Allowable warm ischemic time and morphological and biochemical changes in uterine ischemia/reperfusion injury in cynomolgus macaque: a basic study for uterus transplantation

The significant reduction in ‘ischemic time’ through capillary diffusion of primary percutaneous intervention (pPCI) has rendered myocardial-ischemia reperfusion injury (MIRI) prevention a major issue in order to improve the prognosis of ST elevation myocardial infarction (STEMI) patients. In fact, while the ischemic damage increases with the severity and the duration of blood flow reduction, reperfusion injury reaches its maximum with a moderate amount of ischemic injury. MIRI leads to the development of post-STEMI left ventricular remodeling (post-STEMI LVR), thereby increasing the risk of arrhythmias and heart failure. Single pharmacological and mechanical interventions have shown some benefits, but have not satisfactorily reduced mortality. Therefore, a multitarget therapeutic strategy is needed, but no univocal indications have come from the clinical trials performed so far. On the basis of the results of the consistent clinical studies analyzed in this review, we try to design a randomized clinical trial aimed at evaluating the effects of a reasoned multitarget therapeutic strategy on the prevention of post-STEMI LVR. In fact, we believe that the correct timing of pharmacological and mechanical intervention application, according to their specific ability to interfere with survival pathways, may significantly reduce the incidence of post-STEMI LVR and thus improve patient prognosis.

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The Effect of Poly (Adenosine Diphosphate-Ribose) Polymerase Inhibitors on Biochemical Changes in Testicular Ischemia-Reperfusion Injury

The Journal of Urology ◽

10.1097/01.ju.0000049228.37887.4d ◽

2003 ◽

Vol 169 (5) ◽

pp. 1870-1873 ◽

Cited By ~ 31

Author(s):

MURAT BOZLU ◽

GÜLÇİN ESKANDARİ ◽

SELAHİTTİN ÇAYAN ◽

BÜLENT CANPOLAT ◽

ERDEM AKBAY ◽

...

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Adenosine Diphosphate ◽

Biochemical Changes ◽

Polymerase Inhibitors ◽

Testicular Ischemia

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p21 and mTERT are novel markers for determining different ischemic time periods in renal ischemia-reperfusion injury

AJP Renal Physiology ◽

10.1152/ajprenal.00084.2006 ◽

2007 ◽

Vol 292 (2) ◽

pp. F762-F768 ◽

Cited By ~ 26

Author(s):

Kathrin Hochegger ◽

Christian Koppelstaetter ◽

Andrea Tagwerker ◽

Julia M. Huber ◽

Dorothea Heininger ◽

...

Keyword(s):

Renal Failure ◽

Acute Renal Failure ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Renal Ischemia ◽

Cdk Inhibitors ◽

Cdk Inhibitor ◽

Ischemic Time ◽

Renal Ischemia Reperfusion Injury

In many clinical settings, the duration of renal ischemia and therefore the outcome of acute renal failure cannot be determined adequately. Renal ischemia reperfusion injury is known to shorten telomeres and upregulate stress-induced genes, such as the cyclin-dependent kinase (CDK) inhibitor p21. So far, the expression and role of CDK inhibitors, as well as mouse telomerase reverse transcriptase (mTERT), has not been investigated in a model with variable lasting ischemic periods. Male C57Bl/6 mice were subjected to renal ischemia reperfusion injury by clamping both renal pedicles for 10, 20, 30, and 45 min, and the kidneys were allowed to be reperfused for 3, 24, and 48 h. Expression of different CDK inhibitors and mTERT was evaluated. Mice developed signs of acute renal failure linear to the duration of the ischemic period. Real-time PCR revealed that mTERT was only significantly upregulated in kidneys after short ischemic periods (20 min). In contrast, p21 was constantly upregulated in kidneys after long ischemic intervals (30 and 45 min), but not in kidneys, which were clamped for shorter periods. Mainly, tubular cells contributed to the observed increase in p21 expression. Targeting p21 via the selective p53 inhibitor pifithrin-α was able to prevent acute renal failure when administered immediately before ischemia. The expression of another CDK inhibitor, namely p16, was differentially regulated, depending on the time of reperfusion. Taken together, we detected mTERT and p21 as “indicator” genes for short and long ischemic intervals, respectively. These two proteins might also be possible new therapeutic targets in the treatment and prevention of acute renal failure.

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Rapid postmortem ventilation improves donor lung viability by extending the tolerable warm ischemic time after cardiac death in mice

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00011.2021 ◽

2021 ◽

Author(s):

Junyi Yu ◽

Che Xu ◽

Janet S. Lee ◽

Jonathan K. Alder ◽

Zongmei Wen ◽

...

Keyword(s):

Reperfusion Injury ◽

Cardiac Death ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Warm Ischemia ◽

Warm Ischemia Time ◽

Lung Injury Score ◽

Ischemic Time ◽

Ischemia Time ◽

Donor Lung

Uncontrolled donation after cardiac death (uDCD) contributes little to ameliorating donor lung shortage due to rapidly progressive warm ischemia after circulatory arrest. Here, we demonstrated non-hypoxia improves donor lung viability in a novel uDCD lung transplant model undergoing rapid ventilation after cardiac death and compared the evolution of ischemia-reperfusion injury in mice that underwent pulmonary artery ligation (PAL). The tolerable warm ischemia time at 37ºC was initially determined in mice using a modified PAL model. The donor lung following PAL was also transplanted into syngeneic mice and compared to those that underwent rapid ventilation or no ventilation at 37ºC prior to transplantation. Twenty-four hours following reperfusion, lung histology, PaO2/FIO2 ratio, and inflammatory mediators were measured. Four hours of PAL had little impact on PaO2/FIO2 ratio and acute lung injury score in contrast to significant injury induced by 5 hours of PAL. Four-hour PAL lungs showed an early myeloid-dominant inflammatory signature when compared to naïve lungs and substantially injured five-hour PAL lungs. In the context of transplantation, unventilated donor lungs showed severe injury after reperfusion, whereas ventilated donor lungs showed minimal changes in PaO2/FIO2 ratio, histologic score, and expression of inflammatory markers. Taken together, the tolerable warm ischemia time of murine lungs at 37oC can be extended by maintaining alveolar ventilation for up to 4 hours. Non-hypoxic lung warm ischemia-reperfusion injury shows an early transcriptional signature of myeloid cell recruitment and extracellular matrix proteolysis prior to blood-gas barrier dysfunction and significant tissue damage.

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How to Interpret Relationship Between Ischemic Time and Ischemia/Reperfusion Injury in Langendorff Perfused Rat Hearts

Turkiye Klinikleri Journal of Medical Sciences ◽

10.5336/medsci.2012-30601 ◽

2013 ◽

Vol 33 (2) ◽

pp. 493-500

Author(s):

Elif ERTUNA ◽

Saadet TÜRKSEVEN ◽

Hatice Mürvet HAYRAN ◽

Mustafa Fevzi SARGON ◽

Mukadder YASA

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Ischemic Time ◽

Rat Hearts ◽

Perfused Rat Hearts

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A Preclinical Systematic Review of Curcumin for Protecting the Kidney with Ischemia Reperfusion Injury

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/4546851 ◽

2020 ◽

Vol 2020 ◽

pp. 1-17

Author(s):

Zi-Hao Wang ◽

Li-Hui Deng ◽

Chang-Wei Chi ◽

Hong Wang ◽

Yue-Yue Huang ◽

...

Keyword(s):

Systematic Review ◽

Animal Models ◽

Serum Creatinine ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Biological Activities ◽

Ischemia Reperfusion ◽

Risk Of Bias ◽

Control Group ◽

Ischemic Time

Renal ischemia-reperfusion injury (RIRI) refers to a phenomenon associated with dysfunction of the kidney and tissue damage. Unfortunately, no specific drugs have been found that effectively prevent and treat RIRI. Curcumin (Cur), a polyphenol extracted from turmeric, possesses a variety of biological activities involving antioxidation, inhibition of apoptosis, inhibition of inflammation, and reduction of lipid peroxidation. Eight frequently used databases were searched using prespecified search strategies. The CAMARADES 10-item quality checklist was used to evaluate the risk of bias of included studies, and the RevMan 5.3 software was used to analyze the data. The risk of bias score of included studies ranged from 3 to 6 with an average score of 5.22. Compared with the control group, Cur significantly alleviated renal pathology, reduced blood urea nitrogen and serum creatinine levels, and improved inflammatory indexes, oxidant, and apoptosis in RIRI animal models. Despite the heterogeneity of the response to Cur in terms of serum creatinine, BUN, TNF-alpha, and SOD, its effectiveness for improving the injury of RIRI was remarkable. In the mouse model subgroup of serum creatinine, the effect size of the method of unilateral renal artery ligation with contralateral nephrectomy and shorter ischemic time showed a greater effect than that of the control group. No difference was seen in the methods of model establishment, mode administration, or medication times. The preclinical systematic review provided preliminary evidence that Cur partially improved RIRI in animal models, probably via anti-inflammatory, antioxidant, antiapoptosis, and antifibrosis activities and via improving microperfusion. ARRIVE guidelines are recommended; blinding and sample size calculation should be focused on in future studies. These data suggest that Cur is a potential renoprotective candidate for further clinical trials of RIRI.

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Delayed graft function and perfusion parameters of kidneys from uncontrolled donors after circulatory death

Perfusion ◽

10.1177/0267659120938928 ◽

2020 ◽

pp. 026765912093892

Author(s):

Adriano Peris ◽

Giorgio Enzo Fulceri ◽

Chiara Lazzeri ◽

Manuela Bonizzoli ◽

Vincenzo Li Marzi ◽

...

Keyword(s):

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Graft Function ◽

Delayed Graft Function ◽

Machine Perfusion ◽

Hemodynamic Parameters ◽

Ischemic Time ◽

Warm Ischemic Time ◽

Hypothermic Machine Perfusion ◽

Circulatory Death

Better preservation and evaluation of kidneys from donors after circulatory death serve to increase the number of kidneys available for transplantation and hypothermic machine perfusion has been shown to decrease ischemia reperfusion injury and delayed graft function. Data on relation between hemodynamic parameters during hypothermic machine perfusion and delayed graft function in kidneys from donors after circulatory death are so far scarce and not univocal. We aimed at assessing whether hemodynamic parameters measured during hypothermic machine perfusion (flow, mean perfusion pressure, and renal resistance) are associated with delayed graft function in 26 kidneys retrieved from uncontrolled donors after circulatory death. In our series, the incidence of delayed graft function was 57.7% (15/26). Recipients who developed delayed graft function had a longer warm ischemic time (p = 0.04). All hemodynamic parameters measured during hypothermic machine perfusion were comparable between recipients with delayed graft function and those without. According to our data, in kidneys from uncontrolled donors after circulatory death, a longer warm ischemic time (that is the overall time of no flow, as the sum of the no-flow and the no-touch period) is associated with delayed graft function. This finding underscores the pivotal role of ischemic injury in terms of absence of flow in affecting graft function. No association was detectable between hemodynamic parameters during hypothermic machine perfusion and the development of delayed graft function in our series.

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Ex Vivo Lung Perfusion with K(ATP) Channel Modulators Antagonize Ischemia Reperfusion Injury

Cells ◽

10.3390/cells10092296 ◽

2021 ◽

Vol 10 (9) ◽

pp. 2296

Author(s):

Stephan Arni ◽

Tatsuo Maeyashiki ◽

Tsogyal Latshang ◽

Isabelle Opitz ◽

Ilhan Inci

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ex Vivo ◽

Ischemia Reperfusion ◽

Lung Perfusion ◽

Metabolic Parameters ◽

Physiological Data ◽

Control Group ◽

Ex Vivo Lung Perfusion ◽

Ischemic Time

Ex vivo lung perfusion (EVLP) has been implemented to increase the number of donor lungs available for transplantation. The use of K(ATP) channel modulators during EVLP experiments may protect against lung ischemia-reperfusion injury and may inhibit the formation of reactive oxygen species. In a rat model of donation after circulatory death with 2 h warm ischemic time, we evaluated rat lungs for a 4-hour time in EVLP containing either mitochondrial-specific or plasma membrane and/or sarcolemmal-specific forms of K(ATP) channel modulators. Lung physiological data were recorded, and metabolic parameters were assessed. When compared to the control group, in the EVLP performed with diazoxide or 5-hydroxydecanoic acid (5-HD) we recorded significantly lower pulmonary vascular resistance and only in the diazoxide group recorded significant lung weight loss. In the perfusate of the 5-HD group, interleukin-1β and interleukin-1α were significantly lower when compared to the control group. Perfusate levels of calcium ions were significantly higher in both 5-HD and cromakalim groups, whereas the levels of calcium, potassium, chlorine and lactate were reduced in the diazoxide group, although not significantly when compared to the control. The use of a diazoxide mitochondrial-specific K(ATP) channel opener during EVLP improved lung physiological and metabolic parameters and reduced edema.

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