Extracellular adenosine levels and cellular energy metabolism in ischemically preconditioned rat heart

Harrison, Glenn; Willis, Roger J.; Headrick, John P.

doi:10.1016/s0008-6363(98)00123-0

Cited by 62 publications

(60 citation statements)

References 46 publications

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“…Enzyme efflux tends to match functional outcome, being lowest in hearts displaying greater functional recovery. Consistently higher LDH versus CK efflux was observed, in agreement with our previous observations in the rat (Harrison et al 1998). Enzyme efflux data reveals an absence of significant tissue necrosis with 1&15 min of ischaemia in both isovolumic and apicobasally contracting models, with a pronounced increase in tissue damage as the period of ischaemia is increased to 220 min (Fig.…”

Section: Post-ischaemic Enzyme Leakagesupporting

confidence: 92%

“…The coronary circulation in the current model operates at -40'%1 of the peak flow of 45mlmin-' g-' (Headrick et al 2000h), and is responsive to varied stimuli. Although it has been suggested that crystalloid buffer may not adequately oxygenate inuriiie hearts and that added erythrocytes are required (Brooks & Apstein, 1996), the model exhibits the hallmarks of 02-sufficient tissue: ventricular pressure, heart rate and contractility are all high; the vasculature is sub-maximally dilated; substantial dilatation occurs during p-adrenoceptor or A2 adenosine receptor stimulation (Headrick et al 2000b); cellular energy state is high; myocardial purine and enzyme effluxes are low ( (Headrick et al 1998a), we estimate a AG,,, (the Gibbs free energy of ATP hydrolysis) of -61.4 kJ mol-I, exceeding the values for rat inyocardium (Harrison et al 1998;Headrick et al 1998b), and reflecting efficient oxidative ATP generation at the expense of ADP and P,.…”

Section: Normoxic Function and Stabilitymentioning

confidence: 53%

“…Commercially available spectrophotometric assays for LDH and CK (Sigma) were optimised for sensitivity. Venous levels of adenosine, inosine and hypoxanthine levels were assessed by HPLC as described by us previously (Harrison et al 1998;Headrick et al 1998a,h). Normoxic enzyme or purine effluxes were calculated as the product of coronary flow (in1 min-' g-') x effluent concentrations (U or nmol ml-', respectively).…”

Section: Measurement Of Enzyme Efflux and Purine Moiety Washoutmentioning

confidence: 99%

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Functional properties and responses to ischaemia‐reperfusion in Langendorff perfused mouse heart

Headrick¹,

Peart²,

Hack³

et al. 2001

Experimental Physiology

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112

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Despite minimal model characterisation Langendorff perfused murine hearts are increasingly employed in cardiovascular research, and particularly in studies of myocardial ischaemia and reperfusion. Reported contractility remains poor and ischaemic recoveries variable. We characterised function in C57/BL6 mouse hearts using a ventricular balloon or apicobasal displacement and assessed responses to 10-30 min global ischaemia. We examined the functional effects of pacing, ventricular balloon design, perfusate filtration, [Ca"] and temperature. Contractility was high in isovolumically functioning mouse hearts (measured as the change in pressure with time (+dP/dt), 6000-7000 mmHg s-I) and was optimal at a heart rate of -420 beats min-', with the vasculature sub-maximally dilated, and the cellular energy state high. Post-ischaemic recovery (after 40 min reperfusion) was related to the ischaemic duration: developed pressure recovered by 82 f YO, 73 f 4u/, 68 f 3%, 57 f 2% and 41 f 5% after 10, 15, 20, 25 and 30 min ischaemia, respectively. Ventricular compliance and elastance were both reduced post-ischaemia. Post-ischaemic recoveries were lower in the apicobasal model (80 +-4 YO, 58 k 7 YO, 40 +-3 %, 32 +-7 % and 25 2 5 YO) despite greater reflow and lower metabolic rate (pre-ischaemic myocardial O2 consumption (Vo2,,,,) 127 f 15 vs. 198 k 17 p l O2 min-' g-'), contracture, enzyme and purine efflux. Electrical pacing slowed recovery in both models, small ventricular balloons (unpressurised volumes C 50-60 p1) artificially depressed ventricular function and recovery from ischaemia, and failure to filter the perfusion fluid to C 0.45 pm depressed pre-and post-ischaemic function. With attention to these various experimental factors, the buffer perfused isovolumically contracting mouse heart is shown to be stable and highly energised, and to possess a high level of contractility, The isovolumic model is more reliable in assessing ischaemic responses than the commonly employed apicobasal model. Experimental Physiology (200 1) 86.6, 703-7 16.

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Section: Post-ischaemic Enzyme Leakagesupporting

confidence: 92%

Section: Normoxic Function and Stabilitymentioning

confidence: 53%

Section: Measurement Of Enzyme Efflux and Purine Moiety Washoutmentioning

confidence: 99%

See 1 more Smart Citation

Functional properties and responses to ischaemia‐reperfusion in Langendorff perfused mouse heart

Headrick¹,

Peart²,

Hack³

et al. 2001

Experimental Physiology

Self Cite

112

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“…Thus, successively lower peak levels of adenosine were observed following each ischemia/reperfusion cycle. These findings were also observed by others (146)(147)(148)(149). It was suggested that the die away curve pattern of adenosine was due to diminished nucleotide decay induced by IP (146).…”

Section: Our Experimental Findingssupporting

confidence: 81%

Understanding myocardial ischemic preconditioning, and the implications for a role of adenosine catabolism

Kavianipour

2002

Upsala Journal of Medical Sciences

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“…Although calcium flux, 3 acidosis, 4 ATP depletion, 5 and reactive oxygen species 6 have been defined as putative causative factors, there may be other mediator factors that remain to be identified. Indeed, besides necrosis, apoptosis is one of the early events of either warm ischemia and reperfusion injury 7,8 or cold ischemia and reperfusion injury 2 in the heart.…”

Section: See Pmentioning

confidence: 99%

Bcl-xL Gene Transfer Inhibits Bax Translocation and Prolongs Cardiac Cold Preservation Time in Rats

et al. 2005

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Background-Apoptosis is an important cause of early graft loss after heart transplantation. Bcl-xL was reported to protect the heart against normothermic ischemia and reperfusion injury. In this study, we determined whether overexpression of Bcl-xL could inhibit tissue injury resulting from prolonged cold preservation followed by warm reperfusion of heart transplants. Methods and Results-Lewis rat hearts were transduced with an adenovirus vector harboring Bcl-xL cDNA (AxCAhBclxL) 4 days before collection of tissue. After preservation in University of Wisconsin solution at 4°C for 24 hours, the heart was either perfused with a Langendorff device ex vivo or used for heterotopic heart transplantation in vivo. Bcl-xL gene transfer significantly reduced the infarct size (23.0Ϯ2.6% versus 47.7Ϯ7.0% in saline control and 48.6Ϯ6.1% in vector control, PϽ0.01) after 2-hour reperfusion at 37°C with the Langendorff device and significantly decreased creatine kinase release (0.82Ϯ0.27 IU, versus 1.57Ϯ0.33 and 1.50Ϯ0.37 IU in saline and vector controls, respectively; PϽ0.05). In heart transplantation, overexpresson of Bcl-xL inhibited Bax translocation from the cytosol to the mitochondria, resulting in decreased cytochrome c release from the mitochondria; it also significantly decreased cardiac cell apoptosis and improved graft survival rate after long cold preservation, followed by warm reperfusion. Conclusions-Bcl-xL

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Extracellular adenosine levels and cellular energy metabolism in ischemically preconditioned rat heart

Cited by 62 publications

References 46 publications

Functional properties and responses to ischaemia‐reperfusion in Langendorff perfused mouse heart

Functional properties and responses to ischaemia‐reperfusion in Langendorff perfused mouse heart

Understanding myocardial ischemic preconditioning, and the implications for a role of adenosine catabolism

Bcl-xL Gene Transfer Inhibits Bax Translocation and Prolongs Cardiac Cold Preservation Time in Rats

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