Sustained benefit of temporary limited reperfusion in skeletal muscle following ischemia (original) (raw)
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Skeletal Muscle Ischaemia-reperfusion Injury: Further Characterisation of a Rodent Model
European Journal of Vascular and Endovascular Surgery, 2001
Background: postischaemic damage in skeletal muscle may be reflected in changes to microvascular blood flow, vascular permeability, and subsequent tissue viability. Previous preclinical studies have not addressed all these parameters, and have not used periods of ischaemia and reperfusion relevant to the clinical setting. This study aimed to develop an animal model hindlimb ischaemia-reperfusion to simulate acute lower limb ischaemia. Methods: a rodent model of hindlimb tourniquet-induced ischaemia-reperfusion was employed. Gastrocnemius muscle blood flow (GMBF; radio-labelled microspheres), oedema (GMO; using a wet:dry ratio method) and viability (GMV; histochemistry and computerised planimetry) were quantified. Results: 6 h ischaemia per se resulted in neither muscle oedema nor loss of viability, but these changes were apparent following 4 h reperfusion. Early reperfusion at 10 min demonstrated low reflow, with GMBF improving at 120 min before declining sharply at 240 min. Conclusion: prolonged hindlimb ischaemia followed by reperfusion in this rodent model caused significant reductions in gastrocnemius muscle blood flow, associated with muscle oedema and necrosis. These three parameters have not been previously reported together in the same model. This reproducible model could be used in the evaluation of potential therapeutic intervention strategies aimed at ameliorating skeletal muscle reperfusion injury.
Quantitative histochemical evaluation of skeletal muscle ischemia and reperfusion injury
Journal of Surgical Research, 1987
Acute arterial obstruction to the extremities is associated with significant morbidity and mortality. The evaluation of accompanying skeletal muscle injury has thus far been indirect and imprecise. Triphenyltetrazolium chloride (TTC) is an oxidation-reduction indicator which allows for the histochemical quantitation of skeletal muscle injury. In 21 anesthetized nonheparinized adult mongrel dogs, the isolated in vivo gracilis muscle underwent 4, 6, or 8 hr of ischemia with and without reperfusion. The muscles were excised and cut into 1-cm segments, representative muscle biopsies for electron microscopy were taken, each segment was stained in 1% TTC, and the total area of staining was measured with computerized planimetry. All control muscles stained completely with a dark red color. After 4, 6, or 8 hr of ischemia, quantitative measurements of muscle staining indicative of normal tissue were present in 98 +/- 1%, 59 +/- 5%, and 23 +/- 9% of the total muscle areas, respectively. Six hours of ischemia followed by reperfusion was associated with only 36 +/- 9% of the muscle being stained. Segmental TTC staining demonstrated that reperfusion was associated with greater injury, and less TTC staining, in the proximal portion of the gracilis muscle at the site of entry of the major arterial pedicle. The distal muscle did not demonstrate increased damage with reperfusion. It is hypothesized that protection of the distal muscle from reperfusion injury may be due to an absence of reflow farther away from the artery.
Pharmacologic intervention in ischemia-induced reperfusion injury in the skeletal muscle
Microsurgery, 1993
muscle. Special emphasis is placed on the recent observation of the acute ischemic preconditioning phenomenon for prevention of I/R injury in skeletal muscle. Finally, the mechanism of ischemic preconditioning and its clinical applications for augmentation of skeletal muscle tolerance to prolonged ischemic insult are discussed. o im wiiey-~iss, inc.
Acta Cirurgica Brasileira, 2013
To investigate the protective effects of ischemic pre and postconditioning, as well as the association of both methods, in skeletal muscle injury produced by ischemia and reperfusion in rats. METHODS: An experimental study was designed using 40 Wistar rats divided in four groups (n=10): Control-rats submitted to ischemia for 240 minutes (min) and reperfusion for 60 min; Ischemic preconditioning (Pre)-animals submitted to three cycles of clamping and releasing the aorta for five min before being submitted to the ischemia/reperfusion procedure; Ischemic postconditioning (Post)-rats submitted to three cycles of clamping and releasing the aorta for one min after the 240-minute ischemic phase; Ischemic pre and postconditioning (Pre-post)-animals submitted to the same procedures of Pre and Post groups. Skeletal muscle injury was evaluated by measuring serum levels of aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatine phosphokinase (CPK); and muscular levels of malondialdehyde (MDA) and glycogen. RESULTS: AST levels were significantly higher in Pre and Pre-post groups (P<.01). There were no differences in LDH and CPK levels. Muscular MDA levels were similar. Glycogen levels were significantly higher in Pre and Pre-post groups (P<.01). CONCLUSIONS: Both preconditioning and its association with postconditioning had a protective effect by avoiding glycogen depletion in skeletal muscle in rats submitted to ischemia and reperfusion. Association of pre and postconditioning did not show advantage compared to preconditioning alone. Postconditioning alone did not show protective effect.
Acta Cirurgica Brasileira, 2006
Purpose: Verify the role of ischemic preconditioning (IPC) in ischemia and reperfusion injury on gracilis muscle of rats. Methods: Wistar rats (n=30) were distributed in three groups, I/R and IPC groups were subdivided concerning ischemia time. A near-amputation model of the posterior limb was produced by a hip joint level incision, preserving the vascular bundle and the femur bone and ischemia was induced for 2h and 4h, G-I 2h/R (n=6) and G-I 4h/R (n=6), followed by 1h of vascular reperfusion. The preconditioned groups, G-PCI 2h (n=6) and G-PCI 4h (n=6), were preceded by 3 cycles of 5min of ischemia followed by 5min of vascular reperfusion before sustained ischemia. In the Control Group, C-G (n=6) animals were subjected to regional approach. The analysis was done with Light Microscopy (LM). Results: The levels of fibril fragmentation were progressive in the G-I 2h/R (67% of muscle preservation) and in the G-I4 h/R (0% of muscle preservation). However in the group of the precondition the lesion degree being in level similar to the group controls in the G-I 2h/R (100% of muscle preservation) while at G-I 4h/r occur less protection (67% of muscle preservation). The degree of tissue inflammatory reaction was worst at G-I 4h/R (0% without inflammation signals) than at G-I 2h/R (50% without inflammation signals); while in the precondition group G-IPC-2h (83% without inflammation signals) was better than the G-IPC-4h (67% without inflammation signals). The vascular stasis was absent only in 17% of the G-I 4h/R and in 33% of the G-I 2h/R. In precondition group, however, the vascular stasis was absent in 33% at G-IPC 2h and absent in 50% at G-IPC 4h. Conclusion: The IPC showed, in an earlier phase, a benefic role at I/R derived injury on gracilis muscle of rats, as proven for the largest preservation of the fibers muscular, smaller inflammatory reaction and smaller vascular stasis.
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2008
We tested our hypothesis that postischemic conditioning (PostC) is effective in salvage of ischemic skeletal muscle from reperfusion injury and the mechanism involves inhibition of opening of the mitochondrial permeability transition pore (mPTP). In bilateral 8 × 13 cm pig latissimus dorsi muscle flaps subjected to 4 h ischemia, muscle infarction increased from 22 ± 4 to 41 ± 1% between 2 and 24 h reperfusion and remained unchanged at 48 (38 ± 6%) and 72 (40 ± 1%) h reperfusion ( P < 0.05; n = 4 pigs). PostC induced by four cycles of 30-s reperfusion/reocclusion at the onset of reperfusion after 4 h ischemia reduced muscle infarction from 44 ± 2 to 22 ± 2% at 48 h reperfusion. This infarct protective effect of PostC was mimicked by intravenous injection of the mPTP opening inhibitor cyclosporin A or NIM-811 (10 mg/kg) at 5 min before the end of 4 h ischemia and was abolished by intravenous injection of the mPTP opener atractyloside (10 mg/kg) at 5 min before PostC ( P < 0.05; ...
An isolated skeletal muscle model suitable for acute ischemia studies
Journal of Surgical Research, 1986
A modified isolated canine gracilis model of acute complete muscle ischemia was developed and then tested metabolically and histologically in 25 animals to assess its validity. In each dog, both gracili were isolated on their major vascular pcdicles. One muscle underwent &hernia and reperfusion by placing and removing microvascular clips on the artery and vein. The other gracilis muscle was used as a control. Total muscle blood flow measurements, blood samples, and muscle biopsies were taken every other hour for up to 1 I hr after preparation. The fiber-type profile of the gracilis was determined bilaterally using a myosin ATPase stain (n = 10). The results verified these hypotheses: (1) after surgical preparation, the right and left muscles in the same dog are equivalent metabolically, (2) after a 2-hr stabilization period, gracilis blood flow, oxygen and glucose uptake, lactate release, and tissue glycogen, lactate, phosphocreatine, and ATP levels remain within normal limits and unchanged for the next 9 hr, (3) the surgical isolation of the gracilis muscle on a single vascular pedicle does not result in significant metabolic changes, (4) in this model, a 2-hr ischemia is reversible, but a 7-hr ischemia results in irreversible ischemic injury. As well, fiber-type protile, muscle blood flow, and metabolic parameters can vary significantly among animals supporting the necessity of a contralateral control. Therefore, this modified gracilis muscle model with its contralateral muscle as a control is suitable for acute skeletal muscle ischemia experiments of at least 9-hr duration. 0
Journal of the American College of Surgeons, 2006
BACKGROUND: Severe extremity wounds with vascular injury are common in military trauma, and tourniquets are commonly used for hemorrhage control. The complications of tourniquet use in the setting of trauma are not well studied. This study investigated the combined effect of hemorrhagic shock and fluid resuscitation with Hextend (HX; BioTime, Inc) or lactated Ringer's (LR) on skeletal muscle subjected to tourniquet-induced ischemia-reperfusion injury. STUDY DESIGN: Thirty male Sprague-Dawley rats underwent 33% arterial hemorrhage followed by 3 hours of tourniquet application. Before reperfusion, 10 animals each were resuscitated with lactated Ringer's (3 times shed volume) or HX (shed volume). Ten control animals received no resuscitation. Rats were euthanized 2 hours after tourniquet release and the tibialis anterior and medial gastrocnemius muscles were examined for edema (muscle wet weight) and viability (nitroblue tetrazolium reduction). Contralateral muscles served as controls for each animal, with results expressed as the ratio of the tourniquet limb to contralateral limb values. RESULTS: Competing interests declared: None.