Preconditioning by brief ischaemic episodes in the isolated rat heart assessed by<sup>31</sup>P NMR spectroscopy: dissociation between metabolic and functional recovery?

Schjøtt, Jan; Bakøy, O. E.; Jones, Richard A.; Southon, Timothy E.; Jynge, Per

doi:10.3109/00365519509075380

Cited by 8 publications

(3 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, reperfusion function is enhanced by preconditioning, and this is consistent with the enhanced recovery of ATP during reperfusion. Previous studies have shown no improvement of reperfusion ATP repletion or an enhanced repletion in preconditioned hearts (3,24,26,27). It is difficult to understand how reperfusion function can be enhanced with poor ATP repletion, unless the ATP is somehow more accessible or is being used more efficiently.…”

Section: Discussionmentioning

confidence: 95%

“…Therefore, it is difficult to reconcile the results of Asimakis et al with the findings of Vuorinen et al (27), in which significant inhibition of the mitochondrial hydrolase by preconditioning caused ATP conservation in isolated rat hearts. Schjott et al (24) found preconditioning to decrease the time to contracture, despite ATP conservation, suggesting that ATP levels may not be the only mediator of contracture.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Preconditioning in rat hearts is independent of mitochondrial F₁F₀ATPase inhibition

Green

Murray

Sleph

et al. 1998

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Mitochondrial F1F0adenosinetriphosphatase (ATPase) is responsible for the majority of ATP synthesis during normoxic conditions, but under ischemic conditions it accounts for significant ATP hydrolysis. A previous study showed that preconditioning in isolated rat hearts is mediated by inhibition of this ATPase during ischemia. We tested this hypothesis in our isolated rat heart model of preconditioning. Preconditioning was accomplished by three 5-min periods of global ischemia separated by 5 min of reperfusion. This was followed by 20 min of global ischemia and 30 min of reperfusion. Preconditioning significantly enhanced reperfusion contractile function and reduced lactate dehydrogenase release but paradoxically reduced the time to onset of contracture during global ischemia. Myocardial ATP was depleted at a faster rate during the prolonged ischemia in preconditioned than in sham-treated hearts, which is consistent with the reduced time to contracture. ATP during reperfusion was repleted more rapidly in preconditioned hearts, which is consistent with their enhanced contractile function. Preconditioning significantly reduced lactate accumulation during the prolonged ischemia. We were not able to demonstrate that mitochondrial F1F0ATPase (measured in submitochondrial particles) was inhibited by preconditioning before or during the prolonged ischemia. The mitochondrial ATPase inhibitor oligomycin significantly conserved ATP during ischemia and increased the time to the onset of contracture, which is consistent with inhibition of the mitochondrial ATPase. Our results show that preconditioning in rat hearts can be independent of mitochondrial ATPase inhibition as well as ATP conservation.

show abstract

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Preconditioning in rat hearts is independent of mitochondrial F₁F₀ATPase inhibition

Green

Murray

Sleph

et al. 1998

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…ATP and phosphocreatine (Pcr), measured in the ischemic myocardium before reflow, and the functional postischemic recovery. This link appears non-existent in some studies [1][2][3][4]. In contrast, a causal relationship emerged in other models, where the ischemic level of high-energy phosphates was altered either by changing the length of ischemia [5,6], or by replenishing hearts with diffusable substrates [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Untitled

Samaja

Allibardi

Chierchia

1999

Molecular and Cellular Biochemistry

View full text Add to dashboard Cite

It is still unclear if performance recovery in postischemic hearts is related to their tissue level of high-energy phosphates before reflow. To test the existence of this link, we monitored performance, metabolism and histological damage in isolated, crystalloid-perfused rat hearts during 20 min of low-flow ischemia (90% coronary flow reduction) and reflow. To prevent interference from different ischemia times and perfusing media compositions, the ischemic ATP level was varied by changing energy demand (electrical pacing at 330 min(-1)). Under full coronary flow conditions, work output, as well as ATP and phosphocreatine contents were the same in control, spontaneously contracting (n = 23) and paced (n = 21) hearts. During low-flow ischemia, the higher work output (p < 0.0001) in paced hearts decreased their tissue content of ATP, phosphocreatine and total adenylates and purines (p < 0.05), as opposed to maintained values in control hearts. During reflow, the recovery of mechanical performance and O2 uptake was 94 +/- 5% and 110 +/- 9% (p = NS vs. baseline) in controls, vs. 71 +/- 5% and 74 +/- 6% in paced hearts (p < 0.004 vs. baseline). The levels of ATP and total adenylates and purines remained constant in control, but were markedly depressed (p < 0.05 vs. baseline) in paced hearts. Phosphocreatine+creatine was the same in both groups. These data, together with the observed lack of creatine kinase leakage and of structural damage, indicate that myocardial recovery during reflow reflects the tissue level of ATP, phosphocreatine and total adenylates and purines during ischemia, regardless of physical cell damage.

show abstract

Substrate dependence of the postischemic cardiomyocyte recovery: Dissociation between functional, metabolic and injury markers

Tissier¹,

Vandroux²,

Devillard³

et al. 2005

Mol Cell Biochem

View full text Add to dashboard Cite

Defining the substrate that influences the most favourably the myocardial post-ischemic recovery is subject of debates, due to dissociation between functional and biochemical benefits. Hence, we studied the effects of either glucose or different fatty acids on the functional and metabolic recovery of post-ischemic cardiomyocytes in a substrate-free hypoxia model of simulated ischemia-reperfusion. Rat cardiomyocytes were submitted to a 2.5 h simulated ischemia followed by a 2 h reoxygenation without substrate (control), or with either glucose, octanoic acid, oleic acid, or elaidic acid. During simulated ischemia, electromechanical function gradually disappeared while the cellular viability and mitochondrial function declined. During control simulated reperfusion, cardiomyocytes recovered near normal function but a significant reduction in the action potential amplitude and rate persisted. The addition of glucose or oleic acid during simulated reperfusion promoted a faster, better and sustain functional recovery. Amongst the fatty acids, the functional recovery was slower with elaidic and octanoic acids as compared with oleic acid. The mitochondrial function was better improved during simulated reperfusion with glucose than with the tested fatty acids, among which elaidic acid was the less unfavourable. Paradoxically, the addition of whichever substrate during simulated reperfusion tended to worsen the cellular viability. Thus, cardiomyocytes recovery strongly relies on the characteristics of the substrate supplied at the onset of simulated reperfusion: glucidic or lipidic nature, chain-length, insaturation degree. Moreover, these data suggest that defining the appropriateness of a given substrate for the post-ischemic cardiomyocyte recovery is closely related to the functional and the biological endpoints in consideration.

show abstract

Preconditioning by brief ischaemic episodes in the isolated rat heart assessed by³¹P NMR spectroscopy: dissociation between metabolic and functional recovery?

Cited by 8 publications

References 14 publications

Preconditioning in rat hearts is independent of mitochondrial F₁F₀ATPase inhibition

Preconditioning in rat hearts is independent of mitochondrial F₁F₀ATPase inhibition

Untitled

Substrate dependence of the postischemic cardiomyocyte recovery: Dissociation between functional, metabolic and injury markers

Contact Info

Product

Resources

About

Preconditioning by brief ischaemic episodes in the isolated rat heart assessed by31P NMR spectroscopy: dissociation between metabolic and functional recovery?

Cited by 8 publications

References 14 publications

Preconditioning in rat hearts is independent of mitochondrial F1F0ATPase inhibition

Preconditioning in rat hearts is independent of mitochondrial F1F0ATPase inhibition

Untitled

Substrate dependence of the postischemic cardiomyocyte recovery: Dissociation between functional, metabolic and injury markers

Contact Info

Product

Resources

About

Preconditioning by brief ischaemic episodes in the isolated rat heart assessed by³¹P NMR spectroscopy: dissociation between metabolic and functional recovery?

Preconditioning in rat hearts is independent of mitochondrial F₁F₀ATPase inhibition

Preconditioning in rat hearts is independent of mitochondrial F₁F₀ATPase inhibition