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R D Lasley

Publications and source records attributed to R D Lasley.

At least 19 recordsLinked to original sources
PubMed2001

Adenosine A1 receptor activation reduces reactive oxygen species and attenuates stunning in ventricular myocytes.

Reactive oxygen species (ROS) formation following brief periods of ischemia or hypoxia is thought to be the underlying cause of myocardial stunning. Adenosine A1 receptor activation prior to ischemia/hypoxia attenuates stunning, although the mechanism for this effect remains unknown. Isolated rat ventricular myocytes loaded with the ROS-sensitive indicator dichlorofluorescin were subjected to 30 min glucose-free hypoxia followed by reoxygenation. Intracellular ROS increased approximately 175% (from pre-hypoxic levels) during reoxygenation while cell shortening decreased approximately 50%. In myocytes pretreated with the adenosine A1 agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA), reoxygenation-induced ROS formation was attenuated by 40% and stunning was attenuated by 50% (compared to untreated myocytes). The mitochondrial K(ATP) channel opener diazoxide mimicked the effects of CCPA. Pretreatment with the mitochondrial K(ATP) channel blocker 5-hydroxydecanoate, or the non-selective K(ATP) channel blocker glibenclamide, blocked the effects of CCPA. These results suggest that adenosine A1 receptor activation attenuates stunning by reducing ROS formation. These effects of A1 receptor activation appear to be dependent on the opening of K(ATP) channels.

Adenosine↗
PubMed2001

Cardiac myocyte adenosine receptors and caveolae.

The purine nucleoside adenosine exerts numerous effects in the mammalian heart, the most well-recognized being regulation of coronary blood flow and cardiac conduction. These effects are mediated via activation of G protein linked adenosine receptor subtypes, A(2a) and A(1) receptors, located primarily on vascular cells and cardiac myocytes, respectively. Although adenosine A(1) receptors are also expressed in ventricular myocytes, adenosine exerts no significant direct effects in these cells. A recent report from our laboratory indicates that ventricular myocyte A(1) receptors are concentrated in caveolin enriched plasma membrane microdomains referred to as caveolae. This review focuses on these recent findings and their relevance to subcellular compartmentalization of A(1) receptor signaling in ventricular myocardium.

Animals↗
PubMed2001

Beneficial effects of adenosine A(2a) agonist CGS-21680 in infarcted and stunned porcine myocardium.

Although there are conflicting results on whether adenosine infusion during reperfusion alters infarct size, there are several reports that indicate adenosine A(2a) agonists reduce infarct size. There are also reports that the A(2a) agonist CGS-21680 increases cAMP and contractility in ventricular myocytes. The purpose of this study was to determine whether low-dose intracoronary infusions of CGS-21680 during reperfusion exert any beneficial effects in irreversibly and reversibly injured myocardium. Open-chest pigs were submitted to 60 min of coronary artery occlusion and 3 h of reperfusion. Treated pigs were administered intracoronary CGS-21680 (0.2 microg x kg(-1) x min(-1)) for the first 60 min of reperfusion. Pigs submitted to regional stunning (15 min ischemia) were treated with intracoronary CGS-21680 (0.15 microg x kg(-1) x min(-1)) after 2 h of reperfusion. In the infarct protocol, CGS-21680 reduced infarct size from 62 +/- 2% of the region at risk to 36 +/- 2%. In stunned myocardium, CGS increased load-independent regional preload recruitable stroke work and area by > or =70%, but the same infusion in normal myocardium was associated with no inotropic effect. Both beneficial effects were associated with little systemic hemodynamic effects. These findings suggest that reperfusion infusions of low doses of the A(2a) agonist CGS-21680 exert beneficial effects in reversibly and irreversibly injured myocardium.

Adenosine↗
PubMed2001

Adenosine A3 agonist cardioprotection in isolated rat and rabbit hearts is blocked by the A1 antagonist DPCPX.

Adenosine A3 agonists have been shown to protect ischemic rat and rabbit myocardium. However, these agonists have been reported to exert A3 independent effects, and no cardiac A3 receptor has yet been identified. We thus tested whether A3 agonist protection is due to A1 receptor activation. Isolated rat and rabbit hearts were subjected to 25 and 45 min of global ischemia, respectively. Rat hearts pretreated with adenosine (100 microM), the A3 agonist 2-chloro-N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (Cl-IB-MECA, 50 nM), and vehicle recovered 73 +/- 2%, 75 +/- 4%, and 46 +/- 4%, respectively, of preischemic left ventricular developed pressure (LVDP) after 30 min of reperfusion. The A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 100 nM) blocked the beneficial effects of Cl-IB-MECA (51 +/- 5%) and adenosine (47 +/- 6%). In rabbit hearts, the beneficial effects of the A3 agonist N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (50 nM) and the A1 agonist 2-chloro-N6-cyclopentyladenosine (100 nM) on postischemic LVDP (75 +/- 4 and 74 +/- 5%, respectively) were blocked by DPCPX (34 +/- 4 and 36 +/- 3%, respectively). The reduction in infarct size with both agonists was also completely blocked by DPCPX. These results suggest that these A3 agonists protect ischemic myocardium via A1 receptor activation.

Animals↗
PubMed2001

Annexin V staining during reperfusion detects cardiomyocytes with unique properties.

With the use of markers of sarcolemmal membrane permeability, cardiomyocyte models of ischemic injury have primarily addressed necrotic death during ischemia. In the present study, we used annexin V-propidium iodide staining to examine apoptosis and necrosis after simulated ischemia and simulated reperfusion in rat ventricular myocytes. Annexin V binds phosphatidylserine, a phosphoaminolipid thought to be externalized during apoptosis or programmed cell death. Propidium iodide is a marker of cell necrosis. Under baseline conditions, <1% of cardiomyocytes stained positive for annexin V. After 20 or 60 min of simulated ischemia, there was no increase in annexin V staining, although 60-min simulated ischemia resulted in significant propidium iodide staining. Twenty minutes of simulated ischemia, followed by 20 or 60 min of simulated reperfusion, resulted in 8-10% of myocytes staining positive for annexin V. Annexin V-positive cells retained both rod-shaped morphology and contractile function but exhibited the decreased cell width indicative of cell shrinkage. Baseline mitochondrial free Ca2+ (111 +/- 14 nM) was elevated in reperfused annexin V-negative cells (214 +/- 22 nM), and further elevated in annexin V-positive myocytes (382 +/- 9 nM). After 60 min of simulated reperfusion, caspase-3-like activity was observed in approximately 3% of myocytes, which had a rounded appearance and membrane blebs. These results suggest that the use of annexin V after simulated ischemia-reperfusion uncovers a population of cardiomyocytes whose characteristics appear to be consistent with cells undergoing apoptosis.

Animals↗
PubMed2001

Novel short-acting A2A adenosine receptor agonists for coronary vasodilation: inverse relationship between affinity and duration of action of A2A agonists.

Several potent and selective A2A adenosine receptor agonists are currently available. These compounds have a high affinity for the A2A receptor and a long duration of action. However, in situations where a short duration of action is desired, currently available A2A receptor agonists are less than ideal. From a series of recently synthesized A2A receptor agonists, two agonists (CVT-3146 and CVT-3033) with low affinity were selected for further characterization as selective and short-acting coronary vasodilators. Both compounds were selective for the A2A adenosine receptor (AdoR) versus the A1, A2B, and A3AdoR in binding and functional studies. CVT-3146 and CVT-3033 appeared to be weak partial agonists to cause cAMP accumulation in PC12 cells, but were full and potent agonists to cause coronary vasodilation, a response that has a very large A2A receptor reserve. However, the durations of action of CVT-3146 and CVT-3033 were remarkably shorter than those of the high-affinity agonists CGS21680 or WRC0470, presumably due to the relative lower affinity of CVT-3146 and CVT-3033 for the A2A receptor. Indeed, an inverse relationship was found between the affinity of the various agonists for the A2A receptor and the duration of their actions. These data indicate that low-affinity agonists can produce a response that is of equivalent magnitude but more rapid in termination than that caused by a high-affinity agonist. Hence, the low-affinity A2A agonists CVT-3146 and CVT-3033 may prove to be superior to currently available high-affinity agonists as coronary vasodilators during myocardial imaging with radionuclide agents.

Adenosine↗
PubMed2000

Activated cardiac adenosine A(1) receptors translocate out of caveolae.

The cardiac affects of the purine nucleoside, adenosine, are well known. Adenosine increases coronary blood flow, exerts direct negative chronotropic and dromotropic effects, and exerts indirect anti-adrenergic effects. These effects of adenosine are mediated via the activation of specific G protein-coupled receptors. There is increasing evidence that caveolae play a role in the compartmentalization of receptors and second messengers in the vicinity of the plasma membrane. Several reports demonstrate that G protein-coupled receptors redistribute to caveolae in response to receptor occupation. In this study, we tested the hypothesis that adenosine A(1) receptors would translocate to caveolae in the presence of agonists. Surprisingly, in unstimulated rat cardiac ventricular myocytes, 67 +/- 5% of adenosine A(1) receptors were isolated with caveolae. However, incubation with the adenosine A(1) receptor agonist 2-chlorocyclopentyladenosine induced the rapid translocation of the A(1) receptors from caveolae into non-caveolae plasma membrane, an effect that was blocked by the adenosine A(1) receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine. An adenosine A(2a) receptor agonist did not alter the localization of A(1) receptors to caveolae. These data suggest that the translocation of A(1) receptors out of caveolae and away from compartmentalized signaling molecules may explain why activation of ventricular myocyte A(1) receptors are associated with few direct effects.

Adenosine↗
PubMed2000

Phosphatase inhibitor cantharidin blocks adenosine A(1) receptor anti-adrenergic effect in rat cardiac myocytes.

Experiments were performed to examine whether the protein phosphatase inhibitor cantharidin blocks the anti-adrenergic effect of adenosine A(1) receptor stimulation. In electrically stimulated adult rat ventricular myocytes loaded with the intracellular calcium concentration ([Ca(2+)](i)) indicator fluo-3, isoproterenol (10 nM) increased systolic [Ca(2+)](i) by 46%, increased twitch amplitude by 56%, and increased total cellular cAMP content by 140%. The adenosine A(1) receptor agonist 2-chloro-N(6)-cyclopentlyadenosine (CCPA) reduced isoproterenol-stimulated [Ca(2+)](i) and contractility by 87 and 80%, respectively, but reduced cAMP content by only 18%. Cantharidin had no effects on myocyte [Ca(2+)](i), contractility, or cAMP in the absence or presence of isoproterenol but blocked the effects of CCPA on [Ca(2+)](i) and contractility by approximately 44%. Cantharidin had no effect on CCPA attenuation of isoproterenol-induced increases in cAMP. Pretreatment with CCPA also reduced the increase in contractile parameters produced by the direct cAMP-dependent protein kinase A (PKA) activator 8-bromocAMP. These results suggest that activation of protein phosphatases mediate, in part, the anti-adrenergic effect of adenosine A(1) receptor activation in ventricular myocardium.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1999

Evidence that cytosolic and ecto 5'-nucleotidases contribute equally to increased interstitial adenosine concentration during porcine myocardial ischemia.

The purpose of this study was to determine the roles of cytosolic and ecto 5'-nucleotidase in myocardial ischemia-induced increases in interstitial fluid (ISF) adenosine. Pentobarbital anesthetized, open chest pigs were instrumented with two microdialysis fibers in the distally perfused bed of the left anterior descending (LAD) coronary artery to estimate ISF metabolites. Fibers in control hearts were perfused with standard Krebs buffer. In two additional groups, after collecting one dialysate sample with normal Krebs, fibers were perfused with buffer supplemented with either L-homocysteine thiolactone (5 mM) or the ecto 5'-nucleotidase inhibitor alpha, beta-methylene adenosine 5'-diphosphate (AOPCP, 5 mM). Hearts were then submitted to 60 minutes LAD occlusion and two hours reperfusion. Dialysate nucleosides and AMP were measured by high performance liquid chromatography. The local delivery of homocysteine did not alter preischemic dialysate adenosine concentration (0.30 +/- 0.04 microM) compared to pre-homocysteine infusion (0.39 +/- 0.04 microM) or control hearts (0.36 +/- 0.04 microM), but AOPCP significantly decreased preischemic dialysate adenosine levels (from 0.36 +/- 0.02 to 0.14 +/- 0.03 microM). During LAD occlusion both homocysteine and AOPCP reduced dialysate levels by approximately 50%. At 30 minutes ischemia dialysate adenosine concentrations were 19.47 +/- 2.72, 11.41 +/- 2.44, and 7.93 +/- 1.01 microM in control, homocysteine, and AOPCP hearts, respectively. AOPCP significantly increased dialysate AMP levels; at 60 minutes ischemia AMP levels were 6.22 +/- 2.97 microM in control hearts and 38.60 +/- 5.69 microM in AOPCP treated hearts. These results suggest that both cytosolic and ecto 5'-nucleotidase contribute to ischemia-induced increases in ISF adenosine in porcine myocardium.

5'-Nucleotidase↗
PubMed1999

Heart preservation for transplantation: principles and strategies.

While transplantation is a proven modality for the treatment of end stage organ disease, an important determinant of outcome is the adequacy of organ preservation. Currently, heart preservation is limited to 4 to 6 hours of cold ischemic storage, and the effectiveness depends to a great extent on the solution and its temperature. The formulation of the solution is based on three basic principles: (a) hypothermic arrest of metabolism, (b) provision of a physical and biochemical environment to maintain viability of the structural components of the tissue during hypothermic metabolic slowing, and (c) minimization of reperfusion injury. This review presents the physiologic principles underlying the use of hypothermia and the chemical components of preservation fluids, specifically pertaining to preservation of the heart for transplantation. New approaches designed to protect the heart from surgical ischemic-reperfusion injury are presented as well. The object is to survey current strategies and generate insight into new and promising solutions designed to optimize donor heart preservation.

Animals↗
PubMed1999

Ischemic preconditioning does not acutely improve load-insensitive parameters of contractility in in vivo stunned porcine myocardium.

OBJECTIVE: Ischemic preconditioning has been shown to have no beneficial effect on segment shortening in in vivo regionally stunned myocardium. The purpose of this study was to determine whether ischemic preconditioning improves the recovery of postischemic ventricular function when contractility is assessed by load-insensitive measurements including end-systolic pressure length relations, preload recruitable stroke work, and preload recruitable stroke work area in in vivo regionally stunned porcine myocardium. METHODS: Open chest, pentobarbital-anesthetized pigs were used. Regional ventricular function was monitored by measurements of segment shortening, stroke work, end systolic pressure length relations, preload recruitable stroke work, and preload recruitable stroke work area. The control group was submitted to 15 minutes of left anterior descending coronary artery occlusion and 3 hours of reperfusion. The preconditioned group underwent 2 cycles of 5-minute left anterior descending coronary artery occlusion and 10-minute reperfusion before 15 minutes of occlusion. RESULTS: There was no infarct in either group. The preconditioning protocol significantly depressed preischemic segment shortening but not regional stroke work. Ischemic preconditioning had no significant beneficial effect on regional stroke work, end-systolic pressure length relations, preload recruitable stroke work, or preload recruitable stroke work area. CONCLUSIONS: These results confirm that ischemic preconditioning does not ameliorate in vivo porcine myocardial stunning and indicate that ischemic preconditioning may have a limited cardioprotective role during cardiac operation.

Animals↗
PubMed1999

Adenosine myocardial protection: preliminary results of a phase II clinical trial.

OBJECTIVE: To evaluate the safety, tolerance, and efficacy of adenosine in patients undergoing coronary artery bypass surgery. SUMMARY BACKGROUND DATA: Inadequate myocardial protection in patients undergoing coronary artery bypass surgery contributes to overall hospital morbidity and mortality. For this reason, new pharmacologic agents are under investigation to protect the regionally and globally ischemic heart. METHODS: In a double-blind, placebo-controlled trial, 253 patients were randomized to one of three cohorts. The treatment arms consisted of the intraoperative administration of cold blood cardioplegia, blood cardioplegia containing 500 microM adenosine, and blood cardioplegia containing 2 mM adenosine. Patients receiving adenosine cardioplegia were also given an infusion of adenosine (200 microg/kg/min) 10 minutes before and 15 minutes after removal of the aortic crossclamp. Invasive and noninvasive measurements of ventricular performance were obtained before, during, and after surgery. RESULTS: The high-dose adenosine cohort was associated with a trend toward a decrease in high-dose dopamine support and a lower incidence of myocardial infarction. A composite outcome analysis demonstrated that patients who received high-dose adenosine were less likely to experience one of five adverse events: high-dose dopamine use, epinephrine use, insertion of intraaortic balloon pump, myocardial infarction, or death. The operative mortality rate for all patients studied was 3.6% (9/253). CONCLUSIONS: Adenosine treatment is safe and well tolerated and may be associated with fewer postoperative complications.

Adenosine↗
PubMed1999

Species-dependent hemodynamic effects of adenosine A3-receptor agonists IB-MECA and Cl-IB-MECA.

The purpose of this study was to compare the hemodynamic effects of the adenosine A3-receptor agonists N6-(3-iodobenzyl)-9-[5-(methylcarbamoyl)-beta-D-ribofuranosyl]aden ine (IB-MECA) and 2-chloro-N6-(3-iodobenzyl)-9-[5-(methylcarbamoyl)-beta-D-ribofu ranosy l]adenine (Cl-IB-MECA) in isolated rat and rabbit hearts and in the intact, open-chest pig. Isolated hearts perfused with Krebs-Henseleit buffer at a constant pressure (70 mmHg) were treated with 50 nM of either IB-MECA or Cl-IB-MECA. Neither IB-MECA nor Cl-IB-MECA altered ventricular function or heart rate in the isolated rat and rabbit hearts, and neither agent altered coronary flow in the rabbit. However, 2 min of IB-MECA treatment in the isolated rat heart increased coronary flow by 25%, an effect that did not exhibit tachyphylaxis. The IB-MECA-induced coronary dilation was only partially attenuated by the adenosine A3-receptor antagonist MRS-1191 (50 nM). IB-MECA-induced coronary dilation was completely blocked by the adenosine A2a-receptor antagonist 7-(2-phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2, 4-triazolo[1,5-c]pyrimidine (Sch-58261, 50 nM). Cl-IB-MECA (50 nM) did not increase coronary flow in the rat, but 100 nM did increase flow by 18%. In pentobarbital sodium-anesthetized pigs IB-MECA (5 micrograms/kg iv) decreased systemic blood pressure and increased pulmonary artery pressure, effects that did exhibit tachyphylaxis. These results illustrate that adenosine A3-receptor agonists produce species-dependent effects, which in the rat heart appear to be caused by adenosine A2a-receptor activation.

Adenosine↗
PubMed1999

Effects of adenosine and acadesine on interstitial nucleosides and myocardial stunning in the pig.

5-Amino-4-imidazolecarboxamide riboside (AICAr) or acadesine has been proposed to exert cardioprotection by enhancing adenosine production in ischemic myocardium. However, there are conflicting reports on acadesine's effects in ischemic myocardium and few studies in which myocardial adenosine levels have been measured. The purpose of this study was to determine whether acadesine increases interstitial fluid adenosine levels and attenuates myocardial stunning or potentiates the effects of adenosine in the intact pig. In pentobarbital-anesthetized pigs, myocardial stunning was induced by 10 min left anterior descending coronary artery occlusion and 90 min reperfusion. Regional ventricular function was assessed by measuring systolic wall thickening, and interstitial nucleosides were estimated by cardiac microdialysis. Control hearts were compared with hearts treated with acadesine, adenosine, and adenosine plus acadesine. Adenosine pretreatment (100 microg x kg(-1) x min(-1), intracoronary) immediately prior to ischemia increased interstitial adenosine levels 9-fold and improved postischemic functional recovery from a control value of 17.6 +/- 4.1% to 43.6 +/- 3.4% of preischemic systolic wall thickening. In contrast, acadesine (20 mg/kg i.v. bolus 10 min prior to ischemia + 0.5 mg x kg (-1) x min(-1), i.v. infusion through 60 min reperfusion) had no effect on interstitial fluid adenosine levels or the recovery of regional function (21.5 +/- 5.9% recovery), nor were the functional effects of adenosine potentiated by acadesine. These findings indicate that acadesine does not enhance myocardial adenosine levels, attenuate myocardial stunning, or potentiate the cardioprotective effects of adenosine in the pig.

Adenosine↗
PubMed1998

Tacrolimus as a rescue immunosuppressant after heart and lung transplantation. The U.S. Multicenter FK506 Study Group.

BACKGROUND: Organ transplant recipients with refractory rejection or intolerance to conventional immunosuppressants may respond to rescue therapy with tacrolimus. METHODS: Tacrolimus was used as a rescue immunosuppressant for 16 heart and 15 lung recipients. Heart recipients were converted to tacrolimus therapy because of cyclosporine intolerance, acute rejection despite treatment with cyclosporine, or humoral rejection. Lung recipients were converted because of cyclosporine intolerance, chronic rejection, or acute rejection. All immunosuppressive medications except corticosteroids were discontinued before tacrolimus therapy was begun. Patients remained in the study until they were converted to commercial tacrolimus. RESULTS: The duration of follow-up after conversion varied widely (heart recipients: 183+/-65 days; lung recipients: 169+/-86 days). For the heart recipients, patient and graft survivals were 100%. Twenty percent of recipients experienced no rejection episodes after conversion to tacrolimus; 60% experienced none or only one. For the lung recipients, patient survival was 67% and graft survival was 60%. Eighty percent of recipients experienced no rejections and 13% experienced one episode of rejection each. The remaining patient experienced two biopsy-confirmed episodes of rejection. Five lung patients died within the year and one patient required retransplantation. The most common adverse events were diarrhea, headache, abnormal kidney function, depression, dyspnea, nausea, and pneumonia. CONCLUSIONS: Tacrolimus is an effective and safe immunosuppressant for the rescue of heart transplant patients. Lung transplant patients may receive more benefit if rescued earlier.

Adult↗
PubMed1998

Adenosine A1 receptor stimulation antagonizes the negative inotropic effects of the PKC activator dioctanoylglycerol.

It has been suggested that adenosine cardioprotection occurs via adenosine A1 receptor-mediated activation of protein kinase C (PKC). However, adenosine has well-known vasodilatory effects in the myocardium, whereas PKC is a vasoconstrictor. This study examined whether adenosine A1 receptor activation alters the effects of the PKC activator. 1,2-dioctanoyl-s,n-glycerol (DOG) in isolated perfused rat hearts (left-ventricular developed pressure) and rat ventricular myocytes ([Ca2+]i and cell shortening). Exposure to DOG decreased left-ventricular developed pressure by 30%, an effect that was completely reversible. Pretreatment of isolated hearts with either the PKC inhibitor chelerythrine or the adenosine A1 agonist 2-chloro-N6-cyclo-cyclo-isolated pentlyadenosine (CCPA) attenuated the negative inotropic effects of DOG. In the isolated myocytes, DOG decreased [Ca2+]i and cell shortening by 25 and 28%, respectively, effects that were attenuated by both chelerythrine and CCPA. The CCPA attenuation of the DOG-induced decrease in [Ca2+]i and cell shortening was blocked by pretreating the myocytes with the adenosine A1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). These results indicate that in rat ventricular myocardium, adenosine A1 receptor activation attenuates the apparent PKC-dependent negative inotropic effects of DOG via preservation of [Ca2+]i levels.

Adenosine↗
PubMed1998

Comparison of interstitial fluid and coronary venous adenosine levels in in vivo porcine myocardium.

There are numerous reports of interstitial fluid (ISF) and coronary venous adenosine measurements in isolated perfused hearts. This study was designed to simultaneously compare ISF and coronary venous adenosine concentrations during various interventions in in vivo porcine myocardium. In anesthetized, open-chest pigs, ISF adenosine, inosine, and hypoxanthine were sampled with cardiac microdialysis. Coronary sinus or venous purines were sampled with a metabolism-stop solution. During basal conditions, ISF adenosine was greater than coronary venous adenosine, but vascular inosine and hypoxanthine were greater than corresponding ISF levels. Dobutamine (20 micrograms/kg/min, i.v.) and systemic hypoxia produced three- and two-fold increases in ISF adenosine, but had no significant effect on coronary sinus adenosine concentration. Hypoxia, but not dobutamine, increased coronary sinus total purines 50%. In contrast to these interventions, intracoronary adenosine infusion (0.5-50 micrograms/kg/min) was associated with significantly greater coronary venous adenosine concentrations than ISF levels. Only during a coronary artery occlusion/reperfusion protocol were ISF and coronary venous adenosine concentrations comparable. The results of this study thus provide in vivo evidence of the powerful endothelial and red blood cell metabolic barriers to both exogenous and endogenous adenosine. These results also illustrate the differences in adenosine concentrations in the ISF and vascular spaces.

Adenosine↗