Dynacleine ATP Injection

[JasonR]

Effect of continuous ATP injection on human hemodynamics.

Komukai K, Hashimoto K, Shibata T, Iwano K, Muto M, Mogi J, Imai K, Horie T, Mochizuki S.
Department of Internal Medicine, The Jikei University School of Medicine, Tokyo Japan. [email protected]
Continuous ATP injection is used clinically for Tl imaging or coronary flow measurement and because the effect on human hemodynamics is unknown, the present study investigated it in 14 patients undergoing heart catheter examination. Continuous ATP injection induced chest symptoms in 13 of the patients and second-degree atrioventricular block in one, but these complications disappeared immediately after the end of ATP infusion. Continuous ATP injection decreased aortic pressure, but increased pulmonary artery pressure, right atrial pressure and pulmonary capillary wedge pressure. ATP increased heart rate, stroke volume and cardiac output, the latter the result of an increase in preload, a decrease in afterload, and the increase in heart rate.
PMID: 12381087 [PubMed - indexed for MEDLINE]






and:
Posted By: Anthony Klon, Staff, Molecular Modeling, Pharmacopeia, Inc.
Area of science: Biochemistry



ATP does not freely diffuse across plasma membranes (PM) due to the fact that ATP is a highly charged polar molecule, which is a substantial barrier to crossing the hydrophobic portion of the PM. In general, small, polar molecules such as amino acids and nucleotides (including adenosine) are not freely permeable to the PM. Further complicating the specific case you describe is the fact that ATP has a total net charge of -4. The electric potential across the PM is ~70 mV, with the inside of the cell being more negative relative to the outside, meaning that there would be no passive diffusion up the electrical gradient across the PM. Thus, using 3-bromopyruvate in your example to deplete ATP followed by administration of ATP via an injection would not rescue the cells. One complication of injection is that extracellular ATP is that ATP is converted to adenosine in less than a second. ATP is readily hydrolyzed to ADP and AMP by membrane-bound CD39 (aka EctoATP diphosphohydrolase). AMP is further hydrolyzed by the intracellular enzymes 5-nucleotidase and adenosylhomocysteine hydrolase to adenosine. Adenosine itself has a half life of ~ 1 sec in the blood, as it is taken up by erythrocytes (red blood cells) and is itself a substrate for adenosine deaminase, which converts adenosine into inosine. Because ATP is rapidly catabolized, direct ATP injection would therefore have to occur close to the specific site of action in the body, and its effects would depend heavily upon the target tissue. But, to answer the specific question of what would happen if ATP were injected directly into a vein, the answer is probably not much.

[IntenseAthlete]

Effect of continuous ATP injection on human hemodynamics.

Komukai K, Hashimoto K, Shibata T, Iwano K, Muto M, Mogi J, Imai K, Horie T, Mochizuki S.
Department of Internal Medicine, The Jikei University School of Medicine, Tokyo Japan. [email protected]
Continuous ATP injection is used clinically for Tl imaging or coronary flow measurement and because the effect on human hemodynamics is unknown, the present study investigated it in 14 patients undergoing heart catheter examination. Continuous ATP injection induced chest symptoms in 13 of the patients and second-degree atrioventricular block in one, but these complications disappeared immediately after the end of ATP infusion. Continuous ATP injection decreased aortic pressure, but increased pulmonary artery pressure, right atrial pressure and pulmonary capillary wedge pressure. ATP increased heart rate, stroke volume and cardiac output, the latter the result of an increase in preload, a decrease in afterload, and the increase in heart rate.
PMID: 12381087 [PubMed - indexed for MEDLINE]






and:
Posted By: Anthony Klon, Staff, Molecular Modeling, Pharmacopeia, Inc.
Area of science: Biochemistry



ATP does not freely diffuse across plasma membranes (PM) due to the fact that ATP is a highly charged polar molecule, which is a substantial barrier to crossing the hydrophobic portion of the PM. In general, small, polar molecules such as amino acids and nucleotides (including adenosine) are not freely permeable to the PM. Further complicating the specific case you describe is the fact that ATP has a total net charge of -4. The electric potential across the PM is ~70 mV, with the inside of the cell being more negative relative to the outside, meaning that there would be no passive diffusion up the electrical gradient across the PM. Thus, using 3-bromopyruvate in your example to deplete ATP followed by administration of ATP via an injection would not rescue the cells. One complication of injection is that extracellular ATP is that ATP is converted to adenosine in less than a second. ATP is readily hydrolyzed to ADP and AMP by membrane-bound CD39 (aka EctoATP diphosphohydrolase). AMP is further hydrolyzed by the intracellular enzymes 5-nucleotidase and adenosylhomocysteine hydrolase to adenosine. Adenosine itself has a half life of ~ 1 sec in the blood, as it is taken up by erythrocytes (red blood cells) and is itself a substrate for adenosine deaminase, which converts adenosine into inosine. Because ATP is rapidly catabolized, direct ATP injection would therefore have to occur close to the specific site of action in the body, and its effects would depend heavily upon the target tissue. But, to answer the specific question of what would happen if ATP were injected directly into a vein, the answer is probably not much.

Short story, Atp can produce short term cardiac output and direct effect on the muscle injected