Postconditioning the Isolated Working Rat Heart

Vuuren, Derick van; Genis, Amanda; Genade, Sonia; Lochner, Amanda

doi:10.1007/s10557-008-6119-6

Cited by 18 publications

(11 citation statements)

References 19 publications

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“…Such a dissociation between changes in IFS and changes in functional recovery, as observed here, have been reported by us 44,74,75 and others 76-78. Although it is unexpected, it is therefore not without precedent or possible explanation through combination of the diverse effects of FTY720 on the heart.…”

Section: Discussionsupporting

confidence: 91%

The differential effects of FTY720 on functional recovery and infarct size following myocardial ischaemia/ reperfusion

Vuuren

Marais

Genade

et al. 2016

CVJA

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SummaryAimThe aim of this study was to evaluate the effects of the sphingosine analogue, FTY720 (Fingolimod), on the outcomes of myocardial ischaemia/reperfusion (I/R) injury.MethodsTwo concentrations of FTY720 (1 or 2.5 μM) were administered either prior to (PreFTY), or following (PostFTY) 20 minutes’ global (GI) or 35 minutes’ regional ischaemia (RI) in the isolated, perfused, working rat heart. Functional recovery during reperfusion was assessed following both models of ischaemia, while infarct size (IFS) was determined following RI.ResultsFTY720 at 1 μM exerted no effect on functional recovery, while 2.5 μM significantly impaired aortic output (AO) recovery when administered prior to GI (% recovery: control: 33.88 ± 6.12% vs PreFTY: 0%, n = 6–10; p < 0.001), as well as before and after RI (% recovery: control: 27.86 ± 13.22% vs PreFTY: 0.62%; p < 0.05; and PostFTY: 2.08%; p = 0.0585, n = 6). FTY720 at 1 μM administered during reperfusion reduced IFS [% of area at risk (AAR): control: 39.89 ± 3.93% vs PostFTY: 26.56 ± 4.32%, n = 6–8; p < 0.05), while 2.5 μM FTY720 reduced IFS irrespective of the time of administration (% of AAR: control: 39.89 ± 3.93% vs PreFTY: 29.97 ± 1.03%; and PostFTY: 30.45 ± 2.16%, n = 6; p < 0.05).ConclusionFTY720 exerted divergent outcomes on function and tissue survival depending on the concentration administered, as well as the timing of administration.

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Section: Discussionsupporting

confidence: 91%

The differential effects of FTY720 on functional recovery and infarct size following myocardial ischaemia/ reperfusion

Vuuren

Marais

Genade

et al. 2016

CVJA

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“…Hearts were cannulated via the aorta and initially perfused in a retrograde non-working mode (coronary flow rate = 12.0 ± 1.0 ml/min), with prefiltered, oxygenated (O 2 95%, CO 2 5%) Krebs-Henseleit buffer solution according to the Langendorff method [22] under constant pressure conditions (100 mmHg) at 37°C for 15 min. The left ventricle was vented through the apex with a polyethylene catheter to avoid the retention by the ventricle of coronary perfusate from the Thebesian veins.…”

Section: Isolated Heart Preparationmentioning

confidence: 99%

The effect of diazepam on myocardial function and coronary vascular tone after endotoxemia in the isolated rat heart model

Neethling

Hodge

2010

Inflamm. Res.

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“…In the classical in vivo IPC and IPoC models, a reduction in the size of the infarct is chosen as the relevant end point in most cases even though this was often not accompanied by a corresponding functional recovery 4, 5. However, no information can be gleaned about long‐term functional improvements or positive remodeling using these short‐term models.…”

Section: Introductionmentioning

confidence: 99%

Adverse Effects on β‐Adrenergic Receptor Coupling: Ischemic Postconditioning Failed to Preserve Long‐Term Cardiac Function

Schreckenberg

Bencsik

Weber

et al. 2017

JAHA

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BackgroundIschemic preconditioning (IPC) and ischemic postconditioning (IPoC) are currently among the most efficient strategies protecting the heart against ischemia/reperfusion injury. However, the effect of IPC and IPoC on functional recovery following ischemia/reperfusion is less clear, particularly with regard to the specific receptor‐mediated signaling of the postischemic heart. The current article examines the effect of IPC or IPoC on the regulation and coupling of β‐adrenergic receptors and their effects on postischemic left ventricular function.Methods and ResultsThe β‐adrenergic signal transduction was analyzed in 3‐month‐old Wistar rats for each of the intervention strategies (Sham, ischemia/reperfusion, IPC, IPoC) immediately and 7 days after myocardial infarction. Directly after the infarction a cardioprotective potential was demonstrated for both IPC and IPoC: the infarct size was reduced, apoptosis and production of reactive oxygen species were lowered, and the myocardial tissue was preserved. Seven days after myocardial ischemia, only IPC hearts showed significant functional improvement. Along with a deterioration in fractional shortening, IPoC hearts no longer responded adequately to β‐adrenergic stimulation. The stabilization of β‐adrenergic receptor kinase‐2 via increased phosphorylation of Mdm2 (an E3‐ubiquitin ligase) was responsible for desensitization of β‐adrenergic receptors and identified as a characteristic specific to IPoC hearts.ConclusionsImmediately after myocardial infarction, rapid and transient activation of β‐adrenergic receptor kinase‐2 may be an appropriate means to protect the injured heart from excessive stress. In the long term, however, induction and stabilization of β‐adrenergic receptor kinase‐2, with the resultant loss of positive inotropic function, leads to the functional picture of heart failure.

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Postconditioning the Isolated Working Rat Heart

Cited by 18 publications

References 19 publications

The differential effects of FTY720 on functional recovery and infarct size following myocardial ischaemia/ reperfusion

The differential effects of FTY720 on functional recovery and infarct size following myocardial ischaemia/ reperfusion

The effect of diazepam on myocardial function and coronary vascular tone after endotoxemia in the isolated rat heart model

Adverse Effects on β‐Adrenergic Receptor Coupling: Ischemic Postconditioning Failed to Preserve Long‐Term Cardiac Function

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