Adrenergic activation confers cardioprotection mediated by adenosine, but is not required for ischemic preconditioning

Haessler, R.; Kuzume, Kazuyo; Ra, Wolff; Gl, Chien; Rf, Davis; Dm, Van Winkle

doi:10.1097/00019501-199604000-00007

Cited by 14 publications

(7 citation statements)

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“…Based on these important actions of adenosine, it has been postulated that AR antagonism would have negative effects during acute ischemia/reperfusion injury. However, previous studies are conflicting, and have reported that AR antagonists increase, decrease, or have no effect on infarct size (Auchampach and Gross, 1993;Thornton et al, 1993;Zhao et al, 1994;Haessler et al, 1996;Neely et al, 1996;Todd et al, 1996;Auchampach et al, 1997b;Kitakaze et al, 1997;Domenech et al, 1998;Forman et al, 2000). How can these discrepant data be reconciled?…”

Section: Discussionmentioning

confidence: 99%

“…Blockade of these actions of adenosine in the heart may be undesirable in patients with ischemic heart disease. Interestingly, however, many studies in experimental animal models have found that AR antagonists have no effect on the extent of tissue injury induced by acute ischemia and reperfusion (Auchampach and Gross, 1993;Thornton et al, 1993;Zhao et al, 1994;Haessler et al, 1996;Todd et al, 1996;Auchampach et al, 1997b;Kitakaze et al, 1997;Domenech et al, 1998). On the contrary, it has recently been proposed that selective blockade of A 1 ARs during reperfusion may actually be an effective means to reduce myocardial infarct size (Neely et al, 1996;Forman et al, 2000).…”

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confidence: 99%

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Comparison of Three Different A₁Adenosine Receptor Antagonists on Infarct Size and Multiple Cycle Ischemic Preconditioning in Anesthetized Dogs

Auchampach

Jin

Moore

et al. 2003

J Pharmacol Exp Ther

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A 1 adenosine receptor (AR) antagonists are effective diuretic agents that may be useful for treating fluid retention disorders including congestive heart failure. However, antagonism of A 1 ARs is potentially a concern when using these agents in patients with ischemic heart disease. To address this concern, the present study was designed to compare the actions of the A 1 AR antagonists CPX (1,3-dipropyl-8-cyclopentylxanthine), BG 9719 (1,3-dipropyl-8-[2-(5,6-epoxynorbornyl)]xanthine), and BG 9928 (1,3-dipropyl-8-[1-(4-propionate)-bicyclo-[2,2,2]octyl]xanthine) on acute myocardial ischemia/reperfusion injury and ischemic preconditioning (IPC) in an in vivo dog model of infarction. Barbital-anesthetized dogs were subjected to 60 min of left anterior descending coronary artery occlusion followed by 3 h of reperfusion, after which infarct size was assessed by staining with triphenyltetrazolium chloride. IPC was elicited by four 5-min occlusion/5-min reperfusion cycles produced 10 min before the 60-min occlusion. Multiple-cycle IPC produced a robust reduction (ϳ65%) in infarct size; this effect of IPC on infarct size was not abrogated in dogs pretreated with any of the three AR antagonists. Surprisingly, in the absence of IPC, pretreatment with CPX or BG 9928 before occlusion or immediately before reperfusion resulted in significant reductions (ϳ40 -50%) in myocardial infarct size. However, treatment with an equivalent dose of BG 9719 had no similar effect. We conclude that the A 1 AR antagonists BG 9719, BG 9928, and CPX do not exacerbate cardiac injury and do not interfere with IPC induced by multiple ischemia/reperfusion cycles. We discuss the possibility that the cardioprotective actions of CPX and BG 9928 may be related to antagonism of A 2B ARs.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Comparison of Three Different A₁Adenosine Receptor Antagonists on Infarct Size and Multiple Cycle Ischemic Preconditioning in Anesthetized Dogs

Auchampach

Jin

Moore

et al. 2003

J Pharmacol Exp Ther

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“…Indeed, the use of diÂerent anaesthetic not protect the kidney from ischaemic injury, as assessed by DMSA and histology. IP alone had no significant agents has been cited as a possible variable in IP [21]. One of the most important considerations in a study of adverse eÂect on renal tissue integrity compared with sham-operated controls.…”

Section: Dmsa Imagingmentioning

confidence: 99%

Ischaemia‐reperfusion injury in the rat kidney: the effect of preconditioning

Islam¹,

Mathie²,

Dinneen

et al. 1997

British Journal of Urology

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Objectives To design and establish a model to examine in left renal tissue integrity on day 2 only (P<0.001), whereas RI for 40 min caused significant left renal whether brief periods of renal artery occlusion (ischaemic preconditioning, IP) confers protection dysfunction on day 0, day 2 and day 9 (P∏0.01). For a given duration of ischaemia, there was no significant from the eÂects of a subsequent period of ischaemia and reperfusion of the rat kidney.diÂerence between results from (IP+RI) rats compared with RI-only rats at any of the three times. There was Materials and methods Ninety rats were randomized into six groups, i.e. sham-operated controls; IP alone; no significant alteration in renal tissue integrity in the IP-only rats compared with sham-operated controls. a 20 or 40 min period of left renal ischaemia (RI) alone; and IP followed by a 20 or 40 min period of Histological findings paralleled the data obtained from DMSA uptake. RI. Preconditioning involved the sequential clamping of the left renal artery for 4 min and its release for 11Conclusions The IP regimen and 30 min 'critical interval' confers no protection to the kidney from a 20 or min, a total of four times, a 'critical interval' of 30 min before the ischaemic insult. Left renal tissue integrity 40 min ischaemic episode. The IP regimen itself appears to have no eÂect, confirming the validity of was determined by dimercapto-succinic acid (DMSA) radionuclide imaging on a c-camera both immediately our experimental model.

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“…Second, all of the studies that have assessed the role of PKC in ischemic PC have been performed in anesthestized, open-chest animal models, in which a variety of unphysiological conditions (e.g., anesthesia, surgical trauma, elevated catecholamines, excessive production of free radicals, release of cytokines, fluctuations in temperature, etc. [39,40]) may obfuscate the role of PKC in ischemic PC and/or interfere with the phenomenon of ischemic PC (41)(42)(43)(44). Accordingly, the present experiment was conducted in conscious, unsedated rabbits, which are devoid of the potentially confounding interference of the aforementioned factors.…”

Section: Introductionmentioning

confidence: 99%

Direct evidence that protein kinase C plays an essential role in the development of late preconditioning against myocardial stunning in conscious rabbits and that epsilon is the isoform involved.

Qiu¹,

Ping²,

Tang³

et al. 1998

J. Clin. Invest.

153

181

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Brief ischemic episodes confer marked protection against myocardial stunning 1-3 d later (late preconditioning [PC] against stunning). The mechanism of this powerful protective effect is poorly understood. Although protein kinase C (PKC) has been implicated in PC against infarction, it is unknown whether it triggers late PC against stunning. In addition, the entire PKC hypothesis of ischemic PC remains controversial, possibly because the effects of PKC inhibitors on PC protection have not been correlated with their effects on PKC activity and/or translocation in vivo. Thus, conscious rabbits underwent a sequence of six 4-min coronary occlusion (O)/4-min reperfusion (R) cycles for three consecutive days (days 1, 2, and 3). In the control group (group I, n ϭ 7), the recovery of systolic wall thickening after the six O/R cycles was markedly improved on days 2 and 3 compared with day 1, indicating the development of late PC against stunning. Administration of the PKC inhibitor chelerythrine at a dose of 5 mg/kg before the first O on day 1 (group II, n ϭ 10) abrogated the late PC effect against stunning, whereas a 10-fold lower dose (0.5 mg/kg; group III, n ϭ 7) did not. Administration of 5 mg/kg of chelerythrine 10 min after the sixth reperfusion on day 1 (group IV, n ϭ 6) failed to block late PC against stunning. When rabbits were given 5 mg/kg of chelerythrine in the absence of O/R (group V, n ϭ 5), the severity of myocardial stunning 24 h later was not modified. Pretreatment with phorbol 12-myristate 13-acetate (4 g/kg) on day 1 without ischemia (group VI, n ϭ 11) induced late PC against stunning on day 2 and the magnitude of this effect was equivalent to that observed after ischemic PC. In vehicle-treated rabbits (group VIII, n ϭ 5), the six O/R cycles caused translocation of PKC isoforms ⑀ and from the cytosolic to the particulate fraction without significant changes in total PKC activity, in the subcellular distribution of total PKC activity, or in the subcellular distribution of the ␣ , ␤ 1 , ␤ 2 , ␥ , ␦ , , , , and isoforms. The higher dose of chelerythrine (5 mg/kg; group X, n ϭ 5) prevented the translocation of both PKC ⑀ and induced by ischemic PC, whereas the lower dose (0.5 mg/kg; group XI, n ϭ 5) prevented the translocation of PKC but not that of ⑀ , indicating that the activation of ⑀ is necessary for late PC to occur whereas that of is not. To our knowledge, this is the first demonstration that a PKC inhibitor actually prevents the translocation of PKC induced by ischemic PC in vivo, and that this inhibition of PKC translocation results in loss of PC protection. Taken together, the results demonstrate that the mechanism of late PC against myocardial stunning in conscious rabbits involves a PKCmediated signaling pathway, and implicate ⑀ as the specific PKC isoform responsible for the development of this cardioprotective phenomenon.

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Adrenergic activation confers cardioprotection mediated by adenosine, but is not required for ischemic preconditioning

Cited by 14 publications

References 0 publications

Comparison of Three Different A₁Adenosine Receptor Antagonists on Infarct Size and Multiple Cycle Ischemic Preconditioning in Anesthetized Dogs

Comparison of Three Different A₁Adenosine Receptor Antagonists on Infarct Size and Multiple Cycle Ischemic Preconditioning in Anesthetized Dogs

Ischaemia‐reperfusion injury in the rat kidney: the effect of preconditioning

Direct evidence that protein kinase C plays an essential role in the development of late preconditioning against myocardial stunning in conscious rabbits and that epsilon is the isoform involved.

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Adrenergic activation confers cardioprotection mediated by adenosine, but is not required for ischemic preconditioning

Cited by 14 publications

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Comparison of Three Different A1Adenosine Receptor Antagonists on Infarct Size and Multiple Cycle Ischemic Preconditioning in Anesthetized Dogs

Comparison of Three Different A1Adenosine Receptor Antagonists on Infarct Size and Multiple Cycle Ischemic Preconditioning in Anesthetized Dogs

Ischaemia‐reperfusion injury in the rat kidney: the effect of preconditioning

Direct evidence that protein kinase C plays an essential role in the development of late preconditioning against myocardial stunning in conscious rabbits and that epsilon is the isoform involved.

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Product

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Comparison of Three Different A₁Adenosine Receptor Antagonists on Infarct Size and Multiple Cycle Ischemic Preconditioning in Anesthetized Dogs

Comparison of Three Different A₁Adenosine Receptor Antagonists on Infarct Size and Multiple Cycle Ischemic Preconditioning in Anesthetized Dogs