Pentostatin-augmented interstitial adenosine prevents postcardioplegia injury in damaged hearts

Hudspeth, Dudley A.; Williams, Mark W.; Zhi, Zhao; Sato, Hiroki; Hammon, John W.; Wylen, David Van; Vinten‐Johansen, Jakob

doi:10.1016/0003-4975(94)90733-1

Cited by 19 publications

(4 citation statements)

References 22 publications

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“…8 ¡ 14 Microdialysis has been used, only rarely, in cardiac surgery. Langemann et al , 15 and Habicht 16 have analysed the stage of myocardial ischaemia at cardiac arrest during cardiac surgery by means of microdialysis probes inserted into the ventricular septum. They analysed identical substances during Changes in peripheral tissue during cardiac surgery with CPB J Mand'á k et al…”

Section: Discussionmentioning

confidence: 99%

Changes in metabolism and blood flow in peripheral tissue (skeletal muscle) during cardiac surgery with cardiopulmonary bypass: the biochemical microdialysis study

et al. 2004

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The aim of this study was to monitor the metabolism and blood flow in the interstitium of the skeletal muscle during cardiac surgery with cardiopulmonary bypass (CPB) and in the early postoperative period by means of microdialysis and to compare metabolic changes during CPB at normothermia (NT) and hypothermia (HT). Surgical revascularization using CPB was performed in 50 patients, 25 patients (group HT) were operated using hypothermic CPB, 25 (group NT) using normothermic CPB. Interstitial microdialysis was performed by two CMA 60 probes (CMA Microdialysis AB, Solna, Sweden) inserted into the patient's deltoid muscle. Constituents analysed in the obtained dialysates, collected at intervals, were glucose, urea, glycerol and lactate. Tissue blood flow was monitored by dynamic microdialysis with gentamicin as a marker. In both groups, NT versus HT, similar dynamics of concentrations were found. Low initial concentrations were followed by gradual increases during CPB and in the following phase of the operation. Concentrations were higher in the NT group. Immediately after the operation, the decrease in values continued, with a gradual increase in the succeeding postoperative period in both groups. Similar dynamic changes in the lactate concentration were found in both groups. The gentamicin concentrations were lower in the NT group (versus the HT group). The results showed dynamic changes in the interstitial concentrations of glucose, urea, glycerol and lactate, which depend on the phase of the surgery in the CPB and early postoperative phase in the both groups of patients. Higher tissue perfusion of the skeletal muscle was noted in those patients operated on in normothermia. The dynamics of the concentration changes of these substances in the interstitium of the skeletal muscle has been proven to be caused by both the metabolic activity of the tissue and by the blood flow through the interstitium of the muscle.

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Section: Discussionmentioning

confidence: 99%

Changes in metabolism and blood flow in peripheral tissue (skeletal muscle) during cardiac surgery with cardiopulmonary bypass: the biochemical microdialysis study

et al. 2004

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“…Supplementation of cardioplegic solutions with adenosine, or agents used to amplify adenosine receptor-mediated actions, improve myocardial functional recovery after arrest [1,2,34,35]. Still, the end-effector molecules responsible for the improved contractile recovery with adenosine are not clear.…”

Section: Discussionmentioning

confidence: 95%

Adenosine attenuates C-terminal but not N-terminal proteolysis of cTnI during cardioplegic arrest

Law

Ross

Jonjev

2005

Journal of Surgical Research

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“…However, these side effects are less problematic if ADA inhibitors are applied in an isolated organ rather than the whole body, e.g., in a heart to be transplanted. ADA inhibitors have been found to reduce hypoxic injury during cardiac surgery (Zhu et al 1994 ; Hudspeth et al 1994 ; Abd-Elfattah et al 2013 ).…”

Section: Discussionmentioning

confidence: 99%

“…Adenosine deaminase (ADA), by converting adenosine into inosine, plays an important, although not pivotal, role in the nucleic acid metabolism of the heart (Fredholm et al 2001 , 2011 ; Headrick et al 2011 ). Inhibition (or deficiency) of ADA increases both the intra- and extra-cellular adenosine concentrations that enables the surplus adenosine to exert its effects via both intra- and extra-cellular binding sites (Sandhu et al 1993 ; Zhu et al 1994 ; Hudspeth et al 1994 ; Manthei et al 1998 ; Peart et al 2001 , 2003 ; Willems et al 2006 ; Abd-Elfattah et al 2012 ). Consistently, the inhibition of ADA augments actions of exogenous adenosine as well (Szentmiklosi et al 1982 ; Gesztelyi et al 2003b ).…”

Section: Introductionmentioning

confidence: 99%

The effect of adenosine deaminase inhibition on the A1 adenosinergic and M2 muscarinergic control of contractility in eu- and hyperthyroid guinea pig atria

Pák

Zsuga

Képes

et al. 2015

Naunyn-Schmiedeberg's Arch Pharmacol

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The A1 adenosine and M2 muscarinic receptors exert protective (including energy consumption limiting) effects in the heart. We investigated the influence of adenosine deaminase (ADA) inhibition on a representative energy consumption limiting function, the direct negative inotropic effect elicited by the A1 adenosinergic and M2 muscarinergic systems, in eu- and hyperthyroid atria. Furthermore, we compared the change in the interstitial adenosine level caused by ADA inhibition and nucleoside transport blockade, two well-established processes to stimulate the cell surface A1 adenosine receptors, in both thyroid states. A classical isolated organ technique was applied supplemented with the receptorial responsiveness method (RRM), a concentration estimating procedure. Via measuring the contractile force, the direct negative inotropic capacity of N6-cyclopentyladenosine, a selective A1 receptor agonist, and methacholine, a muscarinic receptor agonist, was determined on the left atria isolated from 8-day solvent- and thyroxine-treated guinea pigs in the presence and absence of 2′-deoxycoformycin, a selective ADA inhibitor, and NBTI, a selective nucleoside transporter inhibitor. We found that ADA inhibition (but not nucleoside transport blockade) increased the signal amplification of the A1 adenosinergic (but not M2 muscarinergic) system. This action of ADA inhibition developed in both thyroid states, but it was greater in hyperthyroidism. Nevertheless, ADA inhibition produced a smaller rise in the interstitial adenosine concentration than nucleoside transport blockade did in both thyroid states. Our results indicate that ADA inhibition, besides increasing the interstitial adenosine level, intensifies the atrial A1 adenosinergic function in another (thyroid hormone-sensitive) way, suggesting a new mechanism of action of ADA inhibition.

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Pentostatin-augmented interstitial adenosine prevents postcardioplegia injury in damaged hearts

Cited by 19 publications

References 22 publications

Changes in metabolism and blood flow in peripheral tissue (skeletal muscle) during cardiac surgery with cardiopulmonary bypass: the biochemical microdialysis study

Changes in metabolism and blood flow in peripheral tissue (skeletal muscle) during cardiac surgery with cardiopulmonary bypass: the biochemical microdialysis study

Adenosine attenuates C-terminal but not N-terminal proteolysis of cTnI during cardioplegic arrest

The effect of adenosine deaminase inhibition on the A1 adenosinergic and M2 muscarinergic control of contractility in eu- and hyperthyroid guinea pig atria

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