The Loss of Pacing-induced Preconditioning in Atherosclerotic Rabbits: Role of Hypercholesterolaemia

Interaction of Cardiovascular Risk Factors with Myocardial Ischemia/Reperfusion Injury, Preconditioning, and Postconditioning

“…When these animals were re-exposed to a normal diet, normalization of serum lipid levels recaptured the protective effect of preconditioning in the presence of a constant degree of intimal lesions (Szilvassy et al, 1995). This result indicated that hypercholesterolemia, irrespective of the development of atherosclerosis, interferes with the cardioprotective mechanisms of preconditioning (Szilvassy et al, 1995). The loss of classic preconditioning was subsequently confirmed in isolated hearts from rats with chronic exposure to dietary cholesterol without development of atherosclerosis because rats do not develop significant atherosclerosis from consumption of a high-cholesterol diet .…”

“…Wang et al (2003) showed that experimental hyperlipidemia induced by an 8-week hyperlipidemic diet increased infarct size and apoptotic cell death and demonstrated for the first time that these effects could be inhibited by pharmacological blockade of the caspase cascade in an open-chest acute coronary occlusion/reperfusion rabbit model. Ferdinandy's group have also shown that a cholesterol-enriched diet for 8 weeks led to increased ST-segment elevation in response to rapid pacing-induced ischemia (a model of demand ischemia) in conscious rabbits (Szilvassy et al, 1995). Hearts of apolipoprotein E and low-density lipoprotein receptor double knockout mice (ApoE/LDLr Ϫ/Ϫ ) fed an atherogenic diet for 6 to 8 months had worse postischemic function and increased infarct size and troponin T release compared with genetic controls ).…”

“…Szilvassy et al (1995) reported for the first time that protection conferred by classic preconditioning against myocardial stunning and electrophysiological changes was lost when rabbits developed hypercholesterolemia and atherosclerosis after 8 weeks of exposure to 1.5% dietary cholesterol. When these animals were re-exposed to a normal diet, normalization of serum lipid levels recaptured the protective effect of preconditioning in the presence of a constant degree of intimal lesions (Szilvassy et al, 1995). This result indicated that hypercholesterolemia, irrespective of the development of atherosclerosis, interferes with the cardioprotective mechanisms of preconditioning (Szilvassy et al, 1995).…”

Clinical cardioprotection and the value of conditioning responses

“…The effect of atherosclerosis on dyslipidemia is equivocal, with opposing data acquired from different laboratories and in different models. Early evidence that hyperlipidemia might alter Precon responses arose from the study of Szilvássy et al (206), where Precon was shown to be substantially inhibited in hypercholesterolemic rats. These investigators presented evidence that hyperlipidemia rather than resultant atherosclerosis is the key factor, since the effect was reversed by normalizing diet despite persistent atherosclerosis.…”

Understanding myocardial ischemic preconditioning, and the implications for a role of adenosine catabolism

“…Moreover, the presence of a critical coronary stenosis did not abolish the protective effect of IP in pigs (105). However, Szilvassy et al (106) using a model of pacing induced ischemia in the rabbit heart reported the loss of the beneficial effects of IP in hypercholesterolemic subjects. This was also demonstrated in the rat (107).…”