Effect of Exogenous Adenosine Triphosphate on the Metabolic State of the Excised Hypothermic Dog Heart

Abstract

Solutions of adenosine triphosphate (ATP) were injected into the left coronary artery of isolated nonperfused dog hearts kept for 30 to 180 minutes at temperatures varying from 4 to 34°C. The amount of ATP administered varied from 0.5 to 7 /xmoles/g heart. The left ventricles of the ATP-treated hearts had a higher content of adenine nucleotides and of phosphocreatine than did the left ventricles of control hearts not exposed to ATP. This effect was temperature-dependent and was maximal at 14°C. Glycogen disappearance in the hypothermic myocardial tissue was markedly slowed in a dose-dependent fashion by the administration of ATP. Injections of adenine and adenosine were without effect.An analysis of the intra-and extracellular distribution of simultaneously administered adenosine-8-14 C-triphosphate and adenosine triphosphate-a-32 P shows that the injected ATP was mainly split into ADP, AMP, adenosine, and inorganic phosphate and indicates that a minor percentage of these fission products entered the myocardial cells, some of the ADP and AMP being rephosphorylated there to ATP. The results suggest that intravascular introduction of ATP into the arrested hypothermic heart might help in the survival of the organ. ADDITIONAL KEY WORDS ATP penetration into cells heart conservationtissue storage hypothermia myocardial glycogenolysis

Acadesine and myocardial protection. Studies of time of administration and dose-response relations in the rat.

“…The experimental protocol for these studies was similar to that used in study 1 Contractile function: Single-dose cardioplegia study. The in vivo pretreatment of the rats with acadesine or saline had no effect on blood pressure or heart rate measured during the 15 minutes before excision of the heart.…”

The effect of adenosine triphosphate on propofol-induced myopathy in rats: a biochemical and histopathological evaluation

“…This literature information supports our experimental results obtained by the intraperitoneal application of ATP. In another study, it was reported that injected ATP was converted to ADP, AMP, adenosine, and inorganic phosphate products, and these products entered cells and some of ADP and AMP were re-phosphorylated to ATP in cells [46]. In a recent study, it is understood that our idea about ATP is supported [47].…”

High-Energy Phosphates and Ischemic Heart Disease: From Bench to Bedside

“…Furthermore, exogenous ATP is a charged molecule containing three negative charges that is not freely permeable through cell membranes ( 77 – 79 ). In addition, there are enzymes that decompose ATP on the surface of cell membrane, including ATPase, adenylate kinase and AMP deaminase, which can split ATP into ADP, AMP, adenosine, and inorganic phosphate ( 80 , 81 ). Since the first publication by Parrat and Marshall ( 82 ), CrP has been substantially demonstrated to be effective in protection of ischemic myocardium.…”

“…To better understand the pathophysiological and pharmacological effects, we specified the context for all cited researches as cell study ( 19 , 23 – 27 , 29 – 35 , 48 – 54 , 69 , 70 , 91 – 103 , 118 , 128 ), animal study ( 12 , 41 , 42 , 45 , 46 , 65 , 66 , 68 , 71 – 74 , 76 – 78 , 81 – 90 , 99 , 104 , 111 , 116 – 119 , 129 , 133 – 135 ) and human study ( 15 – 18 , 20 , 21 , 37 – 40 , 44 , 58 , 108 – 110 , 143 – 156 ). Furthermore, we detailed the indications, contraindications, side effects, and application instructions of CrP supplement in Table 2 .…”