Transient adenosine infusion before ischemia and reperfusion protects against metabolic damage in pig hearts

Yokota, Ryoji; Fujiwara, Hisayoshi; Miyamae, Masami; Tanaka, Masaru; Yamasaki, Kyoko; Itoh, Shimpei; Koga, Keiko; Yabuuchi, Youichi; Sasayama, Shígetake

doi:10.1152/ajpheart.1995.268.3.h1149

Cited by 22 publications

(12 citation statements)

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“…There are two temporally and mechanistically distinct types of protection induced by preconditioning stimuli: acute and delayed preconditioning. 53,54 Various factors such as nitric oxide, 54,55 heat-shock proteins, 56À58 adenosine, 59,60 ATP-sensitive K+ channels, 61 cyclooxygenase-2, 62 or bradykinin through sensory nerve stimulation 52 seem to be involved in the ischemic preconditioning mechanism. However, the protective effects of acute preconditioning are protein synthesis-independent, whereas delayed preconditioning requires de novo protein synthesis.…”

Section: The Role Of Nitric Oxide In the Preconditioning Mechanismmentioning

confidence: 99%

Remote ischemic preconditioning of flaps: A review

2005

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Ischemic preconditioning (IP) is defined as a brief period of ischemia ("preclamping") followed by tissue reperfusion, thereby increasing ischemic tolerance for a subsequent longer ischemic period. Several studies showed the effectiveness of classic local IP by preclamping the flap pedicle. There are two temporally and mechanically different types of IP: acute preconditioning, which is induced by preclamping the flap pedicle briefly before flap ischemia, and late preconditioning, induced by a preclamping procedure 24-48 h before flap ischemia. However, both types of local ischemic preconditioning are rarely used clinically, most likely since they can be applied only by invasive means, significantly increase operation time, or even require a second surgical procedure. Several studies from our laboratory showed, in different experimental models, that acute IP, enhancement of flap survival, and improvement of reperfusion microcirculation can be achieved not only by preclamping the flap pedicle, but also by induction of an ischemia/reperfusion event in a body area distant from the flap prior to elevation. This new acute remote IP procedure can be applied without invasive means, using limb tourniquet ischemia briefly before flap ischemia. The effectiveness of acute remote IP was confirmed by other authors in large animal models. Another of our studies showed that late remote IP using a limb tourniquet 24 h before flap ischemia attenuates ischemia/reperfusion in muscle flaps, whereas it was ineffective in adipocutaneous flaps. The exact mechanism of "classic" as well as remote IP is not yet finally determined, although several studies demonstrated that endogenous nitric oxide plays an important role. In summary, the use of a tourniquet to induce limb ischemia before flap ischemia could provide a new, alternative, noninvasive remote IP protocol, although late remote IP might be effective only in muscle flaps. However, the possible future clinical application for late IP is elective flap surgery, whereas acute remote IP could even be used in emergency flaps.

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Section: The Role Of Nitric Oxide In the Preconditioning Mechanismmentioning

confidence: 99%

Remote ischemic preconditioning of flaps: A review

2005

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“…[83] Finally, a significant effect was seen in 181 adenosine on LV function could be the dose and the route of patients with anterior MI and depressed LV systolic function (wall administration of the drug. In animal models IV doses of adenomotion score index >1.5), with the 1-year all-cause mortality being sine ranging from 20-375 μg/kg/min have been used, [73][74][75]92,93] and 2 (2%) in the adenosine group versus 10 (12.1%) in the placebo doses as low as 20 μg/kg/min seem to be effective in decreasing group [OR 0.16 (95% CI 0.03, 0.7; p = 0.007)]; cardiovascular the reperfusion injury during preconditioning. [92] mortality was 2 (2%) versus 9 (10.8%) [OR 0.19 (95% CI 0.03,…”

Section: Dosage and Administration Routementioning

confidence: 99%

Pharmacological Prevention of Reperfusion Injury in Acute Myocardial Infarction

Quintana

Kahan

Hjemdahl

2004

American Journal of Cardiovascular Drugs

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The concept of reperfusion injury, although first recognized from animal studies, is now recognized as a clinical phenomenon that may result in microvascular damage, no-reflow phenomenon, myocardial stunning, myocardial hibernation and ischemic preconditioning. The final consequence of this event is left ventricular (LV) systolic dysfunction leading to increased morbidity and mortality. The typical clinical case of reperfusion injury occurs in acute myocardial infarction (MI) with ST segment elevation in which an occlusion of a major epicardial coronary artery is followed by recanalization of the artery. This may occur either spontaneously or by means of thrombolysis and/or by primary percutaneous coronary intervention (PCI) with efficient platelet inhibition by aspirin (acetylsalicylic acid), clopidogrel and glycoprotein IIb/IIIa inhibitors. Although the pathophysiology of reperfusion injury is complex, the major role that neutrophils play in this process is well known. Neutrophils generate free radicals, degranulation products, arachidonic acid metabolites and platelet-activating factors that interact with endothelial cells, inducing endothelial injury and neutralization of nitrous oxide vasodilator capacity. Adenosine, through its multi-targeted pharmacological actions, is able to inhibit some of the above-mentioned detrimental effects. The net protective of adenosine in in vivo models of reperfusion injury is the reduction of the infarct size, the improvement of the regional myocardial blood flow and of the regional function of the ischemic area. Additionally, adenosine preserves the post-ischemic coronary flow reserve, coronary blood flow and the post-ischemic regional contractility. In small-scale studies in patients with acute MI, treatment with adenosine has been associated with smaller infarcts, less no-reflow phenomenon and improved LV function. During elective PCI adenosine reduced ST segment shifts, lactate production and ischemic symptoms. During the last years, three relatively large placebo-controlled clinical trials have been conducted: Acute Myocardial Infarction Study of Adenosine Trial (AMISTAD) I and II and Attenuation by Adenosine of Cardiac Complications (ATTACC). In the AMISTAD trials, the final infarct size was reduced and the LV systolic function was improved by adenosine treatment, mainly in patients with anterior MI localization. However, morbidity and mortality were not affected. In the ATTACC study, the LV systolic function was not affected by adenosine, however, trends towards improved survival were observed in patients with anterior MI localization. The possibility of obtaining a Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow in the infarct-related artery in up to 95% of patients with acute MI (increasing the occurrence of reperfusion injury) has turned back the interest towards the protection of myocardial cells from the impending ischemic and reperfusion injury in which adenosine alone or together with other cardio-protective agents may exert important clinical effects.

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“…There are two temporally and mechanistically distinct types of protection induced by preconditioning stimuli, i.e., acute and delayed preconditioning. 12,13 Various factors such as nitric oxide, 12,14 heat shock proteins, 15À17 adenosine, 18,19 ATP-sensitive K + channels, 20 cyclooxygenase-2, 21 or bradykinin (through sensory nerve stimulation) 22 seem to be involved in the ischemic preconditioning mechanism. However, the protective effects of acute preconditioning are protein synthesis-independent, whereas delayed preconditioning requires de novo protein synthesis.…”

Section: à3mentioning

confidence: 99%

Acute remote ischemic preconditioning on a rat cremasteric muscle flap model

Küntscher¹,

Kastell²,

Sauerbier³

et al. 2002

Microsurgery

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A previous study showed, in a rat adipocutaneous flap model, that acute ischemic preconditioning (IP) can be achieved not only by preclamping of the flap pedicle, but also by a brief extremity ischemia prior to flap ischemia. The purpose of this study was to determine whether remote IP is also effective in other tissues such as muscle flaps. Twenty male Wistar rats were divided into three experimental groups. The rat cremaster flap in vivo microscopy model was used for assessment of ischemia/reperfusion injury. In the control group (CG, n = 8), a 2-hr flap ischemia was induced after preparation of the cremaster muscle. In the "classic" IP group (cIP, n = 6), a brief flap ischemia of 10 min was induced by preclamping the pedicle, followed by 30 min of reperfusion. A 10-min ischemia of the contralateral hindlimb was induced in the remote IP group (rIP, n = 6). The limb was then reperfused for 30 min. Flap ischemia and the further experiment were performed as in the CG. In vivo microscopy was performed after 1 hr of flap reperfusion in each animal. A significantly higher red blood cell velocity in the first-order arterioles and capillaries, a higher capillary flow, and a decreased number of leukocytes adhering to the endothelium of the postcapillary venules were observed in both preconditioned groups by comparison to the control group (P < 0.05). The differences within the preconditioned groups were not significant for these parameters. Our data show that ischemic preconditioning and improvement of flap microcirculation can be achieved not only by preclamping of the flap pedicle, but also by induction of an ischemia/reperfusion event in a body area distant from the flap prior to elevation. These findings indicate that remote IP is a systemic phenomenon, leading to an enhancement of flap survival. Our data suggest that remote IP could be performed simultaneously with flap elevation in the clinical setting without prolongation of the operation and without invasive means.

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Transient adenosine infusion before ischemia and reperfusion protects against metabolic damage in pig hearts

Cited by 22 publications

References 0 publications

Remote ischemic preconditioning of flaps: A review

Remote ischemic preconditioning of flaps: A review

Pharmacological Prevention of Reperfusion Injury in Acute Myocardial Infarction

Acute remote ischemic preconditioning on a rat cremasteric muscle flap model

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