KATP Channels, Adenosine Receptors and Ischemic Preconditioning

1996 ◽  
pp. 459-467 ◽  
Author(s):  
Garrett J. Gross ◽  
Zhenhai Yao ◽  
John A. Auchampach
Keyword(s):  
Ischemic Preconditioning ◽  
Adenosine Receptors ◽  
Katp Channels

Transgenic overexpression of cardiac A1adenosine receptors mimics ischemic preconditioning

2000 ◽  
Vol 279 (3) ◽  
pp. H1071-H1078 ◽  
Author(s):  
R. Ray Morrison ◽  
Rachael Jones ◽  
Anne M. Byford ◽  
Alyssa R. Stell ◽  
Jason Peart ◽  
...  
Keyword(s):  
Infarct Size ◽  
Functional Recovery ◽  
Ischemic Preconditioning ◽  
Adenosine Receptors ◽  
Myocardial Function ◽  
Wild Type ◽  
Beneficial Effects ◽  
Pressure Development ◽  
Ldh Release

The role of A1adenosine receptors (A1AR) in ischemic preconditioning was investigated in isolated crystalloid-perfused wild-type and transgenic mouse hearts with increased A1AR. The effect of preconditioning on postischemic myocardial function, lactate dehydrogenase (LDH) release, and infarct size was examined. Functional recovery was greater in transgenic versus wild-type hearts (44.8 ± 3.4% baseline vs. 25.6 ± 1.7%). Preconditioning improved functional recovery in wild-type hearts from 25.6 ± 1.7% to 37.4 ± 2.2% but did not change recovery in transgenic hearts (44.8 ± 3.4% vs. 44.5 ± 3.9%). In isovolumically contracting hearts, pretreatment with selective A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine attenuated the improved functional recovery in both wild-type preconditioned (74.2 ± 7.3% baseline rate of pressure development over time untreated vs. 29.7 ± 7.3% treated) and transgenic hearts (84.1 ± 12.8% untreated vs. 42.1 ± 6.8% treated). Preconditioning wild-type hearts reduced LDH release (from 7,012 ± 1,451 to 1,691 ± 1,256 U · l−1 · g−1 · min−1) and infarct size (from 62.6 ± 5.1% to 32.3 ± 11.5%). Preconditioning did not affect LDH release or infarct size in hearts overexpressing A1AR. Compared with wild-type hearts, A1AR overexpression markedly reduced LDH release (from 7,012 ± 1,451 to 917 ± 1,123 U · l−1 · g−1 · min−1) and infarct size (from 62.6 ± 5.1% to 6.5 ± 2.1%). These data demonstrate that murine preconditioning involves endogenous activation of A1AR. The beneficial effects of preconditioning and A1AR overexpression are not additive. Taken with the observation that A1AR blockade equally eliminates the functional protection resulting from both preconditioning and transgenic A1AR overexpression, we conclude that the two interventions affect cardioprotection via common mechanisms or pathways.

Effect of adenosine receptor blockade: preventing protective preconditioning depends on time of initiation

1993 ◽  
Vol 265 (2) ◽  
pp. H504-H508 ◽  
Author(s):  
J. D. Thornton ◽  
C. S. Thornton ◽  
J. M. Downey
Keyword(s):  
Protective Effect ◽  
Ischemic Preconditioning ◽  
Adenosine Receptor ◽  
Adenosine Receptors ◽  
Receptor Blockade ◽  
Risk Zone ◽  
Time Points ◽  
Adenosine Receptor Antagonist ◽  
Rabbit Myocardium ◽  
Ischemic Period

Ischemic preconditioning protects the rabbit myocardium from infarction from a subsequent ischemia, and adenosine receptors appear to be involved in this protection. The present study attempts to determine when adenosine receptors must be occupied to achieve protection by infusing the adenosine receptor antagonist PD-115,199 at various time points during the study. Open-chest rabbits were subjected to 30 min of regional ischemia followed by 3 h of reperfusion and had 38 +/- 4% infarction of the risk zone. When hearts were preconditioned by 5 min of ischemia and 10 min reperfusion before the 30-min period of ischemia, only 9 +/- 2% infarction occurred. PD-115,199 given 5 min before the ischemic preconditioning episode blocked the protective effect of preconditioning (39 +/- 5% infarction). PD-115,199 also blocked the protection when given between the ischemic preconditioning episode and the 30-min period of ischemia (30 +/- 4% infarction). PD-115,199 given at the end of 30 min of ischemia did not block protection in preconditioned (PC) hearts (17 +/- 5% infarction) and had no effect on non-PC hearts (44 +/- 6% infarction). In prior studies we found that exogenous adenosine could substitute for ischemia to precondition the heart, indicating that adenosine is an initiator of preconditioning. These results, however, indicate that adenosine receptors must also be occupied during the long ischemic period for preconditioning to be protective and suggest that adenosine is a mediator of preconditioning as well.

Cardioprotection by KATP channels in wild-type hearts and hearts overexpressing A1-adenosine receptors

2000 ◽  
Vol 279 (4) ◽  
pp. H1690-H1697 ◽  
Author(s):  
John P. Headrick ◽  
Naomi S. Gauthier ◽  
Ray Morrison ◽  
G. Paul Matherne
Keyword(s):  
Adenosine Receptors ◽  
Diastolic Pressure ◽  
Ischemia Reperfusion ◽  
Wild Type Mouse ◽  
Katp Channels ◽  
Wild Type ◽  
Functional Responses ◽  
Ischemic Contracture ◽  
Developed Pressure ◽  
Time To Onset

We studied the role of mitochondrial ATP-sensitive K+(KATP) channels in modifying functional responses to 20 min global ischemia and 30 min reperfusion in wild-type mouse hearts and in hearts with ∼250-fold overexpression of functionally coupled A1-adenosine receptors (A1ARs). In wild-type hearts, time to onset of contracture (TOC) was 303 ± 24 s, with a peak contracture of 89 ± 5 mmHg. Diastolic pressure remained elevated at 52 ± 6 mmHg after reperfusion, and developed pressure recovered to 40 ± 6% of preischemia. A1AR overexpression markedly prolonged TOC to 517 ± 84 s, reduced contracture to 64 ± 6 mmHg, and improved recovery of diastolic (to 9 ± 4 mmHg) and developed pressure (to 82 ± 8%). 5-Hydroxydecanoate (5-HD; 100 μM), a mitochondrial KATPblocker, did not alter ischemic contracture in wild-type hearts, but increased diastolic pressure to 69 ± 8 mmHg and reduced developed pressure to 10 ± 5% during reperfusion. In transgenic hearts, 5-HD reduced TOC to 348 ± 18 s, increased postischemic contracture to 53 ± 4 mmHg, and reduced recovery of developed pressure to 22 ± 4%. In summary, these data are the first to demonstrate that endogenous activation of KATP channels improves tolerance to ischemia-reperfusion in murine myocardium. This functional protection occurs without modification of ischemic contracture. The data also support a role for mitochondrial KATP channel activation in the pronounced cardioprotection afforded by overexpression of myocardial A1ARs.

Mechanisms of Isoflurane-induced Myocardial Preconditioning in Rabbits 

1999 ◽  
Vol 90 (3) ◽  
pp. 812-821 ◽  
Author(s):  
Mohamed S. Ismaeil ◽  
Igor Tkachenko ◽  
Kurt A. Gamperl ◽  
Robert F. Hickey ◽  
Brian A. Cason
Keyword(s):  
At Risk ◽  
Potassium Channels ◽  
Infarct Size ◽  
Adenosine Triphosphate ◽  
Ischemic Preconditioning ◽  
Adenosine Receptors ◽  
Coronary Occlusion ◽  
Myocardial Infarct ◽  
Myocardial Infarct Size ◽  
Area At Risk

Background Isoflurane has cardioprotective effects that mimic the ischemic preconditioning phenomenon. Because adenosine triphosphate-sensitive potassium channels and adenosine receptors are implicated in ischemic preconditioning, the authors wanted to determine whether the preconditioning effect of isoflurane is mediated through these pathways. Methods Myocardial infarct size was measured in seven groups of propofol-anesthetized rabbits, each subjected to 30 min of anterolateral coronary occlusion followed by 3 h of reperfusion. Groups differed only in the pretreatments given, and controls received no pretreatment. An ischemia-preconditioned group was pretreated with 5 min of coronary occlusion and 15 min of reperfusion. An isoflurane-preconditioned group was pretreated with 15 min end-tidal isoflurane, 1.1%, and then 15 min of washout. An isoflurane-plus-glyburide group was administered 0.33 mg/kg glyburide intravenously before isoflurane pretreatment. An isoflurane plus 8-(p-sulfophenyl)-theophylline (SPT) group received 7.5 mg/kg SPT intravenously before isoflurane. Additional groups were administered identical doses of glyburide or SPT, but they were not pretreated with isoflurane. Infarct size and area at risk were defined by staining. Data were analyzed by analysis of variance or covariance. Results Infarct size, expressed as a percentage of the area at risk (IS:AR) was 30.2+/-11% (SD) in controls. Ischemic preconditioning and isoflurane preexposure reduced myocardial infarct size significantly, to 8.3+/-5% and 13.4+/-8.2% (P<0.05), respectively. Both glyburide and SPT pretreatment eliminated the preconditioning-like effect of isoflurane (IS:AR = 30.0+/-9.1% and 29.2+/-12.6%, respectively; P = not significant). Neither glyburide nor SPF alone increased infarct size (IS:AR = 33.9+/-7.6% and 31.8+/-12.7%, respectively; P = not significant). Conclusions Glyburide and SPT abolished the preconditioning-like effects of isoflurane but did not increase infarct size when administered in the absence of isoflurane. Isoflurane-induced preconditioning and ischemia-induced preconditioning share similar mechanisms, which include activation of adenosine triphosphate-sensitive potassium channels and adenosine receptors.

Differential role of sarcolemmal and mitochondrial KATP channels in adenosine-enhanced ischemic preconditioning

2000 ◽  
Vol 279 (6) ◽  
pp. H2694-H2703 ◽  
Author(s):  
Yoshiya Toyoda ◽  
Ingeborg Friehs ◽  
Robert A. Parker ◽  
Sidney Levitsky ◽  
James D. McCully
Keyword(s):  
Infarct Size ◽  
Functional Recovery ◽  
Ischemic Preconditioning ◽  
Channel Blocker ◽  
Katp Channels ◽  
Size Reduction ◽  
Ischemia And Reperfusion ◽  
Infarct Size Reduction ◽  
Mitochondrial Katp Channels

Adenosine-enhanced ischemic preconditioning (APC) extends the protection afforded by ischemic preconditioning (IPC) by both significantly decreasing infarct size and significantly enhancing postischemic functional recovery. The purpose of this study was to determine whether APC is modulated by ATP-sensitive potassium (KATP) channels and to determine whether this modulation occurs before ischemia or during reperfusion. The role of KATP channels before ischemia (I), during reperfusion (R), or during ischemia and reperfusion (IR) was investigated using the nonspecific KATP blocker glibenclamide (Glb), the mitochondrial (mito) KATP channel blocker 5-hydroxydecanoate (5-HD), and the sarcolemmal (sarc) KATPchannel blocker HMR-1883 (HMR). Infarct size was significantly increased ( P < 0.05) in APC hearts with Glb-I, Glb-R, and 5-HD-I treatment and partially with 5-HD-R. Glb-I and Glb-R treatment significantly decreased APC functional recovery ( P < 0.05 vs. APC), whereas 5-HD-I and 5-HD-R had no effect on APC functional recovery. HMR-IR significantly decreased postischemic functional recovery ( P < 0.05 vs. APC) but had no effect on infarct size. These data indicate that APC infarct size reduction is modulated by mitoKATP channels primarily during ischemia and suggest that functional recovery is modulated by sarcKATP channels during ischemia and reperfusion.

KATP channels and memory of ischemic preconditioning in dogs: synergism between adenosine and KATP channels

1997 ◽  
Vol 272 (1) ◽  
pp. H334-H342 ◽  
Author(s):  
Z. Yao ◽  
T. Mizumura ◽  
D. A. Mei ◽  
G. J. Gross
Keyword(s):  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Katp Channels ◽  
Canine Heart ◽  
Ischemic Insult ◽  
Area At Risk ◽  
Adenosine Receptor Antagonist ◽  
Anesthetized Dogs ◽  
Drug Free ◽  
Occlusion Period

Results from numerous studies have shown that there is an important link between adenosine A1 receptors and ATP-sensitive potassium (KATP) channels in mediating the cardioprotective effects of ischemic preconditioning (PC). The major aim of the present study was to determine whether occupation of A1 receptors and/or the opening of KATP channels is involved in the time delay between the PC stimulus and the prolonged ischemic insult or the “memory” of PC to reduce infarct size. Barbital sodium-anesthetized dogs were subjected to 1 h of left anterior descending coronary artery (LAD) occlusion followed by 4 h of reperfusion. Ischemic PC was elicited by 10 min of LAD occlusion followed by 1 h of reperfusion (1-h memory) before the 1-h occlusion period. Either adenosine (800 g/min), bimakalim (3 g/min), a combination of two lower doses of each agent (400 g/min of adenosine and 0.3 g/min of bimakalim), or an equivalent volume of saline was infused into the LAD for 10 min followed by a 1-h drug-free period before the 1-h ischemic insult. In another series, glibenclamide, 8-cyclopentyl-1,3-dipropylxanthine (a selective A1-receptor blocker), or PD-115199 (a nonselective adenosine-receptor antagonist) was administered 50 min after ischemic PC (10 min before the 1-h occlusion period). Infarct size (IS) was expressed as a percentage of the area at risk. PC with 1 h of reperfusion resulted in a marked reduction in IS (8.1 +/- 6.5 vs. 29.8 +/- 5.8% in control dogs). Administration of adenosine or bimakalim followed by a 1-h drug-free period had no effect on IS; however, the simultaneous administration of adenosine and bimakalim resulted in a marked decrease in IS (11.5 +/- 2.7%). One hour after ischemic PC, administration of glibenclamide blocked the protective effect of ischemic PC, whereas 8-cyclopentyl-1,3-dipropylxanthine or PD-115199 did not affect it. These results provide evidence that the opening of myocardial KATP channels may play an important role in the memory of ischemic PC in the canine heart and also suggest that adenosine and the KATP channel may have a synergistic interaction that is important for the memory phase of PC.

Mitochondrial KATP channels are possible triggers of ischemic preconditioning protective effect against reperfusion arrhythmias

2002 ◽  
Vol 34 (6) ◽  
pp. A44
Author(s):  
Danina M. Muntean ◽  
Alexandru Cristescu ◽  
Ovidiu Fira-Mladinescu ◽  
Dan Mihaicuta ◽  
Daniel Lighezan
Keyword(s):  
Protective Effect ◽  
Ischemic Preconditioning ◽  
Katp Channels ◽  
Reperfusion Arrhythmias ◽  
Mitochondrial Katp Channels

Ischemic preconditioning modulates ischemia-reperfusion injury in the rat lung: Role of adenosine receptors

2007 ◽  
Vol 556 (1-3) ◽  
pp. 144-150 ◽  
Author(s):  
Gülüzar Yıldız ◽  
Abdullah T. Demiryürek ◽  
Bülent Gümüşel ◽  
Howard Lippton
Keyword(s):  
Reperfusion Injury ◽  
Ischemic Preconditioning ◽  
Adenosine Receptors ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Rat Lung

Adenosine-enhanced ischemic preconditioning: adenosine receptor involvement during ischemia and reperfusion

2001 ◽  
Vol 280 (2) ◽  
pp. H591-H602 ◽  
Author(s):  
James D. McCully ◽  
Yoshiya Toyoda ◽  
Masahisa Uematsu ◽  
Robert D. Stewart ◽  
Sidney Levitsky
Keyword(s):  
Infarct Size ◽  
Functional Recovery ◽  
Ischemic Preconditioning ◽  
Adenosine Receptor ◽  
Adenosine Receptors ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Myocardial Infarct Size ◽  
Ischemia And Reperfusion ◽  
Infarct Size Reduction

Adenosine-enhanced ischemic preconditioning (APC) extends the cardioprotection of ischemic preconditioning (IPC) by both significantly decreasing myocardial infarct size and significantly enhancing postischemic functional recovery. In this study, the role of adenosine receptors during ischemia-reperfusion was determined. Rabbit hearts ( n = 92) were used for Langendorff perfusion. Control hearts were perfused for 180 min, global ischemia hearts received 30-min ischemia and 120-min reperfusion, and IPC hearts received 5-min ischemia and 5-min reperfusion before ischemia. APC hearts received a bolus injection of adenosine coincident with IPC. Adenosine receptor (A1, A2, and A3) antagonists were used with APC before ischemia and/or during reperfusion. GR-69019X (A1/A3) and MRS-1191/MRS-1220 (A3) significantly increased infarct size in APC hearts when administered before ischemia and significantly decreased functional recovery when administered during both ischemia and reperfusion ( P < 0.05 vs. APC). DPCPX (A1) administered either before ischemia and/or during reperfusion had no effect on APC cardioprotection. APC-enhanced infarct size reduction is modulated by adenosine receptors primarily during ischemia, whereas APC-enhanced postischemic functional recovery is modulated by adenosine receptors during both ischemia and reperfusion.

KATP Channels Mediate the Effect of Ischemic Preconditioning on Free Radical Production in a Rabbit Heart Model

2002 ◽  
Vol 96 (Sup 2) ◽  
pp. A629
Author(s):  
Yaacov Gozal ◽  
Jacob Raphael ◽  
Mordechai Chevion ◽  
Benjamin Drenger
Keyword(s):  
Free Radical ◽  
Ischemic Preconditioning ◽  
Katp Channels ◽  
Rabbit Heart ◽  
Heart Model ◽  
Free Radical Production ◽  
Radical Production
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