Effect of ischemia-reperfusion on diaphragm strength and fatigability

1993 ◽  
Vol 75 (5) ◽  
pp. 2180-2187 ◽  
Author(s):  
G. Supinski ◽  
D. Stofan ◽  
A. DiMarco

Although episodes of prolonged limb skeletal muscle ischemia followed by periods of reperfusion and reoxygenation are known to elicit free radical-mediated injury, the susceptibility of the diaphragm to this form of injury is not known. The purpose of the present study was to determine the effects of a period of severe partial ischemia, followed by reperfusion, on diaphragm contractile function. We also examined the effect of administration of a free radical scavenger, dimethyl sulfoxide (DMSO), on the diaphragmatic response to ischemia-reperfusion. Experiments were performed on three groups of anesthetized dogs in which a vascularly isolated strip of diaphragm was dissected in situ: 1) a control group in which the diaphragm was perfused at the ambient systemic pressure, 2) a group in which the diaphragm was made ischemic for 3 h and reperfused for 1 h, and 3) a group given DMSO before periods of ischemia and reperfusion. In all groups, we measured diaphragm strip strength and fatigability; we also assessed diaphragm blood flow at several levels of contractile activity. Periods of ischemia, followed by reperfusion, were found to produce a downward shift of the diaphragm force-frequency relationship and also to markedly increase diaphragm fatigability. Diaphragm blood flow at rest and at low levels of contractile activity was unaffected by ischemia-reperfusion, but the flow achieved during fatiguing contractions was appreciably lower than that in nonischemic control animals. DMSO administration protected the diaphragm from the effects of ischemia-reperfusion, preventing alterations in fatigability and strength. Diaphragm flow in DMSO-treated animals was similar to that in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Neurosurgery ◽  
2004 ◽  
Vol 55 (5) ◽  
pp. 1060-1067 ◽  
Author(s):  
Kuniaki Ogasawara ◽  
Takashi Inoue ◽  
Masakazu Kobayashi ◽  
Hidehiko Endo ◽  
Takeshi Fukuda ◽  
...  

Abstract OBJECTIVE: Cerebral hyperperfusion syndrome after carotid endarterectomy (CEA) is a rare but potentially devastating complication. The purpose of the present study, which was not a randomized controlled trial but a case cohort study with historical control, was to determine whether pretreatment with a novel free radical scavenger, edaravone, could prevent occurrence of cerebral hyperperfusion after CEA. METHODS: Fifty patients with ipsilateral internal carotid artery stenosis (≥70%) underwent CEA with administration of edaravone before internal carotid artery clamping. Preoperative cerebral blood flow and cerebrovascular reactivity (CVR) to acetazolamide were assessed with single-photon emission computed tomography (SPECT). Cerebral blood flow also was measured immediately after CEA and on the 3rd postoperative day. RESULTS: Cerebral hyperperfusion (cerebral blood flow increase ≥100% compared with preoperative values) was revealed by SPECT performed immediately after CEA in only one patient (2%), who also exhibited reduced preoperative CVR. The incidence of post-CEA hyperperfusion as revealed by SPECT in the control group (51 CEA patients without administration of edaravone) was significantly higher (16%) (P= 0.0310, control versus treatment group). In addition, in a subgroup of patients with reduced preoperative CVR, the incidence of post-CEA hyperperfusion as revealed by SPECT in the edaravone group (7%) was significantly lower than that in the control group (67%) (P= 0.0029). Logistic regression analysis demonstrated that reduced preoperative CVR and absence of pretreatment with edaravone were significant independent predictors of post-CEA hyperperfusion as revealed by SPECT. CONCLUSION: Pretreatment with edaravone can prevent occurrence of cerebral hyperperfusion after CEA.


2016 ◽  
Vol 229 (3) ◽  
pp. R129-R146 ◽  
Author(s):  
Eduardo Esteban-Zubero ◽  
Francisco Agustín García-Gil ◽  
Laura López-Pingarrón ◽  
Moisés Alejandro Alatorre-Jiménez ◽  
Pablo Iñigo-Gil ◽  
...  

Organ transplantation is a useful therapeutic tool for patients with end-stage organ failure; however, graft rejection is a major obstacle in terms of a successful treatment. Rejection is usually a consequence of a complex immunological and nonimmunological antigen-independent cascade of events, including free radical-mediated ischemia-reperfusion injury (IRI). To reduce the frequency of this outcome, continuing improvements in the efficacy of antirejection drugs are a top priority to enhance the long-term survival of transplant recipients. Melatonin (N-acetyl-5-methoxytryptamine) is a powerful antioxidant and ant-inflammatory agent synthesized from the essential amino acid l-tryptophan; it is produced by the pineal gland as well as by many other organs including ovary, testes, bone marrow, gut, placenta, and liver. Melatonin has proven to be a potentially useful therapeutic tool in the reduction of graft rejection. Its benefits are based on its direct actions as a free radical scavenger as well as its indirect antioxidative actions in the stimulation of the cellular antioxidant defense system. Moreover, it has significant anti-inflammatory activity. Melatonin has been found to improve the beneficial effects of preservation fluids when they are enriched with the indoleamine. This article reviews the experimental evidence that melatonin is useful in reducing graft failure, especially in cardiac, bone, otolaryngology, ovarian, testicular, lung, pancreas, kidney, and liver transplantation.


2008 ◽  
Vol 139 (2_suppl) ◽  
pp. P113-P114
Author(s):  
Benoit J Gosselin ◽  
Louise Davies

Objectives In a prior communication, we showed that ischemic rat groin flaps exposed to the free radical scavenger N-2 mercaptopropionylglycine (MPG) at the time of arterial and venous occlusion had a higher rate of survival than untreated flaps. In this study, the objective is to test the efficacy and timing of administration of MPG in salvaging rat groin flaps subjected to venous occlusion alone. Methods Randomized controlled trial. Main outcome is mean percentage of flap survival at 7 days. 30 mature Sprague-Dawley rats were randomized to 3 groups based on timing of treatment with MPG: 1- flap raised, no MPG, no venous occlusion (sham group); 2- flap raised, no MPG, 10-hour period of venous occlusion (control group); 3- flap raised, MPG after 10 hours venous occlusion (post-reperfusion group). Results There was no statistical difference noted in mean survival of venous occluded flaps when comparing the control and post-reperfusion groups, after 7 days. Specifically, the mean flap survival in the control group at 7 days was 10.9% (median 0%, range 0–100%). The mean flap survival in the post-reperfusion group was 14.6% (median 0%, range 0–100%). The mean flap survival in the sham group was 90.0% (median 100%, range 0–100%). Conclusions Post-reperfusion MPG administration is not helpful for flaps subjected to venous occlusion alone. The free-radical scavenger activity of MPG is potentiated within the tissues prior to vein occlusion. Potential applications for free flap salvage would need further study.


2008 ◽  
Vol 40 (7) ◽  
pp. 2171-2174 ◽  
Author(s):  
A. Nakamura ◽  
Y. Akamatsu ◽  
S. Miyagi ◽  
T. Fukumori ◽  
S. Sekiguchi ◽  
...  

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Satoshi Ikeda ◽  
Katsuhiro Harada ◽  
Akihiko Ohwatashi ◽  
Yurie Kamikawa

Edaravone is a free radical scavenger that protects the adjacent cortex during cerebral infarction. We created a hemiparetic model of cerebral thrombosis from a photochemically induced infarction with the photosensitive dye, rose bengal, in rats. We examined the effects of edaravone on recovery in the model. A total of 36 adult Wistar rats were used. The right sensorimotor area was irradiated with green light with a wavelength of 533 nm (10 mm diameter), and the rose bengal was injected intravenously to create an infarction. The edaravone group was injected intraperitoneally with edaravone (3 mg/kg), and the control group was injected with saline. The recovery process of the hemiplegia was evaluated with the 7-step scale of Fenny. The infarcted areas were measured after fixation. The recovery of the paralysis in the edaravone-treated group was significantly earlier than that in the untreated group. Seven days later, both groups were mostly recovered and had scores of 7, and the infarction region was significantly smaller in the edaravone-treated group. Edaravone reduced the infarction area and promoted the functional recovery of hemiparesis from cerebral thrombosis in a rat model. These findings suggest that edaravone treatment would be effective in clinical patients recovering from cerebral infarction.


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