Effect of serial brief ischemic episodes on extracellular K+, pH, and activation in the pig.

Fleet, William F.; Johnson, TA; Graebner, C; Gettes, L. S.

doi:10.1161/01.cir.72.4.922

Cited by 102 publications

(54 citation statements)

References 60 publications

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“…4,32 In addition, it reacts to a second episode of ischemia much differently than virgin myocardium in that it utilizes ATP and accumulates lactate and H ϩ much more slowly. 32,37,56,57 This situation of slowed anaerobic glycolysis (the principal pathway of ATP synthesis in severe ischemia) despite slowed depletion of high energy phosphate (HEP) is best explained by hypothesizing that energy demand is reduced in ischemic preconditioned tissue. 32,37,45,58 Because low intracellular ATP and high tissue lactate and H ϩ are strongly associated with ischemic cell death, it has been postulated that preconditioned tissue dies more slowly because of this reduction in energy demand.…”

Section: Mechanism(s) Of Preconditioningmentioning

confidence: 99%

Consequences of Brief Ischemia: Stunning, Preconditioning, and Their Clinical Implications

2001

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Abstract-In experimental studies in the dog, total proximal coronary artery occlusions of up to 15 minutes result in reversible injury, meaning that the myocytes survive this insult. The 15 minutes of ischemia, however, induce numerous changes in the myocardium, including certain monuments to the brief episode of ischemia that may persist for days. One of these monuments is stunned myocardium, which represents "prolonged postischemic contractile dysfunction of myocardium salvaged by reperfusion." The mechanism of stunning involves generation of oxygen radicals as well as alteration in calcium homeostasis and possibly alteration in contractile protein structure. Stunning has been observed in several clinical scenarios, including after percutaneous transluminal coronary angioplasty, unstable angina, stressinduced ischemia, after thrombolysis, and after cardiopulmonary bypass. Oxygen radical scavengers and calcium channel blockers have been shown to enhance function of stunned myocardium in experimental studies, and in a few clinical studies, calcium channel blockers have been shown to ameliorate stunning. Although brief periods of ischemia can contribute to prolonged left ventricular dysfunction and even heart failure, they paradoxically play a cardioprotective role. Episodes of ischemia as short as 5 minutes, followed by reperfusion, protect the heart from a subsequent longer coronary artery occlusion by markedly reducing the amount of necrosis that results from the test episode of ischemia. This phenomenon, called ischemic preconditioning, has been observed in virtually every species in which it has been studied and is a powerful cardioprotective effect. The mechanism of ischemic preconditioning involves both triggers and mediators and involves complex second messenger pathways that appear to involve such components as adenosine, adenosine receptors, the epsilon isoform of protein kinase C, the ATP-dependent potassium channels, as well as others, including a paradoxical protective role of oxygen radicals. Both an early and a late phase of preconditioning have been described, and the mechanisms underlying their induction are under investigation. That preconditioning may occur in humans is suggested by the observations that repetitive balloon inflations in the coronary artery are associated with progressively less chest pain, ST-segment elevation, lactate production, the protective effects of preinfarction angina, the anginal "warm-up phenomenon," and studies performed on human cardiac biopsies that show metabolic properties suggesting preconditioning. Development of pharmacological agents that stimulate second messenger pathways thought to be involved in preconditioning, but without causing ischemia, could result in novel approaches to treating ischemia. Hence, on one hand, brief episodes of ischemia can have a negative effect on the heart: stunning; and on the other hand, they have a protective effect: preconditioning. The future challenge is how to minimize the stunning phenomenon and maximize the preconditioni...

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Section: Mechanism(s) Of Preconditioningmentioning

confidence: 99%

Consequences of Brief Ischemia: Stunning, Preconditioning, and Their Clinical Implications

2001

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“…The change of local pH decreases in consecutive periods of ischemia. 8 We measured a larger area of activation block during Figure 7). This is in line with the findings of Saito et al18 who described that conduction velocity only decreases at a [K'].…”

Section: Potassium Accumulation and Monophasic Electrogramsmentioning

confidence: 99%

“…8 We performed six experiments to test reproducibility of the increase of K' and of the electrophysiologic changes during subsequent periods of ischemia in our experimental setup. The time course of change of [K4], during the second and third onestage occlusions is shown in Figure 1.…”

Section: Subsequent Occlusionsmentioning

confidence: 99%

Distribution of extracellular potassium and electrophysiologic changes during two-stage coronary ligation in the isolated, perfused canine heart.

et al. 1989

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“…[21], [22] Moreover, the lactate/pyruvate ratio, intracellular acidosis and the absence of regenerated essential cofactors, such as NADH,H + , affect the catalytic activity of the other enzymes involved in the initial step of glycolysis and prevent the optimal performance of anaerobic glycolysis. [23] …”

Section: Glycolysis Pathwaysmentioning

confidence: 99%

Impact of Ischemia on Cellular Metabolism

Gourdin¹,

Dubois²

2013

Artery Bypass

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Effect of serial brief ischemic episodes on extracellular K+, pH, and activation in the pig.

Abstract: This study was performed to determine the reproducibility of the ionic and electrical changes associated with serial ischemic episodes. We used ion-selective and bipolar plunge electrodes to determine the changes in left ventricular extracellular potassium (

Cited by 102 publications

References 60 publications

Consequences of Brief Ischemia: Stunning, Preconditioning, and Their Clinical Implications

Consequences of Brief Ischemia: Stunning, Preconditioning, and Their Clinical Implications

Distribution of extracellular potassium and electrophysiologic changes during two-stage coronary ligation in the isolated, perfused canine heart.

Impact of Ischemia on Cellular Metabolism

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