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BMC Nephrology Apr 2022Renal perfusion may redistribute from cortex to medulla during systemic hypovolaemia and after renal ischaemia for other reasons, but there is no consensus on this...
BACKGROUND
Renal perfusion may redistribute from cortex to medulla during systemic hypovolaemia and after renal ischaemia for other reasons, but there is no consensus on this matter. We studied renal perfusion after renal ischaemia and reperfusion.
METHODS
Renal perfusion distribution was examined by use of Gadolinium-labeled microspheres (MS) after 2 h (hrs) and 4 h ischaemia of the pig kidney followed by 4 h of reperfusion. Intra-arterial injected MS are trapped in the glomeruli in renal cortex, which means that MS are not present in the medulla under normal physiological conditions.
RESULTS
Visual evaluation after reperfusion demonstrated that MS redistributed from the renal cortex to the medulla in 6 out of 16 pigs (38%) subjected to 4 h ischaemia and in one out of 18 pigs subjected to 2 h ischaemia. Central renal uptake of MS covering the medullary/total renal uptake was significantly higher in kidneys subjected to 4 h ischaemia compared with pigs subjected to 2 h ischaemia (69 ± 5% vs. 63 ± 1%, p < 0.001), and also significantly higher than in the contralateral kidney (69 ± 5% vs. 63 ± 2%, p < 0.001). Analysis of blood and urine demonstrated no presence of radioactivity.
CONCLUSION
The study demonstrated the presence of MS in the renal medulla in response to renal ischaemia and reperfusion suggesting that severe ischaemia and reperfusion of the pig kidney leads to opening of functional shunts bypassing glomeruli.
Topics: Animals; Humans; Ischemia; Kidney; Kidney Medulla; Reperfusion; Reperfusion Injury; Swine
PubMed: 35428270
DOI: 10.1186/s12882-022-02780-0 -
EuroIntervention : Journal of EuroPCR... Nov 2023Reperfusion therapy is challenging in the elderly. Catheter-directed therapies are an alternative for higher-risk pulmonary embolism (PE) patients if systemic...
BACKGROUND
Reperfusion therapy is challenging in the elderly. Catheter-directed therapies are an alternative for higher-risk pulmonary embolism (PE) patients if systemic thrombolysis (ST) is contraindicated or has failed. Their safety has not been evaluated in specific vulnerable populations.
AIMS
We aimed to assess the safety of reperfusion therapies in elderly and frail patients in the real world.
METHODS
In the US Nationwide Inpatient Sample from 2016 to 2020, we identified hospitalisations of patients ≥65 years with PE and defined a frailty subgroup using the Johns Hopkins Adjusted Clinical Groups frailty-defining diagnosis indicator. We investigated reperfusion therapies (ST, catheter-directed thrombolysis [CDT], catheter-based thrombectomy [CBT], surgical embolectomy [SE]) and their associated safety outcomes (overall and major bleeding).
RESULTS
Among 980,245 hospitalisations of patients ≥65 years with PE (28.0% frail), reperfusion therapies were used in 4.9% (17.6% among high-risk PE). ST utilisation remained stable, while the use of catheter-directed therapies increased from 1.7% in 2016 to 3.2% in 2020. Among all hospitalisations with reperfusion, CDT, compared to ST, was associated with reduced major bleeding (5.8% vs 12.2%, odds ratio [OR] 0.58, 95% confidence interval [CI]: 0.49-0.70); these results also applied to frail patients. CBT, compared to SE, was also associated with reduced major bleeding (11.0% vs 22.4%, OR 0.63, 95% CI: 0.43-0.91), but not among frail patients. These differences were particularly significant in patients with non-high-risk PE. Differences persisted for overall bleeding as well.
CONCLUSIONS
Catheter-directed therapies may be a safer alternative to classical reperfusion therapies for elderly and frail patients with PE requiring reperfusion treatment.
Topics: Humans; Aged; Thrombolytic Therapy; Fibrinolytic Agents; Frailty; Treatment Outcome; Pulmonary Embolism; Hemorrhage; Reperfusion
PubMed: 37767997
DOI: 10.4244/EIJ-D-23-00399 -
Free Radical Biology & Medicine Aug 2023Ischemia-reperfusion injury is a critical liver condition during hepatic transplantation, trauma, or shock. An ischemic deprivation of antioxidants and energy...
Ischemia-reperfusion injury is a critical liver condition during hepatic transplantation, trauma, or shock. An ischemic deprivation of antioxidants and energy characterizes liver injury in such cases. In the face of increased reactive oxygen production, hepatocytes are vulnerable to the reperfusion driving ROS generation and multiple cell-death mechanisms. In this study, we investigate the importance of hydrogen sulfide as part of the liver's antioxidant pool and the therapeutic potency of the hydrogen sulfide donors sodium sulfide (NaS, fast releasing) and sodium thiosulfate (STS, NaSO, slow releasing). The mitoprotection and toxicity of STS and NaS were investigated on isolated mitochondria and a liver perfusion oxidative stress model by adding text-butyl hydroperoxide and hydrogen sulfide donors. The respiratory capacity of mitochondria, hepatocellular released LDH, glutathione, and lipid-peroxide levels were quantified. In addition, wild-type and cystathionine-γ-lyase knockout mice were subjected to warm selective ischemia-reperfusion injury by clamping the main inflow for 1 h followed by reperfusion of 1 or 24 h. A subset of animals was treated with STS shortly before reperfusion. Glutathione, plasma ALT, and lipid-peroxide levels were investigated alongside mitochondrial changes in structure (electron microscopy) and function (intravital microscopy). Liver tissue necrosis quantified 24 h after reperfusion indicates the net effects of the treatment on the organ. STS refuels and protects the endogenous antioxidant pool during liver ischemia-reperfusion injury. In addition, STS-mediated ROS scavenging significantly reduced lipid peroxidation and mitochondrial damage, resulting in better molecular and histopathological preservation of the liver tissue architecture. STS prevents tissue damage in liver ischemia-reperfusion injury by increasing the liver's antioxidant pool, thereby protecting mitochondrial integrity.
Topics: Mice; Animals; Antioxidants; Hydrogen Sulfide; Reactive Oxygen Species; Chemical and Drug Induced Liver Injury, Chronic; Liver; Reperfusion Injury; Ischemia; Glutathione; Peroxides; Reperfusion; Lipids
PubMed: 37105418
DOI: 10.1016/j.freeradbiomed.2023.04.012 -
American Journal of Physiology. Heart... Jul 2021There is a lack of understanding in the cardiac remodeling field regarding the use of nonreperfused myocardial infarction (MI) and reperfused MI in animal models of MI....
There is a lack of understanding in the cardiac remodeling field regarding the use of nonreperfused myocardial infarction (MI) and reperfused MI in animal models of MI. This Perspectives summarizes the consensus of the authors regarding how to select the optimum model for your experiments and is a part of ongoing efforts to establish rigor and reproducibility in cardiac physiology research.
Topics: Animals; Disease Models, Animal; Heart; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion
PubMed: 34114891
DOI: 10.1152/ajpheart.00234.2021 -
The Journal of Neuroscience : the... May 2020Despite the success of reperfusion therapy in significantly reducing the extent of infarct expansion after stroke, the effect of revascularization on poststroke...
Despite the success of reperfusion therapy in significantly reducing the extent of infarct expansion after stroke, the effect of revascularization on poststroke neuroinflammation and the role of anti-inflammatory strategies in postreperfusion era are yet to be explored. Here, we investigate whether the neuroinflammatory response may still contribute to neurologic deficits after reperfused stroke by using targeted complement inhibition to suppress poststroke neuroinflammation in mice with or without concurrent reperfusion therapy. Complement inhibition was achieved using B4Crry, an injury site-targeted inhibitor of C3 activation. Following embolic stroke in male C57bl/6 mice, thrombolysis using tissue-plasminogen activator (t-PA) reduced injury and improved motor deficits, but did not improve cognitive outcomes. After both reperfused and non-reperfused stroke, complement activation and opsonization of hippocampal synapses directed ongoing microglia-dependent phagocytosis of synapses for at least 30 d after stroke, leading to a loss of synaptic density that was associated with cognitive decline. B4Crry treatment, alone or in combination with tPA, limited perilesional complement deposition, reduced microgliosis and synaptic uptake, and improved cognitive outcome without affecting regenerative responses. Furthermore, complement inhibition improved the safety, efficacy, and treatment window of reperfusion therapy with t-PA by limiting hemorrhagic transformation. This work thus demonstrates that poststroke neuroinflammation contributes to hemorrhagic transformation and progression of neurodegenerative responses in the brain even following early and successful revascularization. This study addresses two major challenges facing the treatment of stroke in the era of reperfusion therapy: hemorrhagic transformation and the disconnect between successful revascularization and functional outcomes. We studied how complement-dependent neuroinflammation drives the pathophysiology behind these challenges using a translationally relevant strategy. Complement inhibition was achieved using B4Crry, an injury site-targeted inhibitor of C3 activation. Following embolic stroke, pharmacological thrombolysis limited infarct size, but did not prevent complement activation. In reperfused and non-reperfused stroke, complement activation and opsonization of hippocampal synapses resulted in synaptic phagocytosis and subsequent cognitive decline. B4Crry treatment limited perilesional complement deposition, reduced microgliosis and synaptic uptake, and improved cognitive outcomes. Complement inhibition also improved the safety, efficacy, and treatment window of thrombolytic therapy.
Topics: Aged; Aged, 80 and over; Animals; Cognitive Dysfunction; Complement System Proteins; Female; Humans; Infarction, Middle Cerebral Artery; Male; Mice; Mice, Inbred C57BL; Middle Aged; Recovery of Function; Reperfusion; Stroke; Stroke Rehabilitation; Synapses; Thrombectomy; Thrombolytic Therapy; Tissue Plasminogen Activator; Treatment Outcome
PubMed: 32291326
DOI: 10.1523/JNEUROSCI.2462-19.2020 -
European Journal of Neurology Jul 2022Reperfusion therapy is the mainstay of treatment for acute ischaemic stroke (AIS); however, little is known about the use of reperfusion therapy and time delay amongst...
BACKGROUND AND PURPOSE
Reperfusion therapy is the mainstay of treatment for acute ischaemic stroke (AIS); however, little is known about the use of reperfusion therapy and time delay amongst immigrants.
METHODS
This is a Danish nationwide register-based cohort study of patients with AIS aged ≥18 years (n = 49,817) recruited from 2009 to 2018. Use of reperfusion therapy (intravenous thrombolysis and/or mechanical thrombectomy) and time delay between immigrants and Danish-born residents were compared using multivariable logistics and quantile regression.
RESULTS
Overall, 10,649 (39.8%) Danish-born residents and 452 (39.0%) immigrants with AIS were treated with reperfusion therapy in patients arriving <4.5 h following stroke onset. Compared with Danish-born residents, immigrants had lower odds of receiving reperfusion therapy after adjustment for prehospital delay, age, sex, stroke severity, sociodemographic factors and comorbidities (adjusted odds ratio 0.67; 95% confidence interval 0.49-0.92, p = 0.01). The lowest odds were observed amongst immigrants originating from Poland and non-Western countries. Similarly, immigrants had a longer prehospital delay than Danish-born residents in the fully adjusted model in patients arriving <4.5 h after stroke onset (15 min; 95% confidence interval 4-26 min, p = 0.03). No evidence was found that system delay and clinical outcome differed between immigrants and Danish-born residents in patients eligible for reperfusion therapy after adjustment for sociodemographic factors and comorbidities.
CONCLUSION
Immigration status was significantly associated with lower chances of receiving reperfusion therapy and there may be differences in patient delay between immigrants and Danish-born residents in patients arriving to a stroke unit <4.5 h after stroke onset.
Topics: Adolescent; Adult; Brain Ischemia; Cohort Studies; Denmark; Emigration and Immigration; Humans; Ischemic Stroke; Reperfusion; Stroke; Treatment Outcome
PubMed: 35212085
DOI: 10.1111/ene.15303 -
JAMA Neurology Dec 2020A significant proportion of acute ischemic strokes occur while patients are hospitalized. Limited contemporary data exist on the utilization rates of intravenous...
IMPORTANCE
A significant proportion of acute ischemic strokes occur while patients are hospitalized. Limited contemporary data exist on the utilization rates of intravenous thrombolysis or endovascular therapy for in-hospital stroke.
OBJECTIVE
To use a national registry to examine temporal trends in the use of intravenous and endovascular reperfusion therapies for treatment of in-hospital stroke.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study analyzed data from 267 956 patients who underwent reperfusion therapy for stroke with in-hospital or out-of-hospital onset reported in the Get With the Guidelines-Stroke national registry from January 2008 to September 2018.
EXPOSURES
In-hospital onset vs out-of-hospital onset of stroke symptoms.
MAIN OUTCOMES AND MEASURES
Temporal trends in the use of reperfusion therapy, process measures of quality, and the association between functional outcomes and key patient characteristics, comorbidities, and treatments.
RESULTS
Of 67 493 patients with in-hospital stroke onset, this study observed increased rates of vascular risk factors (standardized mean difference >10%) but no significant differences in age or sex in patients undergoing intravenous thrombolysis only (mean [interquartile range {IQR}] age, 72 [80-62] y; 53.2% female) or those undergoing endovascular therapy (mean [IQR] age, 69 [59-79] y; 49.8% female). Of these patients, 10 481 (15.5%) received intravenous thrombolysis and 2494 (3.7%) underwent endovascular therapy. Compared with 2008, in 2018 the proportion of in-hospital stroke among all stroke hospital discharges was higher (3.5% vs 2.7%; P < .001), as was use of intravenous thrombolysis (19.1% vs 9.1%; P < .001) and endovascular therapy (6.4% vs 2.5%; P < .001) in patients with in-hospital stroke, with a significant increase in endovascular therapy in mid-2015 (P < .001). Compared with patients who received intravenous thrombolysis for out-of-hospital stroke onset, those with in-hospital onset were associated with longer median (IQR) times from stroke recognition to cranial imaging (33 [18-60] vs 16 [9-26] minutes; P < .001) and to thrombolysis bolus (81 [52-125] vs 60 [45-84] minutes; P < .001). In adjusted analyses, patients with in-hospital stroke onset who were treated with intravenous thrombolysis were less likely to ambulate independently at discharge (adjusted odds ratio, 0.78; 95% CI, 0.74-0.82; P < .001) and were more likely to die or to be discharged to hospice (adjusted odds ratio, 1.39; 95% CI, 1.29-1.50; P < .001) than patients with out-of-hospital onset who also received intravenous thrombolysis treatment. Comparisons among patients treated with endovascular therapy yielded similar findings.
CONCLUSIONS AND RELEVANCE
In this cohort study, in-hospital stroke onset was increasingly reported and treated with reperfusion therapy. Compared with out-of-hospital stroke onset, in-hospital onset was associated with longer delays to reperfusion and worse functional outcomes, highlighting opportunities to further care for patients with in-hospital stroke onset.
Topics: Aged; Aged, 80 and over; Cohort Studies; Endovascular Procedures; Female; Hospitalization; Humans; Ischemic Stroke; Male; Middle Aged; Reperfusion; Retrospective Studies; Thrombolytic Therapy
PubMed: 32955582
DOI: 10.1001/jamaneurol.2020.3362 -
Ophthalmic Plastic and Reconstructive...Free skin grafts are frequently used in reconstructive surgery. However, little is known about the course of reperfusion due to the previous lack of reliable perfusion...
PURPOSE
Free skin grafts are frequently used in reconstructive surgery. However, little is known about the course of reperfusion due to the previous lack of reliable perfusion monitoring techniques. The aim of this study was to use state-of-the-art laser speckle contrast imaging to monitor free skin grafts in the periocular area.
METHODS
Seven patients needing surgery due to tumor removal or cicatricial ectropion in the periocular region underwent reconstructive surgery using free skin grafts from either the contralateral upper eyelid or the upper inner arm. The free skin grafts measured 10-30 mm horizontally and 9-30 mm vertically. Blood perfusion was monitored using laser speckle contrast imaging immediately postoperatively (0 weeks) and at follow-up after 1, 3, and 7 weeks.
RESULTS
All grafts were reperfused gradually during healing, the median value being 46% in the central part of the graft after 1 week and 79% after 3 weeks. The grafts were completely reperfused after 7 weeks. No difference was observed in the rate of reperfusion between the center and periphery of the grafts (p = not significant). The cosmetic and functional outcome was excellent in all but 1 patient, who developed ectropion that had to be surgically corrected.
CONCLUSIONS
Skin grafts in the periorbital area are fully reperfused after 7 weeks. The periocular area is known to be well-vascularized and thus forgiving to reconstructive surgery. Future investigations of the reperfusion of free skin grafts in other parts of the body or in higher-risk populations should be carried out.
Topics: Humans; Laser Speckle Contrast Imaging; Plastic Surgery Procedures; Reperfusion; Retrospective Studies; Skin Transplantation
PubMed: 32991497
DOI: 10.1097/IOP.0000000000001851 -
Revista Medica de Chile May 2021Background The coronavirus disease (COVID-19) pandemic affected the prompt diagnosis and treatment of Acute myocardial infarction (AMI).
UNLABELLED
Background The coronavirus disease (COVID-19) pandemic affected the prompt diagnosis and treatment of Acute myocardial infarction (AMI).
AIM
To characterize the clinical profile of patients with AMI during the COVID-19 pandemic, comparing them with a historical cohort.
MATERIAL AND METHODS
A case-control study of 96 patients with AMI transferred to a high-volume percutaneous coronary intervention (PCI) hospital between March and July 2020, and a historical cohort of 269 patients transferred during the same period in 2019.
RESULTS
When comparing patients transferred during the pandemic with those of the historical cohort, the former were younger (63 ± 12 vs 68 ± 12 years, p < 0.01), had a higher frequency of hypertension (66 vs 45%, p < 0.01) and of smoking (40% vs 25%, p < 0.01). Also, during COVID-19 outbreak a higher proportion of patients had ST-elevation AMI consulting > 12 hours from the onset of symptoms (44 vs 0%, p < 0.01), a higher median door-to-device time (4 vs 3 hours, p < 0.01), a higher use of primary percutaneous coronary intervention (97 vs 71%, p < 0.01), and higher frequencies of cardiogenic shock (20 vs 4%, p < 0.01) and mechanical complications (10% vs 2%, p < 0.01). Patients during COVID pandemic had a higher thirty-day overall (20 vs 1.4%, p < 0.01) and cardiovascular mortality (13 vs 1%, p < 0.01). During the outbreak, 40% of patients had positive COVID-19 status, which was a predictor for thirty-day overall mortality (Risk ratio 2.90; 95% confidence intervals 1.14-7.36).
CONCLUSIONS
During the pandemic patients with AMI exhibited delays in consultations and treatment, higher morbidity, and increased mortality. COVID-19 positivity was associated to worse thirty-day overall survival.
Topics: Angioplasty, Balloon, Coronary; COVID-19; Case-Control Studies; Electrocardiography; Humans; Myocardial Infarction; Pandemics; Percutaneous Coronary Intervention; Prognosis; Reperfusion; SARS-CoV-2; Treatment Outcome
PubMed: 34751319
DOI: 10.4067/s0034-98872021000500672 -
Journal of Integrative Neuroscience Mar 2023Early neurological deterioration (END), generally defined as the increment of National Institutes of Health Stroke Scale (NIHSS) score ≥4 within 24 hours, lead to poor... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Early neurological deterioration (END), generally defined as the increment of National Institutes of Health Stroke Scale (NIHSS) score ≥4 within 24 hours, lead to poor clinical outcome in acute ischemic stroke (AIS) patients receiving reperfusion therapies including intravenous thrombolysis (IVT) and/or endovascular treatment (EVT). This systematic review and meta-analysis aimed to explore multiple predictors of END following reperfusion therapies.
METHODS
We searched PubMed, Web of Science and EBSCO for all studies on END in AIS patients receiving IVT and/or EVT published between January 2000 and December 2022. A random-effects meta-analysis was conducted and presented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The quality of each included studies was assessed by calculating a total score according to the STROBE or CONSORT criteria. Publication bias and heterogeneity were also evaluated using the Eggers/Peters test, funnel plots and sensitivity analysis.
RESULTS
A total of 29 studies involving 65,960 AIS patients were included. The quality of evidence is moderate to high, and all studies have no publication bias. The overall incidence of END occurring after reperfusion therapy in AIS patients was 14% ((95% confidence intervals (CI), 12%-15%)). Age, systolic blood pressure (SBP), glucose levels at admission, the onset to treatment time (OTT), hypertension, diabetes mellitus, arterial fibrillation, and internal cerebral artery occlusion were significantly associated with END following reperfusion therapy.
CONCLUSIONS
Numerous factors are associated with END occurrence in AIS patients receiving reperfusion therapy. Management of the risk factors of END may improve the functional outcome after reperfusion treatment.
Topics: Humans; Stroke; Brain Ischemia; Ischemic Stroke; Fibrinolytic Agents; Treatment Outcome; Reperfusion
PubMed: 36992598
DOI: 10.31083/j.jin2202052