Although positron-emission tomography (PET) with labeled fatty acid delineates infarct size and permits qualitative assessment of fatty acid utilization, quantification of oxidative metabolism is limited by complex alterations in the pattern of utilization of fatty acid during ischemia and reperfusion. Because metabolism of acetate by myocardium is less complex than that of glucose or palmitate, we characterized kinetics of utilization of radiolabeled acetate in 37 isolated rabbit hearts perfused with modified Krebs-Henseleit buffer and performed a pilot tomographic study in man.Results of initial experiments with carbon-14-labeled acetate ("4C-acetate) indicated that the steadystate extraction fraction of acetate averaged 61.5 + 4.0% in control hearts (n = 4), 93.6 ± 0.9% in hearts rendered ischemic (n = 4), and 54.8 + 4.0% in hearts reperfused after 60 min of ischemia (n = 3). Oxidation of "4C-acetate, assessed from the rate of efflux of "4CO2 in the venous effluent, correlated closely with the rate of oxygen consumption under diverse metabolic conditions (r = .97, p < .001). In addition, no significant differences were observed between rates of efflux of total 14C in all chemical species (reflecting total clearance of tracer from myocardium) and efflux of 4'CO2.

The efficacy of increasing glycolysis during ischemia for enhancing the salutary effects of reperfusion was evaluated in isolated perfused rabbit hearts subjected to low-flow ischemia followed by reperfusion. Control hearts were perfused with buffer containing 0.4 mM palmitate, 5 mM glucose, and 70 mU/l insulin. Additional groups of hearts were perfused with double glucose/insulin and 1 mM dichloroacetate or were subjected to substrate priming to increase preischemic glycogen content. Ischemic contracture was completely prevented in hearts perfused with high glucose/insulin and was delayed markedly by either dichloroacetate or enhanced preischemic glycogen [45 +/- 14 and 31 +/- 20 min, respectively; P < 0.01 each vs. control (11 +/- 10 min)] and inversely related to the rate of lactate production. With reperfusion, recovery of developed pressure was 56 +/- 23% of baseline in control hearts, 90 +/- 8% in hearts receiving high glucose/insulin, 92 +/- 5% in hearts receiving dichloroacetate, and 79 +/- 19% in hearts with increased glycogen (P < 0.05 each vs. control hearts). Creatine kinase release was reduced by > 55% in treated hearts. Thus enhancement of glycolysis by diverse mechanisms during ischemia decreased ischemic damage and improved the recovery of contractile function with reperfusion.

The total synthesis of octalactins A and B has been achieved in 15 steps (longest linear sequence) and 10% overall yield from commercially available materials. Key steps include the Paterson-Aldol reaction for the rapid assembly of the carbonate 46, methylenation of 46 and subsequent Claisen rearrangement of the corresponding alkenyl-substituted cyclic ketene acetal to provide the core unsaturated medium-ring lactone 47, and the use of enzyme-mediated acetate deprotection in the presence of a medium-ring lactone.

i l s t u d y ) r e q u i r e d , a r e m o t e l y -c o n t r o l l e d system f o r t h e pr e p a r a t i o n o f L1-llClpalmitic a c i d has been constructed. The system i s small (0.04 m3), c o m p l e t e l y p o r t a b l e and contained t o t a l l y w i t h i n a small lead-shielded hood. Large q u a n t i t i e s o f C -1 1 p a l m i t i c a c i d (up t o 675 mCi) have been prepared, w i t h minimum r a d i a t i o n exposure t o t h e operator. system has been i n f u l l o p e r a t i o n f o r two years, and has been used f o r more than 200 syntheses w i t h a f a i l u r e r a t e o f l e s s than 5%. This INTRODUCTION

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