Protection by acidotic pH against anoxia/reoxygenation injury to rat neonatal cardiac myocytes

Bond, John M.; Herman, Brian; Lemasters, John J.

doi:10.1016/0006-291x(91)91887-i

Cited by 131 publications

(95 citation statements)

References 17 publications

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“…Cell viability was assessed with the exclusion fluorescent dye propidium iodide (PI, 5 M; Invitrogen, Gland Island, New York) measured at excitation 540 nm/emission 590 nm (5). The dye was used to quantify cell death throughout the entire experiment in a selected field of cardiomyocytes.…”

Section: Chemicals Nmentioning

confidence: 99%

Hypothermia-induced cardioprotection using extended ischemia and early reperfusion cooling

Shao

Chang

Chan

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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timing of therapeutic hypothermia for cardiac ischemia is unknown. Our prior work suggests that ischemia with rapid reperfusion (I/R) in cardiomyocytes can be more damaging than prolonged ischemia alone. Also, these cardiomyocytes demonstrate protein kinase C (PKC) activation and nitric oxide (NO) signaling that confer protection against I/R injury. Thus we hypothesized that hypothermia will protect most using extended ischemia and early reperfusion cooling and is mediated via PKC and NO synthase (NOS). Chick cardiomyocytes were exposed to an established model of 1-h ischemia/3-h reperfusion, and the same field of initially contracting cells was monitored for viability and NO generation. Normothermic I/R resulted in 49.7 Ϯ 3.4% cell death. Hypothermia induction to 25°C was most protective (14.3 Ϯ 0.6% death, P Ͻ 0.001 vs. I/R control) when instituted during extended ischemia and early reperfusion, compared with induction after reperfusion (22.4 Ϯ 2.9% death). Protection was completely lost if onset of cooling was delayed by 15 min of reperfusion (45.0 Ϯ 8.2% death). Extended ischemia/early reperfusion cooling was associated with increased and sustained NO generation at reperfusion and decreased caspase-3 activation. The NOS inhibitor N -nitro-L-arginine methyl ester (200 M) reversed these changes and abrogated hypothermia protection. In addition, the PKC⑀ inhibitor myr-PKC⑀ v1-2 (5 M) also reversed NO production and hypothermia protection. In conclusion, therapeutic hypothermia initiated during extended ischemia/early reperfusion optimally protects cardiomyocytes from I/R injury. Such protection appears to be mediated by increased NO generation via activation of protein kinase C⑀; nitric oxide synthase.

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Section: Chemicals Nmentioning

confidence: 99%

Hypothermia-induced cardioprotection using extended ischemia and early reperfusion cooling

Shao

Chang

Chan

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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“…The lack of effect of HOE642 on hypercontracture induced by reoxygenation is in agreement with its lack of effect on intracellular Ca¥ rise secondary to rigor contracture. On the other hand, the maintenance of an acidotic pH during the first few minutes of reoxygenation has been shown to attenuate transient Ca¥ oscillations and to protect cardiomyocytes against reoxygenation-induced hypercontracture (Bond et al 1991Harper et al 1993;Ladilov et al 1995).…”

Section: Protective Effect Against Rigormentioning

confidence: 99%

Protective Effect of HOE642, a Selective Blocker of Na⁺‐H⁺ Exchange, Against the Development of Rigor Contracture in Rat Ventricular Myocytes

Ruiz‐Meana

Garcı́a-Dorado

Julià

et al. 2000

Experimental Physiology

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The objective of this study was to investigate the effect of Na+‐H+ exchange (NHE) and HCO3−‐Na+ symport inhibition on the development of rigor contracture. Freshly isolated adult rat cardiomyocytes were subjected to 60 min metabolic inhibition (MI) and 5 min re‐energization (Rx). The effects of perfusion of HCO3− or HCO3−‐free buffer with or without the NHE inhibitor HOE642 (7 μM) were investigated during MI and Rx. In HCO3−‐free conditions, HOE642 reduced the percentage of cells developing rigor during MI from 79 ± 1% to 40 ± 4% (P < 0.001) without modifying the time at which rigor appeared. This resulted in a 30% reduction of hypercontracture during Rx (P < 0.01). The presence of HCO3− abolished the protective effect of HOE642 against rigor. Cells that had developed rigor underwent hypercontracture during Rx independently of treatment allocation. Ratiofluorescence measurement demonstrated that the rise in cytosolic Ca2+ (fura‐2) occurred only after the onset of rigor, and was not influenced by HOE642. NHE inhibition did not modify Na+ rise (SBFI) during MI, but exaggerated the initial fall of intracellular pH (BCEFC). In conclusion, HOE642 has a protective effect against rigor during energy deprivation, but only when HCO3−‐dependent transporters are inhibited. This effect is independent of changes in cytosolic Na+ or Ca2+ concentrations.

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“…8,9 Acidosis treatment at reperfusion induces cardioprotection. [10][11][12][13] Cohen et al 11 provided the experimental evidence, in the isolated rabbit heart, that alkalotic buffer blocked ischemic postconditioningconferred protection, and transient acidic reperfusion immediately applied at the onset of reperfusion protected against cardiac ischemia. The studies of acidosis treatment on hearts have provided much theoretical support for the acidosis therapeutic strategy toward ischemic stroke.…”

Section: Introductionmentioning

confidence: 99%

A Novel Neuroprotective Strategy for Ischemic Stroke: Transient Mild Acidosis Treatment by CO₂ Inhalation at Reperfusion

Fan

Shen

et al. 2013

J Cereb Blood Flow Metab

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Acidosis is one of the key components in cerebral ischemic postconditioning that has emerged recently as an endogenous strategy for neuroprotection. We set out to test whether acidosis treatment at reperfusion can protect against cerebral ischemia/reperfusion injury. Adult male C57BL/6 J mice were subjected to 60-minute middle cerebral arterial occlusion followed by 24-hour reperfusion. Acidosis treatment by inhaling 10%, 20%, or 30% CO 2 for 5 or 10 minutes at 5, 50, or 100 minutes after reperfusion was applied. Our results showed that inhaling 20% CO 2 for 5 minutes at 5 minutes after reperfusion-induced optimal neuroprotection, as revealed by reduced infarct volume. Attenuating brain acidosis with NaHCO 3 significantly compromised the acidosis or ischemic postconditioning-induced neuroprotection. Consistently, both acidosis-treated primary cultured cortical neurons and acute corticostriatal slices were more resistant to oxygen-glucose deprivation/reperfusion insult. In addition, acidosis inhibited ischemia/reperfusion-induced apoptosis, caspase-3 expression, cytochrome c release to cytoplasm, and mitochondrial permeability transition pore (mPTP) opening. The neuroprotection of acidosis was inhibited by the mPTP opener atractyloside both in vivo and in vitro. Taken together, these findings indicate that transient mild acidosis treatment at reperfusion protects against cerebral ischemia/reperfusion injury. This neuroprotection is likely achieved, at least partly, by inhibiting mPTP opening and mitochondria-dependent apoptosis. Keywords: acidosis treatment; cerebral ischemia; mPTP; neuroprotection INTRODUCTION Ischemic postconditioning, a neuroprotective strategy for ischemic stroke, has attracted much attention over the past 7 years. It is defined as a series of cycles of brief reperfusion and ischemia applied at the onset of reperfusion, which can mobilize the brain's own endogenous adaptive mechanisms and limit the extent of reperfusion injury. In 2006, Zhao et al 1 first reported that ischemic postconditioning reduces infarct volume in experimental cerebral ischemia and reperfusion (I/R) injury. Since then, its cerebral protective effects have been confirmed in several distinct ischemia models.2-5 However, the clinical application of ischemic postconditioning may be limited because of the difficulties in achieving well-controlled interruptions of reperfusion and the risks associated with these manipulations.6 Hypoxia, as a key component of ischemia, is a feasible treatment for ischemic stroke in theory. Surprisingly, we have recently found that an early application of hypoxic postconditioning after reperfusion does not induce neuroprotection against cerebral I/R injury.7 Thus, attempts should be undertaken to identify the other key factors, which are responsible for the protection afforded by ischemic postconditioning, and to develop a new therapeutic strategy, which is relatively safe and practical.Acidosis is another key component of ischemia besides hypoxia and glucose depletion. Extracellular pH can fall...

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Protection by acidotic pH against anoxia/reoxygenation injury to rat neonatal cardiac myocytes

Cited by 131 publications

References 17 publications

Hypothermia-induced cardioprotection using extended ischemia and early reperfusion cooling

Hypothermia-induced cardioprotection using extended ischemia and early reperfusion cooling

Protective Effect of HOE642, a Selective Blocker of Na⁺‐H⁺ Exchange, Against the Development of Rigor Contracture in Rat Ventricular Myocytes

A Novel Neuroprotective Strategy for Ischemic Stroke: Transient Mild Acidosis Treatment by CO₂ Inhalation at Reperfusion

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Protection by acidotic pH against anoxia/reoxygenation injury to rat neonatal cardiac myocytes

Cited by 131 publications

References 17 publications

Hypothermia-induced cardioprotection using extended ischemia and early reperfusion cooling

Hypothermia-induced cardioprotection using extended ischemia and early reperfusion cooling

Protective Effect of HOE642, a Selective Blocker of Na+‐H+ Exchange, Against the Development of Rigor Contracture in Rat Ventricular Myocytes

A Novel Neuroprotective Strategy for Ischemic Stroke: Transient Mild Acidosis Treatment by CO2 Inhalation at Reperfusion

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Protective Effect of HOE642, a Selective Blocker of Na⁺‐H⁺ Exchange, Against the Development of Rigor Contracture in Rat Ventricular Myocytes

A Novel Neuroprotective Strategy for Ischemic Stroke: Transient Mild Acidosis Treatment by CO₂ Inhalation at Reperfusion