.7 +/- 7.0%) than those for the normal diet group (51.4 +/- 5.5%) and the group fed a HCD for 6 wee ks (44.4 +/- 5.2%). Additionally, there was significantly less infiltration of neutrophils into the ischemic-reperfused mouse hearts for mice fed a HC D for 1 week. Levels of reduced and oxidized glutathione in the hearts of C ETP mice were measured for separate groups of animals. The reduced: oxidize d-glutathione ratio was significantly (P < 0.01) lower for mice fed a HCD f or 1 week (1.5 +/- 0.1) than it was for mice fed a normal diet (3.6 +/- 0.3 ) and a HCD for 6 weeks (3.3 +/- 0.2). Conclusions These data suggest that activity of CETP in hypercholesterolemi c mice has an acute effect on size of infarct after 1 week of a HCD. This s uggests that CETP induces tolerance of ischemia in the mice fed a HCD via m ild oxidative stress. Coron Artery Dis 12: 37-44 (C) 2001 Lippincott Willia ms & Wilkins.