Therapeutic potential of ischaemic preconditioning

Edwards, Richard; Saurin, Adrian T.; Rakhit, Roby; Marber, Michael

doi:10.1046/j.1365-2125.2000.00236.x

Cited by 23 publications

(19 citation statements)

References 138 publications

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“…Also, we could -as expected -confirm the previously described ischemic preconditioning effect with a progressively increasing time delay from balloon inflation to the onset of first ECG changes after subsequent coronary occlusions [20][21][22]. However, this effect was observed in both groups alike and is therefore independent of age, at least in our experimental model.…”

Section: Discussionsupporting

confidence: 91%

Influence of age on pain perception in acute myocardial ischemia: A possible cause for delayed treatment in elderly patients

Rittger¹,

Rieber²,

Breithardt³

et al. 2011

International Journal of Cardiology

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Section: Discussionsupporting

confidence: 91%

Influence of age on pain perception in acute myocardial ischemia: A possible cause for delayed treatment in elderly patients

Rittger¹,

Rieber²,

Breithardt³

et al. 2011

International Journal of Cardiology

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“…This protocol is known as IP (ischaemic preconditioning) and was first described in the dog heart by Murry et al in 1986 [215] but has since been confirmed in all species including humans [216][217][218]. Preconditioned hearts exhibit a smaller infarct size, less release of intracellular enzyme (indicators of necrotic cell death) and fewer arrhythmias [215,219], while contractile function is preserved [220].…”

Section: Preconditioningmentioning

confidence: 96%

A pore way to die: the role of mitochondria in reperfusion injury and cardioprotection

Halestrap

2010

Biochemical Society Transactions

272

239

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In addition to their normal physiological role in ATP production and metabolism, mitochondria exhibit a dark side mediated by the opening of a non-specific pore in the inner mitochondrial membrane. This mitochondrial permeability transition pore (MPTP) causes the mitochondria to breakdown rather than synthesize ATP and, if unrestrained, leads to necrotic cell death. The MPTP is opened in response to Ca(2+) overload, especially when accompanied by oxidative stress, elevated phosphate concentration and adenine nucleotide depletion. These conditions are experienced by the heart and brain subjected to reperfusion after a period of ischaemia as may occur during treatment of a myocardial infarction or stroke and during heart surgery. In the present article, I review the properties, regulation and molecular composition of the MPTP. The evidence for the roles of CyP-D (cyclophilin D), the adenine nucleotide translocase and the phosphate carrier are summarized and other potential interactions with outer mitochondrial membrane proteins are discussed. I then review the evidence that MPTP opening mediates cardiac reperfusion injury and that MPTP inhibition is cardioprotective. Inhibition may involve direct pharmacological targeting of the MPTP, such as with cyclosporin A that binds to CyP-D, or indirect inhibition of MPTP opening such as with preconditioning protocols. These invoke complex signalling pathways to reduce oxidative stress and Ca(2+) load. MPTP inhibition also protects against congestive heart failure in hypertensive animal models. Thus the MPTP is a very promising pharmacological target for clinical practice, especially once more specific drugs are developed.

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“…Neuronal ischemic preconditioning is an endogenous neuroprotective strategy that provides sustained and robust ischemic tolerance (Davis and Patel, 2003). IPC occurs in several species, including human, rat, mouse, rabbit, and pig, and in several organs, including brain, spinal cord, heart, kidney, and intestine (Edwards et al, 2000). Other forms of preconditioning have been investigated, such as pharmacological, thermal, and gas inhalation.…”

Section: Introductionmentioning

confidence: 99%

Pharmacological preconditioning by milrinone: Memory preserving and neuroprotective effect in ischemia-reperfusion injury in mice

2010

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We tested the neuroprotective effect of milrinone, a phosphodiesterase III inhibitor, in pharmacological preconditioning. Bilateral carotid artery occlusion for 12 min followed by reperfusion for 24 h produced ischemia-reperfusion (I/R) cerebral injury in male Swiss albino mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was assessed using the Morris water maze test, and motor coordination was evaluated using the inclined beam walking test, rota-rod test, and lateral push test. Milrinone (50 microg/kg & 100 microg/kg i.v.) was administered 24 h before surgery in a separate group of animals to induce pharmacological preconditioning. I/R increased cerebral infarct size and impaired memory and motor coordination. Milrinone treatment significantly decreased cerebral infarct size and reversed I/R-induced impairments in memory and motor coordination. This neuroprotective effect was blocked by ruthenium red (3 mg/kg, s.c.), an intracellular ryanodine receptor blocker. These findings indicate that milrinone preconditioning exerts a marked neuroprotective effect on the ischemic brain, putatively due to increased intracellular calcium levels activating calcium-sensitive signal transduction cascades.

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Therapeutic potential of ischaemic preconditioning

Cited by 23 publications

References 138 publications

Influence of age on pain perception in acute myocardial ischemia: A possible cause for delayed treatment in elderly patients

Influence of age on pain perception in acute myocardial ischemia: A possible cause for delayed treatment in elderly patients

A pore way to die: the role of mitochondria in reperfusion injury and cardioprotection

Pharmacological preconditioning by milrinone: Memory preserving and neuroprotective effect in ischemia-reperfusion injury in mice

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