Citations

Background — The TIMI myocardial perfusion grade (TMPG) and ST-segment resolution both reflect perfusion and are associated with mortality after thrombolysis for acute myocardial infarction. We hypothesized that these measures would also be associated with infarct size by single photon emission computed tomography (SPECT). Methods and Results — In the LIMIT AMI trial (Limitation of Myocardial Injury following Thrombolysis in Acute Myocardial Infarction) of lytic monotherapy versus lytic plus rhuMAb CD18, early 90-minute TMPG (n=221) and ST segment resolution (n=242) were compared with subsequent SPECT Technetium-99 m Sestamibi, measuring the percentage of the left ventricle with no Sestamibi uptake. Infarct sizes were larger with TMPG 0 or 1 (a closed or stained myocardium) than with TMPG 2 or 3 (open myocardium, median 13% versus 7%, P =0.004). Infarcts were also larger in patients with no ST segment resolution (median 15%) or incomplete resolution (11%) than in those with complete resolution (6%, overall P =0.0001). The difference in infarct size by TMPG persisted when stratified by category of ST resolution. Conclusions — There may be a pathophysiological link between early restoration of tissue-level perfusion and reduced subsequent infarct size that may partially explain why these early angiographic and electrocardiographic measures are associated with long-term survival.

Abnormalities of fatty acid metabolism are recognized to play a significant role in human disease, but the mechanisms remain poorly understood. Long-chain acyl-CoA dehydrogenase (LCAD) catalyzes the initial step in mitochondrial fatty acid oxidation (FAO). We produced a mouse model of LCAD deficiency with severely impaired FAO. Matings between LCAD +/− mice yielded an abnormally low number of LCAD +/− and −/− offspring, indicating frequent gestational loss. LCAD −/− mice that reached birth appeared normal, but had severely reduced fasting tolerance with hepatic and cardiac lipidosis, hypoglycemia, elevated serum free fatty acids, and nonketotic dicarboxylic aciduria. Approximately 10% of adult LCAD −/− males developed cardiomyopathy, and sudden death was observed in 4 of 75 LCAD −/− mice. These results demonstrate the crucial roles of mitochondrial FAO and LCAD in vivo .