The "border zone" in myocardial ischemia. An electrophysiological, metabolic, and histochemical correlation in the pig heart.

Janse, M J; Cinca, Juan; Morena, H; Fiolet, J.W.T.; Kléber, André-Georges; Vries, G. P. de; Becker, Amanda; Durrer, D

doi:10.1161/01.res.44.4.576

Cited by 187 publications

(57 citation statements)

References 32 publications

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“…The normal sinus rhythm observed in graftbearing animals is noteworthy, as the border zone between healthy myocardium and scar tissue frequently gives rise to circus loops, resulting in clinically significant arrhythmias in patients suffering from myocardial infarct (43,44). This observation, as well as the absence of long-term changes in the plasma enzyme profile, suggests that intracardiac grafts do not have an overtly negative effect on the host heart.…”

Section: Discussionmentioning

confidence: 95%

Differentiation and long-term survival of C2C12 myoblast grafts in heart.

Koh

Klug

Soonpaa³

et al. 1993

J. Clin. Invest.

261

132

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We have assessed the ability of skeletal myoblasts to form long-term, differentiated grafts in ventricular myocardium.C2C12 myoblasts were grafted directly into the heart of syngeneic mice. Viable grafts were observed as long as 3 mo after implantation. Immunohistological analyses revealed the presence of differentiated myotubes that stably expressed the skeletal myosin heavy chain isoform. Thymidine uptake studies indicated that virtually all of the grafted skeletal myocytes were withdrawn from the cell cycle by 14 d after grafting. Graft myocytes exhibited ultrastructural characteristics typical of differentiated myotubes. Graft formation and the associated myocardial remodeling did not induce overt cardiac arrhythmia. This study indicates that the myocardium can serve as a stable platform for skeletal myoblast grafts. The long-term survival, differentiated phenotype, and absence of sustained proliferative activity observed in myoblast grafts raise the possibility that similar grafting approaches may be used to replace diseased myocardium. Furthermore, the genetic tractability of myoblasts could provide a useful means for the local delivery of recombinant molecules to the heart. (J. Clin. Invest. 1993.

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Section: Discussionmentioning

confidence: 95%

Differentiation and long-term survival of C2C12 myoblast grafts in heart.

Koh

Klug

Soonpaa³

et al. 1993

J. Clin. Invest.

261

132

View full text Add to dashboard Cite

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“…However, in diseased hearts, acute ischemia typically occurs only in the myocardial region supplied by the occluded blood vessel. In this case, the coexistence of both normal and ischemic myocardium leads to spatial heterogeneities in refractoriness and conduction velocity that have been proven to favor the establishment of reentrant circuits (10,11,19). Thus the ULV is expected to increase in regional compared with global ischemia, with the exact value depending first, on the degree of ischemia, and second, on how proarrhythmic is the spatial distribution of heterogeneities in each particular case of regional ischemia.…”

Section: Discussionmentioning

confidence: 99%

Effect of acute global ischemia on the upper limit of vulnerability: a simulation study

Rodríguez

Tice²,

Eason³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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. Effect of acute global ischemia on the upper limit of vulnerability: a simulation study. Am J Physiol Heart Circ Physiol 286: H2078 -H2088, 2004. First published January 29, 2004 10.1152/ajpheart.01175.2003The goal of this modeling research is to provide mechanistic insight into the effect of altered membrane kinetics associated with 5-12 min of acute global ischemia on the upper limit of cardiac vulnerability (ULV) to electric shocks. We simulate electrical activity in a finiteelement bidomain model of a 4-mm-thick slice through the canine ventricles that incorporates realistic geometry and fiber architecture. Global acute ischemia is represented by changes in membrane dynamics due to hyperkalemia, acidosis, and hypoxia. Two stages of acute ischemia are simulated corresponding to 5-7 min (stage 1) and 10 -12 min (stage 2) after the onset of ischemia. Monophasic shocks are delivered in normoxia and ischemia over a range of coupling intervals, and their outcomes are examined to determine the highest shock strength that resulted in induction of reentrant arrhythmia. Our results demonstrate that acute ischemia stage 1 results in ULV reduction to 0.8A from its normoxic value of 1.4A. In contrast, no arrhythmia is induced regardless of shock strength in acute ischemia stage 2. An investigation of mechanisms underlying this behavior revealed that decreased postshock refractoriness resulting mainly from 1) ischemic electrophysiological substrate and 2) decrease in the extent of areas positively-polarized by the shock is responsible for the change in ULV during stage 1. In contrast, conduction failure is the main cause for the lack of vulnerability in acute ischemia stage 2. The insight provided by this study furthers our understanding of mechanisms by which acute ischemia-induced changes at the ionic level modulate cardiac vulnerability to electric shocks. ionic channels; computer simulations; arrhythmias ELECTRICAL DEFIBRILLATION is recognized as the most effective therapy against the malignant arrhythmias that lead to sudden cardiac death. However, although the majority of the patients that undergo defibrillation typically suffer from some form of coronary disease, little is known about the effect of acute ischemia on defibrillation efficacy. Experimental studies provide conflicting evidence: some report an increase in defibrillation threshold (DFT) (3,29,38,43), whereas others find no change (5,20,22,32) or even a decrease (2) in DFT during acute ischemia.Numerous studies (5,7,18) have demonstrated that the DFT is strongly linked to the upper limit of vulnerability (ULV) of cardiac tissue to electric shocks. Much research has focused on investigating the mechanisms of cardiac vulnerability in an attempt to better understand how failed defibrillation shocks reinitiate cardiac arrhythmias. During the past decade, experiments using optical mapping techniques (8,12,13,46) and computer simulation studies (25,30,37,41) have significantly improved the understanding of the mechanisms of shockinduced arrhythmogenesis, cul...

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“…However, they could not rule out the possibility that the gradients were the result of a mixed population of normal and severely damaged cells in this zone, rather than a uniform gradation of cellular injury. In a comparable study in the pig, Janse et al (1979) concluded that, in fact, no metabolic or electrical gradients were present in the border zone after 2 hours of ischemia followed by reperfusion. These authors demonstrated that this region is composed of sharply demarcated interdigitating normal and ischemic tissue.…”

Section: Comparison With Other Studies Of the "Border Zone"mentioning

confidence: 94%

“…Isolated islands of normal myocardium, thought by some to represent a border zone of ischemic but viable tissue (Edwards, 1957;Braunwald et al, 1974), were shown to be peninsulas of myocardium in continuity with the main mass of normal heart muscle (Factor et al, 1978). Several recent studies, employing different analytical techniques, also have confirmed that when myocardial infarctions are analyzed spatially, the boundary between necrotic and normal tissue is remarkably discrete, with no obvious border zone present (Mar-cus et al, 1975;Barlow and Chance, 1976;Hirzel et al, 1977;Factor et al, 1978;Harken et al, 1978;Janse et al, 1979).…”

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confidence: 95%