NMR evaluation of changes in myocardial high energy metabolism produced by repeated short periods of ischemia.
Following our previous results which demonstrated that repeated short periods (2 min) of ischemia are capable of protecting the isolated rat heart from a subsequent global ischemia (30 min), in the present study we have concentrated on the metabolic changes occurring in rat hearts during six 2 min ischemia/3 min reperfusion cycles. Cardiac high-energy phosphates were monitored using 31P-NMR. Phosphocreatine levels fell (50-60%) during each ischemic period, and recovered to 70-80% of their initial values during reperfusion. P(i) rose by 59% during the first ischemic period, but increased less during subsequent ischemias (30% during the 6th occlusion, P < 0.05 vs. the first ischemic period) returning to baseline levels after each reperfusion. [ATP], pH, and [Mg2+] remained almost unaffected, but there was a decrease in HPLC-determined effluent ATP catabolites. The first occlusion led to a 95% drop in contractile function (P < 0.001 vs. baseline), but this recovered to 73% upon reperfusion (P < 0.02 vs. baseline), and was 65% at the end of the protocol. Phosphorylation potential (PP = [ATP]/([ADP].[P(i)]) correlated exponentially with total purine (r = 0.90) and with adenosine + inosine release (r = 0.81), and by the 6th ischemia/reperfusion cycle, exceeded that observed in controls by 21% (P < 0.05). We conclude that repeated short periods of ischemia do not lead to any significant alteration in the absolute myocardial ATP, but are associated with an enhanced cytosolic energy state in the heart, that enables the myocardium to reach a steady albeit lower functional state. Adenosine (+inosine) release may be involved in the regulation of the energy supply-demand balance.
Bradamante
S
S
CNR-Centro Sintesi e Stereochimica Speciali Sistemi Organici, Universita' di Milano, Italy.
Piccinini
F
F
Delu
C
C
Janssen
M
M
de Jong
J W
JW
D000222:Adaptation, Physiological; D000818:Animals; D004734:Energy Metabolism; D005069:Evaluation Studies as Topic; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000378:metabolism*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D010755:Organophosphates / Q000378:metabolism*; D010507:Periodicity; D010710:Phosphates / Q000032:analysis; D010759:Phosphorus Isotopes; D011685:Purine Nucleotides / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D010755:Organophosphates; D010710:Phosphates; D010759:Phosphorus Isotopes; D011685:Purine Nucleotides