[Effects of exogenous apelin-12 on functional and metabolic recovery of isolated rat heart after ischemia].
Apelin 12 (A 12) was synthesized by the automatic solid phase method with the use of Fmoc technology. The synthesized peptide was purified by preparative HPLC and identified by 1H NMR spectroscopy and mass spectrometry. Effects of A 12 were studied on isolated working rat hearts perfused with Krebs buffer (KB) containing 11 mM glucose. The hearts were subjected to 35 min global ischemia followed by 30 min reperfusion. A short term infusion of A 12 in KB (35, 70, 140, 280, and 560 M) was applied prior to ischemia (A 12 I) or at onset of reperfusion (A 12 R). KB infusion without A 12 was used in control. A 12 infusion enhanced recovery of coronary flow, contractile and pump function during reperfusion with the largest augmentation of these indices in A 12 I group. Thus after infusion of 140 M A 12 recovery of coronary flow, the LVDP HR product and cardiac output were 92+/-5, 81+/-5, and 77+/-5% of the initial values, respectively, in A 12 I group, 83+/-6, 61+/-5, and 52+/-5% in A 12 R group, and 76+/-2, 42+/-2, 32+/-2% in control by the end of reperfusion. Both A 12 groups exhibited significant reduction of ischemia/reperfusion contracture compared with control. Enhanced functional recovery in A 12 I group was combined with a decrease in lactate dehydrogenase leakage in perfusate at early reperfusion (at the average by 36+/-5% compared with control, &lt;0.05). Preischemic infusion of 140 M A 12 markedly increased myocardial ATP content and twice decreased AMP accumulation at the end of reperfusion. These alterations resulted in enhanced preservation of the total adenine nucleotide pool (to 81+/-5% of the initial value vs. 66+/-3% in control, &lt;0.05) and better recovery of the energy charge potential (0.77+/-0.01 vs. 0.60+/-0.06 in control, &lt;0.005) in reperfused hearts. At the end of experiment myocardial lactate and lactate/pyruvate ratio were on average 5 fold lower in A 12 I treated hearts compared with control one and did not differ significantly from initial values. This finding implies that better restoration of energy metabolism in hearts protected with A 12 before ischemia might be attributed to ameliorated glucose oxidation during reperfusion. Therefore enhanced functional recovery of ischemic heart and lesser cell membrane damage induced by A 12 were associated with maintaining high energy phosphates, particularly ATP, in reperfused myocardium. Cardioprotective mechanisms of apelin action are discussed.
O I
OI
Pisarenko
V S
VS
Shulzhenko
Iu A
IuA
Pelogeĭkina
I M
IM
Studneva
D N
DN
Kkhatri
Zh D
ZhD
Bespalova
A A
AA
Az'muko
M V
MV
Sidorova
M E
ME
Pal'keeva
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D036341:Intercellular Signaling Peptides and Proteins / Q000138:chemical synthesis / Q000494:pharmacology; D008297:Male; D023421:Models, Animal; D009200:Myocardial Contraction / Q000187:drug effects*; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D020011:Protective Agents / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects*
D036341:Intercellular Signaling Peptides and Proteins; D020011:Protective Agents; C495200:apelin-12 peptide