Myocardial ischemia revisited. The osmolar load, membrane damage, and reperfusion

Jennings, Robert B.; Reimer, Keith A.; Steenbergen, Charles

doi:10.1016/s0022-2828(86)80952-x

Cited by 282 publications

(101 citation statements)

References 50 publications

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“…Furthermore, survival of neonatal cardiomyocytes is directly proportional to tissue perfusion, with the greatest survival in the normal heart, intermediate survival in cardiac granulation tissue, and the lowest survival in acutely necrotic myocardium [49]. It seems likely that ischemic injury in transplanted cells follows the course characteristic of intact tissue, including ATP depletion, activation of anaerobic glycolysis with resulting acidosis, dysregulation of calcium and other ionic homeostasis, and swelling due to an osmotic load, culminating in membrane damage and cell death [50]. Ischemia also can lead to reactive oxygen species formation and subsequent mitochondrial permeability increases [51].…”

Section: Death In Cell Transplantation: Progression and Pathwaysmentioning

confidence: 99%

Systems approaches to preventing transplanted cell death in cardiac repair

Robey

Saiget

Reinecke

et al. 2008

Journal of Molecular and Cellular Cardiology

365

294

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Stem cell transplantation may repair the injured heart, but tissue regeneration is limited by death of transplanted cells. Most cell death occurs in the first few days post-transplantation, likely from a combination of ischemia, anoikis and inflammation. Interventions known to enhance transplanted cell survival include heat shock, over-expressing anti-apoptotic proteins, free radical scavengers, anti-inflammatory therapy and co-delivery of extracellular matrix molecules. Combinatorial use of such interventions markedly enhances graft cell survival, but death still remains a significant problem. We review these challenges to cardiac cell transplantation and present an approach to systematically address them.Most anti-death studies use histology to assess engraftment, which is time-and labor-intensive. To increase throughput, we developed two biochemical approaches to follow graft viability in the mouse heart. The first relies on LacZ enyzmatic activity to track genetically modified cells, and the second quantifies human genomic DNA content using repetitive Alu sequences. Both show linear relationships between input cell number and biochemical signal, but require correction for the time lag between cell death and loss of signal. Once optimized, they permit detection of as few as 1 graft cell in 40,000 host cells. Pro-survival effects measured biochemically at three days predict long-term histological engraftment benefits. These methods permitted identification of carbamylated erythropoietin (CEPO) as a pro-survival factor for human embryonic stem cell-derived cardiomyocyte grafts. CEPO's effects were additive to heat shock, implying independent survival pathways. This system should permit combinatorial approaches to enhance graft viability in a fraction of the time required for conventional histology.

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Section: Death In Cell Transplantation: Progression and Pathwaysmentioning

confidence: 99%

Systems approaches to preventing transplanted cell death in cardiac repair

Robey

Saiget

Reinecke

et al. 2008

Journal of Molecular and Cellular Cardiology

365

294

View full text Add to dashboard Cite

show abstract

“…[19][20][21][22][23][24][25][26][27][28][29][30] The role of explosive myocardial swelling and calcium overload is also controversial because many consider these changes to be the consequences rather than the causes of myocardial necrosis. 31,32 The controversy concerning the mechanisms and treatments of reperfusion-induced extension of necrosis is compounded by the fact that there is no See p 1070 direct and unequivocal evidence that reperfusion does extend necrosis. The only study33 directly concerned with this issue did not produce evidence for an extension of necrosis by reperfusion.…”

mentioning

confidence: 99%

Does reperfusion extend necrosis? A study in a single territory of myocardial ischemia--half reperfused and half not reperfused.

et al. 1990

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The purpose of this study was to confirm or disprove the existence of reperfusion-induced extension of necrosis. To avoid the effect of the variability of collateral circulation when groups of dogs are compared, we compared the effect of reperfusion and nonreperfusion on myocardial necrosis in a single ischemic territory, half of which was reperfused and half of which was not. The left anterior descending coronary artery (LAD) territory between its last diagonal branch and the apex was studied because it was found to have uniform collateral blood flow. In 20 dogs, the LAD was occluded for 90-240 minutes to produce necrosis of different degrees of transmurality. Before release of this occlusion, the LAD was occluded distally halfway to the apex to keep the distal half nonreperfused. After 5 minutes of proximal reperfusion, Monastral blue dye was injected into the left atrium for demarcation of the reperfused region, and the heart was arrested, excised, cut parallel to the LAD, and placed into triphenyl tetrazolium chloride (T1C) solution for delineation of the region of necrosis. The validity of TTC staining under the conditions of this study was confirmed by light and electron microscopy. The transmurality of necrosis, measured within 1 or 0.5 cm on either side of the boundary, ranged from 30o to 88o of wail thickness and was not different in the reperfused compared with the nonreperfused region (paired t test). Reperfusion did not advance the epicardial edge ofnecrosis compared with the nonreperfused region. In conclusion, at 5 minutes after reperfusion, comparson of necrosis in the reperfused and nonreperfused halves of a single ischemic territory could not demonstrate an extension of necrosis by reperfusion.

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“…Extensive evidence shows that cardiac cells undergo significant swelling during ischaemia and reperfusion [2][3][4][5][6] . During myocardial ischemia, cell metabolites such as inorganic phosphates and lactate accumulate intracellularly and to a certain degree extracellularly.…”

Section: Discussionmentioning

confidence: 99%

“…Extensive evidence indicates that cardiac cell swelling occurs under abnormal conditions such as ischemia and reperfusion [2][3][4][5][6] . It has been shown that cell swelling can modulate the function of a number of membrane channels and ion transporters.…”

Section: Introductionmentioning

confidence: 99%

Hyposmotic challenge modulates function of L-type calcium channel in rat ventricular myocytes through protein kinase C

Luo

et al. 2010

Acta Pharmacol Sin

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Aim: To study the effects and mechanisms by which hyposmotic challenge modulate function of L-type calcium current (I Ca,L ) in rat ventricular myocytes. Methods: The whole-cell patch-clamp techniques were used to record I Ca,L in rat ventricular myocytes. Conclusion: Hyposmotic challenge induced biphasic changes of I Ca,L , a transient increase followed by a sustained decrease, in rat ventricular myocytes through PKC pathway, but not PKG pathway. PKA system could be responsible for the transient increase of I Ca,L during short exposure to hyposmotic solution.

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Myocardial ischemia revisited. The osmolar load, membrane damage, and reperfusion

Cited by 282 publications

References 50 publications

Systems approaches to preventing transplanted cell death in cardiac repair

Systems approaches to preventing transplanted cell death in cardiac repair

Does reperfusion extend necrosis? A study in a single territory of myocardial ischemia--half reperfused and half not reperfused.

Hyposmotic challenge modulates function of L-type calcium channel in rat ventricular myocytes through protein kinase C

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