Allopurinol Improves Postischemic Muscle Function but Not High‐Energy Phosphate Levels

Marx, A.; Gürke, Lorenz; Sutter, P.-M.; Erhard, Peter; Landmann, J; Harder, F.; Heberer, Michael

doi:10.1111/j.1749-6632.1994.tb36762.x

Cited by 3 publications

(5 citation statements)

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“…Es wurde ein etabliertes experimentelles Modell zur differenzierten In-vitro-Analyse der Skelettmuskelfunktion nach standardisierter Ischämie und Reperfusion [20,29,32] verwendet. 86-23, revised 1985).…”

Section: Methodenunclassified

“…Die Reduktion freier Radikale durch Radikalfänger (Scavenger) [24], die kompetitive Hemmung der Xanthinoxidase mit Allopurinol [24], die Blockierung von Adhäsionsmolekülen mit monoklonalen Antikörpern [25], die Verbesserung der Mikrozirkulation durch hyperosmolare Dextraninfusion [22] und der Einsatz lokaler Hypothermie [20] erwiesen sich als wirksame Maßnahmen zur Reduktion des ischämie-und reperfusionsinduzierten Skelettmuskelschadens. Unter experimentellen Bedingungen konnte die Ischämietoleranz der Skelettmuskulatur durch verschiedene Maßnahmen verbessert werden.…”

Section: Diskussionunclassified

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Die Anzahl der Präkonditionierungszyklen beeinflusst die Skelettmuskelprotektion durch ischämische Präkonditionierung

et al. 2000

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Zusammenfassung Die ischämische Präkonditionierung (IP) ist ein neues Konzept zur Verbesserung der Ischämietoleranz, welches bisher fast ausschließlich am Herzmuskel untersucht wurde. Unter IP versteht man eine schnelle Gewebereaktion auf einen oder mehrere kurze Zyklen alternierender Ischämie und Reperfusion, welche die Toleranz für eine kurz darauffolgende, längerdauernde Ischämie verbessert. Das Ziel dieser Studie ist die Wirksamkeit der IP auf die postischämische Funktion der Skelettmuskulatur zu prüfen und die Wirksamkeit verschiedener Präkonditionierungsprotokolle zu vergleichen. Ratten wurden in 4 Gruppen (je n=12) eingeteilt. Gruppe A wurde nicht präkonditioniert und diente als Kontrolle. Bei den Gruppen B-D wurde der rechte Hinterlauf mit 1, 2 bzw. 3 Zyklen von je 10 min Ischämie und 10 min Reperfusion präkonditioniert. Danach wurden die Schlüsselwörter Ischämische Präkonditionierung · Skelettmuskulatur · Ratten · Ischämie · Muskelfunktion Gefässchirurgie (2000) 5:154-158

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Die Anzahl der Präkonditionierungszyklen beeinflusst die Skelettmuskelprotektion durch ischämische Präkonditionierung

et al. 2000

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“…Previously, we had found mild hypothermia to increase HEP tissue levels in post-ischaemic muscle biopsies and to improve post-ischaemic mus- cle function using in vitro 3IP-and 'H-MR spectroscopy [13]. This in vitro technique was subsequently used to investigate the effect of AP on HEP levels in post-ischaemic skeletal muscle specimens [7], AP pretreatment did not alter levels of ATP and PCr in musculi gastrocnemii after 3 h of ischaemia and 2 h of reperfusion. These experiments, however, re fer to only one point of time and, therefore, could not detect possible effects of AP on the 104 Eur Surg Res 1997:29:10 1 -106…”

Section: Discussionmentioning

confidence: 99%

“…McCutchan et al [5], Ofarrell et al [6] and Marx et al [7] have previous ly described improved post-ischaemic skeletal muscle function following AP pretreatment. AP-mediated inhibition of xanthine oxidase (XO) reduces xanthine formation from hypoxanthine during reperfusion and may increase ischaemic tolerance by two principal mecha nisms: (1) the generation of oxygen-derived free radicals during reperfusion may be atten uated and free radical mediated tissue injury may thereby be reduced, and (2) irreversible breakdown of hypoxanthine may be prevent ed enabling rapid post-ischaemic purine resvnthesis (salvage pathway) [8][9][10][11][12], We have not been able to find support for the salvage pathway mechanism by measurements of high-energy phosphates and degradation products at a distinct point of time (3 h of ischaemia and 2 h of reperfusion) [7], This observational window, however, does not ex clude changes in high-energy phosphate kinet ics. Magnetic resonance (MR) spectroscopy enables the determination of both high-energy phosphate (HEP) tissue levels and kinetics during ischaemia and reperfusion.…”

Section: Introductionmentioning

confidence: 99%

Kinetics of High-Energy Phosphates in Allopurinol-Pretreated Ischaemic and Post-lschaemic Skeletal Muscle: An in vivo Magnetic Resonance Spectroscopy Study

Gürke

Erhard²,

Marx³

et al. 1997

Eur Surg Res

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AUopurinol (AP) protects skeletal muscle function against ischaemia-induced injury, but the mechanism is not yet clear. As AP acts as a competitive xanthine oxidaxe inhibitor, both a reduction of oxygen-derived free radicals and an enhancement of purine resynthesis (salvage pathway) might be involved. We investigated the in vivo kinetics of high-energy phosphates in skeletal muscle after AP pretreatment using ³¹P-magnetic resonance spectroscopy during 2 h of ischaemia and 3 h of reperfusion in rat hindlimbs. Three animals (group A) were pre-treated with a total of 160 mg/kg AP i.p., 3 control animals (group B) received the same amount of 0.9% saline solution. ATP decreased to 18.6 ± 1.3% of the pre-ischaemic value in group A and to 17.3 ± 2.8% in group B after 2 h of ischaemia, and rose to only 47.7 ± 1.5 and 50.5 ± 1.8%, respectively, after 3 h of reperfusion. Phosphocreatine fell to 7.2 ± 2.9 and 7.6 ± 2.2% of pre-ischaemic values after 2 h of ischaemia and rose again to 36.5 ± 12.9 and 45.4 ± 20.4% after 3 h of reperfusion. Inorganic phosphate (Pi) increased 5-fold after 2 h of ischaemia, irrespective of the treatment. After 3 h of reperfusion, Pi was still 4 times the pre-ischaemic value. The kinetics of ATP, PCr, and Pi levels were not statistically different between the two groups. These results indicate that the ATP salvage pathway does not play an important role in AP-induced attenuation of ischaemia/reperfusion-induced muscle damage.

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“…Prolonged regional ischemia is often required during vascular and musculoskeletal reconstructive surgery such as pedicled or free transfer of myocutaneous or free transfer of skin flaps, but excessive ischemia may cause tissue or muscle infarction and subsequent necrosis 15, 38, 43. By decreasing the duration of ischemia or tissue temperature, such potential muscle damage can be partially prevented 26. Nevertheless, if alternative approaches could be identified, such as pharmacological preconditioning, then limiting the duration of ischemia might be less of a concern.…”

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Hibernation induction trigger reduces hypoxic damage of swine skeletal muscle

et al. 2005

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A link between the cardioprotective benefits of pharmacological preconditioning and natural mammalian hibernation is considered to involve the cellular activation of opioid receptors and subsequent opening of K(ATP) channels. In previous studies, we have demonstrated the protective effects of specific delta-opioid agonists against porcine cardiac ischemia/reperfusion injury. We hypothesize here that preincubation with hibernation induction trigger (HIT) should confer a similar protection in skeletal muscles. Therefore, muscle bundles from swine were pretreated with plasma from hibernating woodchucks (HWP) for 30 min, then exposed to hypoxia for 90 min and reoxygenation for 120 min. Stimulated twitch forces were assessed. The functional effects of pretreatment with nonhibernation (summer) woodchuck plasma, a K(ATP) blocker, or opioid antagonist were also studied. During the reoxygenation period, significantly greater force recoveries were observed only for bundles pretreated with HWP; this response was blocked by naloxone (P < 0.05). We conclude that HIT pretreatment could be used to confer protection against hypoxia/reperfusion injury of skeletal muscles of nonhibernators; it could potentially be utilized to prevent injury during surgical procedures requiring ischemia.

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Allopurinol Improves Postischemic Muscle Function but Not High‐Energy Phosphate Levels

Cited by 3 publications

References 5 publications

Die Anzahl der Präkonditionierungszyklen beeinflusst die Skelettmuskelprotektion durch ischämische Präkonditionierung

Die Anzahl der Präkonditionierungszyklen beeinflusst die Skelettmuskelprotektion durch ischämische Präkonditionierung

Kinetics of High-Energy Phosphates in Allopurinol-Pretreated Ischaemic and Post-lschaemic Skeletal Muscle: An in vivo Magnetic Resonance Spectroscopy Study

Hibernation induction trigger reduces hypoxic damage of swine skeletal muscle

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