Is the development of myocardial tolerance to repeated ischemia in humans due to preconditioning or to collateral recruitment?

Billinger, Michael; Fleisch, Martin; Eberli, Franz R.; Garachemani, Ali; Meier, Bernhard; Seiler, Christian

doi:10.1016/s0735-1097(98)00674-3

Cited by 107 publications

(60 citation statements)

References 38 publications

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“…Patients receiving intracoronary adenosine tolerated significantly longer balloon inflation times, 18 but there is controversy as to whether preconditioning was induced 19 or not. 7 Intracoronary adenosine did not improve significantly the left ventricular dysfunction normally observed during angioplasty; by comparison, increasing endogenous adenosine by intracoronary infusion of dipyridamole completely prevented angioplastyinduced ventricular dysfunction. 8,9 There is also controversy about the effectiveness of intravascular adenosine to induce myocardial protection during cardiac surgery.…”

Section: Discussionmentioning

confidence: 81%

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Blockade of Nucleoside Transport Is Required for Delivery of Intraarterial Adenosine Into the Interstitium

et al. 2003

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Background-Adenosine, a known mediator of preconditioning, has been infused into the coronary circulation to induce therapeutic preconditioning, eg, in preparation for angioplasty. However, results have been disappointing. We tested the hypothesis that endothelial nucleoside transporter acts as a barrier impeding the delivery of intravascular adenosine into the underlying myocardium and that this can be overcome with dipyridamole, a nucleoside transporter blocker. Methods and Results-We infused saline or adenosine (0.125 and 0.5 mg/min) into the brachial artery while monitoring forearm blood flow (FBF) and interstitial adenosine levels with microdialysis probes implanted in the flexor digitorum superficialis of the forearm in 7 healthy volunteers during intravenous administration of saline or dipyridamole (loading dose, 0.142 mg/kg per min for 5 minutes followed by 0.004 mg/kg per min). Adenosine produced near maximal forearm vasodilation, increasing FBF from 4.0Ϯ0.7 to 10.4Ϯ1.9 and 13.1Ϯ1.6 mL/100 mL per min for the low and high doses, respectively, but did not increase muscle dialysate adenosine concentration (from 88Ϯ21 to 65Ϯ23 and 85Ϯ26 nmol/L). Intravenous dipyridamole enhanced resting muscle dialysate adenosine (from 77Ϯ25 to 147Ϯ50 nmol/L), adenosineinduced increase in FBF (from 4.1Ϯ0.8 to 12.6Ϯ3 and 15.1Ϯ3 mL/100 mL per min for the low and high dose, respectively), and the delivery of adenosine into the interstitium (to 290Ϯ80 and 299Ϯ143 nmol/L for the low and high dose, respectively, Pϭ0.04). Key Words: adenosine Ⅲ ischemia Ⅲ endothelium Ⅲ blood flow A denosine is an intermediate product in the breakdown of ATP and accumulates in the interstitium of metabolically active tissues when oxygen demands exceed supply, eg, during ischemia. 1,2 Adenosine is considered a retaliatory autacoid, whose main function is to protect tissues against ischemia-related injury. Many of its actions are indeed consistent with such a role. Adenosine contributes to reactive hyperemia and produces maximal coronary vasodilation, inhibits norepinephrine and renin release, and inhibits neutrophil activation and platelet aggregation. Conclusions-IntravascularAdenosine is also considered an important mediator of ischemic preconditioning, a phenomenon by which an initial brief period of ischemia protects the tissue from the damage produced by a subsequent more intense ischemic episode. It is believed that during transient coronary occlusion, adenosine and other mediators are released and initiate a cascade of intracellular events involving protein kinase C activation that are responsible for the protective effect to subsequent ischemia. [3][4][5][6] There has been interest, therefore, in replicating ischemic preconditioning by infusing adenosine and using this pharmacological preconditioning as a therapeutic approach for cardiac protection. A situation where this approach may be of practical relevance is angioplasty, where ischemia may be induced transiently during the procedure. Indeed, adenosine has been infused into the coronary ...

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Section: Discussionmentioning

confidence: 81%

“…Indeed, adenosine has been infused into the coronary circulation to protect the myocardium from subsequent ischemia during balloon inflation. However, results have been disappointing, [7][8][9] and the reason for negative outcomes has not been clear.…”

mentioning

confidence: 99%

Blockade of Nucleoside Transport Is Required for Delivery of Intraarterial Adenosine Into the Interstitium

et al. 2003

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“…chest pain, ST segment elevation, and lactate release) following an initial balloon inflation that at least lasted for 60 to 90 seconds (8,9). These effects were shown to be unrelated to collateral recruitment (10,11). Although such beneficial effects were not observed by all (12), the effects of first balloon inflation have been shown to be influenced by pharmacological modifiers of the IP phenomenon, thus suggesting involvement of IP (13,14).…”

Section: Ip a Phenomenon Merely In Laboratory Animals?mentioning

confidence: 99%

Understanding myocardial ischemic preconditioning, and the implications for a role of adenosine catabolism

Kavianipour

2002

Upsala Journal of Medical Sciences

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“…23a,b,c More recently ischemic adaptation to collateral channel opening was observed during ischemic preconditioning, which is thought to play an important role in the development of ischemic tolerance. 24 In animal experiments "opening" of coronary collateral channels has not been documented; 25 this would suggest that augmented blood flow to ischemic myocardium in animals via capillary vessels does not play a role in the cardioprotective actions induced by preconditioning. Consequently, experimental studies may not provide sufficient evidence to elucidate the underlying mechanisms of action of electrical neuromodulation in humans.…”

Section: Cardiac Microcirculationmentioning

confidence: 99%

Electrical Neuromodulation and the Heart with Special Emphasis on Myocardial Ischemia

DeJongste¹

2012

Topics in Neuromodulation Treatment

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Is the development of myocardial tolerance to repeated ischemia in humans due to preconditioning or to collateral recruitment?

Cited by 107 publications

References 38 publications

Blockade of Nucleoside Transport Is Required for Delivery of Intraarterial Adenosine Into the Interstitium

Blockade of Nucleoside Transport Is Required for Delivery of Intraarterial Adenosine Into the Interstitium

Understanding myocardial ischemic preconditioning, and the implications for a role of adenosine catabolism

Electrical Neuromodulation and the Heart with Special Emphasis on Myocardial Ischemia

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