We investigated whether transient adenosine (Ado) infusion before ischemia had the same effect on myocardial metabolism and function as ischemic preconditioning (IP). The control (C) group underwent 15 min of coronary artery occlusion followed by 120 min of reperfusion. The Ado group received a 15-min infusion of Ado (200 micrograms.kg-1.min-1) into the left atrium starting 20 min before ischemia. IP was elicited by two cycles of 5-min ischemia and 5-min reperfusion. In the area at risk, tissue levels of ATP, creatine phosphate (CP), and intracellular pH (pHi) were serially measured by 31P-nuclear magnetic resonance spectroscopy in 10 pigs from each group, and percent segment shortening (%SS) was measured in 7 pigs from each group. ATP and pHi were preserved after 15 min of ischemia in both Ado and IP groups [ATP = 64 +/- 7, 76 +/- 6, and 74 +/- 9% of baseline; pHi = 6.35 +/- 0.19, 6.54 +/- 0.11, and 6.64 +/- 0.11 in C, Ado, and IP groups, respectively (P < 0.05, Ado and IP vs. C)]. During reperfusion, ATP was restored progressively in both groups [71 +/- 7, 90 +/- 8, and 91 +/- 9% of baseline at 120 min of reperfusion in C, Ado, and IP groups, respectively (P < 0.05, Ado and IP vs. C)]. However, in contrast to the IP group, CP was not preserved during 15-min ischemia nor did it show persistent overshoot during reperfusion in the Ado group. There were no significant differences in %SS during ischemia and reperfusion among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

ATP-binding cassette protein A1 (ABCA1) plays a key role in eliminating excess cholesterol from peripheral cells by generating nascent high-density lipoprotein (HDL). However, it remains unclear whether both phospholipids and cholesterol are directly loaded onto apolipoprotein A-I (apoA-I) by ABCA1. To identify the amino acid residues of ABCA1 involved in substrate recognition and transport, we applied arginine scan mutagenesis to residues L821–E843 of human ABCA1 and predicted the environment to which each residue is exposed. The relative surface expression of each mutant suggested that residues L821–E843 pass through the plasma membrane as TM6, and the four residues (S826, F830, L834, and V837) of TM6 are exposed to the hydrophilic internal cavity of ABCA1. Furthermore, we showed that L834 is critical for the function of ABCA1.

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