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Adenosine is an endogenous nucleoside that has been shown to be beneficial for the myocardium in different settings by a large number of experimental studies. In this article, we 1) outline adenosine's metabolic pathways, 2) address cardioprotective properties of adenosine, and 3) discuss possible implications of the two recently published clinical...
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Context 1
... is a purine nucleoside comprised of adenine and ribose joined by a glycosidic bound (Fig. 1). It is formed in tis- sues via dephosphorylation of adenosine 5'-monophosphate (AMP) by 5'-nucleotidase or via hydrolysis of S-adenosylho- mocysteine (SAH) by SAH-hydrolase, the former being the ma- jor source of cardiac adenosine ...
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Purpose
Current evidence indicates that the common AMPD1 gene variant is associated with improved survival in patients with advanced heart failure. Whilst adenosine has been recognized to mediate the cardioprotective effect of C34T AMPD1, the precise pathophysiologic mechanism involved remains undefined to date. To address this issue, we used cardi...
Citations
... Even though the IPC mechanism is not entirely clarified, it is known that immediately after the ischemia, the organism increases the production of several chemical mediators that trigger the cardio protection process 11 . Amongst these mediators, the most important ones seem to be acetilcholyne 12 , angiotensin II 13 , and mainly adenosine 14 . The connection of these substances to their receptors in the external surface of the sarcolem starts the next phase that occurs in the cytosol. ...
To study the effects of benzodiazepine midazolam in the coronary flow (Cflo), cardiac frequency (CF) and myocardial contractility in isolated hearts of rats subjected to ischemic preconditioning (IPC).
30 Wistar rats were used, undistinguished by gender. After anesthesia with ethyl ether, the hearts were put into perfusion (Krebs-Henseleit solution, 95% O2 and 5% CO2, 37 degrees C, 110-120mmHg), in disposable Langendorff type system. Five groups of six animals were constituted: GI- Control; GII- Ischemia; GIII- IPC; GIV- Ischemia + 100mcg of midazolam; GV- IPC + 100mcg of midazolam. After stabilization (t0), and on times t5, t10, t15, t20 and t25, CF, Cflo, systolic pressure (SP) and diastolic pressure (DP) and dP/dt were recorded. DP was maintained at 5 +/- 2 mmHg. The statistical method ANOVA and Tukey Test were employed for p < or = 0.05.
No significant variations have occurred between Cflo and CF. On Pd/td, differences have occurred (p<0.05) between groups I and II (respectively 94.7+/-23.0 and 62.3+/-12.1%). The preconditioning (GIII), improved significantly the results in the group II (respectively 62.3+/-12.1 and 87.1+/-12.4 %). The decrease in dP/dt in group II was not prevented by midazolam (GIV) (62.3+/-12,1 and 60.5+/-15.8 %). In group III, dP/dt was 87.1+/-12.4%, whereas in group V, only 55.5+/-17.2% (p<0.05)
Midazolam, when administered before the ischemia, was unable to prevent the ischemic deterioration of the myocardium. When administered before the preconditioning, it has abolished its protective effect.
... [1][2][3][4] It is clear that a variety of stimuli potentially modulate the ability of bronchial epithelial cells to disengage from their normal cell-cell and cell-matrix relationships and move into a wound area. 1,[3][4][5] Adenosine, a purine nucleoside known to modulate hypoxic, ischemic, and inflammatory processes critical to both tissue homeostasis and injury through specific cell surface receptors, [6][7][8] has recently been investigated for its impact on the cells and tissues of healing wounds. ...
Migration of neighboring cells into the injury is important for rapid repair of damaged airway epithelium. We previously reported that activation of the A(2A )receptors (A(2A)ARs) mediates adenosine-stimulated epithelial wound healing, suggesting a role for adenosine in migration. Because A(2A)AR increases cyclic adenosine monophosphate (cAMP) levels in many cells, we hypothesized that cAMP-dependent protein kinase A (PKA) is involved in adenosine-mediated cellular migration. To test this hypothesis, we stimulated a human bronchial epithelial cell line with adenosine and/or A(2A)AR agonist (5'-(N-cyclopropyl)-carboxamido-adenosine [CPCA]) in the presence or absence of adenosine deaminase inhibitor (erythro-9-(2-hydroxy-3-nonyl) adenine hydrochloride [EHNA]). Cells treated with adenosine or CPCA demonstrated a concentration-dependent increase in migration. Similar results were observed in the presence and absence of EHNA. To confirm A(2A) involvement, we pretreated the cells for 1 hour with the A(2A) receptor antagonist ZM241385 and then stimulated them with either adenosine or CPCA. To elucidate PKA's role, cells were pretreated for 1 hour with either a PKA inhibitor (KT5720) or a cAMP antagonist analogue (Rp-cAMPS) and then stimulated with adenosine and/or CPCA. Pretreatment with KT5720 or Rp-cAMPS resulted in a significant decrease in adenosine-mediated cellular migration. PKA activity confirmed that bronchial epithelial migration requires cAMP and PKA activity. When cells were wounded and stimulated with CPCA, an increase in PKA activity occurred. Pretreatment for 1 hour with either KT5720 or Rp-cAMPS resulted in a significant decrease in adenosine-mediated PKA activation. These data suggest that adenosine activation of A(2A)AR augments epithelial repair by increasing airway cellular migration by PKA-dependent mechanisms.
... In the myocardium, AMP is produced largely by ATP breakdown. [5][6][7] However, in cardiac fibroblasts and vascular smooth muscle cells, phosphodiesterase has been shown to act on cyclic adenosine monophosphate R E V I E W P A P E R : C M E ...
... Nucleotidase activity exists in a variety of cell types within the ventricle, providing sources of adenosine originating in the myocytes, fibroblasts, pericytes, endothelial cells, and smooth muscle cells. 5 In tissue dependent on oxidative phosphorylation, a decrease in oxygen results in a shift in the metabolism of adenine nucleotides to degradation of ATP with consequent increase production of adenosines diphosphate (ADP) and AMP. Therefore, augmented adenosine production may be regarded as a signal generated by the hypoxic state. ...
... Therefore, augmented adenosine production may be regarded as a signal generated by the hypoxic state. 5 It is thought that the generation of adenosine in response to hypoxic stimuli serves as a means to counteract ischemia and hypoxia. As noted below, through actions on specific adenosine receptors, there is an ultimate negative inotropic and chronotropic state which minimizes oxygen demand. ...
A vast array of gene polymorphisms have been described, and further discovery of these gene variants will continue as the human genome is defined. Therefore, selection of a single polymorphism to investigate in relation to disease evolution or outcome must be motivated by specific physiologic, pathophysiologic, or epidemiologic associations. A significant gene polymorphism may result in an alteration of protein function, or be associated with disease incidence or outcome. Prevalence of the polymorphism in the general population is of extreme importance, as it must be common enough to warrant interest in its clinical impact. The polymorphism of the gene encoding for the enzyme adenosine monophosphate deaminase 1 results in an abnormal protein necessary in skeletal muscle metabolism. While its physiologic effects are not completely understood, it has been associated with improved morbidity and mortality in patients with cardiovascular disease.
