The effect of inhalational anaesthesia during deceased donor organ procurement on post-transplantation graft survival.

PubMed

Perez-Protto, S; Nazemian, R; Matta, M; Patel, P; Wagner, K J; Latifi, S Q; Lebovitz, D J; Reynolds, J D

2018-03-01

Many deceased by neurologic criteria donors are administered inhalational agents during organ recovery surgery-a process that is characterised by warm and cold ischaemia followed by warm reperfusion. In certain settings, volatile anaesthetics (VA) are known to precondition organs to protect them from subsequent ischaemia-reperfusion injury. As such, we hypothesised that exposure to VA during organ procurement would improve post-graft survival. Lifebanc (organ procurement organisation [OPO] for NE Ohio) provided the investigators with a list of death by neurologic criteria organ donors cared for at three large tertiary hospitals in Cleveland between 2006 and 2016-details about the surgical recovery phase were extracted from the organ donors' medical records. De-identified data on graft survival were obtained from the United Network for Organ Sharing (UNOS). The collated data underwent comparative analysis based on whether or not VA were administered during procurement surgery. Records from 213 donors were obtained for analysis with 138 exposed and 75 not exposed. Demographics, medical histories, and organ procurement rates were similar between the two cohorts. For the primary endpoint, there were no significant differences observed in either early (30-day) or late (five-year) graft survival rates for kidney, liver, lung, or heart transplants. Our findings from this retrospective review of a relatively small cohort do not support the hypothesis that the use of VA during the surgical procurement phase improves graft survival. Reviews of larger datasets and/or a prospective study may be required to provide a definitive answer.

Glycogen synthase kinase 3β promotes liver innate immune activation by restraining AMP-activated protein kinase activation.

PubMed

Zhou, Haoming; Wang, Han; Ni, Ming; Yue, Shi; Xia, Yongxiang; Busuttil, Ronald W; Kupiec-Weglinski, Jerzy W; Lu, Ling; Wang, Xuehao; Zhai, Yuan

2018-07-01

Glycogen synthase kinase 3β (Gsk3β [Gsk3b]) is a ubiquitously expressed kinase with distinctive functions in different types of cells. Although its roles in regulating innate immune activation and ischaemia and reperfusion injuries (IRIs) have been well documented, the underlying mechanisms remain ambiguous, in part because of the lack of cell-specific tools in vivo. We created a myeloid-specific Gsk3b knockout (KO) strain to study the function of Gsk3β in macrophages in a murine liver partial warm ischaemia model. Compared with controls, myeloid Gsk3b KO mice were protected from IRI, with diminished proinflammatory but enhanced anti-inflammatory immune responses in livers. In bone marrow-derived macrophages, Gsk3β deficiency resulted in an early reduction of Tnf gene transcription but sustained increase of Il10 gene transcription on Toll-like receptor 4 stimulation in vitro. These effects were associated with enhanced AMP-activated protein kinase (AMPK) activation, which led to an accelerated and higher level of induction of the novel innate immune negative regulator small heterodimer partner (SHP [Nr0b2]). The regulatory function of Gsk3β on AMPK activation and SHP induction was confirmed in wild-type bone marrow-derived macrophages with a Gsk3 inhibitor. Furthermore, we found that this immune regulatory mechanism was independent of Gsk3β Ser9 phosphorylation and the phosphoinositide 3-kinase-Akt signalling pathway. In vivo, myeloid Gsk3β deficiency facilitated SHP upregulation by ischaemia-reperfusion in liver macrophages. Treatment of Gsk3b KO mice with either AMPK inhibitor or SHP small interfering RNA before the onset of liver ischaemia restored liver proinflammatory immune activation and IRI in these otherwise protected hosts. Additionally, pharmacological activation of AMPK protected wild-type mice from liver IRI, with reduced proinflammatory immune activation. Inhibition of the AMPK-SHP pathway by liver ischaemia was demonstrated in tumour resection patients. Gsk3β promotes innate proinflammatory immune activation by restraining AMPK activation. Glycogen synthase kinase 3β promotes macrophage inflammatory activation by inhibiting the immune regulatory signalling of AMP-activated protein kinase and the induction of small heterodimer partner. Therefore, therapeutic targeting of glycogen synthase kinase 3β enhances innate immune regulation and protects liver from ischaemia and reperfusion injury. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Post-ischaemic changes in the response time of oxygen consumption to demand in the isolated rat heart are mediated partly by calcium and glycolysis.

PubMed

Zuurbier, C J; Ince, C

2002-03-01

This study examined whether different durations of ischaemia (I) and reperfusion (R) altered the kinetics of O(2) consumption-to-demand matching and the contribution of changes in calcium and metabolic pathways to possible alterations. The response time of mitochondrial O(2) consumption (t(mito)) to a step in heart rate in isolated rat hearts was used as index for the response time of O(2) consumption-to-demand matching. At baseline, t(mito) was 8.9 +/- 0.4 s for all groups. At 5 min reperfusion, after both reversible (I=5 or I=15 min) or irreversible (I=25 min) ischaemia, matching was accelerated (t(mito) relative to baseline: 53 +/- 8%, 64 +/- 8%, 51+/- 6% and 100 +/- 5% for I=5, 15, 25 min and control). At late reperfusion (>30 min), reversible ischaemia resulted in a slowing of the matching, whereas after irreversible ischaemia t(mito) recovered to control values (156 +/- 16%, 153 +/- 13%, 92 +/- 7%, 114 +/- 6%, for I=5,15, 25 min and control, respectively). High perfusate Ca(2+) mimicked (t(mito): 44 +/- 11%), whereas blocking mitochondrial Ca(2+) uptake attenuated the acceleration observed at early reperfusion (t(mito): 7 +/- 5%). Replacing glucose with substrates used downstream of glycolysis (11 mM lactate or 11 mM pyruvate) abolished the reversible ischaemia-induced slowing of the matching at late reperfusion. It is concluded that I/R-induced changes in the kinetics of O(2) consumption-to demand matching depend critically on the duration of ischaemia and reperfusion. The data indicate that I/R-induced increases in Ca(2+) may, at least partly, explain the faster kinetics at early reperfusion, whereas I/R-induced increases in glycolysis from exogenous glucose result in slower matching of O(2) consumption-to-demand at late reperfusion.

'Trifecta' outcomes of robot-assisted partial nephrectomy in solitary kidney: a Vattikuti Collective Quality Initiative (VCQI) database analysis.

PubMed

Arora, Sohrab; Abaza, Ronney; Adshead, James M; Ahlawat, Rajesh K; Challacombe, Benjamin J; Dasgupta, Prokar; Gandaglia, Giorgio; Moon, Daniel A; Yuvaraja, Thyavihally B; Capitanio, Umberto; Larcher, Alessandro; Porpiglia, Francesco; Porter, James R; Mottrie, Alexander; Bhandari, Mahendra; Rogers, Craig

2018-01-01

To analyse the outcomes of robot-assisted partial nephrectomy (RAPN) in patients with a solitary kidney in a large multi-institutional database. In all, 2755 patients in the Vattikuti Collective Quality Initiative database underwent RAPN by 22 surgeons at 14 centres in nine countries. Of these patients, 74 underwent RAPN with a solitary kidney between 2007 and 2016. We retrospectively analysed the functional and oncological outcomes of these 74 patients. A 'trifecta' of outcomes was assessed, with trifecta defined as a warm ischaemia time (WIT) of <20 min, negative surgical margins, and no complications intraoperatively or within 3 months of RAPN. All 74 patients underwent RAPN successfully with one conversion to radical nephrectomy. The median (interquartile range [IQR]) operative time was 180 (142-230) min. Early unclamping was used in 11 (14.9%) patients and zero ischaemia was used in 12 (16.2%). Trifecta outcomes were achieved in 38 of 66 patients (57.6%). The median (IQR) WIT was 15.5 (8.75-20.0) min for the entire cohort. The overall complication rate was 24.1% and the rate of Clavien-Dindo grade ≤II complications was 16.3%. Positive surgical margins were present in four cases (5.4%). The median (IQR) follow-up was 10.5 (2.12-24.0) months. The median drop in estimated glomerular filtration rate at 3 months was 7.0 mL/min/1.72 m 2 (11.01%). Our findings suggest that RAPN is a safe and effective treatment option for select renal tumours in solitary kidneys in terms of a trifecta of negative surgical margins, WIT of <20 min, and low operative and perioperative morbidity. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Temporal and mechanistic dissociation of ATP and adenosine release during ischaemia in the mammalian hippocampus1

PubMed Central

Frenguelli, Bruno G; Wigmore, Geoffrey; Llaudet, Enrique; Dale, Nicholas

2007-01-01

Abstract Adenosine is well known to be released during cerebral metabolic stress and is believed to be neuroprotective. ATP release under similar circumstances has been much less studied. We have now used biosensors to measure and compare in real time the release of ATP and adenosine during in vitro ischaemia in hippocampal slices. ATP release only occurred following the anoxic depolarisation, whereas adenosine release was apparent almost immediately after the onset of ischaemia. ATP release required extracellular Ca2+. By contrast adenosine release was enhanced by removal of extracellular Ca2+, whilst TTX had no effect on either ATP release or adenosine release. Blockade of ionotropic glutamate receptors substantially enhanced ATP release, but had only a modest effect on adenosine release. Carbenoxolone, an inhibitor of gap junction hemichannels, also greatly enhanced ischaemic ATP release, but had little effect on adenosine release. The ecto-ATPase inhibitor ARL 67156, whilst modestly enhancing the ATP signal detected during ischaemia, had no effect on adenosine release. Adenosine release during ischaemia was reduced by pre-treament with homosysteine thiolactone suggesting an intracellular origin. Adenosine transport inhibitors did not inhibit adenosine release, but instead they caused a twofold increase of release. Our data suggest that ATP and adenosine release during ischaemia are for the most part independent processes with distinct underlying mechanisms. These two purines will consequently confer temporally distinct influences on neuronal and glial function in the ischaemic brain. PMID:17459147

Differences in autonomic nerve function in patients with silent and symptomatic myocardial ischaemia.

PubMed Central

Shakespeare, C. F.; Katritsis, D.; Crowther, A.; Cooper, I. C.; Coltart, J. D.; Webb-Peploe, M. W.

1994-01-01

BACKGROUND--Autonomic neuropathy provides a mechanism for the absence of symptoms in silent myocardial ischaemia, but characterisation of the type of neuropathy is lacking. AIM--To characterise and compare autonomic nerve function in patients with silent and symptomatic myocardial ischaemia. METHODS AND RESULTS--The Valsalva manoeuvre, heart rate variation (HRV) in response to deep breathing and standing, lower body negative pressure, isometric handgrip, and the cold pressor test were performed by patients with silent (n = 25) and symptomatic (n = 25) ambulatory ischaemia and by controls (n = 21). No difference in parasympathetic efferent function between patients with silent and symptomatic ischaemia was recorded, but both had significantly less HRV in response to standing than the controls (p < 0.005 for silent and p < 0.01 for symptomatic). Patients with silent ischaemia showed an increased propensity for peripheral vasodilatation compared with symptomatic patients (p < 0.02) and controls (p < 0.04). Impaired sympathetic function was found in patients with pure silent ischaemia (n = 4) compared with the remaining patients with silent ischaemia whose pain pathways were presumed to be intact. CONCLUSIONS--Patients with silent ischaemia and pain pathways presumed to be intact have an enhanced peripheral vasodilator response, and if this applied to the coronary vasculature it could provide a mechanism for limiting ischaemia to below the pain threshold. Patients with pure silent ischaemia have evidence of sympathetic autonomic dysfunction. Images PMID:8297687

Liver grafts from selected older donors do not have significantly more ischaemia reperfusion injury

PubMed Central

Martins, Paulo N; Chang, Sue; Mahadevapa, Basant; Martins, Ann-Britt; Sheiner, Patricia

2011-01-01

Background There is a general concern that aged organs are more susceptible to ischaemia. In the light of recent proposals to change the liver allocation system by expanding regional sharing, it is feared that increased cold ischaemia time of grafts from older donors may reduce graft survival. The aim of this study was to correlate donor age and the patterns of ischaemia reperfusion injury and synthetic function early after liver transplantation. Methods We performed a retrospective study of first transplants using a single-centre electronic database. Patterns of liver injury (based on transaminases and post-reperfusion biopsy), synthetic function (international normalized ratio [INR]), and graft and patient survival in recipients receiving liver grafts from donors aged ≥65 years (group 1, n= 50) were compared with equivalent patterns in a matched cohort of recipients transplanted with grafts from donors aged <65 years (group 2, n= 50). Results There was no significant difference in transaminase levels from day 0 to day 6 after transplantation. When groups 1 and 2 were subdivided into two subgroups based on the duration of graft cold ischaemia time (<8 h and ≥8 h), there was no statistical difference in transaminase levels during the first 7 days. There were two cases (4%) of primary non-function in group 1 and one (2%) in group 2. Initial poor function did not differ significantly between the groups (26% vs. 24%; P= 0.81). In addition, there was no difference in histological changes in post-reperfusion biopsies (21% vs. 34%; P= 0.078) and rate of acute rejection episodes in the first year (30% vs. 32%; P= 0.99). There was no significant difference between groups 1 and 2 in 1-year patient and graft survivals (78% vs. 90% [P= 0.17]; 88% vs. 94% [P= 0.48], respectively). Conclusions Judiciously selected livers from aged donors are not associated with major increased susceptibility to ischaemia reperfusion injury. PMID:21309940

Selective heart rate reduction with ivabradine slows ischaemia-induced electrophysiological changes and reduces ischaemia–reperfusion-induced ventricular arrhythmias

PubMed Central

Ng, Fu Siong; Shadi, Iqbal T.; Peters, Nicholas S.; Lyon, Alexander R.

2013-01-01

Heart rates during ischaemia and reperfusion are possible determinants of reperfusion arrhythmias. We used ivabradine, a selective If current inhibitor, to assess the effects of heart rate reduction (HRR) during ischaemia–reperfusion on reperfusion ventricular arrhythmias and assessed potential anti-arrhythmic mechanisms by optical mapping. Five groups of rat hearts were subjected to regional ischaemia by left anterior descending artery occlusion for 8 min followed by 10 min of reperfusion: (1) Control n = 10; (2) 1 μM of ivabradine perfusion n = 10; (3) 1 μM of ivabradine + 5 Hz atrial pacing throughout ischaemia–reperfusion n = 5; (4) 1 μM of ivabradine + 5 Hz pacing only at reperfusion; (5) 100 μM of ivabradine was used as a 1 ml bolus upon reperfusion. For optical mapping, 10 hearts (ivabradine n = 5; 5 Hz pacing n = 5) were subjected to global ischaemia whilst transmembrane voltage transients were recorded. Epicardial activation was mapped, and the rate of development of ischaemia-induced electrophysiological changes was assessed. HRR observed in the ivabradine group during both ischaemia (195 ± 11 bpm vs. control 272 ± 14 bpm, p < 0.05) and at reperfusion (168 ± 13 bpm vs. 276 ± 14 bpm, p < 0.05) was associated with reduced reperfusion ventricular fibrillation (VF) incidence (20% vs. 90%, p < 0.05). Pacing throughout ischaemia–reperfusion abolished the protective effects of ivabradine (100% VF), whereas pacing at reperfusion only partially attenuated this effect (40% VF). Ivabradine, given as a bolus at reperfusion, did not significantly affect VF incidence (80% VF). Optical mapping experiments showed a delay to ischaemia-induced conduction slowing (time to 50% conduction slowing: 10.2 ± 1.3 min vs. 5.1 ± 0.7 min, p < 0.05) and to loss of electrical excitability in ivabradine-perfused hearts (27.7 ± 4.3 min vs. 14.5 ± 0.6 min, p < 0.05). Ivabradine administered throughout ischaemia and reperfusion reduced reperfusion VF incidence through HRR. Heart rate during ischaemia is a major determinant of reperfusion arrhythmias. Heart rate at reperfusion alone was not a determinant of reperfusion VF, as neither a bolus of ivabradine nor pacing immediately prior to reperfusion significantly altered reperfusion VF incidence. This anti-arrhythmic effect of heart rate reduction during ischaemia may reflect slower development of ischaemia-induced electrophysiological changes. PMID:23402927

Portal Venous Oxygen Persufflation of the Donation after Cardiac Death pancreas in a rat model is superior to static cold storage and hypothermic machine perfusion.

PubMed

Reddy, Mettu S; Carter, Noel; Cunningham, Anne; Shaw, James; Talbot, David

2014-06-01

Success of clinical pancreatic islet transplantation depends on the mass of viable islets transplanted and the proportion of transplanted islets that survive early ischaemia reperfusion injury. Novel pancreas preservation techniques to improve islet preservation and viability can increase the utilization of donation after cardiac death donor pancreases for islet transplantation. Rat pancreases were retrieved after 30 min of warm ischaemia and preserved by static cold storage, hypothermic machine perfusion or retrograde portal venous oxygen persufflation for 6 h. They underwent collagenase digestion and density gradient separation to isolate islets. The yield, viability, morphology were compared. In vitro function of isolated islets was compared using glucose stimulated insulin secretion test. Portal venous oxygen persufflation improved the islet yield, viability and morphology as compared to static cold storage. The percentage of pancreases with good in vitro function (stimulation index > 1.0) was also higher after oxygen persufflation as compared to static cold storage. Retrograde portal venous oxygen persufflation of donation after cardiac death donor rat pancreases has the potential to improve islet yield. © 2014 Steunstichting ESOT.

Specific caspase inhibitor Q-VD-OPh prevents neonatal stroke in P7 rat: a role for gender.

PubMed

Renolleau, Sylvain; Fau, Sébastien; Goyenvalle, Catherine; Joly, Luc-Marie; Chauvier, David; Jacotot, Etienne; Mariani, Jean; Charriaut-Marlangue, Christiane

2007-02-01

Hypoxia-ischaemia in the developing brain results in brain injury with prominent features of apoptosis. In the present study, a third generation dipeptidyl broad-spectrum caspase inhibitor, quinoline-Val-Asp(Ome)-CH2-O-phenoxy (Q-VD-OPh), was tested in a model of unilateral focal ischaemia with reperfusion in 7-day-old rats. Q-VD-OPh (1 mg/kg, i.p.) reduced cell death, resulting in significant neuroprotection at 48 h of recovery (infarct volume of 12.6 +/- 2.8 vs. 24.3 +/- 2.2%, p = 0.006). The neuroprotective effects observed at 48 h post-ischaemia hold up at 21 days of survival time and attenuate neurological dysfunction. Analysis by gender revealed that females were strongly protected (6.7 +/- 3.3%, p = 0.006), in contrast to males in which there was no significant effect, when Q-VD-OPh was given after clip removal on the left common carotid artery. Immunoblot analysis demonstrated that Q-VD-OPh inhibits caspase 3 cleavage into its p17 active form and caspase 1 up-regulation and cleavage in vivo. Following ischaemia in P7 rats, males and females displayed different time course and pattern of cytochrome c release and active p17 caspase 3 during the first 24 h of recovery. In contrast, no significant difference was observed for caspase 1 expression between genders. These results indicate that ischaemia activates caspases shortly after reperfusion and that the sex of the animal may strongly influences apoptotic pathways in the pathogenesis of neonatal brain injury. The specificity, effectiveness, and reduced toxicity of Q-VD-OPh may determine the potential use of peptide-derived irreversible caspase inhibitors as promising therapeutics.

Donor age as a risk factor in donation after circulatory death liver transplantation in a controlled withdrawal protocol programme.

PubMed

Detry, O; Deroover, A; Meurisse, N; Hans, M F; Delwaide, J; Lauwick, S; Kaba, A; Joris, J; Meurisse, M; Honoré, P

2014-06-01

Results of donation after circulatory death (DCD) liver transplantation are impaired by graft loss, resulting mainly from non-anastomotic biliary stricture. Donor age is a risk factor in deceased donor liver transplantation, and particularly in DCD liver transplantation. At the authors' institute, age is not an absolute exclusion criterion for discarding DCD liver grafts, DCD donors receive comfort therapy before withdrawal, and cold ischaemia is minimized. All consecutive DCD liver transplantations performed from 2003 to 2012 were studied retrospectively. Three age groups were compared in terms of donor and recipient demographics, procurement and transplantation conditions, peak laboratory values during the first post-transplant 72 h, and results at 1 and 3 years. A total of 70 DCD liver transplants were performed, including 32 liver grafts from donors aged 55 years or less, 20 aged 56-69 years, and 18 aged 70 years or more. The overall graft survival rate at 1 month, 1 and 3 years was 99, 91 and 72 per cent respectively, with no graft lost secondary to non-anastomotic stricture. No difference other than age was noted between the three groups for donor or recipient characteristics, or procurement conditions. No primary non-function occurred, but one patient needed retransplantation for artery thrombosis. Biliary complications were similar in the three groups. Graft and patient survival rates were no different at 1 and 3 years between the three groups (P = 0.605). Results for DCD liver transplantation from younger and older donors were similar. Donor age above 50 years should not be a contraindication to DCD liver transplantation if other donor risk factors (such as warm and cold ischaemia time) are minimized. © 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.

Abdominal symptoms during physical exercise and the role of gastrointestinal ischaemia: a study in 12 symptomatic athletes.

PubMed

ter Steege, Rinze W F; Geelkerken, Robert H; Huisman, Ad B; Kolkman, Jeroen J

2012-10-01

Gastrointestinal (GI) symptoms during exercise may be caused by GI ischaemia. The authors report their experience with the diagnostic protocol and management of athletes with symptomatic exercise-induced GI ischaemia. The value of prolonged exercise tonometry in the diagnostic protocol of these patients was evaluated. Patients referred for GI symptoms during physical exercise underwent a standardised diagnostic protocol, including prolonged exercise tonometry. Indicators of GI ischaemia, as measured by tonometry, were related to the presence of symptoms during the exercise test (S+ and S- tests) and exercise intensity. 12 athletes were specifically referred for GI symptoms during exercise (five males and seven females; median age 29 years (range 15-46 years)). Type of sport was cycling, long-distance running and triathlon. Median duration of symptoms was 32 months (range 7-240 months). Splanchnic artery stenosis was found in one athlete. GI ischaemia was found in six athletes during submaximal exercise. All athletes had gastric and jejunal ischaemia during maximum intensity exercise. No significant difference was found in gastric and jejunal Pco(2) or gradients between S+ and S- tests during any phase of the exercise protocol. In S+ tests, but not in S- tests, a significant correlation between lactate and gastric gradient was found. In S+ tests, the regression coefficients of gradients were higher than those in S- tests. Treatment advice aimed at limiting GI ischaemia were successful in reducing complaints in the majority of the athletes. GI ischaemia was present in all athletes during maximum intensity exercise and in 50% during submaximal exercise. Athletes with GI symptoms had higher gastric gradients per mmol/l increase in lactate, suggesting an increased susceptibility for the development of ischaemia during exercise. Treatment advice aimed at limiting GI ischaemia helped the majority of the referred athletes to reduce their complaints. Our results suggest an important role for GI ischaemia in the pathophysiology of their complaints.

Neuroprotective effect of antioxidants on ischaemia and reperfusion-induced cerebral injury.

PubMed

Gupta, Ram; Singh, Manjeet; Sharma, Ajay

2003-08-01

The present study is designed to investigate the effect of dietary flavanoid rutin, micronutrient selenium and garlic oil on ischaemia and reperfusion-induced cerebral injury. Global cerebral ischaemia was induced by occluding right and left common carotid arteries for 10min followed by reperfusion for 24h. Cerebral infarct size was estimated using triphenyltetrazolium chloride staining. Elevated plus maze was employed to estimate short-term memory. Degree of motor incoordination was evaluated using inclined beam-walking test and lateral push test. Mitochondrial thiobarbituric acid reactive substances (TBARS) assay was employed as an index of oxidative stress. Global cerebral ischaemia followed by reperfusion produced a significant impairment in short-term memory and motor coordination and produced a notable increase in mitochondrial TBARS. Administration of rutin and garlic oil before global cerebral ischaemia markedly reduced cerebral infarct size and attenuated impairment in short-term memory and motor coordination. Administration of sodium selenite either before or after global cerebral ischaemia markedly reduced cerebral infarct size and attenuated impairment in short-term memory and motor coordination. The protective effect of rutin, sodium selenite and garlic oil was accompanied by a marked decrease in mitochondrial TBARS. On the basis of these results, it may be suggested that rutin and garlic oil administrated before cerebral ischaemia may scavenge reactive oxygen species and consequently attenuate global cerebral ischaemia and reperfusion-induced cerebral injury. Sodium selenite administrated before and after cerebral ischaemia may be neuroprotective due to its antioxidant effect.

Epigallocatechin-3-gallate protects against hepatic ischaemia-reperfusion injury by reducing oxidative stress and apoptotic cell death.

PubMed

Tak, Eunyoung; Park, Gil-Chun; Kim, Seok-Hwan; Jun, Dae Young; Lee, Jooyoung; Hwang, Shin; Song, Gi-Won; Lee, Sung-Gyu

2016-12-01

Objective To investigate the protective effects of epigallocatechin-3-gallate (EGCG), a major polyphenol source in green tea, against hepatic ischaemia-reperfusion injury in mice. Methods The partial hepatic ischaemia-reperfusion injury model was created by employing the hanging-weight method in C57BL/6 male mice. EGCG (50 mg/kg) was administered via an intraperitoneal injection 45 min before performing the reperfusion. A number of markers of inflammation, oxidative stress, apoptosis and liver injury were measured after the ischaemia-reperfusion injury had been induced. Results The treatment groups were: sham-operated (Sham, n = 10), hepatic ischaemia-reperfusion injury (IR, n = 10), and EGCG with ischaemia-reperfusion injury (EGCG-treated IR, n = 10). Hepatic ischaemia-reperfusion injury increased the levels of biochemical and histological markers of liver injury, increased the levels of malondialdehyde, reduced the glutathione/oxidized glutathione ratio, increased the levels of oxidative stress and lipid peroxidation markers, decreased B-cell lymphoma 2 levels, and increased the levels of Bax, cytochrome c, cleaved caspase-3, and cleaved caspase-9. Pretreatment with EGCG ameliorated all of these changes. Conclusion The antioxidant and antiapoptotic effects of EGCG protected against hepatic ischaemia-reperfusion injury in mice.

[Cooling shell in renal transplantation. Thermometric evaluation of a prototype].

PubMed

Desgrandchamps, F; Eugene, M; Tuchschmid, Y; Muller, F; Teillac, P; Idatte, J M; Le Duc, A

1996-02-01

We have developed a cooling system for renal transplants designed to eliminate the second period of warm ischaemia corresponding to the vascular anastomosis phase of renal transplantation. This is an autonomous and independent system which forms a shell around the transplant. Following application of the system, cooling is achieved by refrigeration of a Multitherm sponge contained in the wall of the shell. The thermometric characteristics of a prototype were evaluated in vitro and in vivo in pigs. This system allows the kidney to be preserved at a temperature of less than 10 degrees C for 1 hour without inducing any risk of lesions of the renal surface. Human applications should be developed in the near future.

Correlation between liver cell necrosis and circulating alanine aminotransferase after ischaemia/reperfusion injuries in the rat liver.

PubMed

Knudsen, Anders R; Andersen, Kasper J; Hamilton-Dutoit, Stephen; Nyengaard, Jens R; Mortensen, Frank V

2016-04-01

Circulating liver enzymes such as alanine transaminase are often used as markers of hepatocellular damage. Ischaemia/reperfusion (I/R) injury is an inevitable consequence of prolonged liver ischaemia. The aim of this study was to examine the correlation between liver enzymes and volume of liver cell necrosis after ischaemia/reperfusion injuries, using design-unbiased stereological methods. Forty-seven male Wistar rats were subjected to 1 h of partial liver ischaemia, followed by either 4 or 24 h of reperfusion. Within each group, one-third of animals were subjected to ischaemic preconditioning and one-third to ischaemic postconditioning. At the end of reperfusion, blood and liver samples were collected for analysis. The volume of necrotic liver tissue was subsequently correlated to circulating markers of I/R injury. Correlation between histological findings and circulating markers was performed using Pearson's correlation coefficient. Alanine transferase peaked after 4 h of reperfusion; however, at this time-point, only mild necrosis was observed, with a Pearson's correlation coefficient of 0.663 (P = 0.001). After 24 h of reperfusion, alanine aminotransferase was found to be highly correlated to the degree of hepatocellular necrosis R = 0.836 (P = 0.000). Furthermore, alkaline phosphatase (R = 0.806) and α-2-macroglobulin (R = 0.655) levels were also correlated with the degree of necrosis. We show for the first time that there is a close correlation between the volume of hepatocellular necrosis and alanine aminotransferase levels in a model of I/R injury. This is especially apparent after 24 h of reperfusion. Similarly, increased levels of alkaline phosphatase and α-2-macroglobulin are correlated to the volume of liver necrosis. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

Enhanced dispersion of epicardial activation-recovery intervals at sites of histological inhomogeneity during regional cardiac ischaemia and reperfusion

PubMed Central

Gottwald, E; Gottwald, M; Dhein, S

1998-01-01

Objective—To examine how epicardial activation and repolarisation patterns change in the course of ischaemia, and how these changes are related to the underlying histological structures.
Methods—Langendorff perfused isolated rabbit hearts were submitted to 30 minutes of left anterior descending coronary artery occlusion followed by 30 minutes of reperfusion. A 256 channel epicardial map was plotted during the various experimental phases. Activation time points were determined as t(dU/dtmin) and repolarisation time points as t(dU/dtmax). From these data the local activation-recovery interval (ARI), its dispersion (SD of ARI), and the geometry of the activation spread could be analysed. After the experiments the hearts were processed histologically and the mapping data were projected onto histological slides.
Results—There was elevation of the ST segment within the occluded area, which recovered during reperfusion. Within this area, ARI was significantly shortened and its dispersion was maximally enhanced. The enhancement of dispersion was pronounced at sites of histological inhomogeneity like fat, connective tissue, or vessels. There was also a change in the preferential direction of activation spread within the occluded zone with a marked transverse propagation of the activation wavefront, whereas under normal conditions the activation followed the longitudinal fibre axis. In addition, the total activation time in the occluded area was significantly prolonged.
Conclusions—Ischaemia alters the local activation pattern with enhanced dispersion, especially at sites of histological irregularity, transverse shift of the activation waves, and a general slowing of conduction, which may explain the increased susceptibility to arrhythmia in hearts with enhanced histological irregularities—for example, an infarct or in multi-infarcted hearts, or after myocarditis. 

 Keywords: dispersion;  epicardial activation-recovery interval;  ischaemia PMID:9659194

Enhanced contractility of intraparenchymal arterioles after global cerebral ischaemia in rat - new insights into the development of delayed cerebral hypoperfusion.

PubMed

Spray, S; Johansson, S E; Radziwon-Balicka, A; Haanes, K A; Warfvinge, K; Povlsen, G K; Kelly, P A T; Edvinsson, L

2017-08-01

Delayed cerebral hypoperfusion is a secondary complication found in the days after transient global cerebral ischaemia that worsens the ischaemic damage inflicted by the initial transient episode of global cerebral ischaemia. A recent study demonstrated increased cerebral vasoconstriction in the large arteries on the brain surface (pial arteries) after global cerebral ischaemia. However, smaller arterioles inside the brain (parenchymal arterioles) are equally important in the regulation of cerebral blood flow and yet their pathophysiology after global cerebral ischaemia is largely unknown. Therefore, we investigated whether increased contractility occurs in the intraparenchymal arterioles. Global cerebral ischaemia was induced in male Wistar rats by bilateral common carotid occlusion for 15 min combined with hypovolaemia. Regional cerebral blood flow was determined by quantitative autoradiography. Intraparenchymal arterioles were isolated and pressurized, and concentration-response curves to endothelin-1 with and without the endothelin B receptor-selective antagonist BQ788 was generated. Endothelin B receptor expression was investigated by quantitative flow cytometry and immunohistochemistry. We observed increased endothelin-1-mediated contractility of parenchymal arterioles correlating with reduced cerebral blood flow of the cortex, hippocampus and caudate nucleus 48 h after global cerebral ischaemia. The increased endothelin-1-mediated contractility was abolished by BQ788, and the vascular smooth muscle cell-specific expression of endothelin B receptors was significantly increased after global cerebral ischaemia. Increased endothelin-1-mediated contractility and expression of endothelin B receptors in the intraparenchymal vasculature contributes to the development of delayed cerebral hypoperfusion after global cerebral ischaemia in combination with vascular changes of the pial vasculature. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Evidence for metaboreceptor stimulation of sweating in normothermic and heat-stressed humans

NASA Technical Reports Server (NTRS)

Shibasaki, M.; Kondo, N.; Crandall, C. G.

2001-01-01

1. Isometric handgrip (IHG) exercise increases sweat rate and arterial blood pressure, and both remain elevated during post-exercise ischaemia. The purpose of this study was to identify whether the elevation in arterial blood pressure during post-exercise ischaemia contributes to the increase in sweating. 2. In normothermia and during whole-body heating, 2 min IHG exercise at 40% maximal voluntary contraction, followed by 2 min post-exercise ischaemia, was performed with and without bolus intravenous administration of sodium nitroprusside during the ischaemic period. Sodium nitroprusside was administered to reduce blood pressure during post-exercise ischaemia to pre-exercise levels. Sweat rate was monitored over two microdialysis membranes placed in the dermal space of forearm skin. One membrane was perfused with the acetylcholinesterase inhibitor neostigmine, while the other was perfused with the vehicle. 3. In normothermia, IHG exercise increased sweat rate at the neostigmine-treated site but not at the control site. Sweat rate remained elevated during post-exercise ischaemia even after mean arterial blood pressure returned to the pre-IHG exercise baseline. Subsequent removal of the ischaemia stimulus returned sweat rate to pre-IHG exercise levels. Sweat rate during post-exercise ischaemia without sodium nitroprusside administration followed a similar pattern. 4. During whole-body heating, IHG exercise increased sweat rate at both neostigmine-treated and untreated sites. Similarly, regardless of whether mean arterial blood pressure remained elevated or was reduced during post-exercise ischaemia, sweat rate remained elevated during the ischaemic period. 5. These results suggest that sweating in non-glabrous skin during post-IHG exercise ischaemia is activated by metaboreflex stimulation and not via baroreceptor loading.

Region-specific expression of vesicular glutamate and GABA transporters under various ischaemic conditions in mouse forebrain and retina.

PubMed

Michalski, D; Härtig, W; Krügel, K; Edwards, R H; Böddener, M; Böhme, L; Pannicke, T; Reichenbach, A; Grosche, A

2013-02-12

There is accumulating evidence that glutamate and GABA release are key mechanisms of ischaemic events in the CNS. However, data on the expression of involved transporters for these mediators are inconsistent, potentially impeding further neuroprotective approaches. Here, we applied immunofluorescence labelling to characterise the expression pattern of vesicular glutamate (VGLUT) and GABA transporters (VGAT) after acute focal cerebral ischaemia and in two models of retinal ischaemia. Mice were subjected to filament-based focal cerebral ischaemia predominantly involving the middle cerebral artery territory, also leading to retinal ischaemia due to central retinal artery occlusion (CRAO). Alternatively, retinal ischaemia was induced by a transient increase of the intraocular pressure (HIOP). One day after ischaemia onset, diminished immunolabelling of neuronal nuclei and microtubule-associated protein 2-positive structures were found in the ipsilateral neocortex, subcortex and the retina, indicating neuronal degeneration. VGLUT1 expression did not change significantly in ischaemic tissues whereas VGLUT2 was down-regulated in specific areas of the brain. VGLUT3 expression was only slightly down-regulated in the ischaemia-affected neocortex, and was found to form clusters on fibrils of unknown origin in the ischaemic lateral hypothalamus. In contrast, retinae subjected to CRAO or HIOP displayed a rapid loss of VGLUT3-immunoreactivity. The expression of VGAT appears resistant to ischaemia as there was no significant alteration in all the regions analysed. In summary, these data indicate a region- and subtype-specific change of VGLUT expression in the ischaemia-affected CNS, whose consideration might help to generate specific neuroprotective strategies. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Evaluation of Haemoglobin and Cytochrome Responses During Forearm Ischaemia Using Multi-wavelength Time Domain NIRS.

PubMed

Lange, Frédéric; Dunne, Luke; Tachtsidis, Ilias

2017-01-01

We demonstrate the ability of a 16-wavelength time domain near-infrared spectroscopy system to monitor changes in oxy- and deoxy haemoglobin ([HbO 2 ] [HHb]) and the oxidation of cytochrome-c-oxidase ([oxCCO]), during forearm ischaemia. We tested two methods to retrieve the concentration changes. The first uses the measured changes in light attenuation and the modified Beer-Lambert law, and the second uses the absorption and scattering estimated by the measured time-point spread function. The system is able to retrieve the concentration changes with both methods, giving similar results. At the end of forearm ischaemia (t = 5 min), we measured an increase in [HHb] of 16.77 ± 2.52 and 16.37 ± 2.33 μMol, and a decrease in [HbO 2 ] of -6.12 ± 1.62 and -5.57 ± 2.02 μMol for method 1 and 2, respectively. At that same time, the changes in [oxCCO] were -0.36 ± 0.33 and -1.40 ± 1.20 μMol, for method 1 and 2, respectively. These small changes in [oxCCO], despite a huge change in haemoglobin, demonstrate the absence of crosstalk and are comparable to previous measurements using broadband NIRS.

Physiologic ischaemic training induces endothelial progenitor cell mobilization and myocardial angiogenesis via endothelial nitric oxide synthase related pathway in rabbits.

PubMed

Xiao, Mingyue; Lu, Xiao; Li, Jianan; Li, Ling; Li, Yongxue

2014-04-01

Ischaemia-induced angiogenesis promises to improve neovascularization by delivery of angiogenic factors or endothelial progenitor cells (EPCs) to cardiac ischaemic areas. In order to avoid the risk of excessive myocardial ischaemia, therefore, we hypothesized that physiological ischaemic training (PIT) of normal skeletal muscle might contribute to myocardial angiogenesis via nitric oxide mediated mobilization of EPCs from the bone marrow in the established rabbit model of controllable myocardial ischaemia. The rabbits were grouped by sham-operation, myocardial ischaemia without PIT, PIT and PIT with pretreatment with the endothelial nitric oxide synthase (eNOS) inhibitor L-nitroarginine methyl ester (L-NAME). Controlled myocardial ischaemia was modelled by a water balloon constrictor implanted on the left ventricular branch in a rabbit. The PIT procedure included three cycles of 3 min of cuff inflation followed by 5 min of deflation on hind limbs of the rabbits for 4 weeks. At the endpoints, circulating EPCs (CD34/Flk-1) were measured by fluorescence-activated cell sorter; capillary density, by immunohistochemistry; blood flow, by a microsphere technique; endothelial nitric oxide synthase (eNOS) mRNA and protein, by real-time reverse transcriptase (RT)-PCR and Western blotting. The mRNA levels of eNOS were significantly higher in the PIT and L-NAME groups than in the sham-operation group (P < 0.05). Phospho-eNOS protein expression was higher in the PIT group than in the sham-operation and myocardial ischaemia without PIT groups (P < 0.05), and the effect was inhibited by L-NAME pretreatment (P < 0.05). Compared with sham-operation and myocardial ischaemia without PIT groups, the PIT group had the highest EPC count (P < 0.001), and the increase of capillary density (P < 0.01) and collateral blood flow (P < 0.05) in the ischaemic myocardium was consistent with the finding of EPC count. These effects were also inhibited by pretreatment with the eNOS inhibitor L-NAME. Capillary density and collateral blood flow were highly correlated with the increase of EPC count (r = 0.913 and r = 0.929, respectively, P = 0.000). PIT improved EPC mobilization and contributed to compensatory neovascularization via eNOS-related pathway. These results might support the future development of strategies for therapeutic neovascularization.

Beneficial effects of n-acetylcysteine on ischaemic brain injury

PubMed Central

Cuzzocrea, Salvatore; Mazzon, Emanuela; Costantino, Giuseppina; Serraino, Ivana; Dugo, Laura; Calabrò, Giusy; Cucinotta, Giovanni; De Sarro, Angela; Caputi, A P

2000-01-01

Nitric oxide (NO), peroxynitrite, formed from NO and superoxide anion, poly (ADP-ribole) synthetase have been implicated as mediators of neuronal damage following focal ischaemia. Here we have investigated the effects of n-acetylcysteine (NAC) treatment in Mongolian gerbils subjected to cerebral ischaemia.Treatment of gerbils with NAC (20 mg kg−1 30 min before reperfusion and 1, 2 and 6 h after reperfusion) reduced the formation of post-ischaemic brain oedema, evaluated by water content.NAC also attenuated the increase in the brain levels of malondialdehyde (MDA) and the increase in the hippocampus of myeloperoxidase (MPO) caused by cerebral ischaemia.Positive staining for nitrotyrosine was found in the hippocampus in Mongolian gerbils subjected to cerebral ischaemia. Hippocampus tissue sections from Mongolian gerbils subjected to cerebral ischaemia also showed positive staining for poly (ADP-ribose) synthetase (PARS). The degree of staining for nitrotyrosine and for PARS were markedly reduced in tissue sections obtained from animals that received NAC.NAC treatment increased survival and reduced hyperactivity linked to neurodegeneration induced by cerebral ischaemia and reperfusion.Histological observations of the pyramidal layer of CA1 showed a reduction of neuronal loss in animals that received NAC.These results show that NAC improves brain injury induced by transient cerebral ischaemia. PMID:10903958

Gender differences in symptoms of myocardial ischaemia.

PubMed

Mackay, Martha H; Ratner, Pamela A; Johnson, Joy L; Humphries, Karin H; Buller, Christopher E

2011-12-01

Better understanding of symptoms of myocardial ischaemia is needed to improve timeliness of treatment for acute coronary syndromes (ACS). Although researchers have suggested sex differences exist in ischaemic symptoms, methodological issues prevent conclusions. Using percutaneous coronary intervention (PCI) balloon inflation as a model of myocardial ischaemia, we explored sex differences in reported symptoms of ischaemia. Patients having non-emergent PCI, but not haemodynamic instability or left bundle branch block or non-acute coronary occlusion, were prospectively recruited. Pre-procedure, descriptions of pre-existing symptoms were obtained using open-ended questioning. Inflation was maintained for 2 min or until moderate discomfort or clinical instability occurred. During inflation, subjects were exhaustively questioned about their symptoms. Concurrent ECG data were collected. The final sample was 305 [39.7% women; mean age 63.9 (± 10.6)]. No sex differences were found in rates of chest or typical ischaemic discomfort, regardless of ischaemic status. Women were significantly more likely to report throat/jaw discomfort [odds ratio: 2.91; 95% confidence interval: 1.58-5.37] even after statistical adjustment for clinical and demographic variables. This prospective study with ECG-affirmed ischaemia found no statistically significant differences in women's and men's rates of chest and other typical symptoms during ischaemia, although women were more likely to experience throat and jaw discomfort. Currently both popular press and some patient education materials suggest women experience myocardial ischaemia differently from men. Steps to ensure women and health professionals are alert for the classic symptoms of myocardial ischaemia in women, as well as men, may be warranted.

Postconditioning effects of argon or xenon on early graft function in a porcine model of kidney autotransplantation.

PubMed

De Deken, J; Rex, S; Lerut, E; Martinet, W; Monbaliu, D; Pirenne, J; Jochmans, I

2018-07-01

Ischaemia-reperfusion injury is inevitable during renal transplantation and can lead to delayed graft function and primary non-function. Preconditioning, reconditioning and postconditioning with argon and xenon protects against renal ischaemia-reperfusion injury in rodent models. The hypothesis that postconditioning with argon or xenon inhalation would improve graft function in a porcine renal autotransplant model was tested. Pigs (n = 6 per group) underwent left nephrectomy after 60 min of warm ischaemia (renal artery and vein clamping). The procured kidney was autotransplanted in a separate procedure after 18 h of cold storage, immediately after a right nephrectomy. Upon reperfusion, pigs were randomized to inhalation of control gas (70 per cent nitrogen and 30 per cent oxygen), argon (70 per cent and 30 per cent oxygen) or xenon (70 per cent and 30 per cent oxygen) for 2 h. The primary outcome parameter was peak plasma creatinine; secondary outcome parameters included further markers of graft function (creatinine course, urine output), graft injury (aspartate aminotransferase, heart-type fatty acid-binding protein, histology), apoptosis and autophagy (western blot, terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) staining), inflammatory mediators and markers of cell survival/growth (mRNA and tissue protein quantification), and animal survival. Results are presented as median (i.q.r.). ANOVA and Kruskal-Wallis tests were used where indicated. Peak plasma creatinine levels were similar between the groups: control 20·8 (16·4-23·1) mg/dl, argon 21·4 (17·1-24·9) mg/dl and xenon 19·4 (17·5-21·0) mg/dl (P = 0·607). Xenon was associated with an increase in autophagy and proapoptotic markers. Creatinine course, urine output, injury markers, histology, survival and inflammatory mediators were not affected by the intervention. Postconditioning with argon or xenon did not improve kidney graft function in this experimental model. Surgical relevance Ischaemia-reperfusion injury is inevitable during renal transplantation and can lead to delayed graft function and primary non-function. Based on mainly small animal experiments, noble gases (argon and xenon) have been proposed to minimize this ischaemia-reperfusion injury and improve outcomes after transplantation. The hypothesis that postconditioning with argon or xenon inhalation would improve graft function was tested in a porcine kidney autotransplantation model. The peak plasma creatinine concentration was similar in the control, argon and xenon groups. No other secondary outcome parameters, including animal survival, were affected by the intervention. Xenon was associated with an increase in autophagy and proapoptotic markers. Despite promising results in small animal models, postconditioning with argon or xenon in a translational model of kidney autotransplantation was not beneficial. Clinical trials would require better results. © 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.

The prognostic role of stress echocardiography in a contemporary population and the clinical significance of limited apical ischaemia.

PubMed

Papachristidis, Alexandros; Roper, Damian; Cassar Demarco, Daniela; Tsironis, Ioannis; Papitsas, Michael; Byrne, Jonathan; Alfakih, Khaled; Monaghan, Mark J

2016-12-01

In this study, we aim to reassess the prognostic value of stress echocardiography (SE) in a contemporary population and to evaluate the clinical significance of limited apical ischaemia, which has not been previously studied. We included 880 patients who underwent SE. Follow-up data with regards to MACCE (cardiac death, myocardial infarction, any repeat revascularisation and cerebrovascular accident) were collected over 12 months after the SE. Mortality data were recorded over 27.02 ± 4.6 months (5.5-34.2 months). We sought to investigate the predictors of MACCE and all-cause mortality. In a multivariable analysis, only the positive result of SE was predictive of MACCE (HR, 3.71; P = 0.012). The positive SE group was divided into 2 subgroups: (a) inducible ischaemia limited to the apical segments ('apical ischaemia') and (b) ischaemia in any other segments with or without apical involvement ('other positive'). The subgroup of patients with apical ischaemia had a significantly worse outcome compared to the patients with a negative SE (HR, 3.68; P = 0.041) but a similar outcome to the 'other positive' subgroup. However, when investigated with invasive coronary angiography, the prevalence of coronary artery disease (CAD) and their rate of revascularisation was considerably lower. Only age (HR, 1.07; P < 0.001) was correlated with all-cause mortality. SE remains a strong predictor of patients' outcome in a contemporary population. A positive SE result was the only predictor of 12-month MACCE. The subgroup of patients with limited apical ischaemia have similar outcome to patients with ischaemia in other segments despite a lower prevalence of CAD and a lower revascularisation rate. © 2016 The authors.

Effect of ischaemia on somatosensory evoked potentials in diabetic patients.

PubMed Central

López-Alburquerque, T; García Miguel, A; Ruiz Ezquerro, J J; de Portugal Alvarez, J

1987-01-01

The nerve action potential at the elbow and somatosensory evoked potentials (SEPs) at the scalp were recorded over 30 minutes of tourniquet-induced limb ischaemia in 10 diabetic patients and 10 controls. According to the SEP changes, an increased resistance to nerve ischaemia in diabetic patients was observed. The pathways involved in SEP conduction are discussed. PMID:3585354

An integrative review of health-related quality of life in patients with critical limb ischaemia.

PubMed

Monaro, Susan; West, Sandra; Gullick, Janice

2017-10-01

To examine the domains and the domain-specific characteristics within a peripheral arterial disease health-related quality of life framework for their usefulness in defining critical limb ischaemia health-related quality of life. Critical Limb Ischaemia presents a highly individualised set of personal and health circumstances. Treatment options include conservative management, revascularisation or amputation. However, the links between treatment decisions and quality of life require further investigation. The framework for this integrative review was the peripheral arterial disease-specific health-related quality of life domains identified by Treat-Jacobson et al. The literature expanded and refined Treat-Jacobson's framework by modifying the characteristics to better describe health-related quality of life in critical limb ischaemia. Given that critical limb ischaemia is a highly individualised situation with powerful health-related quality of life implications, further research focusing on patient and family-centred decision-making relating to therapeutic options and advanced care planning is required. A critical limb ischaemia-specific, health-related quality of life tool is required to capture both the unique characteristics of this disorder, and the outcomes for active or conservative care among this complex group of patients. © 2016 John Wiley & Sons Ltd.

Apoptosis and brain ischaemia.

PubMed

Love, Seth

2003-04-01

There is increasing evidence that some neuronal death after brain ischaemia is mediated by the action of cysteine-requiring aspartate-directed proteases (caspases), the proteases responsible for apoptosis in mammals, although this form of neuronal death is not always accompanied by the morphological changes that are typical of apoptosis in other tissues. Caspase-mediated neuronal death is more extensive after transient than permanent focal brain ischaemia and may contribute to delayed loss of neurons from the penumbral region of infarcts. The activation of caspases after brain ischaemia is largely consequent on the translocation of Bax, Bak, and other BH3-only members of the Bcl-2 family to the mitochondrial outer membrane and the release of cytochrome c, procaspase-9, and apoptosis activating factor-1 (Apaf-1) from the mitochondrial intermembrane space. How exactly ischaemia induces this translocation is still poorly understood. NF-kappaB, the c-jun N-terminal kinase-c-Jun pathway, p53, E2F1, and other transcription factors are probably all involved in regulating the expression of BH3-only proteins after brain ischaemia, and mitochondrial translocation of Bad from sequestering cytosolic proteins is promoted by inactivation of the serine-threonine kinase, Akt. Other processes that are probably involved in the activation of caspases after brain ischaemia include the mitochondrial release of the second mitochondrial activator of caspases (Smac) or direct inhibitor-of-apoptosis-binding protein with low pI (DIABLO), the accumulation of products of lipid peroxidation, a marked reduction in protein synthesis, and the aberrant reentry of neurons into the cell cycle. Non-caspase-mediated neuronal apoptosis may also occur, but there is little evidence to date that this makes a significant contribution to brain damage after ischaemia. The intracellular processes that contribute to caspase-mediated neuronal death after ischaemia are all potential targets for therapy. However, anti-apoptotic interventions in stroke patients will require detailed evaluation using a range of outcome measures, as some such interventions seem simply to delay neuronal death and others to preserve neurons but not neuronal function.

Influence of genetic variations in platelet glycoproteins and eNOS in the development of arterial ischaemia of lower limbs in type 2 diabetes mellitus patients.

PubMed

Carvalhais, Virginia; Ruivães, Ema; Pina-Cabral, Luis Bernardo; Mesquita, Bárbara; Oliveira, Flávio; Monteiro, Maria Céu; Criado, Maria Begoña

2016-12-01

Endothelial and platelet dysfunction increase the atherothrombotic risk in diabetes mellitus patients. Therefore, arterial ischaemia of lower limbs is an important complication in diabetes mellitus. In the present work, type 2 diabetic patients were classified by a podiatrist into presence or absence of arterial ischaemia of lower limbs. Several polymorphisms in platelet glycoproteins and eNOS genes were evaluated. Our results suggest that the -5CC genotype in Kozak sequence of GPIbα may be associated with a higher risk of developing arterial ischaemia of lower limbs in type 2 diabetes mellitus patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Life satisfaction in patients with and without spinal cord ischemia after advanced endovascular therapy for extensive aortic disease at mid-term follow-up.

PubMed

Mehmedagic, Irma; Santén, Stefan; Jörgensen, Sophie; Acosta, Stefan

2016-11-11

Advanced endovascular aortic repair can be used to treat patients with extensive and complex aortic disease who are at risk of spinal cord ischaemia. The aim of this study was to compare whether life satisfaction differs between patients with and without spinal cord ischaemia at mid-term follow-up. Nested case-control study. Among patients undergoing advanced endovascular aortic repair between 2009 and 2012, 18 patients with spinal cord ischaemia and 33 without were interviewed at home. The Life Satisfaction Questionnaire (LiSat-11) and the Satisfaction With Life Scale (SWLS) were used. LiSat-11 found that patients with spinal cord ischaemia were more dissatisfied with their activities of daily living than were patients without spinal cord ischaemia (p=0.012). Both groups had similar, very low, scores in the sexual life domain; median 2.0 (interquartile range (IQR) 1.5-3.0) and 3.0 (IQR 2.0-4.0), respectively. There was no difference in SWLS between the groups. This study cohort of patients who underwent advanced endovascular aortic repair was rather homo-genous in their rating of life satisfaction and there was little difference between mid-term survivors who had spinal cord ischaemia and those who did not.

Detrimental effects of acute hyperglycaemia on the rat heart.

PubMed

Mapanga, R F; Joseph, D; Symington, B; Garson, K-L; Kimar, C; Kelly-Laubscher, R; Essop, M Faadiel

2014-03-01

Hyperglycaemia is an important risk factor for acute myocardial infarction. It can lead to increased induction of non-oxidative glucose pathways (NOGPs) - polyol and hexosamine biosynthetic pathways, advanced glycation end products and protein kinase C - that may contribute to cardiovascular diseases onset. However, the precise underlying mechanisms remain poorly understood. Here we hypothesized that acute hyperglycaemia increases myocardial oxidative stress and NOGP activation resulting in cardiac dysfunction during ischaemia-reperfusion and that inhibition of, and/or shunting flux away from NOGPs [by benfotiamine (BFT) treatment], leads to cardioprotection. We employed several experimental systems: (i) Isolated rat hearts were perfused ex vivo with Krebs-Henseleit buffer containing 33 mm glucose vs. controls (11 mm glucose) ± global ischaemia and reperfusion ± BFT (first 20 min of reperfusion); (ii) Infarct size determination as per the ischaemic protocol, but with regional ischaemia and reperfusion ± BFT treatment; in separate experiments, NOGP inhibitors were also employed for (i) and (ii); and (iii) In vivo coronary ligations performed on streptozotocin-treated rats ± BFT treatment (early reperfusion). Acute hyperglycaemia generated myocardial oxidative stress, NOGP activation and apoptosis, but caused no impairment of cardiac function during pre-ischaemia, thereby priming hearts for later damage. Following ischaemia-reperfusion (under hyperglycaemic conditions), such effects were exacerbated together with cardiac contractile dysfunction. Moreover, inhibition of respective NOGPs and shunting away by BFT treatment (in part) improved cardiac function during ischaemia-reperfusion. Coordinate NOGP activation in response to acute hyperglycaemia results in contractile dysfunction during ischaemia-reperfusion, allowing for the development of novel cardioprotective agents. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Protective effect of protopine on the focal cerebral ischaemic injury in rats.

PubMed

Xiao, Xianghua; Liu, Juntian; Hu, Jingwen; Li, Tianxia; Zhang, Yuanhui

2007-08-01

Protopine, an isoquinoline alkaloidis, is known to produce many effects such as vasodilation, down-regulation of glutamate levels in brain and decrease of intracellular calcium. However, so far there is no report on the effect of protopine in cerebral ischaemia. In this study, the effect of protopine on the focal cerebral ischaemia was investigated in rats. Male Sprague-Dawley rats were divided into five groups: sham-operated group, vehicle-treated group and three doses of protopine-treated groups (0.98, 1.96 and 3.92 mg/kg). Protopine was intraperitoneally administered to rats once daily for 3 days prior to the ischaemia and 0.9% normal saline to rats in the vehicle-treated group in the same pattern. Rats in the sham-operated group were given 0.9% normal saline without the ischaemia. The focal cerebral ischaemia was induced by the middle cerebral artery occlusion for 24 hr via the intraluminal filament technique. The results showed that pre-treatment with protopine reduced the cerebral infarction ratio and serum lactate dehydrogenase activity, and improved the ischaemia-induced neurological deficit score and histological changes of brain in a dose-dependent manner. The further studies demonstrated that protopine increased superoxide dismutase activity in serum, and decreased total calcium and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL)-positive cells in the ischaemic brain tissue in the middle cerebral artery occlusion rats. The results indicate that protopine is able to produce an effective protection on the injury caused by the focal cerebral ischaemia in rats possibly through the multiple effects of calcium antagonism, antioxidation and depression of cell apoptosis.

Methyl-isobutyl amiloride reduces brain Lac/NAA, cell death and microglial activation in a perinatal asphyxia model.

PubMed

Robertson, Nicola J; Kato, Takenori; Bainbridge, Alan; Chandrasekaran, Manigandan; Iwata, Osuke; Kapetanakis, Andrew; Faulkner, Stuart; Cheong, Jeanie; Iwata, Sachiko; Hristova, Mariya; Cady, Ernest; Raivich, Gennadij

2013-03-01

Na⁺/H⁺ exchanger (NHE) blockade attenuates the detrimental consequences of ischaemia and reperfusion in myocardium and brain in adult and neonatal animal studies. Our aim was to use magnetic resonance spectroscopy (MRS) biomarkers and immunohistochemistry to investigate the cerebral effects of the NHE inhibitor, methyl isobutyl amiloride (MIA) given after severe perinatal asphyxia in the piglet. Eighteen male piglets (aged < 24 h) underwent transient global cerebral hypoxia-ischaemia and were randomized to (i) saline placebo; or (ii) 3 mg/kg intravenous MIA administered 10 min post-insult and 8 hourly thereafter. Serial phosphorus-31 (³¹P) and proton (¹H) MRS data were acquired before, during and up to 48 h after hypoxia-ischaemia and metabolite-ratio time-series Area under the Curve (AUC) calculated. At 48 h, histological and immunohistochemical assessments quantified regional tissue injury. MIA decreased thalamic lactate/N-acetylaspartate and lactate/creatine AUCs (both p < 0.05) compared with placebo. Correlating with improved cerebral energy metabolism, transferase mediated biotinylated d-UTP nick end-labelling (TUNEL) positive cell density was reduced in the MIA group in cerebral cortex, thalamus and white matter (all p < 0.05) and caspase 3 immunoreactive cells were reduced in pyriform cortex and caudate nucleus (both p < 0.05). Microglial activation was reduced in pyriform and midtemporal cortex (both p < 0.05). Treatment with MIA starting 10 min after hypoxia-ischaemia was neuroprotective in this perinatal asphyxia model. © 2012 International Society for Neurochemistry.

VEGF released from a fibrin biomatrix increases VEGFR-2 expression and improves early outcome after ischaemia-reperfusion injury.

PubMed

Moritz, Martina; Pfeifer, Sabine; Balmayor, Elizabeth R; Mittermayr, Rainer; Wolbank, Susanne; Redl, Heinz; van Griensven, Martijn

2017-07-01

Skeletal ischaemia-reperfusion (I-R) injury may influence patient outcome after severe vascular trauma or clamping of major vessels. The aim of this study was to observe whether locally applied vascular endothelial growth factor (VEGF) in fibrin could induce the expression of VEGF-receptor-2 (VEGFR-2) and improve the outcome after I-R injury. Transgenic mice expressing VEGFR-2 promoter-controlled luciferase were used for the assessment of VEGFR-2 expression. Ischaemia was induced for 2 h by a tension-controlled tourniquet to the hind limb, followed by 24 h of reperfusion. The animals were locally injected subcutaneously with fibrin sealant containing 20 or 200 ng VEGF; control animals received no treatment or fibrin sealant application. In vivo VEGFR-2 expression was quantified upon administration of luciferin at several observation times. For oedema and inflammation quantification, wet:dry ratio measurements and a myeloperoxidase assay of the muscle tissue were performed. Laser Doppler imaging showed that ischaemia was present and that the blood flow had returned to baseline levels after 24 h of reperfusion. VEGFR-2 expression levels in the fibrin + 200 ng VEGF were significantly higher than in all other groups. Granulocyte infiltration was reduced in both treatment groups, as well as reduced oedema formation. These results showed that VEGF released from fibrin had a positive effect on early I-R outcome in a mouse model, possibly via VEGFR-2. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The UK DCD Risk Score: A new proposal to define futility in donation-after-circulatory-death liver transplantation.

PubMed

Schlegel, Andrea; Kalisvaart, Marit; Scalera, Irene; Laing, Richard W; Mergental, Hynek; Mirza, Darius F; Perera, Thamara; Isaac, John; Dutkowski, Philipp; Muiesan, Paolo

2018-03-01

Primary non-function and ischaemic cholangiopathy are the most feared complications following donation-after-circulatory-death (DCD) liver transplantation. The aim of this study was to design a new score on risk assessment in liver-transplantation DCD based on donor-and-recipient parameters. Using the UK national DCD database, a risk analysis was performed in adult recipients of DCD liver grafts in the UK between 2000 and 2015 (n = 1,153). A new risk score was calculated (UK DCD Risk Score) on the basis of a regression analysis. This is validated using the United Network for Organ Sharing database (n = 1,617) and our own DCD liver-transplant database (n = 315). Finally, the new score was compared with two other available prediction systems: the DCD risk scores from the University of California, Los Angeles and King's College Hospital, London. The following seven strongest predictors of DCD graft survival were identified: functional donor warm ischaemia, cold ischaemia, recipient model for end-stage liver disease, recipient age, donor age, previous orthotopic liver transplantation, and donor body mass index. A combination of these risk factors (UK DCD risk model) stratified the best recipients in terms of graft survival in the entire UK DCD database, as well as in the United Network for Organ Sharing and in our own DCD population. Importantly, the UK DCD Risk Score significantly predicted graft loss caused by primary non-function or ischaemic cholangiopathy in the futile group (>10 score points). The new prediction model demonstrated a better C statistic of 0.79 compared to the two other available systems (0.71 and 0.64, respectively). The UK DCD Risk Score is a reliable tool to detect high-risk and futile combinations of donor-and-recipient factors in DCD liver transplantation. It is simple to use and offers a great potential for making better decisions on which DCD graft should be rejected or may benefit from functional assessment and further optimization by machine perfusion. In this study, we provide a new prediction model for graft loss in donation-after-circulatory-death (DCD) liver transplantation. Based on UK national data, the new UK DCD Risk Score involves the following seven clinically relevant risk factors: donor age, donor body mass index, functional donor warm ischaemia, cold storage, recipient age, recipient laboratory model for end-stage liver disease, and retransplantation. Three risk classes were defined: low risk (0-5 points), high risk (6-10 points), and futile (>10 points). This new model stratified best in terms of graft survival compared to other available models. Futile combinations (>10 points) achieved an only very limited 1- and 5-year graft survival of 37% and less than 20%, respectively. In contrast, an excellent graft survival has been shown in low-risk combinations (≤5 points). The new model is easy to calculate at the time of liver acceptance. It may help to decide which risk combination will benefit from additional graft treatment, or which DCD liver should be declined for a certain recipient. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

The future of partial nephrectomy.

PubMed

Malthouse, Theo; Kasivisvanathan, Veeru; Raison, Nicholas; Lam, Wayne; Challacombe, Ben

2016-12-01

Innovation in recent times has accelerated due to factors such as the globalization of communication; but there are also more barriers/safeguards in place than ever before as we strive to streamline this process. From the first planned partial nephrectomy completed in 1887, it took over a century to become recommended practice for small renal tumours. At present, identified areas for improvement/innovation are 1) to preserve renal parenchyma, 2) to optimise pre-operative eGFR and 3) to reduce global warm ischaemia time. All 3 of these, are statistically significant predictors of post-operative renal function. Urologists, have a proud history of embracing innovation & have experimented with different clamping techniques of the renal vasculature, image guidance in robotics, renal hypothermia, lasers and new robots under development. The DaVinci model may soon no longer have a monopoly on this market, as it loses its stranglehold with novel technology emerging including added features, such as haptic feedback with reduced costs. As ever, our predictions of the future may well fall wide of the mark, but in order to progress, one must open the mind to the possibilities that already exist, as evolution of existing technology often appears to be a revolution in hindsight. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Bilirubin provides perforator flap protection from ischaemia-reperfusion injury in a rat model: a preliminary result.

PubMed

Kim, Sung Young; Rah, Dong Kyun; Chong, Yosep; Lee, Song Hyun; Park, Tae Hwan

2016-10-01

The use of bilirubin, a well-known and powerful antioxidant, has gained popularity in recent years because of its role in the prevention of ischaemic heart disease in patients with Gilbert's syndrome. We investigate the effects of bilirubin on ischaemia-reperfusion (I/R) injury using a rat perforator flap model. Forty-eight rats were randomly divided into two groups: experimental (bilirubin) group (n = 24) and control group (n = 24). In each group, elevated bilateral deep inferior epigastric perforator (DIEP) flaps were created. The right (no ischaemia side) and left (ischaemia side) DIEP flaps were separated according to the presence of ischaemia induction. Ischaemia was induced in anaesthetised rats by perforator clamping for 15 or 30 minutes. After surgery, the flap survival was assessed daily on postoperative days 0 to 5, and overall histological changes of DIEP flaps above the perforator were analysed at postoperative day 5. The flap survival rate in the bilirubin group was significantly higher than that in the control group at the ischaemia side following perforator clamping for 15 or 30 minutes (93·42 ± 4·48% versus 89·63 ± 3·98%, P = 0·002; and 83·96 ± 4·23% versus 36·46 ± 6·38%, P < 0·001, respectively). The difference in flap survival between the two groups was the most prominent on the ischaemic side following 30 minutes of perforator clamping. From a morphologic perspective, pre-treatment with bilirubin was found to alleviate perforator flap necrosis caused by I/R injury in this experimental rat model. © 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Endogenous Sonic Hedgehog limits inflammation and angiogenesis in the ischaemic skeletal muscle of mice.

PubMed

Caradu, Caroline; Guy, Alexandre; James, Chloé; Reynaud, Annabel; Gadeau, Alain-Pierre; Renault, Marie-Ange

2018-04-01

Hedgehog (Hh) signalling has been shown to be re-activated in ischaemic tissues and participate in ischaemia-induced angiogenesis. Sonic Hedgehog (Shh) is upregulated by more than 80-fold in the ischaemic skeletal muscle, however its specific role in ischaemia-induced angiogenesis has not yet been fully investigated. The purpose of the present study was to investigate the role of endogenous Shh in ischaemia-induced angiogenesis. To this aim, we used inducible Shh knock-out (KO) mice and unexpectedly found that capillary density was significantly increased in re-generating muscle of Shh deficient mice 5 days after hind limb ischaemia was induced, demonstrating that endogenous Shh does not promote angiogenesis but more likely limits it. Myosin and MyoD expression were equivalent in Shh deficient mice and control mice, indicating that endogenous Shh is not required for ischaemia-induced myogenesis. Additionally, we observed a significant increase in macrophage infiltration in the ischaemic muscle of Shh deficient mice. Our data indicate that this was due to an increase in chemokine expression by myoblasts in the setting of impaired Hh signalling, using tissue specific Smoothened conditional KO mice. The increased macrophage infiltration in mice deficient for Hh signalling in myocytes was associated with increased VEGFA expression and a transiently increased angiogenesis, demonstrating that Shh limits inflammation and angiogenesis indirectly by signalling to myocytes. Although ectopic administration of Shh has previously been shown to promote ischaemia-induced angiogenesis, the present study reveals that endogenous Shh does not promote ischaemia-induced angiogenesis. On the contrary, the absence of Shh leads to aberrant ischaemic tissue inflammation and a transiently increased angiogenesis.

Polysensory response characteristics of dorsal root ganglion neurones that may serve sensory functions during myocardial ischaemia.

PubMed

Huang, M H; Horackova, M; Negoescu, R M; Wolf, S; Armour, J A

1996-09-01

To determine the response characteristics of dorsal root ganglion neurones that may serve sensory functions during myocardial ischaemia. Extracellular recordings were made from 54 spontaneously active and 5 normally quiescent dorsal root ganglion neurones (T2-T5) in 22 anaesthetized open-chest dogs under control conditions and during epicardial mechanical or chemical stimulation and myocardial ischaemia. The activity of 78% of spontaneously active and all quiescent neurones with left ventricular sensory fields was modified by left ventricular ischaemia. Forty-six spontaneously active neurones (85%) were polysensory with respect to mechanical and chemical stimuli. The 5 quiescent neurones responded only to chemical stimuli. Spontaneously active neurones associated with left ventricular mechanosensory endings (37 neurones) generated four different activity patterns in response to similar mechanical stimuli (high or low pressure active, high-low pressure active, high-low pressure inactive). A fifth group generated activity which was not related to chamber dynamics. Adenosine, adenosine 5'-triphosphate, substance P and bradykinin modified 72, 61, 65 and 63% of the spontaneously active neurones, respectively. Maximum local mechanical or chemical stimuli enhanced activity to similar degrees, as did ischaemia. Each ischaemia-sensitive neurone displayed unique activity patterns in response to similar mechanical or chemical stimuli. Most myocardial ischemia-sensitive dorsal root ganglion neurones associated with epicardial neurites sense mechanical and multiple chemical stimuli, a small population sensing only mechanical or chemical stimuli. Activity patterns generated by these neurones depend on their primary sensory characteristics or those of other neurones that may converge on them, as well as the type and magnitude of the stimuli that impinge upon their sensory fields, both normally and during ischaemia.

Effect of antisense oligodeoxynucleotides for ICAM-1 on renal ischaemia–reperfusion injury in the anaesthetised rat

PubMed Central

Kiew, Lik Voon; Munavvar, Abdul Sattar; Law, Chung Hiong; Azizan, Abdullah Nor; Nazarina, Abdul Rahman; Sidik, Khalifah; Johns, Edward J

2004-01-01

An antisense oligodeoxynucleotide (As-ODN) to the 3′ untranslated region of the mRNA sequence expressing the intracellular adhesion molecule-1 (ICAM-1) was employed to determine ICAM-1's role in renal ischaemia–reperfusion injury in the rat. Wistar-Kyoto rats receiving i.v. either lipofectin–As-ODN (As-ODN group), lipofectin–reverse ODN (Rv-ODN group) or lipofectin (ischaemia control group) 8 h prior to study were anaesthetized and subjected to 30 min of renal artery occlusion. Renal haemodynamic and excretory parameters were monitored before and after renal ischaemia. On termination of the study renal tissue was subjected to histological and Western blot analysis. Renal blood flow decreased in the 3 h post-ischaemia period in the ischaemia control and Rv-ODN groups, but was maintained in the As-ODN group. Glomerular filtration rate was depressed initially but gradually increased to 10% above basal levels in the ischaemia control and Rv-ODN groups, but was below basal levels (20%) in the As-ODN group. There was a three- to fourfold increase in sodium and water excretion following ischaemia in the ischaemia control and reverse-ODN groups but not in the As-ODN treated group. The As-ODN ameliorated the histological evidence of ischaemic damage and reduced ICAM-1 protein levels to a greater extent in the medulla than cortex. These observations suggested that in the post-ischaemic period afferent and efferent arteriolar tone was increased with a loss of reabsorptive capacity which was in part due to ICAM-1. The possibility arises that the action of ICAM-1 at vascular and tubular sites in the deeper regions of the kidney contributes to the ischaemia–reperfusion injury. PMID:15047774

Honey improves spermatogenesis and hormone secretion in testicular ischaemia-reperfusion-induced injury in rats.

PubMed

Gholami, M; Abbaszadeh, A; Khanipour Khayat, Z; Anbari, K; Baharvand, P; Gharravi, A M

2018-02-01

This study was conducted to survey the protective effect of pre-treatment with Persian honey during post-ischaemia reperfusion on ischaemia-reperfusion (IR)-induced testis injury. Animals were divided into four groups of IR, honey + ischaemia- reperfusion (HIR), vitamin C + ischaemia- reperfusion (VIR) and carbohydrates + ischaemia- reperfusion (CIR). The testes were examined for spermatogenesis index. Detection of single- and double-stranded DNA breaks at the early stages of apoptosis was performed. Total serum concentration of FSH, LH and testosterone was measured using ELISA. All data were expressed as mean ± SD in each group, and significance was set at p ≤ .05. Spermatogenesis index was significant in the HIR group (p < .001). Serum levels of FSH and LH were significantly higher in the CIR and HIR groups. Serum levels of testosterone were significantly higher in VIR and HIR groups. Apoptotic cells in IR and CIR groups increased significantly statistically (p < .001), while in HIR and VIR groups, the number of apoptotic cells decreased and the positive cells of TUNEL staining were detected in spermatocytes and spermatid. The present study indicates that honey decreases the cellular damage and apoptosis during testicular I/R injury, with significant protective effects on reproductive hormone production. © 2017 Blackwell Verlag GmbH.

Protective agents used as additives in University of Wisconsin solution to promote protection against ischaemia-reperfusion injury in rat lung.

PubMed

Chiang, C H; Wu, K; Yu, C P; Perng, W C; Yan, H C; Wu, C P; Chang, D M; Hsu, K

1998-09-01

1. An intervention to reduce ischaemia-reperfusion lung injury will be an important advance in transplant medicine. Although the mechanisms associated with producing ischaemia-reperfusion endothelial injury have not been completely elucidated, many of the injury mediators have been studied in detail. While no single pharmacological therapy is likely to be totally effective in eliminating this complex injury, we have developed a mixture of agents that are known to block pathways involved in producing ischaemia-reperfusion-associated lung vascular injury.2. The present study modified University of Wisconsin solution (UW) by adding one of the protective agents prostaglandin E1 (PGE1), dexamethasone (Dex) or dibutyryl cAMP (Bt2-cAMP), or a combination of these, to the perfusate of rat lungs exposed to 4 h of cold ischaemia followed by 1 h of reperfusion. Nine modified UW solutions were studied: (1) UW+Dex, (2) UW+PGE1, (3) UW+Bt2-cAMP, (4) UW+Dexx3, (5) UW+PGE1x3, (6) UW+Bt2-cAMPx3, (7) UW+Dex+PGE1, (8) UW+Dex+Bt2-cAMP, (9) UW+PGE1+Bt2-cAMP. These solutions were utilized in individual experiments to assess haemodynamic changes, lung weight gain, the capillary filtration coefficient (Kfc) and pathology in all lungs.3. The results indicate that lung weight gain and Kfc values were significantly lower than with UW alone in groups 1, 2 and 3, which contained only one additional protective agent. In groups 4, 5 and 6, which contain three times the concentration of each protective agent, both Kfc and lung weight gain were similar to those measured in groups 1, 2 and 3, i.e. lungs were protected but the protection was not dose dependent. In groups 7, 8 and 9, which contained two protective agents, lung weight gain and Kfc were greatly reduced compared with UW alone. Histopathological studies showed similar decreases in the injury profiles of lungs.4. Although UW contains several antioxidant protective agents such as allopurinol and glutathione, it did not provide effective protection in our ischaemia-reperfusion lung injury model. UW modified with an additive of PGE1, Dex or Bt2-cAMP attenuated ischaemia-reperfusion injury. Furthermore, UW containing two of these protective agents augmented the protection. Among the modified solutions, it appears that UW+PGE1+Bt2-cAMP protects the lungs to a greater extent than all other solutions used in our study. We suggest that preservation solutions containing PGE1-Bt2-cAMP will provide additional protective effects to organs stored for transplantation.

To what extent have functional studies of ischaemia in animals been useful in the assessment of potential neuroprotective agents?

PubMed

Hunter, A J; Mackay, K B; Rogers, D C

1998-02-01

A general consensus is being reached on the use of a combination of mortality and functional end-points in clinical trials of neuroprotective agents. However, to date, few preclinical studies have examined the effects of putative neuroprotective agents on functional outcome after ischaemia. The data described in this review show the importance of combining both histopathological and neurobehavioural studies when evaluating the neuroprotective efficacy of anti-ischaemic agents in animal models of cerebral ischaemia. Here, Jackie Hunter, Ken Mackay and Derek Rogers argue that measures of functional improvement in models of ischaemia should be incorporated to characterize further the neuroprotection afforded by a compound that could aid the selection of doses and end-point measures in early clinical trials.

Effects of defibrotide, a novel oligodeoxyribonucleotide, on ischaemia and reperfusion injury of the rat liver.

PubMed

Kim, Kwang Joon; Shin, Yong Kyoo; Song, Jin Ho; Oh, Byung Kwon; Choi, Myung Sup; Sohn, Uy Dong

2002-02-01

1. The purpose of this study was to investigate the protective effects of defibrotide, a single-stranded polydeoxyribonucleotide, on ischaemia-reperfusion injury to the liver using a rat model. 2. Ischaemia of the left and median lobes was created by total inflow occlusion for 30 min followed by 60 min of reperfusion. Hepatic injury was assessed by the release of liver enzymes (alanine transferase, ALT and lactic dehydrogenase, LDH). Hepatic oxidant stress was measured by superoxide production, lipid peroxidation and nitrite/nitrate formation. Leukocyte-endothelium interaction and Kupffer cell mobilization were quantified by measuring hepatic myeloperoxidase (MPO), polymorphonuclear leukocyte adherence to superior mesenteric artery (SMA) and immunostaining of Kupffer cell. 3. Defibrotide treatment resulted in a significant inhibition of postreperfusion superoxide generation, lipid peroxidation, serum ALT activity, serum LDH activity, MPO activity, serum nitrite/nitrate level, leukocyte adherence to SMA, and Kupffer cell mobilization, indicating a significant attenuation of hepatic dysfunction. 4. A significant correlation existed between liver ischaemia/reperfusion and hepatic injury, suggesting that liver ischaemia/reperfusion injury is mediated predominantly by generation of oxygen free radicals and mobilization of Kupffer cells. 5. We conclude that defibrotide significantly protects the liver against liver ischaemia/reperfusion injury by interfering with Kupffer cell mobilization and formation of oxygen free radicals. This study provides strong evidence that defibrotide has important beneficial effects on acute inflammatory tissue injury such as that occurring in the reperfusion of the ischaemic liver.

Crisis management during anaesthesia: myocardial ischaemia and infarction.

PubMed

Ludbrook, G L; Webb, R K; Currie, M; Watterson, L M

2005-06-01

Myocardial ischaemia and infarction are significant perioperative complications which are associated with poor patient outcome. Anaesthetic practice should therefore focus, particularly in the at risk patient, on their prevention, their accurate detection, on the identification of precipitating factors, and on rapid effective management. To examine the role of a previously described core algorithm "COVER ABCD-A SWIFT CHECK" supplemented by a specific sub-algorithm for myocardial ischaemia and infarction in the management of myocardial ischaemia and/or infarction occurring in association with anaesthesia. The potential performance of this structured approach for each of the relevant incidents among the first 4000 reported to the Australian Incident Monitoring Study (AIMS) was compared with the actual management as reported by the anaesthetists involved. Of the 125 incidents retrieved from the 4000 reports, 40 (1%) were considered to demonstrate myocardial infarction or ischaemia. The use of the structured approach described in this paper would have led to appropriate management in 90% of cases, with the remaining 10% requiring other sub-algorithms. It was considered that the application of this structured approach would have led to earlier recognition and/or better management of the problem in 45% of cases. Close and continuous monitoring of patients at risk of myocardial ischaemia during anaesthesia is necessary, using optimal ECG lead configurations, but sensitivity of this monitoring is not 100%. Coronary vasodilatation with glyceryl trinitrate (GTN) should not be withheld when indicated and the early use of beta blocking drugs should be considered even with normal blood pressures and heart rates.

Vinpocetine regulates cation channel permeability of inner retinal neurons in the ischaemic retina.

PubMed

Nivison-Smith, Lisa; Acosta, Monica L; Misra, Stuti; O'Brien, Brendan J; Kalloniatis, Michael

2014-01-01

Vinpocetine is a natural drug which exerts neuroprotective effects in ischaemia of the brain through actions on cation channels, glutamate receptors and other pathways. This study investigated the effect of vinpocetine on cation channel permeability of inner retinal neurons after acute retinal metabolic insult. We focused on amacrine and ganglion cells immunoreactive for calretinin or parvalbumin due to their previously documented susceptibility to ischaemia. Using the probe, 1-amino-4-guanidobutane (AGB), we observed increased cation channel permeability across amacrine and ganglion cells under ischaemia and hypoglycaemia but not anoxia. Calretinin and parvalbumin immunoreactivity was also reduced during ischaemia and hypoglyacemia but not anoxia. Vinpocetine decreased AGB entry into ischaemic and hypoglycaemic ganglion cells indicating that the drug can modulate unregulated cation entry. In addition, vinpocetine prevented the loss of calretinin and parvalbumin immunoreactivity following ischaemia suggesting it may indirectly regulate intracellular calcium. Vinpocetine also reduced AGB permeability in selected amacrine and ganglion cell populations following N-methyl-D-aspartate (NMDA) but not kainate activation suggesting that vinpocetine's regulation of cation channel permeability may partly involve NMDA sensitive glutamate receptors. Copyright © 2014 Elsevier Ltd. All rights reserved.

L-Arginyl-3,4-Spermidine is neuroprotective in several in vitro models of neurodegeneration and in vivo ischaemia without suppressing synaptic transmission

PubMed Central

Morrison, Barclay; Pringle, Ashley K; McManus, Terence; Ellard, John; Bradley, Mark; Signorelli, Francesco; Iannotti, Fausto; Sundstrom, Lars E

2002-01-01

Stroke is the third most common cause of death in the world, and there is a clear need to develop new therapeutics for the stroke victim. To address this need, we generated a combinatorial library of polyamine compounds based on sFTX-3.3 toxin from which L-Arginyl-3,4-Spermidine (L-Arg-3,4) emerged as a lead neuroprotective compound. In the present study, we have extended earlier results to examine the compound's neuroprotective actions in greater detail. In an in vitro ischaemia model, L-Arg-3,4 significantly reduced CA1 cell death when administered prior to induction of 60 min of ischaemia as well as when administered immediately after ischaemia. Surprisingly, L-Arg-3,4 continued to prevent cell death significantly when administration was delayed for as long as 60 min after ischaemia. L-Arg-3,4 significantly reduced cell death in excitotoxicity models mediated by glutamate, NMDA, AMPA, or kainate. Unlike glutamate receptor antagonists, 300 μM L-Arg-3,4 did not suppress synaptic transmission as measured by evoked responses in acute hippocampal slices. L-Arg-3,4 provided significant protection, in vitro, in a superoxide mediated injury model and prevented an increase of superoxide production after AMPA or NMDA stimulation. It also decreased nitric oxide production after in vitro ischaemia and NMDA stimulation, but did so without inhibiting nitric oxide synthase directly. Furthermore, L-Arg-3,4 was significantly neuroprotective in an in vivo model of global forebrain ischaemia, without any apparent neurological side-effects. Taken together, these results demonstrate that L-Arg-3,4 is protective in several models of neurodegeneration and may have potential as a new therapeutic compound for the treatment of stroke, trauma, and other neurodegenerative diseases. PMID:12466235

Early glycogen synthase kinase-3β and protein phosphatase 2A independent tau dephosphorylation during global brain ischaemia and reperfusion following cardiac arrest and the role of the adenosine monophosphate kinase pathway.

PubMed

Majd, Shohreh; Power, John H T; Koblar, Simon A; Grantham, Hugh J M

2016-08-01

Abnormal tau phosphorylation (p-tau) has been shown after hypoxic damage to the brain associated with traumatic brain injury and stroke. As the level of p-tau is controlled by Glycogen Synthase Kinase (GSK)-3β, Protein Phosphatase 2A (PP2A) and Adenosine Monophosphate Kinase (AMPK), different activity levels of these enzymes could be involved in tau phosphorylation following ischaemia. This study assessed the effects of global brain ischaemia/reperfusion on the immediate status of p-tau in a rat model of cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR). We reported an early dephosphorylation of tau at its AMPK sensitive residues, Ser(396) and Ser(262) after 2 min of ischaemia, which did not recover during the first two hours of reperfusion, while the tau phosphorylation at GSK-3β sensitive but AMPK insensitive residues, Ser(202) /Thr(205) (AT8), as well as the total amount of tau remained unchanged. Our data showed no alteration in the activities of GSK-3β and PP2A during similar episodes of ischaemia of up to 8 min and reperfusion of up to 2 h, and 4 weeks recovery. Dephosphorylation of AMPK followed the same pattern as tau dephosphorylation during ischaemia/reperfusion. Catalase, another AMPK downstream substrate also showed a similar pattern of decline to p-AMPK, in ischaemic/reperfusion groups. This suggests the involvement of AMPK in changing the p-tau levels, indicating that tau dephosphorylation following ischaemia is not dependent on GSK-3β or PP2A activity, but is associated with AMPK dephosphorylation. We propose that a reduction in AMPK activity is a possible early mechanism responsible for tau dephosphorylation. © 2016 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Psychological symptom profiles in patients with chest pain.

PubMed

Tennant, C; Mihailidou, A; Scott, A; Smith, R; Kellow, J; Jones, M; Hunyor, S; Lorang, M; Hoschl, R

1994-05-01

Five-hundred and thirty-two patients with ischaemic-like chest pain referred for symptom-limited exercise thallium myocardial perfusion studies, were assessed on a range of psychosocial measures. Three groups of patients were identified on the basis of their perfusion studies: (1) normal thallium perfusion; (2) current myocardial ischaemia; and (3) past myocardial infarction (but no current ischaemia). There were no significant psychological differences between these groups on a wide range of measures which included depression, state and trait anxiety, Type A behaviour, personality, suppression of affect, locus of control, alexythymia, and hypochondriasis. Significant differences were identified, however, on measures of anger and coping style. Subjects with no current ischaemia (normal thallium perfusion and those with past myocardial infarction) had higher scores on 'immature coping' and 'anger in', than subjects with current myocardial ischaemia. These findings are discussed in the light of other published research.

Angiotensin converting enzyme inhibition in chronic stable angina: effects on myocardial ischaemia and comparison with nifedipine.

PubMed Central

Ikram, H.; Low, C. J.; Shirlaw, T. M.; Foy, S. G.; Crozier, I. G.; Richards, A. M.; Khurmi, N. S.; Horsburgh, R. J.

1994-01-01

OBJECTIVES--To determine the anti-ischaemic effects of a new angiotensin converting enzyme inhibitor, benazepril, compared with nifedipine, alone and in combination, in chronic stable angina caused by coronary artery disease. DESIGN--Placebo controlled, double blind, latin square design. SETTING--Regional cardiology service for a mixed urban and rural population. SUBJECTS--40 patients with stable exertional angina producing at least 1 mm ST segment depression on exercise test with the Bruce protocol. 34 patients completed all four phases of the trial. INTERVENTIONS--Each patient was treated with placebo, benazepril (10 mg twice daily), nifedipine retard (20 mg twice daily), and a combination of benazepril and nifedipine in the same doses, in random order for periods of two weeks. MAIN OUTCOME MEASURES AND RESULTS--Total duration of exercise was not increased by any treatment. Exercise time to the development of 1 mm ST segment depression was not significantly changed with benazepril alone or in combination with nifedipine but was increased with nifedipine from 4.18 (1.8) min to 4.99 (1.6) min (95% confidence interval (95% CI) 0.28 to 1.34; p < 0.05). There was a significant relation between increase in duration of exercise and resting renin concentration (r = 0.498; p < 0.01). Myocardial ischaemia during daily activity, as assessed by ambulatory electrocardiographic monitoring, was reduced by benazepril and by the benazepril and nifedipine combination. This was significant for total ischaemic burden (451(628) min v 231(408) min; 95% CI -398 to -41 min; p < 0.05) and maximal depth of ST segment depression (-2.47(1.2) mm v -2.16 mm; 95% CI 0.04 to 0.57; p < 0.05) for the combination and for maximal ST segment depth for benazepril monotherapy (-2.47 (1.2) mm v -1.96(1.2) mm; 95% CI 0.18 to 0.91; p < 0.05). Benazepril significantly altered the circadian rhythm of cardiac ischaemia, abolishing the peak ischaemic periods at 0700 to 1200 and 1700 to 2300 (p < 0.05). CONCLUSIONS--Benazepril, an angiotensin converting enzyme inhibitor, had a modest anti-ischaemic effect in effort angina, but this effect was not as pronounced as with nifedipine. The anti-ischaemic action was more noticeable in asymptomatic ischaemia during daily activity, whereas nifedipine had little effect on this aspect of myocardial ischaemia. The combination of benazepril and nifedipine reduced ischaemia of daily activity. PMID:8297690

Pressure-derived indices of left ventricular isovolumic relaxation in patients with hypertrophic cardiomyopathy.

PubMed Central

Thompson, D S; Wilmshurst, P; Juul, S M; Waldron, C B; Jenkins, B S; Coltart, D J; Webb-Peploe, M M

1983-01-01

High fidelity measurements of left ventricular pressure were made at increasing pacing rates in 21 patients with hypertrophic cardiomyopathy and a control group of 11 patients investigated for chest pain who proved to have normal hearts. In both groups the fall in pressure during isovolumic relaxation from the point of min dp/dt approximated closely to a monoexponential, and could be described by a time constant and asymptote. The time constant shortened and the asymptote increased as heart rate rose in both groups. The time constant was longer and min dp/dt less in the cardiomyopathy group than controls at all heart rates. In the cardiomyopathy patients min dp/dt, but not the time constant, was related to systolic pressure. During pacing, eight cardiomyopathy patients developed metabolic evidence of myocardial ischaemia, but indices of relaxation did not differ between these eight and the other 13 either at basal heart rate or the highest pacing rate. In 10 cardiomyopathy patients measurements were repeated at comparable pacing rates after propranolol (0.2 mg/kg). Left ventricular end-diastolic pressure and indices of contractility decreased after the drug, but the time constant did not change. Eight patients received verapamil (20 mg) after which there were substantial reductions in systolic pressure and contractility. Min dp/dt decreased in proportion to systolic pressure, but the time constant was unchanged. At the highest pacing rate before drug administration three patients had abnormal lactate extraction which was corrected by either propranolol (one patient) or verapamil (two patients). Despite abolition of metabolic evidence of ischaemia, relaxation did not improve. It is concluded that abnormal isovolumic relaxation is common in patients with hypertrophic cardiomyopathy, but its severity correlates poorly with other features of the disease. Abnormal relaxation is not the result of ischaemia, and pressure derived indices of relaxation do not improve after the administration of propranolol or verapamil. PMID:6681978

Added prognostic value of ischaemic threshold in radionuclide myocardial perfusion imaging: a common-sense integration of exercise tolerance and ischaemia severity.

PubMed

Marini, Cecilia; Acampa, Wanda; Bauckneht, Matteo; Daniele, Stefania; Capitanio, Selene; Cantoni, Valeria; Fiz, Francesco; Zampella, Emilia; Dib, Bassam; Assante, Roberta; Bruzzi, Paolo; Sambuceti, Gianmario; Cuocolo, Alberto

2015-04-01

Reversible ischaemia at radionuclide myocardial perfusion imaging (MPI) accurately predicts risk of cardiac death and nonfatal myocardial infarction (major adverse cardiac events, MACE). This prognostic penetrance might be empowered by accounting for exercise tolerance as an indirect index of ischaemia severity. The present study aimed to verify this hypothesis integrating imaging assessment of ischaemia severity with exercise maximal rate pressure product (RPP) in a large cohort of patients with suspected or known coronary artery disease (CAD). We analysed 1,502 consecutive patients (1,014 men aged 59 ± 10 years) submitted to exercise stress/rest MPI. To account for exercise tolerance, the summed difference score (SDS) was divided by RPP at tracer injection providing a clinical prognostic index (CPI). Reversible ischaemia was documented in 357 patients (24 %) and was classified by SDS as mild (SDS 2-4) in 180, moderate (SDS 5-7) in 118 and severe (SDS >7) in 59. CPI values of ischaemic patients were clustered into tertiles with lowest and highest values indicating low and high risk, respectively. CPI modified SDS risk prediction in 119/357 (33 %) patients. During a 60-month follow-up, MACE occurred in 68 patients. Kaplan-Meier analysis revealed that CPI significantly improved predictive power for MACE incidence with respect to SDS alone. Multivariate Cox analysis confirmed the additive independent value of CPI-derived information. Integration of ischaemic threshold and ischaemia extension and severity can improve accuracy of exercise MPI in predicting long-term outcome in a large cohort of patients with suspected or known CAD.

The mitochondria-targeting peptide elamipretide diminishes circulating HtrA2 in ST-segment elevation myocardial infarction.

PubMed

Hortmann, Marcus; Robinson, Samuel; Mohr, Moritz; Mauler, Maximillian; Stallmann, Daniela; Reinöhl, Jochen; Duerschmied, Daniel; Peter, Karlheinz; Carr, James; Gibson, C Michael; Bode, Christoph; Ahrens, Ingo

2017-05-01

The extent of myocardial damage in patients with ST-segment elevation myocardial infarction (STEMI) depends on both the time to reperfusion as well as injury induced by ischaemia-reperfusion resulting in a cascade of cellular and humoral reactions. As a consequence of ischaemia-reperfusion in the heart, the high-temperature requirement serine peptidase 2 (HtrA2) is translocated from the mitochondria to the cytosol, whereupon it induces protease activity-dependent apoptosis mediated via caspases. Myocardial damage induced by reperfusion cannot be monitored due to a current lack in specific biomarkers. We examined the serum level of HtrA2 as a potentially novel biomarker for mitochondrial-induced cardiomyocyte apoptosis. After informed consent, peripheral blood was obtained from patients ( n=19) with first-time acute anterior STEMI after percutaneous coronary intervention. Within this group, 10 of the patients received the mitochondria-targeting peptide elamipretide (phase 2a clinical study EMBRACE (NCT01572909)). Blood was also obtained from a control group of healthy donors ( n=16). The serum level of HtrA2 was measured by an enzyme-linked immunosorbent assay (ELISA). In a murine model of myocardial ischaemia-reperfusion injury, HtrA2 was determined in plasma by ELISA after left anterior descending artery occlusion. HtrA2 median was significantly increased in patients with STEMI compared to healthy controls 392.4 (240.7-502.8) pg/mL vs. 1805.5 (981.3-2220.1) pg/mL ( P⩽0.05). Elamipretide significantly reduced the HtrA2 median serum level after myocardial infarction 1805.5 (981.3-2220.1) pg/mL vs. 496.5 (379.4-703.8) pg/mL ( P⩽0.05). Left anterior descending artery occlusion in mice significantly increased HtrA2 mean in plasma (117.4 fg/ml±SEM 28.1 vs. 525.2 fg/ml±SEM 96; P⩽0.05). Compared to healthy controls, we found significantly increased serum levels of HtrA2 in patients with STEMI. The result was validated in a murine model of myocardial ischaemia-reperfusion injury. In humans the increased serum level was significantly reduced by the mitochondria-targeting peptide elamipretide. In conclusion, HtrA2 is detectable in serum of patients with STEMI and might present a novel biomarker for mitochondrial-induced cardiomyocyte apoptosis. Consequently, HtrA2 may also show promise as a biomarker for the identification of ischaemia-reperfusion injury. However, this must be validated in a lager clinical trial.

Dobutamine stress magnetic resonance imaging suffices for the demonstration of myocardial ischaemia and viability.

PubMed

Lamers, F P L; van Dijkman, P R M; Kuijpers, Th J A; van Herpen, G

2003-02-01

We report three patients in whom dobutamine stress magnetic imaging (DS-MRI) was essential in assessing myocardial ischaemia. Two patients were referred to the cardiologist because of chest pain. Patient A had typical exertional angina and a normal resting electrocardiogram (ECG). Patient B had typical exercise-induced angina and had recently experienced an attack of severe chest pain at rest for 15 minutes. The ECG showed a complete left bundle branch block (LBBB). Patient C was referred for heart failure of unknown origin. There were no symptoms of chest pain during rest or exercise. Echocardiography in this patient demonstrated global left ventricular (LV) dilatation, systolic dysfunction and a small dyskinetic segment in the inferior wall. In all these patients exercise stress testing had failed to demonstrate myocardial ischaemia. Patients A and C produced normal findings whereas in patient B the abnormal repolarisation due to pre-existent LBBB precluded a diagnosis of ischaemia. Breath-hold DS-MRI was performed to study LV wall motion and wall thickening at rest through increasing doses of dobutamine. A test was considered positive for myocardial ischaemia if wall motion abnormalities developed at high-dose levels of the drug (20 μg/kg/min or more with a maximum of 40 μg/kg/min) in previously normal vascular territories or worsened in a segment that was normal at baseline. Recovery of wall thickening in a previously hypokinetic or akinetic segment at a low dose of dobutamine (5-10 μg/kg/min) was taken as proof of viability. Patients A and B developed hypokinesia progressing into akinesia at high-dose dobutamine in the anteroseptal area of the LV indicative of ischaemia. These findings were corroborated by coronary angiography demonstrating severe coronary artery disease which led to coronary artery bypass grafting (CABG) in patient A and balloon angioplasty in patient B. In patient C global recovery of LV contractions during low-dose dobutamine was followed by hypokinesia in the inferoseptal area during high-dose dobutamine. This biphasic response indicates myocardial viability as well as ischaemia. CABG was carried out because of multiple stenoses in the left coronary artery. Post-operatively LV function normalised. DS-MRI is a valuable method for detecting myocardial ischaemia and viability in patients with suspected coronary artery, and can be applied in every hospital with MRI equipment at its disposal.

Performance of highly sensitive cardiac troponin T assay to detect ischaemia at PET-CT in low-risk patients with acute coronary syndrome: a prospective observational study.

PubMed

Morawiec, Beata; Fournier, Stephane; Tapponnier, Maxime; Prior, John O; Monney, Pierre; Dunet, Vincent; Lauriers, Nathalie; Recordon, Frederique; Trana, Catalina; Iglesias, Juan-Fernando; Kawecki, Damian; Boulat, Olivier; Bardy, Daniel; Lamsidri, Sabine; Eeckhout, Eric; Hugli, Olivier; Muller, Olivier

2017-07-10

Highly sensitive troponin T (hs-TnT) assay has improved clinical decision-making for patients admitted with chest pain. However, this assay's performance in detecting myocardial ischaemia in a lowrisk population has been poorly documented. To assess hs-TnT assay's performance to detect myocardial ischaemia at positron emission tomography/CT (PET-CT) in low-risk patients admitted with chest pain. Patients admitted for chest pain with a nonconclusive ECG and negative standard cardiac troponin T results at admission and after 6 hours were prospectively enrolled. Their hs-TnT samples were at T0, T2 and T6. Physicians were blinded to hs-TnT results. All patients underwent a PET-CT at rest and during adenosine-induced stress. All patients with a positive PET-CT result underwent a coronary angiography. Forty-eight patients were included. Six had ischaemia at PET-CT. All of them had ≥1 significant stenosis at coronary angiography. Areas under the curve (95% CI) for predicting significant ischaemia at PET-CT using hs-TnT were 0.764 (0.515 to 1.000) at T0, 0.812(0.616 to 1.000) at T2 and 0.813(0.638 to 0.989) at T6. The receiver operating characteristicbased optimal cut-off value for hs-TnT at T0, T2 and T6 needed to exclude significant ischaemia at PET-CT was <4 ng/L. Using this value, sensitivity, specificity, positive and negative predictive values of hs-TnT to predict significant ischaemia were 83%/38%/16%/94% at T0, 100%/40%/19%/100% at T2 and 100%/43%/20%/100% at T6, respectively. Our findings suggest that in low-risk patients, using the hs-TnT assay with a cut-off value of 4 ng/L demonstrates excellent negative predictive value to exclude myocardial ischaemia detection at PET-CT, at the expense of weak specificity and positive predictive value. ClinicalTrials.gov Identifier: NCT01374607. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Noble gases as cardioprotectants – translatability and mechanism

PubMed Central

Smit, Kirsten F; Weber, Nina C; Hollmann, Markus W; Preckel, Benedikt

2015-01-01

Several noble gases, although classified as inert substances, exert a tissue-protective effect in different experimental models when applied before organ ischaemia as an early or late preconditioning stimulus, after ischaemia as a post-conditioning stimulus or when given in combination before, during and/or after ischaemia. A wide range of organs can be protected by these inert substances, in particular cardiac and neuronal tissue. In this review we summarize the data on noble gas-induced cardioprotection, focusing on the underlying protective mechanisms. We will also look at translatability of experimental data to the clinical situation. PMID:25363501

Microtubule stabilization with paclitaxel does not protect against infarction in isolated rat hearts.

PubMed

Rodríguez-Sinovas, Antonio; Abad, Elena; Sánchez, Jose A; Fernández-Sanz, Celia; Inserte, Javier; Ruiz-Meana, Marisol; Alburquerque-Béjar, Juan José; García-Dorado, David

2015-01-01

What is the central question of this study? The microtubule network is disrupted during myocardial ischaemia-reperfusion injury. It was suggested that prevention of microtubule disruption with paclitaxel might reduce cardiac infarct size; however, the effects on infarction have not been studied. What is the main finding and its importance? Paclitaxel caused a reduction in microtubule disruption and cardiomyocyte hypercontracture during ischaemia-reperfusion. However, it induced a greater increase in cytosolic calcium, which may explain the lack of effect against infarction that we have seen in isolated rat hearts. The large increase in perfusion pressure induced by paclitaxel in this model may have clinical implications, because detrimental effects of the drug were reported after its clinical application. Microtubules play a major role in the transmission of mechanical forces within the myocardium and in maintenance of organelle function. However, this intracellular network is disrupted during myocardial ischaemia-reperfusion. We assessed the effects of prevention of microtubule disruption with paclitaxel on ischaemia-reperfusion injury in isolated rat cardiomyocytes and hearts. Isolated rat cardiomyocytes were submitted to normoxia (1 h) or 45 min of simulated ischaemia (pH 6.4, 0% O2 , 37 °C) and reoxygenation, without or with treatment with the microtubule stabilizer, paclitaxel (10(-5) M), or the inhibitor of microtubule polymerization, colchicine (5 × 10(-6) M). Simulated ischaemia leads to microtubule disruption before the onset of ischaemic contracture. Paclitaxel attenuated both microtubule disruption and the incidence of hypercontracture, whereas treatment with colchicine mimicked the effects of simulated ischaemia and reoxygenation. In isolated normoxic rat hearts, treatment with paclitaxel induced concentration-dependent decreases in heart rate and left ventricular developed pressure and increases in perfusion pressure. Despite protection against hypercontracture, paclitaxel pretreatment did not modify infarct size (60.37 ± 2.27% in control hearts versus 58.75 ± 10.25, 55.44 ± 10.32 and 50.06 ± 10.14% after treatment with 10(-6) , 3 × 10(-6) and 10(-5) m of paclitaxel) after 60 min of global ischaemia and reperfusion in isolated rat hearts. Lack of protection was correlated with a higher increase in cytosolic calcium levels during simulated ischaemia in cardiomyocytes treated with paclitaxel (2.32 ± 0.15 versus 1.13 ± 0.16 a.u. in the presence or absence of 10(-6) m paclitaxel, respectively, P < 0.05), but not with changes in aortic reactivity. In conclusion, microtubule stabilization with paclitaxel reduces hypercontracture in isolated rat cardiomyocytes but does not protect against infarction in isolated rat hearts. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

Regulation of coronary blood flow

PubMed Central

Gorlin, Richard

1971-01-01

Coronary blood flow is dependent upon arterial pressure, diastolic time, and small vessel resistance. The system is regulated to achieve a low flow high oxygen extraction and low myocardial Po2. This setting is sensitive to change in oxygen needs. Regulation of blood flow occurs primarily through local intrinsic regulation, most likely through production of vasodilating metabolites in response to minimal degrees of ischaemia. Local regulation appears to dominate over remote regulation in most circumstances. Blood flow distribution to the myocardium is depth dependent as well as regional in variation. Both types of distribution of blood flow are profoundly disturbed in the presence of obstructive coronary atherosclerosis. This results in either concentric myocardial shells or patchy transmural zones of selective ischaemia with clear-cut but local abnormalities in metabolism and performance. Images PMID:4929442

Effects of oral administration of different doses of purified micronized flavonoid fraction on microvascular reactivity after ischaemia/reperfusion in the hamster cheek pouch

PubMed Central

Bouskela, E; Cyrino, F Z G A; Lerond, L

1997-01-01

The effects of a purified micronized flavonoid fraction (S5682) on mean internal diameter and blood flow of arterioles and venules, as well as the functional capillary density (FCD) were evaluated in the hamster cheek pouch microvasculature before and after 90 min of total ischaemia. Male hamsters were treated for ten days, twice a day, with oral doses of S5682 (5, 20, 80 and 160 mg kg−1 day−1) or placebo (10% lactose solution). The cheek pouch preparation was placed under an intravital microscope coupled to a closed circuit TV system. Local ischaemia was obtained by a cuff mounted around the neck of the everted pouch where it leaves the mouth of the hamster. Measurements were performed before ischaemia, at the onset of reperfusion and 10, 20, 30, 45 and 60 min thereafter. Diameters were measured by means of an image shearing device. Red blood cell (RBC) velocity was analysed by use of the dual-slit photometric technique. Blood flow was calculated from diameters and RBC velocities. FCD, defined as the number of capillaries with flowing blood per field of observation, was also assessed. During reperfusion, placebo-treated animals showed a significant vasodilatation, a decrease in blood flow and FCD and S5682-treated animals showed a clear trend, dose-dependent, towards maintaining these parameters closer to the value found before ischaemia. In conclusion, our results indicate that S5682 improves the microvascular reactivity and FCD after ischaemia/reperfusion. These data suggest that S5682 could function as an antioxidant, which may explain its beneficial therapeutic effect in chronic venous insufficiency where oxidative stress is involved in the pathological mechanism. PMID:9422805

Cholinergic stimulation with pyridostigmine protects against exercise induced myocardial ischaemia

PubMed Central

Castro, R R T; Porphirio, G; Serra, S M; Nóbrega, A C L

2004-01-01

Objective: To determine the acute effects of pyridostigmine bromide, a reversible cholinesterase inhibitor, during exercise in patients with coronary artery disease. Design: Double blind, randomised, placebo controlled, crossover study. Setting: Outpatients evaluated in an exercise test laboratory. Patients: 15 patients with exercise induced myocardial ischaemia. Interventions: Maximal cardiopulmonary exercise test on a treadmill according to an individualised ramp protocol on three days. The first day was used for adaptation to the equipment and to determine exercise tolerance and the presence of exercise induced ischaemia. On the other two days, the cardiopulmonary exercise test was performed two hours after oral administration of pyridostigmine (45 mg) or placebo. All patients were taking their usual medication during the experiments. Main outcome measures: Rate–pressure product and oxygen uptake during exercise. Results: Pyridostigmine inhibited the submaximum chronotropic response (p  =  0.001), delaying the onset of myocardial ischaemia, which occurred at a similar rate–pressure product (mean (SE) placebo 20.55 (1.08) mm Hg × beats/min 103; pyridostigmine 19.75 (1.28) mm Hg × beats/min 103; p  =  0.27) but at a higher exercise intensity (oxygen consumption: placebo 18.6 (1.7) ml/kg/min; pyridostigmine 19.6 (1.8) ml/kg/min; p  =  0.03). Also, pyridostigmine increased peak oxygen consumption (placebo 23.6 (2) ml/kg/min; pyridostigmine 24.8 (2) ml/kg/min; p  =  0.01) and peak oxygen pulse (placebo 12.9 (1) ml/beat; pyridostigmine 13.6 (1) ml/beat; p  =  0.02). Conclusions: Pyridostigmine improved peak exercise tolerance and inhibited the chronotropic response to submaximum exercise, increasing the intensity at which myocardial ischaemia occurred. These results suggest that pyridostigmine can protect against exercise induced myocardial ischaemia. PMID:15367503

Differential patterns of replacement and reactive fibrosis in pressure and volume overload are related to the propensity for ischaemia and involve resistin

PubMed Central

Chemaly, Elie R; Kang, Soojeong; Zhang, Shihong; McCollum, LaTronya; Chen, Jiqiu; Bénard, Ludovic; Purushothaman, K-Raman; Hajjar, Roger J; Lebeche, Djamel

2013-01-01

Pathological left ventricle (LV) hypertrophy (LVH) results in reactive and replacement fibrosis. Volume overload LVH (VOH) is less profibrotic than pressure overload LVH (POH). Studies attribute subendocardial fibrosis in POH to ischaemia, and reduced fibrosis in VOH to collagen degradation favouring dilatation. However, the mechanical origin of the relative lack of fibrosis in VOH is incompletely understood. We hypothesized that reduced ischaemia propensity in VOH compared to POH accounted for the reduced replacement fibrosis, along with reduced reactive fibrosis. Rats with POH (ascending aortic banding) evolved into either compensated-concentric POH (POH-CLVH) or dilated cardiomyopathy (POH-DCM); they were compared to VOH (aorta–caval fistula). We quantified LV fibrosis, structural and haemodynamic factors of ischaemia propensity, and the activation of profibrotic pathways. Fibrosis in POH-DCM was severe, subendocardial and subepicardial, in contrast with subendocardial fibrosis in POH-CLVH and nearly no fibrosis in VOH. The propensity for ischaemia was more important in POH versus VOH, explaining different patterns of replacement fibrosis. LV collagen synthesis and maturation, and matrix metalloproteinase-2 expression, were more important in POH. The angiotensin II-transforming growth-factor β axis was enhanced in POH, and connective tissue growth factor (CTGF) was overexpressed in all types of LVH. LV resistin expression was markedly elevated in POH, mildly elevated in VOH and independently reflected chronic ischaemic injury after myocardial infarction. In vitro, resistin is induced by angiotensin II and induces CTGF in cardiomyocytes. Based on these findings, we conclude that a reduced ischaemia propensity and attenuated upstream reactive fibrotic pathways account for the attenuated fibrosis in VOH versus POH. PMID:24018949

Coronary responses to endothelin-1 and acetylcholine during partial coronary ischaemia and reperfusion in anaesthetized goats.

PubMed

Martínez, Maria Angeles; Fernández, Nuria; Monge, Luis; García-Villalón, Angel Luis; Sanz, Elena; Diéguez, Godofredo

2002-08-01

To examine coronary reactivity to acetylcholine and endothelin-1 (ET-1) during partial ischaemia and reperfusion, flow in the left circumflex coronary artery was measured electromagnetically, and coronary partial ischaemia was induced by stenosis of this artery in anaesthetized goats. In eight animals not treated with N(G)-nitro-l-arginine methyl ester (l-NAME), coronary stenosis reduced coronary flow by 45%, mean arterial pressure by 16% and coronary vascular conductance by 34%. During this ischaemia, coronary vasodilatation to acetylcholine (0.003-0.1 microg) and sodium nitroprusside (SNP; 1-10 microg) was markedly reduced, and coronary vasoconstriction to ET-1 (0.01-0.3 nmol) was attenuated. After 30 min of reperfusion, coronary flow, mean arterial pressure and coronary vascular conductance remained decreased, and the effects of acetylcholine, SNP and ET-1 were as in control animals. In six goats treated with N(G)-nitro-l-arginine methyl ester, coronary stenosis reduced coronary flow by 26% and coronary vascular conductance by 24%, but did not affect mean arterial pressure. During this ischaemia, coronary vasodilatation to acetylcholine and SNP was also markedly reduced, but vasoconstriction to ET-1 was unaffected. After 30 min of reperfusion, coronary flow and coronary vascular conductance remained decreased and mean arterial pressure was normal; in addition, the effects of acetylcholine were lower, those of SNP were similar and those of ET-1 were higher than in control animals. Therefore partial ischaemia reduces the coronary vasodilator reserve and blunts coronary vasoconstriction to ET-1, and reperfusion does not alter the endothelium-dependent and -independent coronary vasodilatation or vasoconstriction to ET-1.

Role of p97/Valosin-containing protein (VCP) and Jab1/CSN5 in testicular ischaemia-reperfusion injury.

PubMed

Cayli, Sevil; Ocakli, Seda; Senel, Ufuk; Eyerci, Nilnur; Delibasi, Tuncay

2016-02-01

The most significant complication of testicular ischaemia is loss of the testis, which may lead to infertility. Testicular ischaemia damages protein degradation pathways which, together with the overproduction of damaged proteins and consequent upregulation of ubiquitin-conjugated protein aggregates. Despite recent advances, the factors leading to impairment of spermatogenesis owing to testicular ischaemia remain poorly understood. This study was undertaken to gain insight into the cellular and molecular mechanism underlying torsion induced germ cell apoptosis. Male rats were subjected to 2 h torsion, and testes were examined at 2, 4, 12 and 24 h after torsion repair (reperfusion). Ischaemia-reperfusion (IR) of the testes resulted in apoptosis which was revealed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) technique. At 12 h after torsion repair germ cell loss reached peak, then decreased at 24 h repair. Western blotting showed that apoptotic proteins (active caspase 3, caspase 9 and Bax) gradually was upregulated at 12 h reperfusion, however anti-apoptotic protein (Bcl2) was downregulated in the relevant IR treatment. Furthermore, Jab1/CSN5 expression was gradually upregulated and p97/VCP expression was downregulated in IR injury according to western blotting and immunohistochemistry. To test further whether polyubiquitination was also involved in IR injury, the expression of polyubiquitinated proteins was examined, which showed that polyubiquitinated proteins were significantly increased in IR injury. These finding suggest that p97/VCP and Jab1/CSN5 provide a novel signaling pathway for testicular ischaemia and may play an important role in IR injury induced cell death in rat testis.

Protective Effect of Creatine Elevation against Ischaemia Reperfusion Injury Is Retained in the Presence of Co-Morbidities and during Cardioplegia.

PubMed

Whittington, Hannah J; McAndrew, Debra J; Cross, Rebecca L; Neubauer, Stefan; Lygate, Craig A

2016-01-01

Ischaemic heart disease is most prevalent in the ageing population and often exists with other comorbidities; however the majority of laboratory research uses young, healthy animal models. Several recent workshops and focus meetings have highlighted the importance of using clinically relevant models to help aid translation to realistic patient populations. We have previously shown that mice over-expressing the creatine transporter (CrT-OE) have elevated intracellular creatine levels and are protected against ischaemia-reperfusion injury. Here we test whether elevating intracellular creatine levels retains a cardioprotective effect in the presence of common comorbidities and whether it is additive to protection afforded by hypothermic cardioplegia. CrT-OE mice and wild-type controls were subjected to transverse aortic constriction for two weeks to induce compensated left ventricular hypertrophy (LVH). Hearts were retrogradely perfused in Langendorff mode for 15 minutes, followed by 20 minutes ischaemia and 30 minutes reperfusion. CrT-OE hearts exhibited significantly improved functional recovery (Rate pressure product) during reperfusion compared to WT littermates (76% of baseline vs. 59%, respectively, P = 0.02). Aged CrT-OE mouse hearts (78±5 weeks) also had enhanced recovery following 15 minutes ischaemia (104% of baseline vs. 67%, P = 0.0007). The cardioprotective effect of hypothermic high K+ cardioplegic arrest, as used during cardiac surgery and donor heart transplant, was further enhanced in prolonged ischaemia (90 minutes) in CrT-OE Langendorff perfused mouse hearts (76% of baseline vs. 55% of baseline as seen in WT hearts, P = 0.02). These observations in clinically relevant models further support the development of modulators of intracellular creatine content as a translatable strategy for cardiac protection against ischaemia-reperfusion injury.

[Management of coronary artery disease in diabetic patients with lower limb critical ischaemia: assessment of operational risk, drug therapy and indications for interventions].

PubMed

Dedov, I I; Kalashnikov, V Iu; Terekhin, S A; Melkozerov, K V

2012-01-01

Despite obvious progress in management of diabetes mellitus, the DM-related complications rate remains inadmissibly high. Macroangiopathy is known to rank first amongst complications of diabetes mellitus, and coronary artery disease remains to be the major cause of death. Analysed herein are peculiarities of the clinical course in diabetic patients presenting with coronary artery disease and lower limb critical ischaemia, followed by discussing the issues concerning drug therapy, preoperative examination, and methods of diagnosis in this cohort of patients prior to vascular operations, assessment of the preoperative risk, indications for coronarography and myocardial revascularization. Also presented are the results of the main clinical trials dedicated to preoperative myocardial revascularization, including those in diabetic patients with limb critical ischaemia, and finally highlighting current importance of optimizing approaches to managing and working out algorithms of treatment policy for diabetic patients with a combination of coronary artery disease, diabetes mellitus, and critical limb ischaemia.

Effect of the non-NMDA receptor antagonist GYKI 52466 on the microdialysate and tissue concentrations of amino acids following transient forebrain ischaemia.

PubMed

Arvin, B; Lekieffre, D; Graham, J L; Moncada, C; Chapman, A G; Meldrum, B S

1994-04-01

The effect of the non-N-methyl-D-aspartate (non-NMDA) receptor antagonist 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI 52466) on ischaemia-induced changes in the microdialysate and tissue concentrations of glutamate, aspartate, and gamma-aminobutyric acid (GABA) was studied in rats. Twenty minutes of four-vessel occlusion resulted in a transient increase in microdialysate levels of glutamate, aspartate, and GABA in striatum, cortex, and hippocampus. Administration of GYKI 52466 (10 mg/kg bolus + 10 mg/kg/60 min intravenously starting 20 min before onset of ischaemia) inhibited ischaemia-induced increases in microdialysate glutamate and GABA in striatum without affecting the increases in hippocampus or cortex. Twenty minutes of four-vessel occlusion resulted in immediate small decreases and larger delayed (72 h) decreases in tissue levels of glutamate and aspartate. Transient increases in tissue levels of GABA were shown in all three structures at the end of the ischaemic period. At 72 h, after the ischaemic period, significantly reduced GABA levels were observed in striatum and hippocampus. GYKI 52466, given under identical conditions as above, augmented the ischaemia-induced decrease in striatal tissue levels of glutamate and aspartate, without significantly affecting the decreases in hippocampus and cortex. Twenty minutes of ischaemia resulted in a large increase in microdialysate dopamine in striatum. GYKI 52466 failed to inhibit this increase. Kainic acid (500 microM infused through the probe for 20 min) caused increases in microdialysate glutamate and aspartate in the striatum. GYKI 52466 (10 mg/kg bolus + 10 mg/kg/60 min) completely inhibited the kainic acid-induced glutamate release. In conclusion, the action of the non-NMDA antagonist, GYKI 52466, in the striatum is different from that in the cortex and hippocampus. The inhibition by GYKI 52466 of ischaemia-induced and kainate-induced increases in microdialysate glutamate concentration in the striatum may be related to the neuroprotection provided by GYKI 52466 in this region.

A positive allosteric modulator of α7 nAChRs augments neuroprotective effects of endogenous nicotinic agonists in cerebral ischaemia

PubMed Central

Kalappa, Bopanna I; Sun, Fen; Johnson, Stephen R; Jin, Kunlin; Uteshev, Victor V

2013-01-01

Background and Purpose Activation of α7 nicotinic acetylcholine receptors (nAChRs) can be neuroprotective. However, endogenous choline and ACh have not been regarded as potent neuroprotective agents because physiological levels of choline/ACh do not produce neuroprotective levels of α7 activation. This limitation may be overcome by the use of type-II positive allosteric modulators (PAMs-II) of α7 nAChRs, such as 1-(5-chloro-2,4-dimethoxyphenyl)-3-(5-methylisoxazol-3-yl)-urea (PNU-120596). This proof-of-concept study presents a novel neuroprotective paradigm that converts endogenous choline/ACh into potent neuroprotective agents in cerebral ischaemia by inhibiting α7 nAChR desensitization using PNU-120596. Experimental Approach An electrophysiological ex vivo cell injury assay (to quantify the susceptibility of hippocampal neurons to acute injury by complete oxygen and glucose deprivation; COGD) and an in vivo middle cerebral artery occlusion model of ischaemia were used in rats. Key Results Choline (20–200 μM) in the presence, but not absence of 1 μM PNU-120596 significantly delayed anoxic depolarization/injury of hippocampal CA1 pyramidal neurons, but not CA1 stratum radiatum interneurons, subjected to COGD in acute hippocampal slices and these effects were blocked by 20 nM methyllycaconitine, a selective α7 antagonist, thus, activation of α7 nAChRs was required. PNU-120596 alone was ineffective ex vivo. In in vivo experiments, both pre- and post-ischaemia treatments with PNU-120596 (30 mg·kg−1, s.c. and 1 mg·kg−1, i.v., respectively) significantly reduced the cortical/subcortical infarct volume caused by transient focal cerebral ischaemia. PNU-120596 (1 mg·kg−1, i.v., 30 min post-ischaemia) remained neuroprotective in rats subjected to a choline-deficient diet for 14 days prior to experiments. Conclusions and Implications PNU-120596 and possibly other PAMs-II significantly improved neuronal survival in cerebral ischaemia by augmenting neuroprotective effects of endogenous choline/ACh. PMID:23713819

Dobutamine stress magnetic resonance imaging suffices for the demonstration of myocardial ischaemia and viability

PubMed Central

Lamers, F.P.L.; van Dijkman, P.R.M.; Kuijpers, Th.J.A.; van Herpen, G.

2003-01-01

We report three patients in whom dobutamine stress magnetic imaging (DS-MRI) was essential in assessing myocardial ischaemia. Two patients were referred to the cardiologist because of chest pain. Patient A had typical exertional angina and a normal resting electrocardiogram (ECG). Patient B had typical exercise-induced angina and had recently experienced an attack of severe chest pain at rest for 15 minutes. The ECG showed a complete left bundle branch block (LBBB). Patient C was referred for heart failure of unknown origin. There were no symptoms of chest pain during rest or exercise. Echocardiography in this patient demonstrated global left ventricular (LV) dilatation, systolic dysfunction and a small dyskinetic segment in the inferior wall. In all these patients exercise stress testing had failed to demonstrate myocardial ischaemia. Patients A and C produced normal findings whereas in patient B the abnormal repolarisation due to pre-existent LBBB precluded a diagnosis of ischaemia. Breath-hold DS-MRI was performed to study LV wall motion and wall thickening at rest through increasing doses of dobutamine. A test was considered positive for myocardial ischaemia if wall motion abnormalities developed at high-dose levels of the drug (20 μg/kg/min or more with a maximum of 40 μg/kg/min) in previously normal vascular territories or worsened in a segment that was normal at baseline. Recovery of wall thickening in a previously hypokinetic or akinetic segment at a low dose of dobutamine (5-10 μg/kg/min) was taken as proof of viability. Patients A and B developed hypokinesia progressing into akinesia at high-dose dobutamine in the anteroseptal area of the LV indicative of ischaemia. These findings were corroborated by coronary angiography demonstrating severe coronary artery disease which led to coronary artery bypass grafting (CABG) in patient A and balloon angioplasty in patient B. In patient C global recovery of LV contractions during low-dose dobutamine was followed by hypokinesia in the inferoseptal area during high-dose dobutamine. This biphasic response indicates myocardial viability as well as ischaemia. CABG was carried out because of multiple stenoses in the left coronary artery. Post-operatively LV function normalised. DS-MRI is a valuable method for detecting myocardial ischaemia and viability in patients with suspected coronary artery, and can be applied in every hospital with MRI equipment at its disposal. ImagesFigure 1Figure 2 PMID:25696185

Undiscovered role of endogenous thromboxane A2 in activation of cardiac sympathetic afferents during ischaemia

PubMed Central

Fu, Liang-Wu; Guo, Zhi-Ling; Longhurst, John C

2008-01-01

Myocardial ischaemia activates blood platelets, which in turn stimulate cardiac sympathetic afferents, leading to chest pain and sympathoexcitatory reflex cardiovascular responses. Previous studies have shown that activated platelets stimulate ischaemically sensitive cardiac sympathetic afferents, and that thromboxane A2 (TxA2) is one of the mediators released from activated platelets during myocardial ischaemia. The present study tested the hypothesis that endogenous TxA2 stimulates cardiac afferents during ischaemia through direct activation of TxA2 (TP) receptors coupled with the phospholipase C–protein kinase C (PLC–PKC) cellular pathway. Nerve activity of single unit cardiac sympathetic afferents was recorded from the left sympathetic chain or rami communicantes (T2–T5) in anaesthetized cats. Single fields of 39 afferents (conduction velocity = 0.27–3.65 m s−1) were identified in the left or right ventricle initially with mechanical stimulation and confirmed with a stimulating electrode. Five minutes of myocardial ischaemia stimulated all 39 cardiac afferents (8 Aδ-, 31 C-fibres) and the responses of these 39 afferents to chemical stimuli were further studied in the following four protocols. In the first protocol, 2.5, 5 and 10 μg of the TxA2 mimetic, U46619, injected into the left atrium (LA), stimulated seven ischaemically sensitive cardiac afferents in a dose-dependent manner. Second, BM13,177, a selective TxA2 receptor antagonist, abolished the responses of six afferents to 5 μg of U46619 injected into the left atrium and attenuated the ischaemia-related increase in activity of seven other afferents by 44%. In contrast, cardiac afferents, in the absence of TP receptor blockade responded consistently to repeated administration of U46619 (n = 6) and to recurrent myocardial ischaemia (n = 7). In the fourth protocol, administration of PKC-(19–36), a selective PKC inhibitor, attenuated the responses of six other cardiac afferents to U46619 by 38%. Finally, using an immunohistochemical staining approach, we observed that TP receptors were expressed in cardiac sensory neurons in thoracic dorsal root ganglia. Taken together, these data indicate that endogenous TxA2 contributes to the activation of cardiac afferents during myocardial ischaemia through direct stimulation of TP receptors probably located in the cardiac sensory nervous system and that the stimulating effect of TxA2 on cardiac afferents is dependent, at least in part, upon the PLC–PKC cellular pathway. PMID:18483073

Effects of ischaemia upon reflex electromyographic responses evoked by stretch and vibration in human wrist flexor muscles.

PubMed Central

Cody, F W; Goodwin, C N; Richardson, H C

1987-01-01

1. The reflex electromyographic responses evoked in a wrist flexor muscle, flexor carpi radialis (f.c.r.), by forcible extension of the wrist ('stretch') and by vibration of the flexor tendon have been studied in normal subjects. Reflexes were elicited during the maintenance of a low level of voluntary flexor contraction (5% maximum). Stretch regularly produced a relatively prolonged (ca. 100 ms duration) increase in e.m.g. activity which was usually divisible into short-latency (ca. 25 ms, M1) and long-latency (ca. 50 ms, M2) peaks. Vibration produced a single, phasic peak, at short latency, with no sign of an accompanying long-latency wave comparable to the M2 stretch response. 2. Ischaemia was induced by inflation of a blood-pressure cuff around the upper arm and its effects upon the reflex patterns were studied. During ischaemia M1 stretch responses showed a more rapid and pronounced decline than did M2 responses and were abolished before voluntary power was appreciably affected. Vibration-evoked short-latency peaks changed in an essentially parallel manner to M1 stretch reflexes. During recovery from ischaemia M2 reflexes were restored before short-latency responses. 3. The patterns of reflex reductions in e.m.g. upon withdrawal of stimulation were also studied. Such troughs in activity, under non-ischaemic conditions, regularly commenced at short latency and were of relatively small amplitude. The records of several of the subjects, and particularly ones obtained during ischaemia, suggested that release of stretch (with concomitant stretch of antagonists) could elicit an additive, long-latency decline in e.m.g. The existence of any such separate, delayed component was never observed upon termination of vibration. 4. Measurements of changes in the latencies and durations of reflex components, accompanying the progression of ischaemia, indicated that depression of early reflex activity resulted in part from increases in the latencies of these initial peaks but predominantly reflected simultaneous and separate reductions in their amplitudes. 5. The generation of short-latency reflexes by stretch and vibration, both of which stimuli powerfully excite muscle spindle primary endings, and the marked susceptibility of these responses to ischaemia supports their being mediated by group Ia afferents. The contrasting behaviour of M2 stretch responses, both regarding their absence with vibration and their resistance to ischaemia, suggests that they depend crucially upon a separate group of reflex afferents.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3443959

Post-operative monitoring of free muscle transfers by Laser Doppler Imaging: A prospective study.

PubMed

Tschumi, Christian; Seyed Jafari, S Morteza; Rothenberger, Jens; Van de Ville, Dimitri; Keel, Marius; Krause, Fabian; Shafighi, Maziar

2015-10-01

Despite different existing methods, monitoring of free muscle transfer is still challenging. In the current study we evaluated our clinical setting regarding monitoring of such tissues, using a recent microcirculation-imaging camera (EasyLDI) as an additional tool for detection of perfusion incompetency. This study was performed on seven patients with soft tissue defect, who underwent reconstruction with free gracilis muscle. Beside standard monitoring protocol (clinical assessment, temperature strips, and surface Doppler), hourly EasyLDI monitoring was performed for 48 hours. Thereby a baseline value (raised flap but connected to its vascular bundle) and an ischaemia perfusion value (completely resected flap) were measured at the same point. The mean age of the patients, mean baseline value, ischaemia value perfusion were 48.00 ± 13.42 years, 49.31 ± 17.33 arbitrary perfusion units (APU), 9.87 ± 4.22 APU, respectively. The LDI measured values in six free muscle transfers were compatible with hourly standard monitoring protocol, and normalized LDI values significantly increased during time (P < 0.001, r = 0.412). One of the flaps required a return to theatre 17 hours after the operation, where an unsalvageable flap loss was detected. All normalized LDI values of this flap were under the ischaemia perfusion level and the trend was significantly descending during time (P < 0.001, r = -0.870). Due to the capability of early detection of perfusion incompetency, LDI may be recommended as an additional post-operative monitoring device for free muscle flaps, for early detection of suspected failing flaps and for validation of other methods. © 2015 Wiley Periodicals, Inc.

Ginkgolide B preconditioning protects neurons against ischaemia-induced apoptosis.

PubMed

Wu, Xiaomei; Qian, Zhongming; Ke, Ya; Du, Fang; Zhu, Li

2009-01-01

Ischaemic preconditioning (IP) has been reported to protect the brain against subsequent lethal ischaemia, but it has not been used clinically to prevent ischaemic injury because of safety concerns. The aim of the present study was to see whether Ginkgolide B (GB) is capable of preconditioning as IP to protect neurons against ischaemic injury; if so, which mechanism is involved. Cultured mouse cortical neurons at day 8 were pre-treated with GB (120 micromol/l) for 24 hrs or exposed to short-term ischaemia (1 hr) followed by 24-hr normal culture to induce IP before being treated with severe ischaemia (5 hrs). GB and IP significantly increased cell viability, expression of hypoxia-inducible factor-1 alpha (HIF-1alpha), erythropoietin (EPO), phosphorylated Bad at serine 136 (136p-Bad) and phosphorylated glycogen synthase kinase- 3beta at serine 9 (p-GSK-3beta), and decreased the percentage of apoptotic cells and the level of active caspase-3 in severely ischaemic neurons. Moreover, LY294002 that is a specific inhibitor of phosphatidylinositol 3-kinase (PI3K) significantly reduced the enhanced expression of HIF-1alpha, EPO and 136p-Bad induced by GB and IP. These results suggest that GB, like IP in neurons, is capable of preconditioning against ischaemia-induced apoptosis, the mechanism of which may involve the PI3K signalling pathway.

Ginkgolide B preconditioning protects neurons against ischaemia-induced apoptosis

PubMed Central

Wu, Xiaomei; Qian, Zhongming; Ke, Ya; Du, Fang; Zhu, Li

2009-01-01

Ischaemic preconditioning (IP) has been reported to protect the brain against subsequent lethal ischaemia, but it has not been used clinically to prevent ischaemic injury because of safety concerns. The aim of the present study was to see whether Ginkgolide B (GB) is capable of preconditioning as IP to protect neurons against ischaemic injury; if so, which mechanism is involved. Cultured mouse cortical neurons at day 8 were pre-treated with GB (120 μmol/l) for 24 hrs or exposed to short-term ischaemia (1 hr) followed by 24-hr normal culture to induce IP before being treated with severe ischaemia (5 hrs). GB and IP significantly increased cell viability, expression of hypoxia-inducible factor-1 alpha (HIF-1α), erythropoietin (EPO), phosphorylated Bad at serine 136 (136p-Bad) and phosphorylated glycogen synthase kinase- 3β at serine 9 (p-GSK-3β), and decreased the percentage of apoptotic cells and the level of active caspase-3 in severely ischaemic neurons. Moreover, LY294002 that is a specific inhibitor of phosphatidylinositol 3-kinase (PI3K) significantly reduced the enhanced expression of HIF-1α, EPO and 136p-Bad induced by GB and IP. These results suggest that GB, like IP in neurons, is capable of preconditioning against ischaemia-induced apoptosis, the mechanism of which may involve the PI3K signalling pathway. PMID:19602048

"Metabolically healthy" obesity: Prevalence, clinical features and association with myocardial ischaemia.

PubMed

De Lorenzo, Andrea; Glerian, Leticia; Amaral, Ana Carolina; Reis, Thiago B; Lima, Ronaldo S L

To evaluate the prevalence of the "metabolically healthy" (MH) or "metabolically unhealthy" (MU) obesity phenotypes and their association with cardiorespiratory fitness and inducible myocardial ischaemia. Individuals without known coronary artery disease undergoing myocardial perfusion single-photon emission computed tomography (MPS) were studied. Those without dyslipidemia, hypertension, or diabetes were considered MH, and when ≥1 of these was present, MU status was considered present. Summed stress and difference perfusion scores (SSS and SDS, respectively) were calculated; a SDS >1 defined ischaemic MPS. MH patients were 35.0% of the nonobese population and 23.5% of the obese (p<0.001). The prevalence of ischaemia was not significantly different between MH patients with obesity or MH patients without obesity (10.9% vs 9.1%, p=0.3), except for patients with body mass index ≥40kg/m 2 (21.9%). MH obese patients were less frequently able to exercise and had lower exercise capacity than the nonobese patients. The prevalence of myocardial ischaemia was not significantly different between MH obese or nonobese individuals, supporting the concept of the "metabolically healthy obesity". However, there are other factors involved, such as the ability to exercise, that influence the risk of myocardial ischaemia, limiting the "safety" of that obesity phenotype. Copyright © 2016 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Treatment of Popliteal Aneurysm by Open and Endovascular Surgery: A Contemporary Study of 592 Procedures in Sweden.

PubMed

Cervin, A; Tjärnström, J; Ravn, H; Acosta, S; Hultgren, R; Welander, M; Björck, M

2015-09-01

Popliteal aneurysm (PA) is traditionally treated by open repair (OR). Endovascular repair (ER) has become more common. The aim was to describe time trends and compare results (OR/ER). The Swedish vascular registry, Swedvasc, has a specific PA module. Data were collected (2008-2012) and supplemented with a specific protocol (response rate 99.1%). Data were compared with previously published data (1994-2002) from the same database. The number of operations for PA was 15.7/million person-years (8.3 during 1994-2001). Of 592 interventions for PA (499 patients), 174 (29.4%) were treated for acute ischaemia, 13 (2.2%) for rupture, 105 (17.7%) for other symptoms, and 300 (50.7%) were asymptomatic (31.5% were treated for acute ischaemia, 1994-2002, p = .58). There were no differences in background characteristics between OR and ER in the acute ischaemia group. The symptomatic and asymptomatic groups treated with ER were older (p = .006, p < .001). ER increased 3.6 fold (4.7% 1994-2002, 16.7% 2008-2012, p = .0001). Of those treated for acute ischaemia, a stent graft was used in 27 (16.4%). Secondary patency after ER was 70.4% at 30 days and 47.6% at 1 year, versus 93.1% and 86.8% after OR (p = .001, <.001). The amputation rate at 30 days was 14.8% after ER, 3.7% after OR (p = .022), and 17.4% and 6.8% at 1 year (p = .098). A stent graft was used in 18.3% for asymptomatic PA. Secondary patency after ER was 94.5% at 30 days and 83.7% at 1 year, compared with 98.8% and 93.5% after OR (p = .043 and 0.026). OR was performed with vein graft in 87.6% (395/451), with better primary and secondary patency at 1 year than prosthetic grafts (p = .002 and <.001), and with a posterior approach in 20.8% (121/581). The number of operations for PA doubled while the indications remained similar. ER patency was inferior to OR, especially after treatment for acute ischaemia, and the amputation risk tended to be higher, despite similar pre-operative characteristics. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Evolving changes in fetal heart rate variability and brain injury after hypoxia-ischaemia in preterm fetal sheep.

PubMed

Yamaguchi, Kyohei; Lear, Christopher A; Beacom, Michael J; Ikeda, Tomoaki; Gunn, Alistair J; Bennet, Laura

2018-01-08

Fetal heart rate variability is a critical index of fetal wellbeing. Suppression of heart rate variability may provide prognostic information on the risk of hypoxic-ischaemic brain injury after birth. In the present study, we report the evolution of fetal heart rate variability after both mild and severe hypoxia-ischaemia. Both mild and severe hypoxia-ischaemia were associated with an initial, brief suppression of multiple measures of heart rate variability. This was followed by normal or increased levels of heart rate variability during the latent phase of injury. Severe hypoxia-ischaemia was subsequently associated with the prolonged suppression of measures of heart rate variability during the secondary phase of injury, which is the period of time when brain injury is no longer treatable. These findings suggest that a biphasic pattern of heart rate variability may be an early marker of brain injury when treatment or intervention is probably most effective. Hypoxia-ischaemia (HI) is a major contributor to preterm brain injury, although there are currently no reliable biomarkers for identifying infants who are at risk. We tested the hypothesis that fetal heart rate (FHR) and FHR variability (FHRV) would identify evolving brain injury after HI. Fetal sheep at 0.7 of gestation were subjected to either 15 (n = 10) or 25 min (n = 17) of complete umbilical cord occlusion or sham occlusion (n = 12). FHR and four measures of FHRV [short-term variation, long-term variation, standard deviation of normal to normal R-R intervals (SDNN), root mean square of successive differences) were assessed until 72 h after HI. All measures of FHRV were suppressed for the first 3-4 h in the 15 min group and 1-2 h in the 25 min group. Measures of FHRV recovered to control levels by 4 h in the 15 min group, whereas the 25 min group showed tachycardia and an increase in short-term variation and SDNN from 4 to 6 h after occlusion. The measures of FHRV then progressively declined in the 25 min group and became profoundly suppressed from 18 to 48 h. A partial recovery of FHRV measures towards control levels was observed in the 25 min group from 49 to 72 h. These findings illustrate the complex regulation of FHRV after both mild and severe HI and suggest that the longitudinal analysis of FHR and FHRV after HI may be able to help determine the timing and severity of preterm HI. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

The influence of intravenous laser irradiation of blood on some metabolic and functional parameters in intact rabbits and experimental cerebral ischaemia

NASA Astrophysics Data System (ADS)

Nechipurenko, N.; Vasilevskaya, L.; Musienko, J.; Maslova, G.

2007-07-01

It has been studied the intravenous laser irradiation of blood (ILIB) influence with helium-neon laser (HNL) of 630 nm wavelength on some of lipid peroxidation (LPO) and antioxidant system (AOS) findings, aside-base status (ABS) and blood oxygen transport (BOT), state of dermal microhaemodynamics (MGD) in the intact rabbits and after modeling of local ischemia of brain (LIB). Depending on conditions of organism functioning (norm or brain ischaemia) ILIB has resulted in stimulating or normalizing effects on the whole metabolic and microhaemocirculation processes which had been studied during our investigation. It is discussed the mechanisms of pathogenetic directivity of ILIB influence in cerebral ischaemia

Curcumin modulates free radical quenching in myocardial ischaemia in rats.

PubMed

Manikandan, Panchatcharam; Sumitra, Miriyala; Aishwarya, Srinivasan; Manohar, Bhakthavatsalam Murali; Lokanadam, Beema; Puvanakrishnan, Rengarajulu

2004-10-01

This study was designed to investigate the protective effect of curcumin (CUR) against isoprenaline induced myocardial ischaemia in rat myocardium. The effect of single oral dose of curcumin (15 mg kg(-1)), administered 30 min before and/or after the onset of ischaemia, was investigated by assessing oxidative stress related biochemical parameters in rat myocardium. Curcumin pre and post-treatment (PPT) was shown to decrease the levels of xanthine oxidase, superoxide anion, lipid peroxides (LPs) and myeloperoxidase while the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) activities were significantly increased after curcumin PPT. Histopathological and transmission electron microscopical studies also confirmed the severe myocardial damage occurring as a consequence of isoprenaline induced ischaemia and they also showed the significant improvement effected by curcumin PPT. These findings provided evidence that curcumin was found to protect rat myocardium against ischaemic insult and the protective effect could be attributed to its antioxidant properties as well as its inhibitory effects on xanthine dehydrogenase/xanthine oxidase (XD/XO) conversion and resultant superoxide anion production.

Involvement of protein kinase B and mitogen-activated protein kinases in experimental normothermic liver ischaemia-reperfusion injury.

PubMed

Cursio, R; Filippa, N; Miele, C; Van Obberghen, E; Gugenheim, J

2006-06-01

This study evaluated the role of protein kinase B (PKB), phosphatidylinositol 3-kinase (PI3-K), Bcl-2-associated death protein (BAD) and mitogen-activated protein kinases (MAPKs) in normothermic ischaemia-reperfusion (IR)-induced apoptosis in rat liver. Rats were divided into two groups that received either phosphate-buffered saline (control) or the caspase inhibitor Z-Asp-2,6-dichorobenzoyloxymethylketone (Z-Asp-cmk), injected intravenously 2 min before the induction of 120 min of normothermic liver ischaemia. Liver apoptosis was assessed by the terminal deoxyribonucleotidyltransferase-mediated dUTP nick end labelling (TUNEL) method. PI3-K, PKB, BAD and MAPK activities were measured in ischaemic and non-ischaemic lobes at various times after reperfusion. The number of TUNEL-positive cells was significantly decreased after pretreatment with Z-Asp-cmk. In controls, PI3-K and PKB activities and BAD phosphorylation were inhibited in ischaemic liver lobes. The MAPKs (extracellular signal-regulated kinases, c-Jun N-terminal kinase and p38) showed different patterns of activation during IR. PKB activity was not modified by pretreatment with Z-Asp-cmk. Induction of apoptosis during IR liver injury might be triggered by inactivation of the antiapoptotic PI3-K-PKB pathway and activation of the proapoptotic MAPKs. Copyright (c) 2006 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Self-reported symptoms and risk factors for digital ischaemia among international world-class beach volleyball players.

PubMed

Van De Pol, Daan; Alaeikhanehshir, Sena; Maas, Mario; Kuijer, P Paul F M

2016-01-01

The prevalence of ischaemia-related symptoms is remarkably high among elite indoor volleyball players. Since the exposure to sport-specific demands may be higher in beach volleyball compared to indoor volleyball, the aim of this study was to assess the prevalence of ischaemia-related symptoms and associated risk factors among world-class beach volleyball players. Therefore, a questionnaire survey was performed among beach volleyball players active during the 2013 Grand Slam Beach Volleyball in the Netherlands. In total, 60 of the 128 beach volleyball players (47%) participated: 26 males and 34 females from 17 countries. The self-reported prevalence of cold or blue or pale digits in the dominant hand during or immediately after practice or competition was 38% (n = 23). Two risk factors were independently associated with symptoms of blue or pale digits: more than 14 years playing volleyball (odds ratio (OR) 4.42, 90% confidence interval (90% CI) 1.30-15.07) and sex (female) (OR 4.62, 90% CI 1.15-18.57). In conclusion, the prevalence of symptoms associated with digital ischaemia is high among international world-class beach volleyball players. Female sex and the length of the volleyball career were independently associated with an increased risk of ischaemia-related symptoms. The high prevalence of these seemingly innocuous symptoms and possible associated risk factors warrant regular monitoring since early detection can potentially prevent thromboembolic complications and irreversible tissue damage.

Aniracetam, a pyrrolidinone-type cognition enhancer, attenuates the hydroxyl free radical formation in the brain of mice with brain ischaemia.

PubMed

Himori, N; Suzuki, T; Ueno, K

1995-03-01

We demonstrate here that aniracetam has the ability to block the formation of cytotoxic hydroxyl radicals (.OH) during ischaemia-reperfusion of mouse brain. The fact that brain ischeamia for 40 min followed by reperfusion increased .OH was evidenced by detection of a peaked increase at 20 min after an ischaemic insult in the formation of 2,3-dihydroxybenzoate (DHBA) from salicylate in cerebroventricular perfusate, a means of monitoring .OH formation. A clearcut increase in dopamine was also observed during and after brain ischaemia. The ischaemia-reperfusion mice given aniracetam at an intraperitoneal dose of 30 or 100 mg kg-1 showed a smaller increase in the formation of DHBA than those given the vehicle only. Aniracetam at 100 mg kg-1 significantly suppressed the formation of DHBA by approximately 80%, becoming evident at 20 min after reperfusion and thereafter. Protection against death in mice insulted with a 40-min brain ischaemia (3/13 vs 13/25) was observed following 100 mg kg-1 aniracetam. The increase in the dopamine levels was substantially reduced following aniracetam treatment and the reduction became significant at 20 min after reperfusion and thereafter in parallel with attenuation by aniracetam of DHBA formation. This finding suggests that the inhibitory activity of aniracetam in attenuating the hydroxyl free-radical formation in ischaemic mice is probably due, at least in part, to its palliative action on the dopaminergic neurons.

Changes in extracellular pH and myocardial ischaemia alter the cardiac effects of diadenosine tetraphosphate and pentaphosphate

PubMed Central

Stavrou, Brigitte M; Beck, Caroline; Flores, Nicholas A

2001-01-01

The structural conformation of diadenosine tetraphosphate (Ap4A) and pentaphosphate (Ap5A) has been reported to alter as pH is reduced. As such, it is possible that the cardiac effects of Ap4A and Ap5A vary during acidosis and myocardial ischaemia due to changes in ligand structure, receptor proteins or intracellular signalling. We investigated whether the cardiac electrophysiological and coronary vasomotor effects of Ap4A and Ap5A are preserved under conditions of extracellular acidosis (pH 6.5) and alkalosis (pH 8.5) and whether Ap4A has any electrophysiological or antiarrhythmic effects during ischaemia. Transmembrane right ventricular action potentials, refractory periods and coronary perfusion pressure were recorded from isolated, Langendorff-perfused guinea-pig hearts under constant flow conditions. The effects of 1 nM and 1 μM Ap4A and Ap5A were studied at pH 7.4, 6.5 and 8.5. The effects of 1 μM Ap4A were studied during global low-flow ischaemia and reperfusion. At pH 7.4, Ap4A and Ap5A increased action potential duration (APD95) and refractory period (RP) and reduced coronary perfusion pressure. The electrophysiological effects were absent at pH 6.5 while the reductions in perfusion pressure were attenuated. At pH 8.5, Ap4A increased RP but the effects of Ap4A and Ap5A on perfusion pressure were attenuated. During ischaemia, Ap4A had no antiarrhythmic or electrophysiological effects. These data demonstrate the importance of extracellular pH in influencing the effects of Ap4A and Ap5A on the heart and indicate that any potentially cardioprotective effects of these compounds during normal perfusion at physiological pH are absent during ischaemia. PMID:11588119

Acidic pre-conditioning suppresses apoptosis and increases expression of Bcl-xL in coronary endothelial cells under simulated ischaemia.

PubMed

Kumar, S; Reusch, H P; Ladilov, Y

2008-01-01

Ischaemic pre-conditioning has a powerful protective potential against ischaemia-induced cell death, and acidosis is an important feature of ischaemia and can lead to apoptosis. Here we tested whether pre-conditioning with acidosis, that is, acidic pre-conditioning (APC), may protect coronary endothelial cells (EC) against apoptosis induced by simulated ischaemia. For pre-conditioning, EC were exposed fo 40 min. to acidosis (pH 6.4) followed by a 14-hrs recovery period (pH 7.4) and finally treated for 2 hrs with simulated ischaemia (glucose-free anoxia at pH 6.4). Cells undergoing apoptosis were visualized by chromatin staining or by determination of caspase-3 activity Simulated ischaemia in untreated EC increased caspase-3 activity and the number of apoptotic cell (31.3 +/- 1.3%versus 3.9 +/- 0.6% in control). APC significantly reduced the rate of apoptosis (14.2 +/- 1.3%) and caspase-3 activity. Western blot analysis exploring the under lying mechanism leading to this protection revealed suppression of the endoplasmic reticulum- (reduced cleavage of caspase-12) and mitochondria-mediated (reduced cytochrome C release) pathways of apoptosis. These effects were associated with an over-expression of the anti-apoptotic protein Bcl-xL 14 hrs after APC, whereas no effect on the expression of Bcl-2, Bax, Bak, procaspase-12, reticulum-localized chaperones (GRP78, calreticulin), HSP70, HSP32 and HSP27 could be detected. Knock-down of Bcl-xL by siRNA-treatment prevented the protective effect of APC. In conclusion, short acidic pre-treatment can protect EC against ischaemic apoptosis. The mechanism of this protection consists of suppression of the endoplasmic reticulum- and mitochondria-mediated pathways. Over-expression of the anti apoptotic protein Bcl-xL is responsible for the increased resistance to apoptosis during ischaemic insult.

Antiplatelet therapy for aneurysmal subarachnoid haemorrhage.

PubMed

Dorhout Mees, S M; van den Bergh, W M; Algra, A; Rinkel, G J E

2007-10-17

Secondary ischaemia is a frequent cause of poor outcome in patients with aneurysmal subarachnoid haemorrhage (SAH). Besides vasospasm, platelet aggregation seems to play a role in the pathogenesis of secondary ischaemia. Experimental studies have suggested that antiplatelet agents can prevent secondary ischaemia. To determine whether antiplatelet agents change outcome in patients with aneurysmal SAH. We searched the Cochrane Stroke Group Trials Register (last searched August 2006), MEDLINE (1966 to August 2006) and EMBASE databases (1980 to August 2006). We also searched reference lists of identified trials. All randomised controlled trials (RCTs) comparing any antiplatelet agent with control in patients with aneurysmal SAH. Two review authors independently extracted the data and assessed trial quality. Relative risks (RR) were calculated with regard to poor outcome, case fatality, secondary ischaemia, haemorrhagic intracranial complications and aneurysmal rebleeding according to the intention-to-treat principle. In case of a statistically significant primary analysis, a worst case analysis was performed. Seven RCTs were included in the review, totalling 1385 patients. Four of these trials met the criteria for good quality studies. For any antiplatelet agent there were reductions of a poor outcome (RR 0.79, 95% confidence interval (CI) 0.62 to 1.01) and secondary brain ischaemia (RR 0.79, 95% CI 0.56 to 1.22) and more intracranial haemorrhagic complications (RR 1.36, 95% CI 0.59 to 3.12), but none of these differences were statistically significant. There was no effect on case fatality (RR 1.01, 95% CI 0.74 to 1.37) or aneurysmal rebleeding (RR 0.98, 95% CI 0.78 to 1.38). For individual antiplatelet agents, only ticlopidine was associated with statistically significant fewer occurrences of a poor outcome (RR 0.37, 95% CI 95% CI 0.14 to 0.98) but this estimate was based on only one small RCT. This review shows a trend towards better outcome in patients treated with antiplatelet agents, possibly due to a reduction in secondary ischaemia. However, results were not statistically significant, thus no definite conclusions can be drawn. Also, antiplatelet agents could increase the risk of haemorrhagic complications. On the basis of the current evidence treatment with antiplatelet agents in order to prevent secondary ischaemia or poor outcome cannot be recommended.

Over-expression of mitochondrial creatine kinase in the murine heart improves functional recovery and protects against injury following ischaemia-reperfusion.

PubMed

Whittington, Hannah J; Ostrowski, Philip J; McAndrew, Debra J; Cao, Fang; Shaw, Andrew; Eykyn, Thomas R; Lake, Hannah; Tyler, Jack; Schneider, Jurgen E; Neubauer, Stefan; Zervou, Sevasti; Lygate, Craig A

2018-03-02

Mitochondrial creatine kinase (MtCK) couples ATP production via oxidative phosphorylation to phosphocreatine in the cytosol, which acts as a mobile energy store available for regeneration of ATP at times of high demand. We hypothesised that elevating MtCK would be beneficial in ischaemia-reperfusion (I/R) injury. Mice were created overexpressing the sarcomeric MtCK gene with αMHC promoter at the Rosa26 locus (MtCK-OE) and compared with wild-type (WT) littermates. MtCK activity was 27% higher than WT, with no change in other CK isoenzymes or creatine levels. Electron microscopy confirmed normal mitochondrial cell density and mitochondrial localisation of transgenic protein. Respiration in isolated mitochondria was unaltered and metabolomic analysis by 1H-NMR suggests that cellular metabolism was not grossly affected by transgene expression. There were no significant differences in cardiac structure or function under baseline conditions by cine-MRI or LV haemodynamics. In Langendorff-perfused hearts subjected to 20min ischaemia and 30 min reperfusion, MtCK-OE exhibited less ischaemic contracture and improved functional recovery (Rate pressure product 58% above WT; P < 0.001). These hearts had reduced myocardial infarct size, which was confirmed in vivo: 55±4% in WT vs 29±4% in MtCK-OE; P < 0.0001). Isolated cardiomyocytes from MtCK-OE hearts exhibited delayed opening of the mitochondrial permeability transition pore (mPTP) compared to WT, which was confirmed by reduced mitochondrial swelling in response to calcium. There was no detectable change in the structural integrity of the mitochondrial membrane. Modest elevation of MtCK activity in the heart does not adversely affect cellular metabolism, mitochondrial or in vivo cardiac function, but modifies mPTP opening to protect against I/R injury and improve functional recovery. Our findings support MtCK as a prime therapeutic target in myocardial ischaemia.

AAV-mediated in vivo functional selection of tissue-protective factors against ischaemia

PubMed Central

Ruozi, Giulia; Bortolotti, Francesca; Falcione, Antonella; Dal Ferro, Matteo; Ukovich, Laura; Macedo, Antero; Zentilin, Lorena; Filigheddu, Nicoletta; Cappellari, Gianluca Gortan; Baldini, Giovanna; Zweyer, Marina; Barazzoni, Rocco; Graziani, Andrea; Zacchigna, Serena; Giacca, Mauro

2015-01-01

Functional screening of expression libraries in vivo would offer the possibility of identifying novel biotherapeutics without a priori knowledge of their biochemical function. Here we describe a procedure for the functional selection of tissue-protective factors based on the in vivo delivery of arrayed cDNA libraries from the mouse secretome using adeno-associated virus (AAV) vectors. Application of this technique, which we call FunSel, in the context of acute ischaemia, revealed that the peptide ghrelin protects skeletal muscle and heart from ischaemic damage. When delivered to the heart using an AAV9 vector, ghrelin markedly reduces infarct size and preserves cardiac function over time. This protective activity associates with the capacity of ghrelin to sustain autophagy and remove dysfunctional mitochondria after myocardial infarction. Our findings describe an innovative tool to identify biological therapeutics and reveal a novel role of ghrelin as an inducer of myoprotective autophagy. PMID:26066847

Supra- and Sub-Baseline Phosphocreatine Recovery in Developing Brain after Transient Hypoxia-Ischaemia: Relation to Baseline Energetics, Insult Severity and Outcome

ERIC Educational Resources Information Center

Iwata, Osuke; Iwata, Sachiko; Bainbridge, Alan; De Vita, Enrico; Matsuishi, Toyojiro; Cady, Ernest B.; Robertson, Nicola J.

2008-01-01

Following hypoxia-ischaemia (HI), an early biomarker of insult severity is desirable to target neuroprotective therapies to patients most likely to benefit; currently there are no biomarkers within the "latent phase" period before the establishment of secondary energy failure. Brief transient phosphocreatine (PCr) recovery overshoot (measured…

Controversies in the treatment of patients with STEMI and multivessel disease: is it time for PCI of all lesions?

PubMed

Ong, Peter; Sechtem, Udo

2016-06-01

Several randomized trials have suggested a benefit for multivessel PCI in patients with STEMI and multivessel disease. However, none of the studies compared multivessel PCI with a staged PCI-approach which is the current guideline recommended approach. The results of the trials may overestimate the beneficial effect of the multivessel PCI approach because the control group did not receive any ischaemia testing for evaluation of the significance of remaining lesions. Thus, unfavourable aspects of the multivessel PCI approach such as overestimation of non-culprit lesions at the time of acute coronary angiography, complications associated with PCI of the non-culprit lesion (i.e. dissection, no-reflow, acute stent thrombosis) or increased risk for contrast induced nephropathy may have gone unnoticed as the comparative management pathway was unusual and likely inferior to the guideline recommended approach. We believe that culprit lesion only PCI and staged evaluation of remaining areas of myocardial ischaemia with subsequent PCI is still preferable in patients with STEMI and multivessel disease but a randomized study comparing this approach with multivessel PCI is needed.

Electrocardiogram ST-Segment Morphology Delineation Method Using Orthogonal Transformations

PubMed Central

2016-01-01

Differentiation between ischaemic and non-ischaemic transient ST segment events of long term ambulatory electrocardiograms is a persisting weakness in present ischaemia detection systems. Traditional ST segment level measuring is not a sufficiently precise technique due to the single point of measurement and severe noise which is often present. We developed a robust noise resistant orthogonal-transformation based delineation method, which allows tracing the shape of transient ST segment morphology changes from the entire ST segment in terms of diagnostic and morphologic feature-vector time series, and also allows further analysis. For these purposes, we developed a new Legendre Polynomials based Transformation (LPT) of ST segment. Its basis functions have similar shapes to typical transient changes of ST segment morphology categories during myocardial ischaemia (level, slope and scooping), thus providing direct insight into the types of time domain morphology changes through the LPT feature-vector space. We also generated new Karhunen and Lo ève Transformation (KLT) ST segment basis functions using a robust covariance matrix constructed from the ST segment pattern vectors derived from the Long Term ST Database (LTST DB). As for the delineation of significant transient ischaemic and non-ischaemic ST segment episodes, we present a study on the representation of transient ST segment morphology categories, and an evaluation study on the classification power of the KLT- and LPT-based feature vectors to classify between ischaemic and non-ischaemic ST segment episodes of the LTST DB. Classification accuracy using the KLT and LPT feature vectors was 90% and 82%, respectively, when using the k-Nearest Neighbors (k = 3) classifier and 10-fold cross-validation. New sets of feature-vector time series for both transformations were derived for the records of the LTST DB which is freely available on the PhysioNet website and were contributed to the LTST DB. The KLT and LPT present new possibilities for human-expert diagnostics, and for automated ischaemia detection. PMID:26863140

PTEN, the Achilles' heel of myocardial ischaemia/reperfusion injury?

PubMed Central

Mocanu, M M; Yellon, D M

2007-01-01

Myocardial ischaemia/reperfusion injury leading to myocardial infarction is one of the most frequent causes of debilitation and death in man. Considerable research has been undertaken to investigate the possibility of reducing myocardial infarction and increasing cell survival by activating certain endogenous prosurvival signaling pathways. Thus, it has been established that the activation of the PI3K (Phosphoinositide-3 kinase)/Akt (Protein kinase B, PKB) signaling pathway is essential for protection against ischaemia/reperfusion injury. This pathway has been shown to be activated by mechanical procedures (e.g. pre and post conditioning) as well as by a number of pharmacological agents. Although the activation of this prosurvival signaling pathway induces the phosphorylation of a large number of substrates implicated in increased cell survival, when activated over a prolonged period this pathway can have detrimental consequences by facilitating unwanted growth and malignancies. Importantly PTEN (phosphatase and tensin homolog deleted on chromosome ten), is the main phosphatase which negatively regulates the PI3K/Akt pathway. In this review we discuss: a) the significance and the limitations of inhibiting PTEN in myocardial ischaemia/reperfusion injury; b) PTEN and its relationship to ischaemic preconditioning, c) the role of PTEN in the development of tolerance to chronic administration of drugs known to limit infarction by activating PI3K/Akt pathway when given acutely, and d) the possible role of PTEN in the ischaemic/reperfused diabetic heart. The experimental evidence discussed in this review illustrates the importance of PTEN inhibition in the protection of the heart against ischaemia/reperfusion injury. PMID:17293884

Quaternion-based study of angular velocity of the cardiac vector during myocardial ischaemia.

PubMed

Cruces, Pablo Daniel; Arini, Pedro David

2017-12-01

Early detection of acute ischaemia through non-invasive methods remains a challenge in health research. Ischaemic condition caused by a decrease in the blood supply in a cardiac region induces hypoxia and metabolic abnormalities that contribute to the electrical instability of the heart and to the development of slow conduction in damaged tissue. Herein, a percutaneous transluminal coronary angiography (PTCA) is considered as a model of supply ischaemia. We use the concept of quaternion to develop a robust method for assessing the angular velocity of cardiac vector in the orthogonal XYZ leads obtained from 92 patients undergoing the PTCA procedure. The maxima of angular velocity in both ventricular depolarization and repolarization are combined with traditional linear velocity indexes in order to obtain a detector of ischaemic episodes (Ischaemia Detector, ID). ID achieves 98%/100% of sensitivity/specificity when differentiating healthy subjects from patients with early ischaemia. Furthermore, it also shows high accuracy when the comparison is made between ischaemic subjects and patients with different non-ischaemic pathologic ST-deviations which are known to cause false positives, reaching 95%/98% of sensitivity/specificity. Moreover, the study of significant reductions (p<0.001) of angular velocity components allows extraction of distinct ischaemic common features which are useful for analyzing the dependence of vectorcardiogram signal on each site of occlusion. The sensitivity of injury location reaches values of 88% (RCA), 87% (LAD) and 80% (LCx). The high performance of the proposed method establishes a promising outcome for application in computerized assistance in clinical practice. Copyright © 2017 Elsevier B.V. All rights reserved.

Remote vs. local ischaemic preconditioning in the rat heart: infarct limitation, suppression of ischaemic arrhythmia and the role of reactive oxygen species.

PubMed

Galagudza, Michael M; Sonin, Dmitry L; Vlasov, Timur D; Kurapeev, Dmitry I; Shlyakhto, Eugene V

2016-02-01

The unmet clinical need for myocardial salvage during ischaemia-reperfusion injury requires the development of new techniques for myocardial protection. In this study the protective effect of different local ischaemic preconditioning (LIPC) and remote ischaemic preconditioning (RIPC) protocols was compared in the rat model of myocardial ischaemia-reperfusion, using infarct size and ischaemic tachyarrhythmias as end-points. In addition, the hypothesis that there is involvement of reactive oxygen species (ROS) in the protective signalling by RIPC was tested, again in comparison with LIPC. The animals were subjected to 30-min coronary occlusion and 90-min reperfusion. RIPC protocol included either transient infrarenal aortic occlusion (for 5, 15 and 30 min followed by 15-min reperfusion) or 15-min mesenteric artery occlusion with 15-min reperfusion. Ventricular tachyarrhythmias during test ischaemia were quantified according to Lambeth Conventions. It was found that the infarct-limiting effect of RIPC critically depends on the duration of a single episode of remote ischaemia, which fails to protect the heart from infarction when it is too short or, instead, too prolonged. It was also shown that RIPC is ineffective in reducing the incidence and severity of ischaemia-induced ventricular tachyarrhythmias. According to our data, the infarct-limiting effect of LIPC could be partially eliminated by the administration of ROS scavenger N-2-mercaptopropionylglycine (90 mg/kg), whereas the same effect of RIPC seems to be independent of ROS signalling. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.

The use of intermittent and continuous recordings of jugular venous bulb oxygen saturation in the unconscious patient.

PubMed

Garlick, R; Bihari, D

1987-01-01

Monitoring clinical signs in unconscious patients provides only late information about cerebral deterioration. Ischaemia and hypoxia are the mechanisms of much of the damage. Cerebral blood flow (CBF) measurements provide direct evidence of ischaemia but are intermittent values for what may be an unstable situation. Continuous recordings of CBF and oxygenation are more likely to reveal harmful tendencies to ischaemia and hypoxia at an early stage than intermittent readings. We report our experience with intermittent and also continuous recording of the jugular venous bulb oxygen saturation (JVO2Sat) obtained by fibreoptic oximetry in a group of 10 head injured and 7 septic patients. Simultaneous measurements of CBF by an isotopic xenon clearance method were also made. The JVO2Sat has been suggested to be a reliable indicator of cerebral oxygenation, a low value being indicative of ischaemia. We discuss whether our findings support this statement. There are also variations in JVO2Sat with mean arterial blood pressure and intracranial pressure. These variations have important implications in the interpretation that can be made of one single value of JVO2Sat.

Surgical results of leg amputation according to Ghormley's technique in the treatment of chronic lower limb ischaemia.

PubMed

Wasiak, K; Paczkowski, P M; Garlicki, J M

2006-01-01

The authors present their experience in the treatment of chronic lower limb ischaemia resulting from atherosclerosis by below knee amputation according to Ghormley's technique, with the immediate application of a semi-rigid plaster cast and early rehabilitation. From a group of 664 patients requiring major amputations, 61 patients (52 men) aged 64 +/- 11 fulfilled the criteria for unilateral below-knee amputation for critical limb ischaemia for atherosclerosis consequences. Peri-operative (30-days) mortality was of 3.28%. Stump healing was very good or good (no need for further surgery) in over 2/3 of patients, but in 20% the need for above-knee amputation developed. Postoperative knee contracture (defined as 15 degrees or more limitation to the movement range) was observed in 11.5% of patients.

How critical is chronic critical leg ischaemia?

PubMed

Kroese, A J; Stranden, E

1998-01-01

"Critical" according to the Oxford dictionary means: a "turning point" where an acute change for better or worse may be anticipated. Thus, the meaning of the word "critical" complies with its use in relation to ischaemia. We don't really know, prospectively, what will happen to the critically ischaemic limb, whether it will improve or worsen. The answer to the question "How critical is critical leg ischaemia (CLI)?" must be: "We don't know!" The addition of ankle systolic pressure as an objective haemodynamic measurement has not made the definition of the Second European Consensus Group significantly better than the original Fontaine classification, grade III and IV. For clinical practice the Fontaine classification will be sufficient. For scientific purposes macro- and microcirculatory assessments and information about the patient's risk profile should be added.

Dexmedetomidine protects from post-myocardial ischaemia reperfusion lung damage in diabetic rats

PubMed Central

Kip, Gülay; Çelik, Ali; Bilge, Mustafa; Alkan, Metin; Kiraz, Hasan Ali; Özer, Abdullah; Şıvgın, Volkan; Erdem, Özlem; Arslan, Mustafa; Kavutçu, Mustafa

2015-01-01

Objective Diabetic complications and lipid peroxidation are known to have a close association. Lipid peroxidation commonly occurs at sites exposed to ischaemia, but distant organs and tissues also get damaged during ischaemia/reperfusion (I/R). Some of these targets are vital organs, such as the lung, liver, and kidney; the lung is the most frequently affected. The aim of our study was to investigate the effects of dexmedetomidine on I/R damage in lung tissue and on the oxidant/anti-oxidant system in diabetic rats. Material and methods Diabetes was induced with streptozotocin (55 mg/kg) in 18 Wistar Albino rats, which were then randomly divided into three groups (diabetes control (DC), diabetes plus ischaemia-reperfusion (DIR), and diabetes plus dexmedetomidine-ischaemia/reperfusion (DIRD)) after the effects of diabetes were clearly evident. The rats underwent a left thoracotomy and then ischaemia was produced in the myocardium muscle by a left anterior descending artery ligation for 30 min in the DIR and DIRD groups. I/R was performed for 120 min. The DIRD group received a single intraperitoneal dose of dexmedetomidine (100 µg/kg); the DIR group received no dexmedetomidine. Group DC was evaluated as the diabetic control group and also included six rats (C group) in which diabetes was not induced. These mice underwent only left thoracotomy and were closed without undergoing myocardial ischaemia. Histopathological changes, activities of catalase (CAT) and glutathione-S-transferase anti-oxidant enzymes, and malondialdehyde (MDA) levels were evaluated in the lung tissues of all rats. Results Neutrophil infiltration/aggregation was higher in the DIR group than in the C, DC, and DIRD groups (p=0.001, p=0.013, and p=0.042, respectively). The lung injury score was significantly higher in the DIR group than in the C and DC groups (p<0.0001 and p=0.024, respectively). The levels of MDA were significantly higher in the DIR group than in the C and DIRD groups. CAT activity was significantly higher in the DIR group than in the DIRD and C groups. Conclusion Our results confirm that dexmedetomidine has protective effects against the lung damage resulting from I/R in diabetic rats. Future studies conducted to evaluate the effects of the use of dexmedetomidine on damage to various organs following different I/R durations may help understanding possible protective effects of dexmedetomidine and underlying mechanisms in tissue damage related to I/R injury. PMID:26387799

Induction of IL-8(CXCL8) and MCP-1(CCL2) with oxidative stress and its inhibition with N-acetyl cysteine (NAC) in cell culture model using HK-2 cell.

PubMed

Kumar, Avneesh; Shalmanova, Liliana; Hammad, Abdul; Christmas, Stephen E

2016-03-01

Renal transplantation can often be complicated due to delayed graft function, which is a direct sequel of ischaemia reperfusion injury. The adverse outcome of delayed graft function is not only short term but the long-term function of the graft is also affected. Therefore, it is important to understand the mechanisms of ischaemia reperfusion injury. Reactive oxygen species are the key mediators in ischaemia reperfusion injury causing direct cell damage which also initiate inflammation by inducing chemokines. The presence of inflammation is a marker of severe delayed graft function. However, the effect of oxidative stress on the expression of key chemokines has not been fully established yet. Therefore, the aim of this study was to measure the oxidative stress response and the secretion of chemokines in a cell culture model that mimics the effects of ischaemia reperfusion injury in immortalised human renal proximal tubular epithelial cells, HK-2. Cells were treated with varying concentrations of hydrogen peroxide and markers of oxidative stress response and chemokine release were measured. Exposure to hydrogen peroxide induced a significant increase in the activity of the antioxidant enzyme glutathione peroxidase and the levels of the chemokines Interleukin-8 (IL-8; CXCL8) and MCP-1 (CCL2). A dose related increase of chemokine secretion was also observed. The cytokine Interleukin-1β (IL-1β) at 1 ng/ml significantly potentiated the expression of both IL-8 (CXCL8) and MCP-1 (CCL2) which showed synergistic response in the presence of hydrogen peroxide. Pre-incubation of the cells with the anti-oxidant N-acetyl cysteine (NAC) strongly suppressed the induction of both IL-8 and MCP-1 when stimulated with hydrogen peroxide and IL-1β. This study demonstrates the potential of anti-oxidants like N-acetyl cysteine in ameliorating the effects of ischaemia reperfusion injury thus suggesting a new therapeutic approach in renal transplantation. These findings can have potential implications for clinical use to prevent ischaemia reperfusion injury in renal transplantation. Copyright © 2016 Elsevier B.V. All rights reserved.

Protective effect of preconditioning and adenosine pretreatment in experimental skeletal muscle reperfusion injury.

PubMed

Papanastasiou, S; Estdale, S E; Homer-Vanniasinkam, S; Mathie, R T

1999-07-01

Prolonged ischaemia followed by reperfusion (I/R) of skeletal muscle results in significant tissue injury. Ischaemic preconditioning (IPC), achieved by repeated brief periods of I/R before prolonged ischaemia or adenosine pretreatment, can prevent I/R injury in cardiac muscle. The aim of this study was to ascertain in a rodent model if damage to skeletal muscle due to global hindlimb tourniquet-induced I/R could be similarly attenuated. Anaesthetized rats were randomized (n = 6-10 per group) to five groups: sham-operated controls; I/R (4 h of ischaemia, 2 h of reperfusion); IPC (three cycles of 10 min of ischaemia/10 min of reperfusion) alone; IPC immediately preceding I/R; or adenosine 1000 microg/kg immediately before I/R. At the end of reperfusion, biopsies were taken from the left gastrocnemius muscle for measurement of myeloperoxidase (MPO) and reduced glutathione (GSH). Before ischaemia and at the end of reperfusion, blood samples were taken for measurement of nitric oxide metabolites, tumour necrosis factor (TNF) alpha and macrophage inflammatory protein (MIP) 2. IPC before I/R resulted in lower levels of MPO (P < 0.001) and TNF-alpha (P = 0.004), and higher levels of GSH (P < 0.001) and nitric oxide metabolites (P = 0.002) than I/R alone. Adenosine had effects comparable to IPC pretreatment (P < 0.001 for MPO, P = 0.002 for GSH, P = 0.02 for nitric oxide metabolites and P = 0.001 for TNF-alpha). There was no difference in the blood pressure or the MIP-2 concentration among the groups. IPC or pretreatment with adenosine ameliorates the I/R injury of skeletal muscle.

A possible mechanism for improvement by a cognition-enhancer nefiracetam of spatial memory function and cAMP-mediated signal transduction system in sustained cerebral ischaemia in rats

PubMed Central

Takeo, Satoshi; Niimura, Makiko; Miyake-Takagi, Keiko; Nagakura, Akira; Fukatsu, Tomoko; Ando, Tsuyoshi; Takagi, Norio; Tanonaka, Kouichi; Hara, Junko

2003-01-01

Accumulated evidence indicates that the adenylyl cyclase (AC)/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP-responsive element binding protein (CREB) signal transduction system may be linked to learning and memory function. The effects of nefiracetam, which has been developed as a cognition enhancer, on spatial memory function and the AC/cAMP/PKA/CREB signal transduction system in rats with sustained cerebral ischaemia were examined. Microsphere embolism (ME)-induced sustained cerebral ischaemia was produced by injection of 700 microspheres (48 μm in diameter) into the right hemisphere of rats. Daily oral administration of nefiracetam (10 mg kg−1 day−1) was started from 15 h after the operation. The delayed treatment with nefiracetam attenuated the ME-induced prolongation of the escape latency in the water maze task that was examined on day 7 to 9 after ME, but it did not reduce the infarct size. ME decreased Ca2+/calmodulin (CaM)-stimulated AC (AC-I) activity, cAMP content, cytosolic PKA Cβ level, nuclear PKA Cα and Cβ levels, and reduced the phosphorylation and DNA-binding activity of CREB in the nucleus in the right parietal cortex and hippocampus on day 3 after ME. The ME-induced changes in these variables did not occur by the delayed treatment with nefiracetam. These results suggest that nefiracetam preserved cognitive function, or prevented cognitive dysfunction, after sustained cerebral ischaemia and that the effect is, in part, attributable to the prevention of the ischaemia-induced impairment of the AC/cAMP/PKA/CREB signal transduction pathway. PMID:12598418

Cardioprotection by GSK-3 inhibition: role of enhanced glycogen synthesis and attenuation of calcium overload.

PubMed

Omar, Mohamed A; Wang, Lianguo; Clanachan, Alexander S

2010-06-01

Glycogen synthase kinase-3 (GSK-3) is a multi-functional kinase that regulates signalling pathways affecting glycogen metabolism, protein synthesis, mitosis, and apoptosis. GSK-3 inhibition limits cardiac ischaemia-reperfusion (IR) injury, but mechanisms are not clearly defined. This study tested the hypothesis that acute GSK-3 inhibition stimulates glycogen synthesis, repartitions glucose away from glycolysis, reduces proton (H+) production from glucose metabolism, and attenuates intracellular Ca2+ (Ca2+(i)) overload. In isolated perfused working rat hearts subjected to global ischaemia and reperfusion, the selective GSK-3 inhibitor, SB-216763 (SB, 3 micromol/L), when added either prior to ischaemia or at the onset of reperfusion, improved recovery of left-ventricular (LV) work. SB increased glycogen synthesis during reperfusion while glycolysis and H+ production were reduced. Rates of glucose and palmitate oxidation were improved by SB. Measurement of Ca2+(i) concentration by rapid acquisition indo-1 fluorescence imaging showed that SB, when added either prior to ischaemia or at the onset of reperfusion, reduced diastolic Ca2+(i) overload during reperfusion. In aerobic hearts depleted of glycogen by substrate-free perfusion to a level similar to that measured at the onset of reperfusion, SB accelerated glycogen synthesis and reduced glycolysis and H+ production independent of changes in LV work. Our study indicates that reduction in H+ production by GSK-3 inhibition is an early and upstream event that lessens Ca2+(i) overload during ischaemia and early reperfusion independent of LV work which enhances the recovery of post-ischaemic LV function and that may ultimately contribute to previously observed reductions in cell death and infarction.

Human bone marrow mesenchymal stem cells for retinal vascular injury.

PubMed

Wang, Jin-Da; An, Ying; Zhang, Jing-Shang; Wan, Xiu-Hua; Jonas, Jost B; Xu, Liang; Zhang, Wei

2017-09-01

To examine the potential of intravitreally implanted human bone marrow-derived mesenchymal stem cells (BMSCs) to affect vascular repair and the blood-retina barrier in mice and rats with oxygen-induced retinopathy, diabetic retinopathy or retinal ischaemia-reperfusion damage. Three study groups (oxygen-induced retinopathy group: 18 C57BL/6J mice; diabetic retinopathy group: 15 rats; retinal ischaemia-reperfusion model: 18 rats) received BMSCs injected intravitreally. Control groups (oxygen-induced retinopathy group: 12 C57BL/6J mice; diabetic retinopathy group: 15 rats; retinal ischaemia-reperfusion model: 18 rats) received an intravitreal injection of phosphate-buffered saline. We applied immunohistological techniques to measure retinal vascularization, spectroscopic measurements of intraretinally extravasated fluorescein-conjugated dextran to quantify the blood-retina barrier breakdown, and histomorphometry to assess retinal thickness and retinal ganglion cell count. In the oxygen-induced retinopathy model, the study group with intravitreally injected BMSCs as compared with the control group showed a significantly (p = 0.001) smaller area of retinal neovascularization. In the diabetic retinopathy model, study group and control group did not differ significantly in the amount of intraretinally extravasated dextran. In the retinal ischaemia-reperfusion model, on the 7th day after retina injury, the retina was significantly thicker in the study group than in the control group (p = 0.02), with no significant difference in the retinal ganglion cell count (p = 0.36). Intravitreally implanted human BMSCs were associated with a reduced retinal neovascularization in the oxygen-induced retinopathy model and with a potentially cell preserving effect in the retinal ischaemia-reperfusion model. Intravitreal BMSCs may be of potential interest for the therapy of retinal vascular disorders. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Melatonin attenuates lung ischaemia-reperfusion injury via inhibition of oxidative stress and inflammation.

PubMed

Wang, Ming-Liang; Wei, Chun-Hua; Wang, Wen-Dong; Wang, Jia-Shun; Zhang, Jun; Wang, Jian-Jun

2018-05-01

Lung ischaemia-reperfusion injury is a complex pathophysiological process due to the production of reactive oxygen species and the generation of inflammatory reaction. We investigated the protective effects and the corresponding mechanism of melatonin (MT), a potent free-radical scavenger, on lung injury induced by ischaemia-reperfusion in a mouse model. Adult male C57BL/6J mice (n = 30) were randomly and equally allocated into 5 groups: sham controls, IR, IR + 10 mg/kg MT, IR + 20 mg/kg MT and IR + 30 mg/kg MT. Lung ischaemia-reperfusion injury was induced by thoracotomy followed by clamping of the left hilum for 1 h and subsequent reperfusion for 2 h. Histological scoring analysis showed that lung parenchymal damage was ameliorated in the melatonin pretreatment groups when compared with the IR group, with the IR + 20 mg/kg MT group showing the strongest effect among the melatonin pretreatment groups. Wet-to-dry weight ratio, detection of malondialdehyde, protein expressions of inflammatory factors (tumour necrosis factor-α, interleukin-1β, NF-κB and IKK-γ) and apoptotic factors (cleaved caspase-3 and Bax/Bcl-2), as well as TUNEL assay showed changes similar to those of the lung injury scores in all groups. In contrast, the examination of superoxide dismutase showed a pattern contrary to that of the lung injury score in all groups. In addition, immunohistochemistry staining showed that the expressions of the antioxidants glutathione peroxidase and glutathione reductase were increased in the melatonin pretreatment groups. This study demonstrated that melatonin pretreatment attenuated lung ischaemia-reperfusion injury via inhibition of oxidative stress, inflammation and apoptosis.

Paroxysmal dyskinesia as an unusual and only presentation of subcortical white matter ischaemia: a report of two cases.

PubMed

Norlinah, M I; Shahizon, A M M

2008-12-01

Secondary paroxysmal dyskinesias (PxD) have been previously reported in patients with multiple sclerosis, lacunar infarcts, head trauma, metabolic disorders such as hyperglycaemia, hypocalcaemia, migraine and central nervous system (CNS) infections. The causative lesions typically involve the basal ganglia structures, medulla and rarely the spinal cord. We report two patients who presented with paroxysmal dyskinesias as the only manifestation of subcortical white-matter ischaemia. Patient 1 presented with 3-year history of paroxysmal kinesigenic dyskinesia (PKD) and patient 2 with 6-month history of paroxysmal nonkinesigenic dyskinesia (PNKD). All investigations, including CSF oligoclonal bands were negative, except for a brain MRI which showed multiple, non-enhancing subcortical white matter lacunar infarcts. Therefore, subcortical white matter ischaemia should also be included in the differential diagnosis of PxD.

Novel cardiac protective effects of urea: from shark to rat

PubMed Central

Wang, Xintao; Wu, Lingyun; Aouffen, M'hamed; Mateescu, Mircea-Alexandru; Nadeau, Réginald; Wang, Rui

1999-01-01

This study was carried out to investigate novel cardioprotective effects of urea and the underlying mechanisms. The cardiac functions under oxidative stress were evaluated using Langendorff perfused isolated heart.Isolated dogfish shark hearts tolerated the oxidative stress generated by electrolysis (10 mA, 1 min) of the perfusion solution (n=4), and also showed normal cardiac functions during post-ischaemia reperfusion (n=4). The high concentration of urea (350 mM) in the heart perfusate was indispensable for maintaining the normal cardiac functions of the shark heart.Urea at 3–300 mM (n=4 for each group) protected the isolated rat heart against both electrolysis-induced heart damage and post-ischaemia reperfusion-induced cardiac injury.A concentration-dependent scavenging effect of urea (3–300 mM, n=4 for each group) against electrolysis-induced reactive oxygen species was also demonstrated in vitro.Urea derivatives as hydroxyurea, dimethylurea, and thiourea had antioxidant cardioprotective effect against the electrolysis-induced cardiac dysfunction of rat heart, but were not as effective as urea in suppressing the post-ischaemia reperfusion injury.Our results suggest that urea and its derivatives are potential antioxidant cardioprotective agents against oxidative stress-induced myocardium damage including the post-ischaemia reperfusion-induced injury. PMID:10602326

Thrombo-embolectomy and thrombolytic therapy in acute lower limb ischaemia. A five year experience.

PubMed

Singh, S; Ackroyd, R; Lees, T; Morris-Jones, W; Gaines, P; Beard, J D

1996-03-01

Between 1988 and 1993, 82 patients with a median age (iq range) of 81 (73-87) years underwent thrombo-embolectomy (TE) and thrombolysis for acute lower limb ischaemia at the Royal Hallamshire Hospital, Sheffield. 28 patients (Group 1) underwent TE prior to the introduction of thrombolysis in 1991. TE with intraoperative thrombolysis (IT) as an adjunct was performed in 34 patients (Group 2) and 20 patients (Group 3) were treated using percutaneous thrombolysis (PT) in the first instance. 41 of these patients were in AF at presentation. Although 24 were on digoxin, only 4 were on warfarin. Group 3 patients were younger (p < 0.05; ANOVA) with a longer duration of ischaemia (p < 0.05; ANOVA) and had less limbs suffering a sensorimotor deficit (p = 0.007; chi 2) compared with Groups 1 and 2 which were similar in these respects. Overall mortality was 17%. Successful revascularisation was achieved in 18 (64%), 28 (82%) and 15 (75%) patients in Groups 1, 2 and 3 respectively. 14 of the 15 patients successfully treated initially by PT required further intervention in order to maintain revascularisation. Revascularisation failure was associated with the presence of a sensorimotor deficit but not associated with patient age or duration of ischaemia.

A novel role of HIF-1α/PROX-1/LYVE-1 axis on tissue regeneration after renal ischaemia/reperfusion in mice.

PubMed

Meng, Fanwei

2018-04-10

Renal ischaemia reperfusion (I/R) is a common clinical condition with a high morbidity and mortality rate. To date, I/R-induced renal injury remains an ineffective treatment. We hypothesis that angiogenesis and lymphangiogenesis markers, prospero homeobox-1 (PROX-1) and lymphatic endothelial hyaluronan receptor-1 (LYVE-1), are critical during I/R. Kunming mice were subjected to I/R and observed for the following eight consecutive days. Pathology analysis and protein distribution were detected by H&E staining, immunohistochemistry and immunofluorescence confocal analysis. After I/R treatment, renal pathology was changed. HIF-1α was induced in the early stage and colocalisation with PROX-1 mainly in the renal tubular region, whereas PROX-1 and LYVE-1 were colocalised in the glomerulus of the endothelial region. In this study, we revealed HIF-1α/PROX-1/LVYE-1 axis dynamic changes in different regions after I/R and demonstrated for the first time it activates during I/R repair.

Role of ivabradine in management of stable angina in patients with different clinical profiles

PubMed Central

Kaski, Juan Carlos; Gloekler, Steffen; Ferrari, Roberto; Fox, Kim; Lévy, Bernard I; Komajda, Michel; Vardas, Panos; Camici, Paolo G

2018-01-01

In chronic stable angina, elevated heart rate contributes to the development of symptoms and signs of myocardial ischaemia by increasing myocardial oxygen demand and reducing diastolic perfusion time. Accordingly, heart rate reduction is a well-known strategy for improving both symptoms of myocardial ischaemia and quality of life (QOL). The heart rate-reducing agent ivabradine, a direct and selective inhibitor of the I f current, decreases myocardial oxygen consumption while increasing diastolic time, without affecting myocardial contractility or coronary vasomotor tone. Ivabradine is indicated for treatment of stable angina and chronic heart failure (HF). This review examines available evidence regarding the efficacy and safety of ivabradine in stable angina, when used as monotherapy or in combination with beta-blockers, in particular angina subgroups and in patients with stable angina with left ventricular systolic dysfunction (LVSD) or HF. Trials involving more than 45 000 patients receiving treatment with ivabradine have shown that this agent has antianginal and anti-ischaemic effects, regardless of age, sex, severity of angina, revascularisation status or comorbidities. This heart rate-lowering agent might also improve prognosis, reduce hospitalisation rates and improve QOL in angina patients with chronic HF and LVSD. PMID:29632676

Doxorubicin induced myocardial injury is exacerbated following ischaemic stress via opening of the mitochondrial permeability transition pore

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gharanei, M.; Hussain, A.; Janneh, O.

Chemotherapeutic agents such as doxorubicin are known to cause or exacerbate cardiovascular cell death when an underlying heart condition is present. However, the mechanism of doxorubicin-induced cardiotoxicity is unclear. Here we assess the cardiotoxic effects of doxorubicin in conditions of myocardial ischaemia reperfusion and the mechanistic basis of protection, in particular the role of the mitochondrial permeability transition pore (mPTP) in such protection. The effects of doxorubicin (1 μM) ± cyclosporine A (CsA, 0.2 μM; inhibits mPTP) were investigated in isolated male Sprague–Dawley rats using Langendorff heart and papillary muscle contraction models subjected to simulated ischaemia and reperfusion injury. Isolatedmore » rat cardiac myocytes were used in an oxidative stress model to study the effects of drug treatment on mPTP by confocal microscopy. Western blot analysis evaluated the effects of drug treatment on p-Akt and p-Erk 1/2 levels. Langendorff and the isometric contraction models showed a detrimental effect of doxorubicin throughout reperfusion/reoxygenation as well as increased p-Akt and p-Erk levels. Interestingly, CsA not only reversed the detrimental effects of doxorubicin, but also reduced p-Akt and p-Erk levels. In the sustained oxidative stress assay to study mPTP opening, doxorubicin decreased the time taken to depolarization and hypercontracture, but these effects were delayed in the presence of CsA. Collectively, our data suggest for the first that doxorubicin exacerbates myocardial injury in an ischaemia reperfusion model. If the inhibition of mPTP ameliorates the cardiotoxic effects of doxorubicin, then more selective inhibitors of mPTP should be further investigated for their utility in patients receiving doxorubicin. - Highlights: ► Doxorubicin exacerbates myocardial ischaemia reperfusion injury. ► Co-treatment with CsA protects against doxorubicin induced myocardial injury. ► CsA delays doxorubicin induced mPTP opening in laser induced stress model. ► Doxorubicin causes increase in p-Akt and p-Erk levels during reperfusion injury. ► CsA or other mPTP inhibitors may be useful against drug-induced cardiotoxicity.« less

Reversible non-ischaemic cardiomyopathy and left ventricular dysfunction after liver transplantation: a single-centre experience.

PubMed

Yataco, Maria L; Difato, Thomas; Bargehr, Johannes; Rosser, Barry G; Patel, Tushar; Trejo-Gutierrez, Jorge F; Pungpapong, Surakit; Taner, C Burcin; Aranda-Michel, Jaime

2014-07-01

Non-ischaemic cardiomyopathy (NIC) is an early complication of liver transplantation (LT). Our aims were to define the prevalence, associated clinical factors, and prognosis of this condition. A retrospective study was performed on patients undergoing LT at our institution from January 2005 to December 2012. Patients who developed NIC were identified. Data collected included demographic and clinical data. A total 1460 transplants were performed in this period and seventeen patients developed NIC. Pretransplant median QTc interval was 459 (range, 405-530), and median E/A ratio was 1 (range, 0.71-1.67). Fourteen patients (82%) were severely malnourished and required nutritional support. Thirteen patients (76%) had renal insufficiency. Median time to onset was 2 days post-transplant (range, 0-20). Echocardiograms showed global left ventricular hypokinesis and a decrease in ejection fraction (EF) from a median of 65% (range, 50-81) pretransplant to a median of 21% (range, 15-32). Median raw model for end-stage liver disease (MELD) score was 29 in patients with NIC vs. 18 in patients without cardiomyopathy (P = 0.01). There was no significant difference between recipients with NIC vs. recipients without cardiomyopathy regarding donor age, donor risk index, and cold and warm ischaemia time. Recovery of cardiac function occurred in 16 patients, with a median EF of 44% (range, 25-65%) at the time of discharge. The last echocardiogram available showed a median EF of 59% (range, 49-73%). One-year survival of NIC patients was 94.1%. Non-ischaemic cardiomyopathy is a rare complication after LT. Patients with NIC are critically ill, with high MELD score, and severe malnutrition. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Mass Spectrometry Based Metabolomics Comparison of Liver Grafts from Donors after Circulatory Death (DCD) and Donors after Brain Death (DBD) Used in Human Orthotopic Liver Transplantation.

PubMed

Hrydziuszko, Olga; Perera, M Thamara P R; Laing, Richard; Kirwan, Jennifer; Silva, Michael A; Richards, Douglas A; Murphy, Nick; Mirza, Darius F; Viant, Mark R

2016-01-01

Use of marginal liver grafts, especially those from donors after circulatory death (DCD), has been considered as a solution to organ shortage. Inferior outcomes have been attributed to donor warm ischaemic damage in these DCD organs. Here we sought to profile the metabolic mechanisms underpinning donor warm ischaemia. Non-targeted Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry metabolomics was applied to biopsies of liver grafts from donors after brain death (DBD; n = 27) and DCD (n = 10), both during static cold storage (T1) as well as post-reperfusion (T2). Furthermore 6 biopsies from DBD donors prior to the organ donation (T0) were also profiled. Considering DBD and DCD together, significant metabolic differences were discovered between T1 and T2 (688 peaks) that were primarily related to amino acid metabolism, meanwhile T0 biopsies grouped together with T2, denoting the distinctively different metabolic activity of the perfused state. Major metabolic differences were discovered between DCD and DBD during cold-phase (T1) primarily related to glucose, tryptophan and kynurenine metabolism, and in the post-reperfusion phase (T2) related to amino acid and glutathione metabolism. We propose tryptophan/kynurenine and S-adenosylmethionine as possible biomarkers for the previously established higher graft failure of DCD livers, and conclude that the associated pathways should be targeted in more exhaustive and quantitative investigations.

Mass Spectrometry Based Metabolomics Comparison of Liver Grafts from Donors after Circulatory Death (DCD) and Donors after Brain Death (DBD) Used in Human Orthotopic Liver Transplantation

PubMed Central

Laing, Richard; Kirwan, Jennifer; Silva, Michael A.; Richards, Douglas A.; Murphy, Nick; Mirza, Darius F.; Viant, Mark R.

2016-01-01

Use of marginal liver grafts, especially those from donors after circulatory death (DCD), has been considered as a solution to organ shortage. Inferior outcomes have been attributed to donor warm ischaemic damage in these DCD organs. Here we sought to profile the metabolic mechanisms underpinning donor warm ischaemia. Non-targeted Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry metabolomics was applied to biopsies of liver grafts from donors after brain death (DBD; n = 27) and DCD (n = 10), both during static cold storage (T1) as well as post-reperfusion (T2). Furthermore 6 biopsies from DBD donors prior to the organ donation (T0) were also profiled. Considering DBD and DCD together, significant metabolic differences were discovered between T1 and T2 (688 peaks) that were primarily related to amino acid metabolism, meanwhile T0 biopsies grouped together with T2, denoting the distinctively different metabolic activity of the perfused state. Major metabolic differences were discovered between DCD and DBD during cold-phase (T1) primarily related to glucose, tryptophan and kynurenine metabolism, and in the post-reperfusion phase (T2) related to amino acid and glutathione metabolism. We propose tryptophan/kynurenine and S-adenosylmethionine as possible biomarkers for the previously established higher graft failure of DCD livers, and conclude that the associated pathways should be targeted in more exhaustive and quantitative investigations. PMID:27835640

Wide sternal retraction may impede internal mammary artery graft flow and reduce myocardial function during off-pump coronary artery bypass grafting: presentation of two cases

PubMed Central

Espinoza, Andreas; Bergsland, Jacob; Lundblad, Runar; Fosse, Erik

2012-01-01

The internal mammary artery (IMA) is routinely used for grafting of the left anterior descending coronary artery (LAD), providing good flow to the anterior left ventricle (LV) wall. Impeded IMA-to-LAD flow may result in myocardial ischaemia and haemodynamic deterioration. From a study population, we describe two incidents where myocardial ischaemia was observed during off-pump coronary artery bypass surgery (CABG), with a confirmed reduction in the IMA-to-LAD flow in one patient. In patient no. 1, normal IMA flow was assessed by transit-time flow measurement after a complete IMA-to-LAD anastomosis. The anterior LV wall thickening was monitored continuously by epicardial ultrasonic transducers. Normal wall thickening was confirmed after IMA grafting. During a wide sternal opening for circumflex grafting the anterior wall motion displayed an ischaemic pattern, with reduced systolic and increased post-systolic wall thickening. IMA flow was reduced simultaneously. When easing the sternal opening, IMA flow normalized, as did the motion pattern in the anterior LV wall. In patient no. 2, similar changes in wall thickening occurred during a wide sternal opening after IMA-to-LAD grafting. When easing the retractor, the wall thickening normalized. It is important for the surgeon to be aware of this possible cause of myocardial ischaemia, with a risk of subsequent haemodynamic deterioration. This may not only be of great importance during off-pump CABG, but can also be significant for successful weaning from the cardiopulmonary bypass machine. PMID:22499803

Emergency revascularisation in a patient with acute mesenteric ischaemia: the role of open revascularisation and compensatory blood flow.

PubMed

Morbi, Abigail H M; Nordon, Ian M

2016-08-01

This case highlights the importance of timely diagnosis and management of acute mesenteric ischaemia and illustrates the compensatory mechanisms of the mesenteric vasculature. A 53-year-old female presented with fever, abdominal pain, and vomiting. The patient had no risk factors for atherosclerosis and was a non-smoker in sinus rhythm with no history of coagulopathy. She was initially treated for viral gastroenteritis. Due to lack of clinical improvement and a rising C-Reactive Protein (416), a CT scan was performed. This demonstrated small bowel ischaemia, chronic occlusion of the coeliac axis, and a long acute-on-chronic occlusion of the superior mesenteric artery (SMA). The length and morphology of the SMA occlusion precluded endovascular treatment. Emergency laparotomy demonstrated 1 m of necrotic small bowel and a pulseless mesentery. An aorto-SMA bypass, using good-quality long saphenous vein was performed, with segmental small bowel resection. Postoperative nutritional support was required with discharge on the 23rd post-operative day. Interval surveillance confirmed graft patency. One year post-discharge, she presented to routine clinic with paroxysmal right iliac fossa pain and decreased appetite. CT angiography showed a long tight 75% stenosis of the graft and she was admitted for mesenteric angioplasty. Angiography confirmed a significantly hypertrophied inferior mesenteric artery, which was now the dominant mesenteric supply. This case demonstrates the importance of emergency mesenteric revascularisation and how it acts as a bridge to anatomical compensation, allowing the collateral circulation to develop and the IMA to hypertrophy, becoming the dominant mesenteric supply.

The effect of dexpanthenol on experimentally induced ovarian ischaemia/reperfusion injury: a biochemical and histopathological evaluation.

PubMed

Soylu Karapinar, Oya; Pinar, Neslihan; Özcan, Oğuzhan; Atik Doğan, Esin; Bayraktar, Suphi; Şahin, Hanifi; Dolapçioğlu, Kenan

2017-03-01

The aim of this study was to evaluate the effect of two different doses of dexpanthenol (Dxp) onexperimentally induced ovarian ischaemia/reperfusion (I/R) injury ina rat model. Forty female rats were randomly divided into fivegroups: Group 1: sham operation; Group 2: 3-h ischaemia; Groups 3: 3-h ischaemia, 3-h reperfusion (I/R); Group 4: I/R + 300 mg/kg Dxp intraperitoneally (i.p) Group 5: I /R + 500 mg/kg Dxpi.p. Total anti-oxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), tissue malondialdehyde (MDA) and activities of glutathione peroxidase and catalase were calculated. Ovarian tissue damage was assessed using a histopathological scoring system. The TOS and OSI values were significantly lower in Group 5, as compared to Groups 2 and 3 (p < 0.05). The MDA levels in Group 1 and Group 5 were significantly lower than those in Group 3 (p < 0.05). CAT and GSH-Px activity was higher in Group 5 than in Group 2 and Group 3 (p = 0.00). Tissue damage scores were elevated in all the groups compared with sham group, but the treatment with the different doses of Dxp before reperfusion ameliorated the tissue damage scores. The results showed that Dxp reduced ovarian I/R injury.

Pre-Conditioning with CDP-Choline Attenuates Oxidative Stress-Induced Cardiac Myocyte Death in a Hypoxia/Reperfusion Model

PubMed Central

González-Pacheco, Héctor; Méndez-Domínguez, Aurelio; Hernández, Salomón; López-Marure, Rebeca; Vazquez-Mellado, Maria J.; Aguilar, Cecilia; Rocha-Zavaleta, Leticia

2014-01-01

Background. CDP-choline is a key intermediate in the biosynthesis of phosphatidylcholine, which is an essential component of cellular membranes, and a cell signalling mediator. CDP-choline has been used for the treatment of cerebral ischaemia, showing beneficial effects. However, its potential benefit for the treatment of myocardial ischaemia has not been explored yet. Aim. In the present work, we aimed to evaluate the potential use of CDP-choline as a cardioprotector in an in vitro model of ischaemia/reperfusion injury. Methods. Neonatal rat cardiac myocytes were isolated and subjected to hypoxia/reperfusion using the coverslip hypoxia model. To evaluate the effect of CDP-choline on oxidative stress-induced reperfusion injury, the cells were incubated with H2O2 during reperfusion. The effect of CDP-choline pre- and postconditioning was evaluated using the cell viability MTT assay, and the proportion of apoptotic and necrotic cells was analyzed using the Annexin V determination by flow cytometry. Results. Pre- and postconditioning with 50 mg/mL of CDP-choline induced a significant reduction of cells undergoing apoptosis after hypoxia/reperfusion. Preconditioning with CDP-choline attenuated postreperfusion cell death induced by oxidative stress. Conclusion. CDP-choline administration reduces cell apoptosis induced by oxidative stress after hypoxia/reperfusion of cardiac myocytes. Thus, it has a potential as cardioprotector in ischaemia/reperfusion-injured cardiomyocytes. PMID:24578622

Silent myocardial ischaemia: the Tan Tock Seng experience.

PubMed

Mak, K H; Tan, E K; Chew, L; Gan, S H; Chan, A L

1991-10-01

The results of treadmill exercise stress test (TMX) for ischaemia is based on ST-segment depression. Patients with positive test may or may not be symptomatic. This study examines if there are any differences between these two groups of patients. A total of thirty-nine patients with coronary artery disease and positive TMX results in 1988 was studied. There were 16 patients with chest pain and 23 without. They were followed-up for a mean period of 16.9 and 15.2 months respectively. The following factors were found not to be statistically significant between these two groups of patients: age, sex, race, height, weight, history of hypertension, diabetes mellitus or smoking, indication for the test, use of drugs, total and HDL-cholesterol, exercise duration and the initial double product. The difference between the maximal double product of the two groups was statistically significant (p = 0.004). In the follow-up period, in the group of patients with silent myocardial ischaemia, one had a cardiac event and one underwent revascularisation. While in the symptomatic group, two had cardiac events and seven underwent revascularisation. There were no deaths in either group. The difference in overall outcome was significant statistically (p = 0.002). Therefore, patients with silent myocardial ischaemia have a higher maximal double product in TMX; hence a higher maximal workload and a less adverse outcome compared to symptomatic patients.

The role of hexokinase in cardioprotection – mechanism and potential for translation

PubMed Central

Pereira, Gonçalo C; Pasdois, Philippe

2015-01-01

Mitochondrial permeability transition pore (mPTP) opening plays a critical role in cardiac reperfusion injury and its prevention is cardioprotective. Tumour cell mitochondria usually have high levels of hexokinase isoform 2 (HK2) bound to their outer mitochondrial membranes (OMM) and HK2 binding to heart mitochondria has also been implicated in resistance to reperfusion injury. HK2 dissociates from heart mitochondria during ischaemia, and the extent of this correlates with the infarct size on reperfusion. Here we review the mechanisms and regulations of HK2 binding to mitochondria and how this inhibits mPTP opening and consequent reperfusion injury. Major determinants of HK2 dissociation are the elevated glucose‐6‐phosphate concentrations and decreased pH in ischaemia. These are modulated by the myriad of signalling pathways implicated in preconditioning protocols as a result of a decrease in pre‐ischaemic glycogen content. Loss of mitochondrial HK2 during ischaemia is associated with permeabilization of the OMM to cytochrome c, which leads to greater reactive oxygen species production and mPTP opening during reperfusion. Potential interactions between HK2 and OMM proteins associated with mitochondrial fission (e.g. Drp1) and apoptosis (B‐cell lymphoma 2 family members) in these processes are examined. Also considered is the role of HK2 binding in stabilizing contact sites between the OMM and the inner membrane. Breakage of these during ischaemia is proposed to facilitate cytochrome c loss during ischaemia while increasing mPTP opening and compromising cellular bioenergetics during reperfusion. We end by highlighting the many unanswered questions and discussing the potential of modulating mitochondrial HK2 binding as a pharmacological target. Linked Articles This article is part of a themed section on Conditioning the Heart – Pathways to Translation. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue‐8 PMID:25204670

In vivo imaging of induction of heat-shock protein-70 gene expression with fluorescence reflectance imaging and intravital confocal microscopy following brain ischaemia in reporter mice.

PubMed

de la Rosa, Xavier; Santalucía, Tomàs; Fortin, Pierre-Yves; Purroy, Jesús; Calvo, Maria; Salas-Perdomo, Angélica; Justicia, Carles; Couillaud, Franck; Planas, Anna M

2013-02-01

Stroke induces strong expression of the 72-kDa heat-shock protein (HSP-70) in the ischaemic brain, and neuronal expression of HSP-70 is associated with the ischaemic penumbra. The aim of this study was to image induction of Hsp-70 gene expression in vivo after brain ischaemia using reporter mice. A genomic DNA sequence of the Hspa1b promoter was used to generate an Hsp70-mPlum far-red fluorescence reporter vector. The construct was tested in cellular systems (NIH3T3 mouse fibroblast cell line) by transient transfection and examining mPlum and Hsp-70 induction under a challenge. After construct validation, mPlum transgenic mice were generated. Focal brain ischaemia was induced by transient intraluminal occlusion of the middle cerebral artery and the mice were imaged in vivo with fluorescence reflectance imaging (FRI) with an intact skull, and with confocal microscopy after opening a cranial window. Cells transfected with the Hsp70-mPlum construct showed mPlum fluorescence after stimulation. One day after induction of ischaemia, reporter mice showed a FRI signal located in the HSP-70-positive zone within the ipsilateral hemisphere, as validated by immunohistochemistry. Live confocal microscopy allowed brain tissue to be visualized at the cellular level. mPlum fluorescence was observed in vivo in the ipsilateral cortex 1 day after induction of ischaemia in neurons, where it is compatible with penumbra and neuronal viability, and in blood vessels in the core of the infarction. This study showed in vivo induction of Hsp-70 gene expression in ischaemic brain using reporter mice. The fluorescence signal showed in vivo the induction of Hsp-70 in penumbra neurons and in the vasculature within the ischaemic core.

Panoramic ECG display versus conventional ECG: ischaemia detection by critical care nurses.

PubMed

Wilson, Nick; Hassani, Aimen; Gibson, Vanessa; Lightfoot, Timothy; Zizzo, Claudio

2012-01-01

To compare accuracy and certainty of diagnosis of cardiac ischaemia using the Panoramic ECG display tool plus conventional 12-lead electrocardiogram (ECG) versus 12-lead ECG alone by UK critical care nurses who were members of the British Association of Critical Care Nurses (BACCN). Critically ill patients are prone to myocardial ischaemia. Symptoms may be masked by sedation or analgesia, and ECG changes may be the only sign. Critical care nurses have an essential role in detecting ECG changes promptly. Despite this, critical care nurses may lack expertise in interpreting ECGs and myocardial ischaemia often goes undetected by critical care staff. British Association of Critical Care Nurses (BACCN) members were invited to complete an online survey to evaluate the analysis of two sets of eight ECGs displayed alone and with the new display device. Data from 82 participants showed diagnostic accuracy improved from 67·1% reading ECG traces alone, to 96·0% reading ECG plus Panoramic ECG display tool (P < 0·01, significance level α = 0·05). Participants' diagnostic certainty score rose from 41·7% reading ECG alone to 66·8% reading ECG plus Panoramic ECG display tool (P < 0·01, α = 0·05). The Panoramic ECG display tool improves both accuracy and certainty of detecting ST segment changes among critical care nurses, when compared to conventional 12-lead ECG alone. This benefit was greatest with early ischaemic changes. Critical care nurses who are least confident in reading conventional ECGs benefit the most from the new display. Critical care nurses have an essential role in the monitoring of critically ill patients. However, nurses do not always have the expertise to detect subtle ischaemic ECG changes promptly. Introduction of the Panoramic ECG display tool into clinical practice could lead to patients receiving treatment for myocardial ischaemia sooner with the potential for reduction in morbidity and mortality. © 2012 The Authors. Nursing in Critical Care © 2012 British Association of Critical Care Nurses.

Raynaud's phenomenon and digital ischaemia--pharmacologic approach and alternative treatment options.

PubMed

Linnemann, Birgit; Erbe, Matthias

2016-01-01

The primary goal of therapy is to reduce the frequency and intensity of Raynaud's attacks and to minimize the related morbidity rather than to cure the underlying condition. Treatment strategies depend on whether Raynaud's phenomenon (RP) is primary or secondary. All patients should be instructed about general measures to maintain body warmth and to avoid triggers of RP attacks. Pharmacologic intervention can be useful for patients with severe and frequent RP episodes that impair the patient's quality of life. Calcium channel blockers are currently the most prescribed and studied medications for this purpose. There has been limited evidence for the efficacy of alpha-1-adrenergic receptor antagonists, angiotensin receptor blockers, topical nitrates or fluoxetine to treat RP. The intravenously administered prostacyclin analogue iloprost can reduce the frequency and severity of RP attacks and is considered a second-line therapy in patients with markedly impaired quality of life, critical digital ischaemia and skin ulcers who are at risk for substantial tissue loss and amputation. Phosphodiesterase inhibitors (e.g., sildenafil) can also improve RP symptoms and ulcer healing whereas endothelin-1 receptor antagonists (e.g., bosentan) are mainly considered treatment options in secondary prevention for patients with digital skin ulcers related to systemic sclerosis. However, their use in clinical practice has been limited by their high cost. Antiplatelet therapy with low-dose aspirin is recommended for all patients who suffer from secondary RP due to ischaemia caused by structural vessel damage. Anticoagulant therapy can be considered during the acute phase of digital ischaemia in patients with suspected vascular occlusive disease attributed to the occurrence of new thromboses. In patients with critical digital ischaemia, consideration should be given to hospitalisation, optimisation of medical treatment in accordance with the underlying disease and evaluation for a secondary, possibly reversible process that is causing or aggravating the clinical symptoms.

Acute peri-operative beta blockade in intermediate-risk patients.

PubMed

Biccard, B M; Sear, J W; Foëx, P

2006-10-01

Peri-operative beta-blockade has been shown to reduce the incidence of postoperative cardio- vascular complications including cardiac death in high-risk non-cardiac surgical patients. However, the recent analysis by Lindenauer et al. suggests that it is inappropriate to administer beta-blockers blindly to all surgical patients. In an attempt to determine the appropriateness of peri-operative beta-blocker administration across patients with a spectrum of cardiovascular risks, we have examined studies of intermediate-risk patient groups (that is those undergoing intermediate risk surgery or those with a Lee Revised Cardiac Risk Score of < or =2). We analysed data from randomised prospective studies of the effects of acute peri-operative beta-blockade on the incidence of peri-operative myocardial ischaemia. By examining the demographics and surgical interventions in these patients, we have compared these studies with other studies of peri-operative silent myocardial ischaemia representing patients of similar risk. We thus estimated the expected long-term postoperative cardiovascular complication rate associated with myocardial ischaemia in these patients in terms of number needed to treat for ischaemia prevention and for prevention of major cardiovascular complications. Prevention of peri-operative myocardial ischaemia with acute beta-blockade in non-cardiac surgical patients with 1-2 RCRI clinical risk factors can be achieved with a number needed to treat of 10. It is not associated with a significant increase in drug associated side-effects. However, acute beta-blockade shows no real benefit in the prevention of major cardiovascular complications in intermediate risk non-vascular surgical patients with a number-needed-to-treat of 833. Vascular surgical patients undergoing intermediate-risk surgery may benefit from the protective effects of acute peri-operative beta-blockade, however, with a number-needed-to-treat of 68 it would require a randomised clinical trial of over 24,000 patients to prove their efficacy.

Endocannabinoids protect the rat isolated heart against ischaemia

PubMed Central

Lépicier, Philippe; Bouchard, Jean-François; Lagneux, Caroline; Lamontagne, Daniel

2003-01-01

The purpose of this study was to determine whether endocannabinoids can protect the heart against ischaemia and reperfusion. Rat isolated hearts were exposed to low-flow ischaemia (0.5–0.6 ml min−1) and reperfusion. Functional recovery as well as CK and LDH overflow into the coronary effluent were monitored. Infarct size was determined at the end of the experiments. Phosphorylation levels of p38, ERK1/2, and JNK/SAPK kinases were measured by Western blots. None of the untreated hearts recovered from ischaemia during the reperfusion period. Perfusion with either 300 nM palmitoylethanolamide (PEA) or 300 nM 2-arachidonoylglycerol (2-AG), but not anandamide (up to 1 μM), 15 min before and throughout the ischaemic period, improved myocardial recovery and decreased the levels of coronary CK and LDH. PEA and 2-AG also reduced infarct size. The CB2-receptor antagonist, SR144528, blocked completely the cardioprotective effect of both PEA and 2-AG, whereas the CB1-receptor antagonist, SR141716A, blocked partially the effect of 2-AG only. In contrast, both ACEA and JWH015, two selective agonists for CB1- and CB2- receptors, respectively, reduced infarct size at a concentration of 50 nM. PEA enhanced the phosphorylation level of p38 MAP kinase during ischaemia. PEA perfusion doubled the baseline phosphorylation level of ERK1/2, and enhanced its increase upon reperfusion. The cardioprotective effect of PEA was completely blocked by the p38 MAP kinase inhibitor, SB203580, and significantly reduced by the ERK1/2 inhibitor, PD98059, and the PKC inhibitor, chelerythrine. In conclusion, endocannabinoids exert a strong cardioprotective effect in a rat model of ischaemia–reperfusion that is mediated mainly through CB2-receptors, and involves p38, ERK1/2, as well as PKC activation. PMID:12813004

The use of old donors in liver transplantation.

PubMed

Dasari, Bobby V M; Schlegel, Andrea; Mergental, Hynek; Perera, M Thamara P R

2017-04-01

The process of ageing has an impact on the entire human body including the organ systems. In transplantation, professionals are daily faced with risk assessment of suitable donor offers , whether to accept a liver graft for a specific recipient. In this context, livers from elderly donors are more frequently accepted for transplantation, to increase the donor pool and compensate the high waiting list mortality. In the current practice it is not unusual to accept 60-year old donor livers for transplantation, as the donor demographics have significantly changed over the years. However, controversy exists regarding the use of livers from donors above 70 or 80 years, particular in combination with other risk factors, e.g. liver steatosis, warm ischaemia or long cold storage. This review focuses first on the impact of ageing on liver morphology and function. Second, we will highlight outcome after transplantation from elderly donors. Finally, we describe further risk factors and donor-recipient selection under the scope of old donor organs and include our institutional experience and policy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Colonic casts: unexpected complications of colonic ischaemia.

PubMed

Mantas, D; Damaskos, C; Bamias, G; Dimitroulis, D

2016-09-01

Introduction Extensive colonic ischaemia can result in passage of a colonic 'cast' (CC) through the rectum. Case Study We report a 69-year-old male who initially underwent surgery to remove a sessile polyp. On postoperative day (POD)15, he was febrile, suffering from diarrhoea, and was treated conservatively. On POD18, the patient returned to our hospital with a CC that presented after defaecation. Computed tomography of the abdomen revealed a CC extending from the descending colon to the anal orifice with presentation of air between the affected colonic wall and the CC. The patient was treated conservatively and discharged on POD20 without complications having passed the CC (≈80cm) completely and becoming afebrile. Conclusions In most cases, the cause of CC passage is surgery for colorectal cancer or repair of an abdominal aortic aneurysm. A mild-to-severe presentation is dependent upon the bowel-wall layers affected by ischaemia and which therefore are included in the CC.

A multiantioxidant supplementation reduces damage from ischaemia reperfusion in patients after lower torso ischaemia. A randomised trial.

PubMed

Wijnen, M H W A; Roumen, R M H; Vader, H L; Goris, R J A

2002-06-01

open repair of intra-abdominal aortic aneurysm (AAA) is associated with lower torso ischaemia and reperfusion. to examine the effect of antioxidants on the activation and sequestration of white blood cells and muscle injury during AAA repair. forty-two patients undergoing elective infrarenal aneurysm repair, were randomised to either standard therapy (22 patients) or standard therapy with additional multiantioxidant supplementation (20 patients). Vitamin E and C, Allopurinol, N-acetylcysteine and mannitol was administered perioperatively. White blood cell count (WBC), serum creatine kinase, aspartateaminotransferase, lactate and lipofuscine were measured. WBC remained higher after reperfusion in the antioxidant group (p = 0.008). CK, ASAT and lipofuscine levels were significantly lower after reperfusion in the antioxidant group (p = 0.02, p = 0.018, p = 0.017). multi-antioxidant supplementation was associated with a reduction in serum CK and ASAT after AAA repair. This is likely due to a reduction in oxidative stress and a decreased leucocyte sequestration and activation. Copyright 2002 Elsevier Science Ltd.

Moderate elevation of intracellular creatine by targeting the creatine transporter protects mice from acute myocardial infarction

PubMed Central

Lygate, Craig A.; Bohl, Steffen; ten Hove, Michiel; Faller, Kiterie M.E.; Ostrowski, Philip J.; Zervou, Sevasti; Medway, Debra J.; Aksentijevic, Dunja; Sebag-Montefiore, Liam; Wallis, Julie; Clarke, Kieran; Watkins, Hugh; Schneider, Jürgen E.; Neubauer, Stefan

2012-01-01

Aims Increasing energy storage capacity by elevating creatine and phosphocreatine (PCr) levels to increase ATP availability is an attractive concept for protecting against ischaemia and heart failure. However, testing this hypothesis has not been possible since oral creatine supplementation is ineffectual at elevating myocardial creatine levels. We therefore used mice overexpressing creatine transporter in the heart (CrT-OE) to test for the first time whether elevated creatine is beneficial in clinically relevant disease models of heart failure and ischaemia/reperfusion (I/R) injury. Methods and results CrT-OE mice were selected for left ventricular (LV) creatine 20–100% above wild-type values and subjected to acute and chronic coronary artery ligation. Increasing myocardial creatine up to 100% was not detrimental even in ageing CrT-OE. In chronic heart failure, creatine elevation was neither beneficial nor detrimental, with no effect on survival, LV remodelling or dysfunction. However, CrT-OE hearts were protected against I/R injury in vivo in a dose-dependent manner (average 27% less myocardial necrosis) and exhibited greatly improved functional recovery following ex vivo I/R (59% of baseline vs. 29%). Mechanisms contributing to ischaemic protection in CrT-OE hearts include elevated PCr and glycogen levels and improved energy reserve. Furthermore, creatine loading in HL-1 cells did not alter antioxidant defences, but delayed mitochondrial permeability transition pore opening in response to oxidative stress, suggesting an additional mechanism to prevent reperfusion injury. Conclusion Elevation of myocardial creatine by 20–100% reduced myocardial stunning and I/R injury via pleiotropic mechanisms, suggesting CrT activation as a novel, potentially translatable target for cardiac protection from ischaemia. PMID:22915766

Case Report of the surgical management of small bowel and colonic ischaemia associated with Anorexia Nervosa binge/purge subtype.

PubMed

Foran, Ann T; Clancy, Cillian; Gorey, Tom F

2016-01-01

Anorexia Nervosa affects up to 1% of the population and can present with binge/purge episodes. A paucity of literature exists regarding small bowel and colonic ischaemia relating to this common condition. We report our own experience and management of a patient with anorexia nervosa binge/purge subtype with small bowel and colon ischaemia and review existing cases in the literature. A 32year old female self-presented to the emergency department complaining of abdominal pain, abdominal distension and vomiting on a background history of binge/purge subtype eating disorder, following consumption of a large amount of carbohydrates. Computed tomography (CT) of the abdomen was performed urgently which revealed extensive pneumatosis involving the stomach and its draining veins with evidence of extensive portal venous gas. A right hemicolectomy followed by re-look laparotomy in 48h with resection of jejunum, jejunojejunal anastomosis and end-ileostomy was performed with a successful outcome. Anorexia nervosa can be a potentially life-threatening disease, with rates of death 10-12 times that of the normal population. Ischaemic bowel is a rare potential complication, with mortality rates of up to 80% having been reported prior to this case. Although the exact mechanism remains to be elucidated, gastric dilation, abnormal digestive motility, and faecal impaction appear to contribute, on a background of impaired blood supply. Clinicians need to exhibit a high index of suspicion for patients with abdominal pain on the background of an eating disorder, particularly in the context of suspected recent refeeding/binge eating. Prompt involvement of appropriate radiology and surgery input are pivotal to outcome. Copyright © 2016. Published by Elsevier Ltd.

Selective blockade of protein kinase B protects the rat and human myocardium against ischaemic injury

PubMed Central

Linares-Palomino, José; Husainy, Muhammad A; Lai, Vien K; Dickenson, John M; Galiñanes, Manuel

2010-01-01

Protein kinase B (PKB/Akt) plays a critical role in cell survival but the investigation of its involvement has been limited by the lack of specific pharmacological agents. In this study, using novel PKB inhibitors (VIII and XI), we investigated the role of PKB in cardioprotection of the rat and human myocardium, the location of PKB in relation to mitoKATP channels and p38 mitogen-activated protein kinase (p38 MAPK), and whether the manipulation of PKB can overcome the unresponsiveness to protection of the diabetic myocardium. Myocardial slices from rat left ventricle and from the right atrial appendage of patients undergoing elective cardiac surgery were subjected to 90 min ischaemia/120 min reoxygenation at 37°C. Tissue injury was assessed by creatine kinase (CK) released and determination of cell necrosis and apoptosis. The results showed that blockade of PKB activity caused significant reduction of CK release and cell death, a benefit that was as potent as ischaemic preconditioning and could be reproduced by blockade of phosphatidylinositol 3-kinase (PI-3K) with wortmannin and LY 294002. The protection was time dependent with maximal benefit seen when PKB and PI-3K were inhibited before ischaemia or during both ischaemia and reoxygenation. In addition, it was revealed that PKB is located downstream of mitoKATP channels but upstream of p38 MAPK. PKB inhibition induced a similar degree of protection in the human and rat myocardium and, importantly, it reversed the unresponsiveness to protection of the diabetic myocardium. In conclusion, inhibition of PKB plays a critical role in protection of the mammalian myocardium and may represent a clinical target for the reduction of ischaemic injury. PMID:20403980

Attenuation of changes in capillary fine structure and leukocyte adhesion improves muscle performance following chronic ischaemia in rats

PubMed Central

Hudlická, O; Garnham, A; Shiner, R; Egginton, S

2008-01-01

Acute ischaemia–reperfusion disrupts capillary fine structure and increases leukocyte adhesion in postcapillary venules. We determined whether chronic muscle ischaemia has similar consequences, and whether it is possible to ameliorate its effect on muscle performance. Following ischaemia (unilateral ligation, common iliac artery) rat hindlimb muscles were examined without other intervention or following treatment with an xanthine oxidase inhibitor (allopurinol), a Na+/H+ exchange blocker (amiloride), or an oxygen free radical scavenger (vitamin E). No significant leukocyte adhesion or rolling, nor changes in capillary fine structure were observed 3 days postsurgery, when limb use was limited. However, leukocyte rolling and adhesion almost trebled by 7 days (P < 0.001), when normal gait was largely restored. Capillary fine structure was disturbed over a similar time course, e.g. relative endothelial volume (control 46%, 7 days 61%; P < 0.05), that resolved by 5 weeks. Where activity was increased by mild electrical stimulation 3 days after ligation muscles showed enhanced capillary swelling (endothelial volume 66%versus 50%, P < 0.005), but improved fatigue index (52%versus 16%, P < 0.001) as a result of greater blood flow. Muscle fatigue after ligation was related to the extent of contraction-induced hyperaemia (R2= 0.725), but not capillary swelling. Amiloride, and to a lesser extent allopurinol but not vitamin E, significantly decreased leukocyte rolling and adhesion, as well as capillary endothelial swelling. We conclude that increased activity of ischaemic muscles on recovery is likely to accentuate acidosis accompanying changes in microcirculation and contribute to enhanced muscle fatigue, whereas formation of oxygen free radicals may be attenuated by endogenous protective mechanisms. PMID:18755748

Effect of novel vitamin D receptor activator paricalcitol on renal ischaemia/reperfusion injury in rats

PubMed Central

Huddam, B; Haberal, N; Koçak, G; Ortabozkoyun, L; Şenes, M; Akdoğan, MF; Denizli, N; Duranay, M

2013-01-01

Introduction Despite the developments in modern medicine, acute renal injury is still a challenging and common health problem. It is well known that ischaemia and reperfusion takes place in pathological mechanisms. Efforts to clarify the pathophysiology and interventions to improve outcomes are essential. Our study aimed to investigate whether the prophylactic use of paricalcitol is beneficial in renal ischaemia/reperfusion (I/R) injury. Methods Twenty-four Wistar albino rats were assigned randomly to four groups. Right nephrectomies were performed at the time of renal arterial clamping. Sham surgery was performed on the rats in group 1. For the rats in group 2, the left renal artery was clamped for 45 minutes. The rats in group 3 received paricalcitol for seven days (0.2µg/kg/day); following this, a right nephrectomy and left renal arterial clamping were not performed. The rats in group 4 received paricalcitol for seven days (0.2µg/ kg/day); following this, a right nephrectomy and left renal arterial clamping for 45 minutes were performed. Tissue thiobarbituric acid reactive substances (TBARS), superoxide dismutase, sulfhydryl groups as well as nitric oxide metabolites, serum urea and creatinine levels were measured for all four groups. Results In group 4, there were some improvements in terms of TBARS, nitrite, nitrate, superoxide dismutase and creatinine levels. In the histopathological evaluation, paricalcitol therapy improved tubular necrosis and medullar congestion but there was no significant difference in terms of tubular cell swelling, cellular vacuolisation or general damage. Immunohistopathological examination revealed lower scores for vascular endothelial growth factor in the group 4 rats than in group 2. Conclusions Paricalcitol therapy improved renal I/R injury in terms of serum and histopathological parameters. These potential beneficial effects need to be further investigated. PMID:24112495

Treatment with the CC chemokine-binding protein Evasin-4 improves post-infarction myocardial injury and survival in mice.

PubMed

Braunersreuther, Vincent; Montecucco, Fabrizio; Pelli, Graziano; Galan, Katia; Proudfoot, Amanda E; Belin, Alexandre; Vuilleumier, Nicolas; Burger, Fabienne; Lenglet, Sébastien; Caffa, Irene; Soncini, Debora; Nencioni, Alessio; Vallée, Jean-Paul; Mach, François

2013-10-01

Chemokines trigger leukocyte trafficking and are implicated in cardiovascular disease pathophysiology. Chemokine-binding proteins, called "Evasins" have been shown to inhibit both CC and CXC chemokine-mediated bioactivities. Here, we investigated whether treatment with Evasin-3 (CXC chemokine inhibitor) and Evasin-4 (CC chemokine inhibitor) could influence post-infarction myocardial injury and remodelling. C57Bl/6 mice were submitted in vivo to left coronary artery permanent ligature and followed up for different times (up to 21 days). After coronary occlusion, three intraperitoneal injections of 10 μg Evasin-3, 1 μg Evasin-4 or equal volume of vehicle (PBS) were performed at 5 minutes, 24 hours (h) and 48 h after ischaemia onset. Both anti-chemokine treatments were associated with the beneficial reduction in infarct size as compared to controls. This effect was accompanied by a decrease in post-infarction myocardial leukocyte infiltration, reactive oxygen species release, and circulating levels of CXCL1 and CCL2. Treatment with Evasin-4 induced a more potent effect, abrogating the inflammation already at one day after ischaemia onset. At days 1 and 21 after ischaemia onset, both anti-chemokine treatments failed to significantly improve cardiac function, remodelling and scar formation. At 21-day follow-up, mouse survival was exclusively improved by Evasin-4 treatment when compared to control vehicle. In conclusion, we showed that the selective inhibition of CC chemokines (i.e. CCL5) with Evasin-4 reduced cardiac injury/inflammation and improved survival. Despite the inhibition of CXC chemokine bioactivities, Evasin-3 did not affect mouse survival. Therefore, early inhibition of CC chemokines might represent a promising therapeutic approach to reduce the development of post-infarction heart failure in mice.

[Comprehensive monitoring of cerebral haemodynamics during surgical interventions on brachiocephalic arteries].

PubMed

Ignat'ev, I M; Bredikhin, R A; Falina, T G; Vinogradova, V V; Khismatullina, L I

2010-01-01

The authors analysed a total of 152 surgical interventions on the brachiocephalic arteries (BCAs) performed in 142 patients. All the patients were subjected to intraoperative monitoring of cerebral haemodynamics by means of transcranial Doppler (TCD) ultrasonography simultaneously accompanied by electroencephalography (EEG). Additionally, the state of the reconstructed carotid arteries was controlled by means of ultrasonographic duplex scanning (USDS). Comparing the findings of the TCD recording and EEG made it possible to single out 5 groups of the operated patients. The EEG technique turned out to have more informative value as compared with TCD ultrasonography in determining the degree of cerebral ischaemia during clamping of the carotid arteries (CAs). Nine (5.9%) patients demonstrated lower tolerance of the brain to ischaemia, and the operation on the BCA was performed with the use of a temporal intraluminal bypass graft. Microembolic signals (MES) were registered in 54.6% of cases. Single MES were detected in six patients, sporadic MES--in 53, and multiple MES--in 24. Mention should be made that the--MES associated with the placement of the bypass graft appeared to be multiple and were registered in all the operated patients. Diffusion-weighted magnetic resonance tomography revealed fresh foci of lacunar cerebral infarctions in 14 (25%) of the 56 patients thus examined. Intraoperative USDS of the reconstructed carotid arteries revealed floatation of the residual remnants of the intima in two patients, which was the cause of a repeat intervention. Combined monitoring of cerebral haemodynamics makes it possible to timely prevent cerebral ischaemia, to narrow the indications for placement of an intraluminal bypass graft, and to dramatically decrease the rate of postoperative complications.

Does the method of expression of venous blood affect ischaemia/reperfusion damage in tourniquet use? An experimental study on rabbits.

PubMed

Iltar, Serkan; Kılınç, Cem Yalın; Alemdaroğlu, Kadir Bahadır; Ozcan, Selahattin; Aydoğan, Nevres Hürriyet; Sürer, Hatice; Kılınç, Aytün Şadan

2013-11-01

The aim of this study was to compare the ischaemia and reperfusion phases of two tourniquet application models (Group 1: expressing the blood by a sterile rubber bandage and Group 2: elevation of the limb for several minutes) using an analysis of ischaemia/reperfusion parameters and blood pH. Sixteen New Zealand rabbits were used. Muscle samples were extracted from the triceps surae; at phase A (baseline: just before tourniquet application), phase B (ischaemia: 3h after tourniquet inflation) and phase C (2h after tourniquet deflation). Nitrite, nitrate, reduced glutathione, myeloperoxidase, malondyaldehyde were measured in the samples. Blood pH was also measured at each phase. Group 2 had significantly decreased nitrite (p=0.007) and nitrate (p=0.01) levels compared to Group 1 while passing from phase A to phase B. The pH decrease through the phases was significant within Group 1 (p=0.006) and was not significant within Group 2 (p=0.052). Lower levels of NO metabolites nitrate and nitrite, result from tourniquet use with incomplete venous blood expression by elevation. Also, with this technique severe acidosis is less likely to occur than when a tourniquet is used with expression of the venous blood by rubber bandage. These findings may help in the decision of which tourniquet technique is to be used for potentially long operations which may exceed 2h. Copyright © 2013 Elsevier Ltd. All rights reserved.

Electrocardiogram interpretation in general practice: relevance to prehospital thrombolysis.

PubMed Central

McCrea, W A; Saltissi, S

1993-01-01

OBJECTIVE--To assess, in the context of their possible role in prehospital thrombolysis, the ability of general practitioners to recognise acute transmural myocardial ischaemia/infarction on an electrocardiogram. DESIGN--150 doctors (every fifth name) were selected from the alphabetical list of 750 on Merseyside general practitioner register and without prior warning were asked to interpret a series of six 12 lead electrocardiograms. Three of these showed acute transmural ischaemia/infarction, one was normal, and two showed non-acute abnormalities. Details of doctors' ages, postgraduate training, and clinical practice were sought. SETTING--General practitioners' surgeries and postgraduate centres within the Merseyside area. PARTICIPANTS--106 general practitioners (mean age 45 years) agreed to participate. MAIN OUTCOME MEASURE--Accuracy of general practitioners' interpretations of the six electrocardiograms. RESULTS--82% of general practitioners correctly recognised a normal electrocardiogram. Recognition of acute abnormalities was less reliable. Between 33% and 61% correctly identified acute transmural ischaemia/infarction depending on the specific trace presented. Accurate localisation of the site of the infarct was achieved only by between 8% and 30% of participants, while between 22% and 25% correctly interpreted non-acute abnormalities. Neither routine use of electrocardiography nor postgraduate hospital experience in general medicine was associated with significantly greater expertise. CONCLUSION--The current level of proficiency of a sample of general practitioners in the Merseyside area in recognising acute transmural ischaemia/infarction on an electrocardiogram suggests that refresher training is needed if general practitioners are to give prehospital thrombolysis. Images PMID:8398491

Daytime warming has stronger negative effects on soil nematodes than night-time warming.

PubMed

Yan, Xiumin; Wang, Kehong; Song, Lihong; Wang, Xuefeng; Wu, Donghui

2017-03-07

Warming of the climate system is unequivocal, that is, stronger warming during night-time than during daytime. Here we focus on how soil nematodes respond to the current asymmetric warming. A field infrared heating experiment was performed in the western of the Songnen Plain, Northeast China. Three warming modes, i.e. daytime warming, night-time warming and diurnal warming, were taken to perform the asymmetric warming condition. Our results showed that the daytime and diurnal warming treatment significantly decreased soil nematodes density, and night-time warming treatment marginally affected the density. The response of bacterivorous nematode and fungivorous nematode to experimental warming showed the same trend with the total density. Redundancy analysis revealed an opposite effect of soil moisture and soil temperature, and the most important of soil moisture and temperature in night-time among the measured environment factors, affecting soil nematode community. Our findings suggested that daily minimum temperature and warming induced drying are most important factors affecting soil nematode community under the current global asymmetric warming.

Daytime warming has stronger negative effects on soil nematodes than night-time warming.

PubMed

Yan, Xiumin; Wang, Kehong; Song, Lihong; Wang, Xuefeng; Wu, Donghui

2017-03-20

Warming of the climate system is unequivocal, that is, stronger warming during night-time than during daytime. Here we focus on how soil nematodes respond to the current asymmetric warming. A field infrared heating experiment was performed in the western of the Songnen Plain, Northeast China. Three warming modes, i.e. daytime warming, night-time warming and diurnal warming, were taken to perform the asymmetric warming condition. Our results showed that the daytime and diurnal warming treatment significantly decreased soil nematodes density, and night-time warming treatment marginally affected the density. The response of bacterivorous nematode and fungivorous nematode to experimental warming showed the same trend with the total density. Redundancy analysis revealed an opposite effect of soil moisture and soil temperature, and the most important of soil moisture and temperature in night-time among the measured environment factors, affecting soil nematode community. Our findings suggested that daily minimum temperature and warming induced drying are most important factors affecting soil nematode community under the current global asymmetric warming.

Daytime warming has stronger negative effects on soil nematodes than night-time warming

PubMed Central

Yan, Xiumin; Wang, Kehong; Song, Lihong; Wang, Xuefeng; Wu, Donghui

2017-01-01

Warming of the climate system is unequivocal, that is, stronger warming during night-time than during daytime. Here we focus on how soil nematodes respond to the current asymmetric warming. A field infrared heating experiment was performed in the western of the Songnen Plain, Northeast China. Three warming modes, i.e. daytime warming, night-time warming and diurnal warming, were taken to perform the asymmetric warming condition. Our results showed that the daytime and diurnal warming treatment significantly decreased soil nematodes density, and night-time warming treatment marginally affected the density. The response of bacterivorous nematode and fungivorous nematode to experimental warming showed the same trend with the total density. Redundancy analysis revealed an opposite effect of soil moisture and soil temperature, and the most important of soil moisture and temperature in night-time among the measured environment factors, affecting soil nematode community. Our findings suggested that daily minimum temperature and warming induced drying are most important factors affecting soil nematode community under the current global asymmetric warming. PMID:28317914

Daytime warming has stronger negative effects on soil nematodes than night-time warming

NASA Astrophysics Data System (ADS)

Yan, Xiumin; Wang, Kehong; Song, Lihong; Wang, Xuefeng; Wu, Donghui

2017-03-01

Warming of the climate system is unequivocal, that is, stronger warming during night-time than during daytime. Here we focus on how soil nematodes respond to the current asymmetric warming. A field infrared heating experiment was performed in the western of the Songnen Plain, Northeast China. Three warming modes, i.e. daytime warming, night-time warming and diurnal warming, were taken to perform the asymmetric warming condition. Our results showed that the daytime and diurnal warming treatment significantly decreased soil nematodes density, and night-time warming treatment marginally affected the density. The response of bacterivorous nematode and fungivorous nematode to experimental warming showed the same trend with the total density. Redundancy analysis revealed an opposite effect of soil moisture and soil temperature, and the most important of soil moisture and temperature in night-time among the measured environment factors, affecting soil nematode community. Our findings suggested that daily minimum temperature and warming induced drying are most important factors affecting soil nematode community under the current global asymmetric warming.

Laparoscopic versus open nephrectomy for live kidney donors.

PubMed

Wilson, Colin H; Sanni, Aliu; Rix, David A; Soomro, Naeem A

2011-11-09

Waiting lists for kidney transplantation continue to grow and live organ donation has become more important as the number of brain stem dead cadaveric organ donors continues to fall. The major disincentive to potential kidney donors is the pain and morbidity associated with open surgery. To identify the benefits and harms of using laparoscopic compared to open nephrectomy techniques to recover kidneys from live organ donors. We searched the online databases CENTRAL (in The Cochrane Library 2010, Issue 2), MEDLINE (January 1966 to January 2010) and EMBASE (January 1980 to January 2010) and handsearched textbooks and reference lists. Randomised controlled trials comparing laparoscopic donor nephrectomy (LDN) with open donor nephrectomy (ODN). Two review authors independently screened titles and abstracts for eligibility, assessed study quality, and extracted data. We contacted study authors for additional information where necessary. Six studies were identified that randomised 596 live kidney donors to either LDN or ODN arms. All studies were assessed as having low or unclear risk of bias for selection bias, allocation bias, incomplete outcome data and selective reporting bias. Four of six studies had high risk of bias for blinding. Various different combinations of techniques were used in each study, resulting in heterogeneity in the results. The conversion rate from LDN to ODN ranged from 1% to 1.8%. LDN was generally found to be associated with reduced analgesia use, shorter hospital stay, and faster return to normal physical functioning. The extracted kidney was exposed to longer warm ischaemia periods (2 to 17 minutes) with no associated short-term consequences. ODN was associated with shorter duration of procedure. For those outcomes that could be meta-analysed there were no significant differences between LDN or ODN for perioperative complications (RR 0.87, 95% CI 0.47 to 4.59), reoperations (RR 0.57, 95% CI 0.09 to 3.64), early graft loss (RR 0.31, 95% CI 0.06 to 1.48), delayed graft function (RR 1.09, 95% CI 0.52 to 2.30), acute rejection (RR 1.41, 95 % CI 0.87 to 2.27), ureteric complications (RR 1.51, 95% CI 0.69 to 3.31), kidney function at one year (SMD 0.15, 95% CI -0.11 to 0.41) or graft loss at one year (RR 0.76, 95% CI 0.15 to 3.85). LDN is associated with less pain compared with open surgery; however, there are equivalent numbers of complications and occurrences of perioperative events that require further intervention. Kidneys obtained using LDN procedures were exposed to longer warm ischaemia periods than ODN-acquired grafts, although this has not been reported as being associated with short-term consequences.

Robotic partial nephrectomy - Evaluation of the impact of case mix on the procedural learning curve.

PubMed

Roman, A; Ahmed, K; Challacombe, B

2016-05-01

Although Robotic partial nephrectomy (RPN) is an emerging technique for the management of small renal masses, this approach is technically demanding. To date, there is limited data on the nature and progression of the learning curve in RPN. To analyse the impact of case mix on the RPN LC and to model the learning curve. The records of the first 100 RPN performed, were analysed at our institution that were carried out by a single surgeon (B.C) (June 2010-December 2013). Cases were split based on their Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score into the following groups: 6-7, 8-9 and >10. Using a split group (20 patients in each group) and incremental analysis, the mean, the curve of best fit and R(2) values were calculated for each group. Of 100 patients (F:28, M:72), the mean age was 56.4 ± 11.9 years. The number of patients in each PADUA score groups: 6-7, 8-9 and >10 were 61, 32 and 7 respectively. An increase in incidence of more complex cases throughout the cohort was evident within the 8-9 group (2010: 1 case, 2013: 16 cases). The learning process did not significantly affect the proxies used to assess surgical proficiency in this study (operative time and warm ischaemia time). Case difficulty is an important parameter that should be considered when evaluating procedural learning curves. There is not one well fitting model that can be used to model the learning curve. With increasing experience, clinicians tend to operate on more difficult cases. Copyright © 2016 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Successful partial ear replantation after prolonged ischaemia time.

PubMed

Shelley, O P; Villafane, O; Watson, S B

2000-01-01

We present the case of a 34-year-old male patient who had successful replantation of upper pole of pinna 33 h after amputation. As no vein was anastomosed, systemic heparinisation and subcutaneous injection of heparin to the replanted ear were used to encourage outflow. Complications included arterial spasm and bleeding. Management of similar cases as planned urgent cases rather than emergency cases is discussed. Copyright 2000 The British Association of Plastic Surgeons.

Bud break responds more strongly to daytime than night-time temperature under asymmetric experimental warming.

PubMed

Rossi, Sergio; Isabel, Nathalie

2017-01-01

Global warming is diurnally asymmetric, leading to a less cold, rather than warmer, climate. We investigated the effects of asymmetric experimental warming on plant phenology by testing the hypothesis that daytime warming is more effective in advancing bud break than night-time warming. Bud break was monitored daily in Picea mariana seedlings belonging to 20 provenances from Eastern Canada and subjected to daytime and night-time warming in growth chambers at temperatures varying between 8 and 16 °C. The higher advancements of bud break and shorter times required to complete the phenological phases occurred with daytime warming. Seedlings responded to night-time warming, but still with less advancement of bud break than under daytime warming. No advancement was observed when night-time warming was associated with a daytime cooling. The effect of the treatments was uniform across provenances. Our observations realized under controlled conditions allowed to experimentally demonstrate that bud break can advance under night-time warming, but to a lesser extent than under daytime warming. Prediction models using daily timescales could neglect the diverging influence of asymmetric warming and should be recalibrated for higher temporal resolutions. © 2016 John Wiley & Sons Ltd.

Endogenous bradykinin activates ischaemically sensitive cardiac visceral afferents through kinin B2 receptors in cats

PubMed Central

Tjen-A-Looi, Stephanie C; Pan, Hui-Lin; Longhurst, John C

1998-01-01

Activity of ischaemically sensitive cardiac visceral afferents during myocardial ischaemia induces both angina and cardiovascular reflexes. Increased production of bradykinin (BK) and cyclo-oxygenase products (i.e. prostaglandins (PGs)) occurs during myocardial ischaemia. However, the role of these agents in activation of ischaemically sensitive cardiac afferents has not been established. The present study tested the hypothesis that BK produced during ischaemia activates cardiac afferents through kinin B2 receptors. Single-unit activity of cardiac afferents innervating the left ventricle was recorded from the left thoracic sympathetic chain (T1–T4) of anaesthetized cats. Ischaemically sensitive cardiac afferents were identified according to their response to 5 min of myocardial ischaemia. The mechanism of BK in activation of ischaemically sensitive cardiac afferents was determined by injection of BK (1 μg kg−1 i.a.), des-Arg9-BK (1 μg kg−1 i.a., a specific kinin B1 receptor agonist), kinin B2 receptor antagonists: HOE140 (30 μg kg−1 i.v.) and NPC-17731 (40 μg kg−1 i.v.), cyclo-oxygenase inhibition with indomethacin (5 mg kg−1 i.v.) and NPC-17731 (40 μg kg−1 i.v.) after pretreatment with indomethacin (5 mg kg−1 i.v.). We observed that BK increased the discharge rate of all eleven ischaemically sensitive cardiac afferents from 0.39 ± 0.12 to 1.47 ± 0.37 impulses s−1 (P < 0.05). Conversely, des-Arg9-BK did not significantly increase the activity of eleven ischaemically sensitive fibres (0.58 ± 0.02 vs. 0.50 ± 0.18 impulses s−1). HOE140 significantly attenuated the response of twelve afferents to ischaemia (0.61 ± 0.22 to 1.85 ± 0.5 vs. 0.53 ± 0.16 to 1.09 ± 0.4 impulses s−1). NPC-17731, another kinin B2 receptor antagonist, had similar inhibitory effects on six other ischaemically sensitive cardiac afferents (0.35 ± 0.14 to 1.19 ± 0.29 vs. 0.22 ± 0.08 to 0.23 ± 0.07 impulses s−1). Indomethacin significantly reduced the responses of seven afferents to ischaemia (0.35 ± 0.13 to 1.89 ± 0.48 vs. 0.40 ± 0.10 to 0.76 ± 0.24 impulses s−1). Indomethacin also significantly reduced the responses of six ischaemically sensitive cardiac afferents to BK (2.65 ± 1.23 to 1.2 ± 0.51 impulses s−1). In six cats pretreated with indomethacin, NPC-17731 attenuated the impulse activity of six ischaemically sensitive cardiac afferents (0.39 ± 0.12 to 1.0 ± 0.3 vs. 0.26 ± 0.14 to 0.48 ± 0.20 impulses s−1). This study demonstrates that BK produced during ischaemia contributes to stimulation of ischaemically sensitive cardiac visceral afferents through activation of kinin B2 receptors. Furthermore, BK stimulates ischaemically sensitive cardiac visceral afferents through a mechanism that is, at least in part, independent of cyclo-oxygenase activation. PMID:9706010

Ameliorating effects of dexpanthenol in cerebral ischaemia reperfusion induced injury in rat brain.

PubMed

Zakaria, Mohammad Mehdi Hosseinian; Hajipour, Babak; Khodadadi, Ali; Afshari, Fatemeh

2011-09-01

To study the attenuating effect of Dexpanthenol (Dxp) provitamin B5 on neuronal damage after cerebral ischaemia/reperfusion. This was a randomized, controlled experimental study conducted at the Islamic Azad University, Tabriz, Iran, from April to September 2008. Male wistar rats were divided into 4 groups randomly (n=13): 1- sham group, Group 2 :two hours occlusion of middle cerebral artery (MCA) and 24 hours reperfusion. Group 3: two hours occlusion of MCA and 24 hours reperfusion + Dxp (250mg/kg) since 3 days before ischaemia. Group 4: two hours occlusion of MCA and 24 hours reperfusion which had received Dxp (500mg/kg) since 3 days before ischaemia. Glutathione (GSH) and malondialdehyde (MDA) levels were studied in brain tissue and numbers of cornu ammonis (CA1 and CA3) pyramidal neurons were studied with light microscopy. The GSH levels were significantly higher in groups 3 and 4 as compared with group 2. In group 3 and group 4 animals, the MDA levels were significantly lower than in group 2 (P < 0.05). Numbers of CA1 and CA3 neurons were completely normal in appearance in the group 1. The surviving neurons in the CA1 and CA3 subfield were markedly decreased in number, in group 2 (P < 0.05). Our pathologic and biochemical study has proven positive effect of Dxp on protection of cerebral tissue after I/R. The present findings correlate with previous studies on the protective effects of Dxp against cell and tissue injury by I/R.

Enhanced effect of gap junction uncouplers on macroscopic electrical properties of reperfused myocardium

PubMed Central

Rodriguez-Sinovas, Antonio; García-Dorado, David; Ruiz-Meana, Marisol; Soler-Soler, Jordi

2004-01-01

Transient inhibition of gap junction (GJ)-mediated communication with heptanol during myocardial reperfusion limits infarct size. However, inhibition of cell coupling in normal myocardium may be arrhythmogenic. The purpose of this study was to test the hypothesis that the consequences of GJ inhibition may be magnified in reperfused myocardium compared with normal tissue, thus allowing the inhibition of GJs in reperfused tissue while only minimally modifying overall macroscopic cell coupling in normal myocardium. Concentration–response curves were defined for the effects of heptanol, 18α-glycyrrhetinic acid, halothane, and palmitoleic acid on conduction velocity, tissue electrical impedance, developed tension and lactate dehydrogenase (LDH) release in normoxically perfused rat hearts (n = 17). Concentrations lacking significant effects on tissue impedance were added during the initial 15 min of reperfusion in hearts submitted to 60 min (n = 43) or 30 min (n = 35) of ischaemia. These concentrations markedly increased myocardial electrical impedance (resistivity and phase angle) in myocardium reperfused after either 30 or 60 min of ischaemia, and reduced reperfusion-induced LDH release after 1 h of ischaemia by 83.6, 57.9, 51.7 and 52.5% for heptanol, 18α-glycyrrhetinic acid, halothane and palmitoleic acid, respectively. LDH release was minimal in hearts submitted to 30 min of ischaemia, independently of group allocation. In conclusion, the present results strongly support the hypothesis that intercellular communication in postischaemic myocardium may be effectively reduced by concentrations of GJ inhibitors affecting only minimally overall electrical impedance in normal myocardium. Reduction of cell coupling during initial reperfusion was consistently associated with attenuated lethal reperfusion injury. PMID:15218064

Short intra-aortic balloon pump in a swine model of myocardial ischaemia: a proof-of-concept study.

PubMed

Gelsomino, Sandro; Lozekoot, Pieter W J; Lorusso, Roberto; de Jong, Monique M J; Parise, Orlando; Matteucci, Francesco; Lucà, Fabiana; La Meir, Mark; Gensini, Gian Franco; Maessen, Jos G

2016-03-01

This proof-of-concept study examined the haemodynamic performance as well as the coronary and visceral organ perfusion using a new short balloon for intra-aortic counterpulsation (IABP) in a swine model of myocardial ischaemia. Eighteen healthy pigs underwent 120-min ligation of the left anterior descending coronary artery followed by 6 h of reperfusion, and they were randomly assigned into 3 groups undergoing IABP implantation with a 35-ml short balloon (n = 6), a 40-ml short balloon (n = 6) or no IABP implantation (controls, n = 6). Haemodynamics, and visceral and coronary flows were measured at baseline (t0), at 2 h of ischaemia (t1) and every hour thereafter until 6 h of reperfusion (from tR1 to tR6), respectively. Mesenteric and renal flows increased significantly at tR1 only in the IABP groups (all, P < 0.001) and were significantly higher than controls throughout the reperfusion periods (P < 0.001). Coronary systolic and diastolic blood flows increased only at tR1 in the IABP groups (all, P < 0.001) but were higher than controls at tR1-tR6. The IABP was associated with enhanced haemodynamics compared with controls. No difference was detected using different balloon volumes (all, P > 0.05). The new short balloon significantly increased visceral flow, enhanced haemodynamics and improved coronary circulation during reperfusion following myocardial ischaemia in our experimental model. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Nitric oxide fails to confer endogenous antiarrhythmic cardioprotection in the primate heart in vitro.

PubMed

Pabla, R; Curtis, M J

2007-04-01

The role of nitric oxide (NO) in cardiac pathophysiology remains controversial. According to data from several studies using rat and rabbit isolated hearts, NO is an endogenous cardioprotectant against reperfusion-induced ventricular fibrillation (VF). Thus, if cardiac NO production is abolished by perfusion with L-N(G)-nitro-L-arginine methylester (L-NAME) (100 microM) there is a concomittant increase in the incidence of reperfusion-induced VF, with L-NAME's effects on NO and VF prevented by L- (but not D-) arginine co-perfusion. To make a better estimate of the clinical relevance of these findings, 100 microM L-NAME was tested in primate hearts under similar conditions. Marmoset (Callithrix jaccus) hearts, isolated and perfused, were subjected to 60 min left regional ischaemia followed by 10 min reperfusion in vitro. The ECG was recorded and NO in coronary effluent measured by chemiluminescence. L-NAME (100 micro M) decreased NO in coronary effluent throughout ischaemia and reperfusion (e.g. from 3720+/-777 pmol min(-1) g(-1) in controls to 699+/-98 pmol min(-1) g(-1) after 5 min of ischaemia) and, during ischaemia, lowered coronary flow and reduced heart rate, actions identical to those seen in rat and rabbit hearts. However, the incidence of reperfusion-induced VF was unchanged (20%, with or without L-NAME). A species difference exists in the effectiveness of endogenous NO to protect hearts against reperfusion-induced VF. The present primate data, which presumably take precedence over rat and rabbit data, cast doubt on the clinical relevance of NO as an endogenous, antiarrhythmic, cardioprotectant.

Visualisation of exercise-induced ischaemia of the right ventricle by thallium-201 single photon emission computed tomography.

PubMed Central

Chiba, J.; Takeishi, Y.; Abe, S.; Tomoike, H.

1997-01-01

OBJECTIVE: Exercise thallium-201 (201T1) single photon emission computed tomography (SPECT) has been used to detect potential ischaemia in the left ventricular myocardium but not in the right ventricle. The purpose of this study was to establish the clinical usefulness of a right ventricular polar map of 201T1 SPECT for visualisation of exercise-induced right ventricular ischaemia. METHODS: Myocardial 201T1 SPECT was obtained immediately after treadmill exercise in 97 patients with suspected coronary artery disease. A region of interest was placed over the right ventricle (RV) on post-stress transaxial images. Short axis images of this region were generated and reconstructed as a bull's eye polar map. Normal ranges of RV 201T1 uptake were determined in 12 patients with normal coronary arteries. Scintigraphic criteria for identifying RV perfusion abnormality were derived from 25 patients with right coronary artery (RCA) stenosis greater than 75%. These criteria were applied to 60 consecutive patients with suspected coronary artery disease. RESULTS: Perfusion defects in the RV were larger in patients with proximal RCA stenosis than in those with distal RCA stenosis (mean (SD) 28 (16)% v 6 (5)%, P < 0.001). The sensitivity and specificity of the RV polar map for the detection of proximal RCA stenosis were 67% (8/12) and 98% (47/48), respectively. RV perfusion defects became undetectable in 9 patients who had successful percutaneous transluminal coronary angioplasty to a proximal RCA lesion. CONCLUSIONS: A right ventricular polar map display was useful for visualising exercise-induced right ventricular ischaemia. Images PMID:9038692

Anti-apoptotic and myocardial protective effects of ethyl pyruvate after regional ischaemia/reperfusion myocardial damage in an in vivo rat model.

PubMed

Shim, Haeng Seon; Lee, Wang Gyu; Kim, Yeon A; Han, Jeong Yeol; Park, Miyeong; Song, Yun Gyu; Kim, Joon Soo; Shin, Il-Woo

2017-09-01

The integration of reactive oxygen species is strongly associated with important pathophysiological mechanisms that mediate myocardial ischaemia/reperfusion (I/R) damage. Pyruvate is an efficacious scavenger of reactive oxygen species and a previous study has shown that ethyl pyruvate (EP) has a myocardial protective effect against regional I/R damage in an in vivo rat model. The purpose of this study was to determine whether the myocardial protective effect of EP is associated with anti-apoptosis. Rats were allocated to receive EP dissolved in lactated Ringer's solution or lactated Ringer's solution alone, via intraperitoneal infusion one hour before ischaemia. They were exposed to 30 minutes of ischaemia followed by reperfusion of the left coronary artery territory over two hours. Anti-apoptotic effects were checked using several biochemical parameters after two hours of reperfusion. Apoptosis was analysed using measured caspase-3 activity, Western blotting of B-cell lymphoma 2 (Bcl-2) family protein cleaved by caspase-3, and assessment of DNA laddering patterns and the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining test. In ischaemic myocardium, EP increased Bcl-2 expression, but reduced Bcl-2-associated X protein and cleaved caspase-3 expressions. EP reduced the expression of DNA laddering and the number of myocardial I/R-damaged TUNEL-positive cells. This study demonstrated that EP has an anti-apoptotic effect after regional I/R damage in an in vivo rat heart model. The myocardial protective effect of EP may be related to its anti-apoptotic effect. Copyright: © Singapore Medical Association

Diagnostic performance of multi-slice CT angiography combined with enterography for small bowel obstruction and intestinal ischaemia.

PubMed

He, Bosheng; Gu, Jinhua; Huang, Sheng; Gao, Xuesong; Fan, Jinhe; Sheng, Meihong; Wang, Lin; Gong, Shenchu

2017-02-01

This study was performed to evaluate the diagnostic performance of multi-slice CT angiography combined with enterography in determining the cause and location of obstruction as well as intestinal ischaemia in patients with small bowel obstruction (SBO). This study retrospectively summarized the image data of 57 SBO patients who received both multi-slice CT angiography and enterography examination between December 2012 and May 2013. The CT diagnoses of SBO and intestinal ischaemia were correlated with the findings at surgery or digital subtraction angiography, which were set as standard references. Multi-slice CT angiography and enterography indicated that the cause of SBO in three patients was misjudged, suggesting a diagnostic accuracy of 94.7%. In one patient the level of obstruction was incorrect, demonstrating a diagnostic accuracy of 98.2%. Based on the results of the receiver operating characteristic (ROC) curve analysis, the diagnostic criterion for ischaemic SBO was at least two of the four CT signs (circumferential bowel wall thickening, reduced enhancement of the intestinal wall, mesenteric oedema and mesenteric vascular engorgement). The criterion yielded a sensitivity of 94.4%, a specificity of 92.3%, a positive predicted value of 85.0% and a negative predicted value of 97.3%, and the area under curve (AUC) was 0.92 (95% CI, 0.85-0.99). Multi-slice CT angiography and enterography have high diagnostic value in identifying the cause and site of SBO. In addition, the suggested diagnostic criterion using CT signs is helpful for diagnosing intestinal ischaemia in SBO patients. © 2016 The Royal Australian and New Zealand College of Radiologists.

Timing of intervention in high-risk non-ST-elevation acute coronary syndromes in PCI versus non-PCI centres : Sub-group analysis of the ELISA-3 trial.

PubMed

Badings, E A; Remkes, W S; Dambrink, J-H E; The, S H K; Van Wijngaarden, J; Tjeerdsma, G; Rasoul, S; Timmer, J R; van der Wielen, M L J; Lok, D J A; van 't Hof, A W J

2016-03-01

To compare the effect of timing of intervention in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) in percutaneous coronary intervention (PCI) versus non-PCI centres. A post-hoc sub-analysis was performed of the ELISA III trial, a randomised multicentre trial investigating outcome of early (< 12 h) versus late (> 48 h) angiography and revascularisation in 542 patients with high-risk NSTE-ACS. 90 patients were randomised in non-PCI centres and tended to benefit more from an early invasive strategy than patients included in the PCI centre (relative risk 0.23 vs. 0.85 [p for interaction = 0.089] for incidence of the combined primary endpoint of death, reinfarction and recurrent ischaemia after 30 days of follow-up). This was largely driven by reduction in recurrent ischaemia. In non-PCI centres, patients randomised to the late group had a 4 and 7 day longer period until PCI or coronary artery bypass grafting, respectively. This difference was less pronounced in the PCI centre. This post-hoc analysis from the ELISA-3 trial suggests that NSTE-ACS patients initially hospitalised in non-PCI centres show the largest benefit from early angiography and revascularisation, associated with a shorter waiting time to revascularisation. Improved patient logistics and transfer between non-PCI and PCI centres might therefore result in better clinical outcome.

Peripheral ischaemic retinopathy and neovascularisation in a patient with subacute streptococcus mitis-induced bacterial endocarditis.

PubMed

Leysen, Laura S; Kreps, Elke O; De Schryver, Ilse; Hoornaert, Kristien P; Smith, Vanessa; De Zaeytijd, Julie

2017-01-01

Objective: To describe a patient with peripheral retinal ischaemia and neovascularisation who was diagnosed with streptococcus mitis-induced bacterial endocarditis. Methods: Retrospective analysis of case report. A 57-year-old man presented with a history of a rapidly progressive, bilateral, painless visual loss. He also suffered from pain in the neck and lower back and a weight loss of 10 kg. He underwent a full ophthalmologic work-up, laboratory investigations, and imaging of the spine. Results: BCVA was reduced to 20/40 in the right eye and 20/32 in the left eye. Fundoscopy showed rare intra-retinal haemorrhages including few Roth spots and cotton wool lesions. Fluorescein angiography demonstrated large areas of peripheral retinal ischaemia and neovascularisation. Imaging of the spine showed spondylodiscitis on several levels. Further imaging and blood cultures confirmed bacterial endocarditis of the mitral valve. Streptococcus mitis was subsequently identified as the causative organism. Conclusion: Peripheral retinal ischaemia and neovascularisation were previously unrecognised as a feature of infectious endocarditis. Therefore, their presence, apart from the classic Roth spots, should prompt the consideration of infectious endocarditis in the etiologic work-up.

Modern treatment of infection and ischaemia to reduce major amputation in the diabetic foot.

PubMed

Edmonds, Michael

2013-01-01

Diabetic patients suffer a high rate of amputation. There are two main reasons; infection which can spread rapidly leading to overwhelming tissue destruction and severe peripheral arterial disease. Studies that have stratified patients according to the presence or absence of both peripheral arterial disease and infection have shown significantly worse outcomes in patients with both peripheral arterial disease and infection. There have been two crucial significant advances in diabetic foot care to improve the outlook of these diabetic patients. First, there has been the realisation that diabetic foot patients experience repeated crises from the rapid onset infection and need a special form of easily accessible care within a multidisciplinary diabetic foot service to provide prompt treatment of infection before it progresses to necrosis. Secondly, within such a service, prompt diagnosis of ischaemia and urgent revascularisation has been established as a further important aspect of successful management. The critical factor in saving limbs is making a rapid diagnosis of infection and ischaemia and administering the appropriate treatment early. In this way speedy healing can be achieved and this can prevent patients from needing amputations.

Involvement of cannabinoids in the cardioprotection induced by lipopolysaccharide

PubMed Central

Lagneux, Caroline; Lamontagne, Daniel

2001-01-01

We have examined the involvement of the endocannabinoid system in the cardioprotection triggered by lipopolysaccharide (LPS). Rats were treated with saline or LPS (10 μg Kg−1). 24 h later, hearts were excised, retrogradely perfused, submitted to a low-flow ischaemia (0.6 ml min−1) for 90 min and reperfused for 60 min. Some hearts were perfused with either SR 141716A (a cannabinoid CB1, receptor antagonist 1 μM), SR 144528 (a CB2 receptor anagonist μM), NNLA (3 μM) or sodium nitroprusside (1 μM) 5 min before ischaemia and during the ischaemic period. The cardioprotective effects of LPS treatment, in terms of infarction and functional recovery, were not altered by the perfusion of SR 141716A but abolished by both SR 144528 and NNLA. Finally, SR 144528 abolished the beneficial effects of SNP perfusion. Our results suggest an involvement of endocannabinoids, acting through the CB2 receptors, in the cardioprotection triggered by LPS against myocardial ischaemia. This could be attributed to a relationship between cannabinoids and NO. PMID:11181418

Permeabilization of brain tissue in situ enables multiregion analysis of mitochondrial function in a single mouse brain.

PubMed

Herbst, Eric A F; Holloway, Graham P

2015-02-15

Mitochondrial function in the brain is traditionally assessed through analysing respiration in isolated mitochondria, a technique that possesses significant tissue and time requirements while also disrupting the cooperative mitochondrial reticulum. We permeabilized brain tissue in situ to permit analysis of mitochondrial respiration with the native mitochondrial morphology intact, removing the need for isolation time and minimizing tissue requirements to ∼2 mg wet weight. The permeabilized brain technique was validated against the traditional method of isolated mitochondria and was then further applied to assess regional variation in the mouse brain with ischaemia-reperfusion injuries. A transgenic mouse model overexpressing catalase within mitochondria was applied to show the contribution of mitochondrial reactive oxygen species to ischaemia-reperfusion injuries in different brain regions. This technique enhances the accessibility of addressing physiological questions in small brain regions and in applying transgenic mouse models to assess mechanisms regulating mitochondrial function in health and disease. Mitochondria function as the core energy providers in the brain and symptoms of neurodegenerative diseases are often attributed to their dysregulation. Assessing mitochondrial function is classically performed in isolated mitochondria; however, this process requires significant isolation time, demand for abundant tissue and disruption of the cooperative mitochondrial reticulum, all of which reduce reliability when attempting to assess in vivo mitochondrial bioenergetics. Here we introduce a method that advances the assessment of mitochondrial respiration in the brain by permeabilizing existing brain tissue to grant direct access to the mitochondrial reticulum in situ. The permeabilized brain preparation allows for instant analysis of mitochondrial function with unaltered mitochondrial morphology using significantly small sample sizes (∼2 mg), which permits the analysis of mitochondrial function in multiple subregions within a single mouse brain. Here this technique was applied to assess regional variation in brain mitochondrial function with acute ischaemia-reperfusion injuries and to determine the role of reactive oxygen species in exacerbating dysfunction through the application of a transgenic mouse model overexpressing catalase within mitochondria. Through creating accessibility to small regions for the investigation of mitochondrial function, the permeabilized brain preparation enhances the capacity for examining regional differences in mitochondrial regulation within the brain, as the majority of genetic models used for unique approaches exist in the mouse model. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

Outcomes of sympathectomy and vascular bypass for digital ischaemia in connective tissue disorders.

PubMed

Shammas, R L; Hwang, B H; Levin, L S; Richard, M J; Ruch, D S; Mithani, S K

2017-10-01

All patients (36 hands) with connective tissue disorders who underwent periarterial sympathectomy of the hand alone or in conjunction with vascular bypass at our institution between 1995-2013 were reviewed. The durable resolution of ulcers was significantly higher in patients treated by periarterial sympathectomy and bypass than in patients treated by periarterial sympathectomy alone. Although there were more digital amputations in patients treated by periarterial sympathectomy alone, the difference was not statistically significant. Vascular bypass in conjunction with sympathectomy may be better than sympathectomy alone in patients with digital ischaemia related to connective tissue disorders. IV.

Multiple therapeutic effects of progranulin on experimental acute ischaemic stroke.

PubMed

Kanazawa, Masato; Kawamura, Kunio; Takahashi, Tetsuya; Miura, Minami; Tanaka, Yoshinori; Koyama, Misaki; Toriyabe, Masafumi; Igarashi, Hironaka; Nakada, Tsutomu; Nishihara, Masugi; Nishizawa, Masatoyo; Shimohata, Takayoshi

2015-07-01

In the central nervous system, progranulin, a glycoprotein growth factor, plays a crucial role in maintaining physiological functions, and progranulin gene mutations cause TAR DNA-binding protein-43-positive frontotemporal lobar degeneration. Although several studies have reported that progranulin plays a protective role against ischaemic brain injury, little is known about temporal changes in the expression level, cellular localization, and glycosylation status of progranulin after acute focal cerebral ischaemia. In addition, the precise mechanisms by which progranulin exerts protective effects on ischaemic brain injury remains unknown. Furthermore, the therapeutic potential of progranulin against acute focal cerebral ischaemia, including combination treatment with tissue plasminogen activator, remains to be elucidated. In the present study, we aimed to determine temporal changes in the expression and localization of progranulin after ischaemia as well as the therapeutic effects of progranulin on ischaemic brain injury using in vitro and in vivo models. First, we demonstrated a dynamic change in progranulin expression in ischaemic Sprague-Dawley rats, including increased levels of progranulin expression in microglia within the ischaemic core, and increased levels of progranulin expression in viable neurons as well as induction of progranulin expression in endothelial cells within the ischaemic penumbra. We also demonstrated that the fully glycosylated mature secretory isoform of progranulin (∼88 kDa) decreased, whereas the glycosylated immature isoform of progranulin (58-68 kDa) markedly increased at 24 h and 72 h after reperfusion. In vitro experiments using primary cells from C57BL/6 mice revealed that the glycosylated immature isoform was secreted only from the microglia. Second, we demonstrated that progranulin could protect against acute focal cerebral ischaemia by a variety of mechanisms including attenuation of blood-brain barrier disruption, neuroinflammation suppression, and neuroprotection. We found that progranulin could regulate vascular permeability via vascular endothelial growth factor, suppress neuroinflammation after ischaemia via anti-inflammatory interleukin 10 in the microglia, and render neuroprotection in part by inhibition of cytoplasmic redistribution of TAR DNA-binding protein-43 as demonstrated in progranulin knockout mice (C57BL/6 background). Finally, we demonstrated the therapeutic potential of progranulin against acute focal cerebral ischaemia using a rat autologous thrombo-embolic model with delayed tissue plasminogen activator treatment. Intravenously administered recombinant progranulin reduced cerebral infarct and oedema, suppressed haemorrhagic transformation, and improved motor outcomes (P = 0.007, 0.038, 0.007 and 0.004, respectively). In conclusion, progranulin may be a novel therapeutic target that provides vascular protection, anti-neuroinflammation, and neuroprotection related in part to vascular endothelial growth factor, interleukin 10, and TAR DNA-binding protein-43, respectively. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Dynamic, in vivo, real-time detection of retinal oxidative status in a model of elevated intraocular pressure using a novel, reversibly responsive, profluorescent nitroxide probe.

PubMed

Rayner, Cassie L; Gole, Glen A; Bottle, Steven E; Barnett, Nigel L

2014-12-01

Changes to the redox status of biological systems have been implicated in the pathogenesis of a wide variety of disorders including cancer, Ischemia-reperfusion (I/R) injury and neurodegeneration. In times of metabolic stress e.g. ischaemia/reperfusion, reactive oxygen species (ROS) production overwhelms the intrinsic antioxidant capacity of the cell, damaging vital cellular components. The ability to quantify ROS changes in vivo, is therefore essential to understanding their biological role. Here we evaluate the suitability of a novel reversible profluorescent probe containing a redox-sensitive nitroxide moiety (methyl ester tetraethylrhodamine nitroxide, ME-TRN), as an in vivo, real-time reporter of retinal oxidative status. The reversible nature of the probe's response offers the unique advantage of being able to monitor redox changes in both oxidizing and reducing directions in real time. After intravitreal administration of the ME-TRN probe, we induced ROS production in rat retina using an established model of complete, acute retinal ischaemia followed by reperfusion. After restoration of blood flow, retinas were imaged using a Micron III rodent fundus fluorescence imaging system, to quantify the redox-response of the probe. Fluorescent intensity declined during the first 60 min of reperfusion. The ROS-induced change in probe fluorescence was ameliorated with the retinal antioxidant, lutein. Fluorescence intensity in non-Ischemia eyes did not change significantly. This new probe and imaging technology provide a reversible and real-time response to oxidative changes and may allow the in vivo testing of antioxidant therapies of potential benefit to a range of diseases linked to oxidative stress. Copyright © 2014 Elsevier Ltd. All rights reserved.

Nitrite activates protein kinase A in normoxia to mediate mitochondrial fusion and tolerance to ischaemia/reperfusion

PubMed Central

Pride, Christelle Kamga; Mo, Li; Quesnelle, Kelly; Dagda, Ruben K.; Murillo, Daniel; Geary, Lisa; Corey, Catherine; Portella, Rafael; Zharikov, Sergey; St Croix, Claudette; Maniar, Salony; Chu, Charleen T.; K. H. Khoo, Nicholas; Shiva, Sruti

2014-01-01

Aims Nitrite (NO2–), a dietary constituent and nitric oxide (NO) oxidation product, mediates cardioprotection after ischaemia/reperfusion (I/R) in a number of animal models when administered during ischaemia or as a pre-conditioning agent hours to days prior to the ischaemic episode. When present during ischaemia, the reduction of nitrite to bioactive NO by deoxygenated haem proteins accounts for its protective effects. However, the mechanism of nitrite-induced pre-conditioning, a normoxic response which does not appear to require reduction of nitrite to NO, remains unexplored. Methods and results Using a model of hypoxia/reoxygenation (H/R) in cultured rat H9c2 cardiomyocytes, we demonstrate that a transient (30 min) normoxic nitrite treatment significantly attenuates cell death after a hypoxic episode initiated 1 h later. Mechanistically, this protection depends on the activation of protein kinase A, which phosphorylates and inhibits dynamin-related protein 1, the predominant regulator of mitochondrial fission. This results morphologically, in the promotion of mitochondrial fusion and functionally in the augmentation of mitochondrial membrane potential and superoxide production. We identify AMP kinase (AMPK) as a downstream target of the mitochondrial reactive oxygen species (ROS) generated and show that its oxidation and subsequent phosphorylation are essential for cytoprotection, as scavenging of ROS prevents AMPK activation and inhibits nitrite-mediated protection after H/R. The protein kinase A-dependent protection mediated by nitrite is reproduced in an intact isolated rat heart model of I/R. Conclusions These data are the first to demonstrate nitrite-dependent normoxic modulation of both mitochondrial morphology and function and reveal a novel signalling pathway responsible for nitrite-mediated cardioprotection. PMID:24081164

Comparing short versus standard-length balloon for intra-aortic counterpulsation: results from a porcine model of myocardial ischaemia-reperfusion.

PubMed

Gelsomino, Sandro; Lozekoot, Pieter W J; Lorusso, Roberto; de Jong, Monique M J; Parise, Orlando; Matteucci, Francesco; Lucà, Fabiana; La Meir, Mark; Gensini, Gian Franco; Maessen, Jos G

2016-05-01

We compare a short and a standard-size balloon with same filling volumes to verify the differences in terms of visceral flow, coronary circulation and haemodynamic performance during aortic counterpulsation in an animal model of myocardial ischaemia-reperfusion injury. Eighteen healthy pigs underwent 120-min ligation of the left anterior descending coronary artery followed by 6 h of reperfusion, and they were randomly assigned to have intra-aortic balloon counterpulsation (IABP) with a 40-ml short-balloon (n = 6) or a 40-ml standard-length balloon (n = 6), or to undergo no IABP implantation (controls, n = 6). Haemodynamics and visceral and coronary flows were measured at baseline (t0), at 2 h of ischaemia (t1) and every hour thereafter until 6 h of reperfusion (from tR1 to tR6), respectively. Mesenteric flows increased significantly at tR1 only in the short-balloon group (P < 0.001) and it was constantly higher than in the standard-balloon group regardless of mean arterial pressure, systemic vascular resistance and cardiac output (CO; all, P < 0.001). Renal blood flows were significantly increased during IABP treatment with values constantly and significantly higher in short balloons at any following experimental step (all, P < 0.05). IABP improved CO and coronary blood flow, and reduced afterload, myocardial resistances and myocardial oxygen consumption without differences between the short and the standard-length balloon (all, P > 0.05). The short balloon prevents visceral ischaemia and, compared with the standard-size balloon, it does not lose IABP beneficial cardiac and coronary-related effects. Further studies are warranted to confirm our findings. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Protective effects of n-6 fatty acids-enriched diet on intestinal ischaemia/reperfusion injury involve lipoxin A4 and its receptor

PubMed Central

Gobbetti, T; Ducheix, S; le Faouder, P; Perez, T; Riols, F; Boue, J; Bertrand-Michel, J; Dubourdeau, M; Guillou, H; Perretti, M; Vergnolle, N; Cenac, N

2015-01-01

Background and Purpose Long-term intake of dietary fatty acids is known to predispose to chronic inflammation, but their effects on acute intestinal ischaemia/reperfusion (I/R) injury is unknown. The aim of this study was to determine the consequences of a diet rich in n-3 or n-6 polyunsaturated fatty acids (PUFA) on intestinal I/R-induced damage. Experimental Approach Mice were fed three different isocaloric diets: a balanced diet used as a control and two different PUFA-enriched diets, providing either high levels of n-3 or of n-6 PUFA. Intestinal injury was evaluated after intestinal I/R. PUFA metabolites were quantitated in intestinal tissues by LC-MS/MS. Key Results In control diet-fed mice, intestinal I/R caused inflammation and increased COX and lipoxygenase-derived metabolites compared with sham-operated animals. Lipoxin A4 (LxA4) was significantly and selectively increased after ischaemia. Animals fed a high n-3 diet did not display a different inflammatory profile following intestinal I/R compared with control diet-fed animals. In contrast, intestinal inflammation was decreased in the I/R group fed with high n-6 diet and level of LxA4 was increased post-ischaemia compared with control diet-fed mice. Blockade of the LxA4 receptor (Fpr2), prevented the anti-inflammatory effects associated with the n-6 rich diet. Conclusions and Implications This study indicates that high levels of dietary n-6, but not n-3, PUFAs provides significant protection against intestinal I/R-induced damage and demonstrates that the endogenous production of LxA4 can be influenced by diet. PMID:25296998

Comparison of the effects of isobutylmethylxanthine and milrinone on ischaemia-induced arrhythmias and platelet aggregation in anaesthetized rabbits.

PubMed Central

Holbrook, M.; Coker, S. J.

1989-01-01

1. The aim of this study was to compare the effects of the non-selective phosphodiesterase (PDE) inhibitor, isobutylmethylxanthine (IBMX) and the selective PDE III inhibitor, milrinone, in a rabbit model of acute myocardial ischaemia. 2. Coronary artery occlusion caused changes in the ST-segment of the ECG and ectopic activity in all control rabbits. Ventricular fibrillation occurred in 10 out of 14 (71%) of these animals. Pretreatment with IBMX 100 micrograms kg-1 plus 10 micrograms kg-1 min-1, starting 10 min before coronary artery occlusion, reduced ischaemia-induced ST-segment changes and ventricular fibrillation occurred in only 10% of this group (n = 10). A similar dose of milrinone had no antiarrhythmic activity, whereas with a lower dose of milrinone, 30 micrograms kg-1 plus 3 micrograms kg-1 min-1 (n = 10), only 30% of rabbits fibrillated and ST-segment changes were attenuated. 3. Acute administration of both IBMX and milrinone reduced arterial blood pressure. With the higher dose of milrinone a significant effect was still present after 10 min of drug infusion. A greater hypotensive response to the higher dose of milrinone was observed in the rabbits which subsequently fibrillated during ischaemia. A marked tachycardia was also observed after administration of the higher dose of milrinone. 4. At the end of the experiment platelet aggregation was studied ex vivo. ADP-induced aggregation was reduced by pretreatment of the rabbits with milrinone but not IBMX. Both PDE inhibitors enhanced the ability of isoprenaline to inhibit ADP-induced platelet aggregation but milrinone was more effective, particularly at the higher dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2478245

Milrinone and levosimendan during porcine myocardial ischemia -- no effects on calcium overload and metabolism.

PubMed

Axelsson, B; Johansson, G; Abrahamsson, P; Gupta, A; Tydén, H; Wouters, P; Haney, M

2013-07-01

Although inotropic stimulation is considered harmful in the presence of myocardial ischaemia, both calcium sensitisers and phosphodiesterase inhibitors may offer cardioprotection. We hypothesise that these cardioprotective effects are related to an acute alteration of myocardial metabolism. We studied in vivo effects of milrinone and levosimendan on calcium overload and ischaemic markers using left ventricular microdialysis in pigs with acute myocardial ischaemia. Anaesthetised juvenile pigs, average weight 36 kg, were randomised to one of three intravenous treatment groups: milrinone 50 μg/kg bolus plus infusion 0.5 μg/kg/min (n = 7), levosimendan 24 μg/kg plus infusion 0.2 μg/kg/min (n = 7), or placebo (n = 6) for 60 min prior to and during a 45 min acute regional coronary occlusion. Systemic and myocardial haemodynamics were assessed, and microdialysis was performed with catheters positioned in the left ventricular wall. (45) Ca(2+) was included in the microperfusate in order to assess local calcium uptake into myocardial cells. The microdialysate was analysed for glucose, lactate, pyruvate, glycerol, and for (45) Ca(2+) recovery. During ischaemia, there were no differences in microdialysate-measured parameters between control animals and milrinone- or levosimendan-treated groups. In the pre-ischaemic period, arterial blood pressure decreased in all groups while myocardial oxygen consumption remained stable. These findings reject the hypothesis of an immediate energy-conserving effect of milrinone and levosimendan during acute myocardial ischaemia. On the other hand, the data show that inotropic support with milrinone and levosimendan does not worsen the metabolic parameters that were measured in the ischaemic myocardium. © 2013 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Acute hyperglycaemia enhances oxidative stress and aggravates myocardial ischaemia/reperfusion injury: role of thioredoxin-interacting protein

PubMed Central

Su, Hui; Ji, Lele; Xing, Wenjuan; Zhang, Wei; Zhou, Heping; Qian, Xinhong; Wang, Xiaoming; Gao, Feng; Sun, Xin; Zhang, Haifeng

2013-01-01

Hyperglycaemia during acute myocardial infarction is common and associated with increased mortality. Thioredoxin-interacting protein (Txnip) is a modulator of cellular redox state and contributes to cell apoptosis. This study aimed to investigate whether or not hyperglycaemia enhances Txnip expression in myocardial ischaemia/reperfusion (MI/R) and consequently exacerbates MI/R injury. Rats were subjected to 30 min. of left coronary artery ligation followed by 4 hrs of reperfusion and treated with saline or high glucose (HG, 500 g/l, 4 ml/kg/h intravenously). In vitro study was performed on cultured rat cardiomyocytes subjected to simulated ischaemia/reperfusion (SI/R) and incubated with HG (25 mM) or normal glucose (5.6 mM) medium. In vivo HG infusion during MI/R significantly impaired cardiac function, aggravated myocardial injury and increased cardiac oxidative stress. Meanwhile, Txnip expression was enhanced whereas thioredoxin activity was inhibited following HG treatment in ischaemia/reperfusion (I/R) hearts. In addition, HG activated p38 MAPK and inhibited Akt in I/R hearts. In cultured cardiomyocytes subjected to SI/R, HG incubation stimulated Txnip expression and reduced thioredoxin activity. Overexpression of Txnip enhanced HG-induced superoxide generation and aggravated cardiomyocyte apoptosis, whereas Txnip RNAi significantly blunted the deleterious effects of HG. Moreover, inhibition of p38 MAPK or activation of Akt markedly blocked HG-induced Txnip expression in I/R cardiomyocytes. Most importantly, intramyocardial injection of Txnip siRNA markedly decreased Txnip expression and alleviated MI/R injury in HG-treated rats. Hyperglycaemia enhances myocardial Txnip expression, possibly through reciprocally modulating p38 MAPK and Akt activation, leading to aggravated oxidative stress and subsequently, amplification of cardiac injury following MI/R. PMID:23305039

Classification of diabetic macular oedema using ultra-widefield angiography and implications for response to anti-VEGF therapy.

PubMed

Xue, Kanmin; Yang, Elizabeth; Chong, N Victor

2017-05-01

To characterise differential pathogeneses of diabetic macular oedema (DMO) using ultra-widefield fluorescein angiography (UWFA) and evaluate responses to anti-vascular endothelial growth factor (anti-VEGF) therapy. Ninety-nine eyes (73 consecutive patients) with anti-VEGF naïve DMO underwent UWFA and optical coherence tomography, of which 60 with central retinal thickness (CRT) >400 μm received monthly intravitreal ranibizumab injections. Best-corrected visual acuity (BCVA) and CRT were measured at baseline and after three injections. After excluding tractional factors, DMO was categorised into three types based on UWFA: (A) microaneurysm driven (49%), (B) peripheral ischaemia (37%) and (C) neovascularisation (15%). While all three types showed similar mean CRT (p=0.257), types B and C were associated with more diffuse oedema, which extended beyond the 6.0 mm central macula (p=0.0034). Following anti-VEGF treatment, all three types showed improvement in CRT and BCVA, which reached statistical significance for types A and B. A positive correlation was found between the Peripheral Ischaemia Index and improvement in CRT (slope=2.09, R 2 =0.1169, p=0.0151) but not BCVA (slope=-0.00037, R 2 =0.001149, p=0.8152). UWFA facilitates the detection of peripheral ischaemia, which is associated with a significant proportion of DMO. While this group of DMO responded well to anti-VEGF therapy, it remains to be determined whether addressing the peripheral ischaemia may reduce recurrence. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Alleviation of ischaemia-reperfusion injury by endogenous estrogen involves maintaining Bcl-2 expression via the ERα signalling pathway.

PubMed

Zhang, Zeng-Li; Qin, Pei; Liu, Yuhong; Zhang, Li-Xia; Guo, Hang; Deng, You-Liang; Yizhao-Liu; Hou, Yu-Shu; Wang, Li-Yang; Miao, Yi; Ma, Yu-Long; Hou, Wu-Gang

2017-04-15

The neuroprotective effects of estrogen against cerebral ischaemia have been confirmed by multiple basic and clinical studies. However, most of these studies used exogenous estrogen administered via different injection methods, and the neuroprotective effects of endogenous estrogen produced by ovaries during different phases of estrous cycle and the underlying mechanisms involved have rarely been explored. In this study, we first identified the stage of estrous cycle via vaginal smears and then measured serum estradiol levels at each phase via radioimmunoassay. We found that the estradiol level was highest in the proestrous and lowest in the diestrous. However, ovariectomy or treatment with the aromatase inhibitor letrozole significantly decreased estradiol levels compared to that of rats in diestrous. Western blotting showed that ovariectomy or letrozole treatment significantly decreased ERα and Bcl-2 protein expression and dramatically increased Bax protein expression compared with the rats in diestrous or proestrous. Rats also underwent 2h of ischaemia via middle cerebral artery occlusion followed by a 24-h reperfusion. Ovariectomy or letrozole treatment significantly decreased the neurological scores and the number of intact neurons detected via Nissl staining and dramatically increased the infarct volume detected via TTC staining and the extent of apoptosis detected via TUNEL staining and Western blotting for cleaved-caspase 3 protein expression. These results demonstrate that endogenous estrogen alleviates ischaemia-reperfusion injury by maintaining Bcl-2 expression via ERα signalling pathway and highlight the neuroprotective effects of endogenous estrogen during different stages of the estrous cycle, providing preliminary information on the underlying mechanism of this process. Copyright © 2017 Elsevier B.V. All rights reserved.

Sigma 1 receptor activation regulates brain-derived neurotrophic factor through NR2A-CaMKIV-TORC1 pathway to rescue the impairment of learning and memory induced by brain ischaemia/reperfusion.

PubMed

Xu, Qian; Ji, Xue-Fei; Chi, Tian-Yan; Liu, Peng; Jin, Ge; Gu, Shao-Li; Zou, Li-Bo

2015-05-01

Sigma-1 receptor (Sig-1R) agonists showed anti-amnesic properties in Alzheimer's disease models and anti-inflammatory properties in cerebrum ischaemia models. The agonist of Sig-1R was reported to up-regulate brain-derived neurotrophic factor (BDNF) levels in the hippocampus of mice. Here, we investigate whether the activation of Sig-1R attenuates the learning and memory impairment induced by ischaemia/reperfusion and how it affects the expression of BDNF. Bilateral common carotid artery occlusion (BCCAO) was induced for 20 min in C57BL/6 mice. Sig-1R agonist, PRE084, sigma 1/2 non-selective agonist, DTG, Sig-1R antagonist and BD1047 were injected once daily throughout the experiment. Behavioural tests were performed from day 8. On day 22 after BCCAO, mice were sacrificed for biochemical analysis. PRE084 and DTG ameliorated learning and memory impairments in the Y maze, novel object recognition, and water maze tasks and prevented the decline of synaptic proteins and BDNF expression in the hippocampus of BCCAO mice. Furthermore, PRE084 and DTG up-regulated the level of NMDA receptor 2A (NR2A), calcium/calmodulin-dependent protein kinase type IV (CaMKIV) and CREB-specific co-activator transducer of regulated CREB activity 1 (TORC1). Additionally, the effects of PRE084 and DTG were antagonised by the co-administration of BD1047. Sig-1R activation showed an attenuation in the ischaemia/reperfusion model and the activation of Sig-1R increased the expression of BDNF, possibly through the NR2A-CaMKIV-TORC1 pathway, and Sig-1R agonists might function as neuroprotectant agents in vascular dementia.

Underlying chronic inflammation alters the profile and mechanisms of acute neutrophil recruitment.

PubMed

Ma, Bin; Whiteford, James R; Nourshargh, Sussan; Woodfin, Abigail

2016-11-01

Chronically inflamed tissues show altered characteristics that include persistent populations of inflammatory leukocytes and remodelling of the vascular network. As the majority of studies on leukocyte recruitment have been carried out in normal healthy tissues, the impact of underlying chronic inflammation on ongoing leukocyte recruitment is largely unknown. Here, we investigate the profile and mechanisms of acute inflammatory responses in chronically inflamed and angiogenic tissues, and consider the implications for chronic inflammatory disorders. We have developed a novel model of chronic ischaemia of the mouse cremaster muscle that is characterized by a persistent population of monocyte-derived cells (MDCs), and capillary angiogenesis. These tissues also show elevated acute neutrophil recruitment in response to locally administered inflammatory stimuli. We determined that Gr1 low MDCs, which are widely considered to have anti-inflammatory and reparative functions, amplified acute inflammatory reactions via the generation of additional proinflammatory signals, changing both the profile and magnitude of the tissue response. Similar vascular and inflammatory responses, including activation of MDCs by transient ischaemia-reperfusion, were observed in mouse hindlimbs subjected to chronic ischaemia. This response demonstrates the relevance of the findings to peripheral arterial disease, in which patients experience transient exercise-induced ischaemia known as claudication.These findings demonstrate that chronically inflamed tissues show an altered profile and altered mechanisms of acute inflammatory responses, and identify tissue-resident MDCs as potential therapeutic targets. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Coronary anatomy in patients with various manifestations of three vessel coronary artery disease.

PubMed Central

Quyyumi, A A; Al-Rufaie, H K; Olsen, E G; Fox, K M

1985-01-01

The histology of coronary arteries was compared in patients with rest and effort angina. The arteries came from six patients with three vessel disease who died within four weeks of arteriography and ambulatory ST segment monitoring. Sections of all macroscopically visible arteries were taken every 5 mm and examined histologically. Episodes of ST segment depression had occurred on exertion in two patients, during exertion and rest (nocturnal) in two, and two patients had had no episodes of ST segment depression during ambulatory monitoring. Concentric (29%) or eccentric (62%) intimal thickening due to atheroma or fibroelastic tissue was found in 91% of sections. All but two normal intimal sections (1%) were found to be diseased in patients with ambulatory ST segment changes. Eccentric lesions with medial smooth muscle preservation in areas without intimal thickening, where further luminal narrowing could occur due to increases in smooth muscle tone, were found in 15% of sections. But these areas were not found in the proximal 3.5 cm of any of the major coronary arteries of the two patients with rest and effort ischaemia. Spasm could not have caused total occlusion in any of these arteries because the lumen was splinted by the lesion. There was no difference in mean luminal narrowing between patients with exertional and rest ischaemia and exertional ischaemia only (mean 74%), but mean luminal narrowing was lower in patients with no ambulatory episodes of ST segment change (39%). Thus medial smooth muscle spasm was unlikely to have caused occlusion in patients with ambulatory ST segment changes, although it could have altered lumen diameter. There are no histological differences in the coronary arteries of patients with rest or effort induced myocardial ischaemia. Images PMID:4052277

Losartan protects liver against ischaemia/reperfusion injury through PPAR-γ activation and receptor for advanced glycation end-products down-regulation

PubMed Central

Koh, Eun-Ji; Yoon, Seong-Jin; Lee, Sun-Mee

2013-01-01

Background and Purpose PPAR-γ has been reported to be a protective regulator in ischaemia/reperfusion (I/R) injury. The receptor for advanced glycation end-products (RAGE) plays a major role in the innate immune response, and its expression is associated with PPAR-γ activation. Several angiotensin receptor blockers possess partial agonist activities towards PPAR-γ. Therefore, this study investigated the action of losartan, particularly with regard to PPAR-γ activation and RAGE signalling pathways during hepatic I/R. Experimental Approach Mice were subjected to 60 min of ischaemia followed by 6 h of reperfusion. Losartan (0.1, 1, 3 and 10 mg·kg−1) was administered 1 h prior to ischaemia and immediately before reperfusion. GW9662, a PPAR-γ antagonist, was administered 30 min prior to first pretreatment with losartan. Key Results Losartan enhanced the DNA-binding activity of PPAR-γ in I/R. Losartan attenuated the increased serum alanine aminotransferase activity, TNF-α and IL-6 levels, and nuclear concentrations of NF-κB in I/R. GW9662 reversed these beneficial effects. Losartan caused a decrease in apoptosis as assessed by TUNEL assay, in release of cytochrome c and in cleavage of caspase-3, and these effects were abolished by GW9662 administration. Losartan attenuated not only I/R-induced RAGE overexpression, but also its downstream early growth response protein-1-dependent macrophage inflammatory protein 2 level; phosphorylation of p38, ERK and JNK; and subsequent c-Jun phosphorylation. GW9662 reversed these effects of losartan administration. Conclusions and Implications Our findings suggest that losartan ameliorates I/R-induced liver damage through PPAR-γ activation and down-regulation of the RAGE signalling pathway. PMID:23647130

[Hand replantation: differences in functional outcome considering patient age and sociomedical aspects].

PubMed

Reichl, H; Schütz, T; Gabl, M; Angermann, P; Russe, E; Wechselberger, G

2013-12-01

By presenting 2 cases of successful hand replantation with similar trauma mechanism, level of amputation and ischaemia time of an 18-year-old female patient and a 48-year-old depressive male patient, the influence of age and sociomedical status on the postoperative outcome is discussed. DASH- (disabilities of the arm, shoulder and hand) score and Biometrics E-LINK power and sensitivity measurement were used to evaluate the outcomes. © Georg Thieme Verlag KG Stuttgart · New York.

Where does the Occluded Artery Trial leave the late open artery hypothesis?

PubMed Central

Lamas, Gervasio A; Hochman, Judith S

2007-01-01

As of April 2007 the early open artery hypothesis is alive and well, but the late open artery hypothesis is adrift. For the foreseeable future, stable patients with persistent occlusion of the infarct artery late after myocardial infarction, and without severe ischaemia or uncontrollable angina, should be managed initially with optimal medical treatment alone, and not with percutaneous coronary intervention. Efforts should focus on establishing reperfusion earlier, including reducing the time to patient presentation. PMID:17933981

Acylcarnitines--old actors auditioning for new roles in metabolic physiology.

PubMed

McCoin, Colin S; Knotts, Trina A; Adams, Sean H

2015-10-01

Perturbations in metabolic pathways can cause substantial increases in plasma and tissue concentrations of long-chain acylcarnitines (LCACs). For example, the levels of LCACs and other acylcarnitines rise in the blood and muscle during exercise, as changes in tissue pools of acyl-coenzyme A reflect accelerated fuel flux that is incompletely coupled to mitochondrial energy demand and capacity of the tricarboxylic acid cycle. This natural ebb and flow of acylcarnitine generation and accumulation contrasts with that of inherited fatty acid oxidation disorders (FAODs), cardiac ischaemia or type 2 diabetes mellitus. These conditions are characterized by very high (FAODs, ischaemia) or modestly increased (type 2 diabetes mellitus) tissue and blood levels of LCACs. Although specific plasma concentrations of LCACs and chain-lengths are widely used as diagnostic markers of FAODs, research into the potential effects of excessive LCAC accumulation or the roles of acylcarnitines as physiological modulators of cell metabolism is lacking. Nevertheless, a growing body of evidence has highlighted possible effects of LCACs on disparate aspects of pathophysiology, such as cardiac ischaemia outcomes, insulin sensitivity and inflammation. This Review, therefore, aims to provide a theoretical framework for the potential consequences of tissue build-up of LCACs among individuals with metabolic disorders.

Peripheral ischaemic retinopathy and neovascularisation in a patient with subacute streptococcus mitis-induced bacterial endocarditis

PubMed Central

Leysen, Laura S.; Kreps, Elke O.; De Schryver, Ilse; Hoornaert, Kristien P.; Smith, Vanessa; De Zaeytijd, Julie

2017-01-01

Objective: To describe a patient with peripheral retinal ischaemia and neovascularisation who was diagnosed with streptococcus mitis-induced bacterial endocarditis. Methods: Retrospective analysis of case report. A 57-year-old man presented with a history of a rapidly progressive, bilateral, painless visual loss. He also suffered from pain in the neck and lower back and a weight loss of 10 kg. He underwent a full ophthalmologic work-up, laboratory investigations, and imaging of the spine. Results: BCVA was reduced to 20/40 in the right eye and 20/32 in the left eye. Fundoscopy showed rare intra-retinal haemorrhages including few Roth spots and cotton wool lesions. Fluorescein angiography demonstrated large areas of peripheral retinal ischaemia and neovascularisation. Imaging of the spine showed spondylodiscitis on several levels. Further imaging and blood cultures confirmed bacterial endocarditis of the mitral valve. Streptococcus mitis was subsequently identified as the causative organism. Conclusion: Peripheral retinal ischaemia and neovascularisation were previously unrecognised as a feature of infectious endocarditis. Therefore, their presence, apart from the classic Roth spots, should prompt the consideration of infectious endocarditis in the etiologic work-up. PMID:28944156

Cardioprotection by remote ischaemic preconditioning.

PubMed

Walsh, S R; Tang, T; Sadat, U; Dutka, D P; Gaunt, M E

2007-11-01

Perioperative myocardial infarction is a leading cause of morbidity and mortality after major non-cardiac surgery. Pharmacological agents such as beta-blockers may reduce the risk but are associated with side-effects and may be contra-indicated in some patients. Basic scientific experiments and preliminary clinical trials in humans suggest that remote ischaemic preconditioning (RIPC), where brief ischaemia in one tissue confers resistance to subsequent sustained ischaemic insults in another tissue, may provide a simple, cost-effective means of reducing the risk of perioperative myocardial ischaemia. The Medline and Pubmed databases were searched for articles concerning RIPC. The mechanism may be humoral, neural, or a combination of both, and involves adenosine, opioids, bradykinins, protein kinase C, and K-ATP channels, although the precise end-effector remains unclear. Small randomized trials in humans undergoing major surgery suggest that RIPC induced by brief lower limb ischaemia significantly reduces myocardial injury. It may also reduce other ischaemic complications of surgery and anaesthesia. Small studies provide some evidence that RIPC could reduce myocardial injury and other ischaemic complications of surgery. However, large-scale clinical trials to assess the effect of RIPC on mortality and morbidity are required before RIPC can be recommended for routine clinical use.

Effects of 1:1, 1:2 or 1:3 intra-aortic balloon counterpulsation/heart support on coronary haemodynamics and cardiac contractile efficiency in an animal model of myocardial ischaemia/reperfusion.

PubMed

Gelsomino, Sandro; Renzulli, Attilio; Rubino, Antonino S; Romano, Salvatore Mario; Lucà, Fabiana; Valente, Serafina; Gensini, Gian Franco; Lorusso, Roberto

2012-08-01

The effects of operational modes of intra-aortic balloon pumping (IABP) on coronary haemodynamics and oxygen delivery/demand ratio are unknown and were investigated in an experimental model of myocardial ischaemia reperfusion. Healthy swine (n = 24) underwent 120-minute ligation of the left anterior descending coronary artery followed by 24 h of reperfusion and were randomly assigned to have IABP 1:1 (n = 6), IABP 1:2 (n = 6), IABP 1:3 (n = 6) in the descending aorta or to no IABP implantation (n = 6) 5 min after the onset of reperfusion. Systolic (CBF(Sys)) and diastolic (CBF(Dia)) coronary blood flow, systolic (CR(Sys)) and diastolic (CR(Dia)) coronary resistances and endocardial viability ratio (EVR), as an expression of the oxygen delivery/demand ratio, were measured at 30 min, 1, 6, 12 and 24 h after coronary reperfusion, respectively. IABP at the 1:1 operational mode significantly increased CBF(Dia) and EVR, and reduced CR(Dia) throughout the experiment. Contrastingly, IABP at 1:3 mode resulted in a significant reduction in CBF(Dia), in a steady increase in CR(Dia), in a steady reduction in O(2) delivery and a constant increase in O(2) demand over time. IABP at the 1:2 mode had no overall effect on assessed parameters. IABP at the 1:1 mode enhanced coronary haemodynamics and cardiac contractile efficiency in an acute animal model of coronary ischaemia/reperfusion. On the contrary, IABP support set at the 1:2 or 1:3 modes failed to provide benefit. Progressive reduction in balloon inflation with a 1:1 mode instead of decreasing the heart/IABP operational ratio might represent a better IABP withdrawal protocol and is currently under investigation.

Mineralocorticoid receptor antagonists in kidney transplantation: time to consider?

PubMed

Girerd, Sophie; Jaisser, Frédéric

2018-04-17

Although patient survival is significantly improved by kidney transplantation (KT) in comparison with dialysis, it remains significantly lower than that observed in the general population. Graft function is one of the major determinants of patient survival after KT. Mineralocorticoid receptor antagonists (MRAs) could be of particular interest in this population to improve graft function and treat or prevent cardiovascular (CV) complications. In KT, ischaemia/reperfusion injury is a major factor involved in delayed graft function, which is often associated with inferior long-term graft survival. Preclinical studies suggest that MRAs may prevent ischaemia/reperfusion-related lesions in addition to having a protective effect in preventing calcineurin inhibitor-induced nephrotoxicity. Clinical data also support the anti-proteinuric effect of MRAs in chronic kidney disease (CKD). Taken together, MRAs may hence be of particular benefit in improving short- and long-term graft function. Numerous randomized controlled trials (RCTs) have shown the efficacy of MRAs in both heart failure and resistant hypertension. As these comorbidities are frequent in kidney transplant recipients before transplantation or during follow-up, MRAs could represent a useful therapeutic option in those with mild renal function impairment. However, CKD patients are under-represented in RCTs and the CV effects of MRAs in kidney transplant recipients have yet to be specifically assessed in large-scale trials. Available evidence indicates a good safety profile for MRAs in patients with a glomerular filtration rate (GFR) >30 mL/min/1.73 m2. However, as for all patients prescribed an MRA, creatinine and potassium should also be closely monitored following MRA initiation in kidney transplant patients. Given the current evidence suggesting that MRAs prevent ischaemia/reperfusion-related lesions and calcineurin inhibitor-induced nephrotoxicity in kidney transplant recipients as well as CV events in patients at high risk of CV complications (such as those in kidney transplant recipients), trials are urgently needed to fully assess the clinical impact of MRA use in this population.

Blockade by N-3 polyunsaturated fatty acid of the Kv4.3 current stably expressed in Chinese hamster ovary cells

PubMed Central

Singleton, C B; Valenzuela, S M; Walker, B D; Tie, H; Wyse, K R; Bursill, J A; Qiu, M R; Breit, S N; Campbell, T J

1999-01-01

The Kv4.3 gene is believed to encode a large proportion of the transient outward current (Ito), responsible for the early phase of repolarization of the human cardiac action potential. There is evidence that this current is involved in the dispersion of refractoriness which develops during myocardial ischaemia and which predisposes to the development of potentially fatal ventricular tachyarrhythmias. Epidemiological, clinical, animal, and cellular studies indicate that these arrhythmias may be ameliorated in myocardial ischaemia by n-3 polyunsaturated fatty acids (n-3 PUFA) present in fish oils. We describe stable transfection of the Kv4.3 gene into a mammalian cell line (Chinese hamster ovary cells), and using patch clamp techniques have shown that the resulting current closely resembles human Ito. The current is rapidly activating and inactivating, with both processes being well fit by double exponential functions (time constants of 3.8±0.2 and 5.3±0.4 ms for activation and 20.0±1.2 and 96.6±6.7 ms for inactivation at +45 mV at 23°C). Activation and steady state inactivation both show voltage dependence (V1/2 of activation=−6.7±2.5 mV, V1/2 of steady state inactivation=−51.3±0.2 mV at 23°C). Current inactivation and recovery from inactivation are faster at physiologic temperature (37°C) compared to room temperature (23°C). The n-3 PUFA docosahexaenoic acid blocks the Kv4.3 current with an IC50 of 3.6 μmol L−1. Blockade of the transient outward current may be an important mechanism by which n-3 PUFA provide protection against the development of ventricular fibrillation during myocardial ischaemia. PMID:10433502

Interaction of clopidogrel and statins in secondary prevention after cerebral ischaemia – a randomized, double-blind, double-dummy crossover study

PubMed Central

Siepmann, Timo; Heinke, Denise; Kepplinger, Jessica; Barlinn, Kristian; Gehrisch, Siegmund; Grählert, Xina; Schwanebeck, Uta; Reichmann, Heinz; Puetz, Volker; Bodechtel, Ulf; Gahn, Georg

2014-01-01

Aims Variability in responsiveness to clopidogrel is a clinical problem in secondary prevention after cerebral ischaemia which has been suggested to be linked to competitive metabolization of clopidogrel and cytochrome P450 (CYP) 3A4-oxidated statins such as simvastatin. We assessed the hypothesis that simvastatin, in contrast to CYP 2C9-metabolized fluvastatin, reduces clopidogrel-mediated platelet inhibition. Methods We performed a randomized, double-blind, double-dummy, two period crossover study in 13 patients with cerebral ischaemia (8F, 5 M), aged 64.1 ± 8.0 years (mean ± SD). After a 14 day period in which all patients received 75 mg clopidogrel day−1, patients additionally received either 20 mg simvastatin day−1 or 80 mg fluvastatin day−1 for 14 days. Regimens were crossed over after a 14 day wash-out period and switched regimens were continued for another 14 days. Platelet aggregation, clopidogrel active metabolite (CAM) plasma concentrations and routine laboratory parameters including prothrombin time (PT) Quick percent value were assessed at baseline and following each treatment phase. Results Clopidogrel reduced platelet aggregation in all patients as expected. Platelet aggregation and CAM plasma concentrations were unaltered when simvastatin or fluvastatin was added to clopidogrel. Simvastatin decreased PT Quick percent value (decrease from 109 ± 10.5% to 103 ± 11%, P < 0.05) when combined with clopidogrel but there was no such change following treatment with fluvastatin and clopidogrel. Conclusions Our data indicate that treatment with CYP 3A4-metabolized simvastatin does not jeopardize clopidogrel-mediated inhibition of platelet aggregation. After co-administration of simvastatin and clopidogrel we observed a decrease in the PT Quick percent value which could be due to simvastatin-induced reduction of activity of prothrombin fragment 1 + 2. PMID:24803100

Optimal timing of coronary angiography and potential intervention in non-ST-elevation acute coronary syndromes.

PubMed

Katritsis, Demosthenes G; Siontis, George C M; Kastrati, Adnan; van't Hof, Arnoud W J; Neumann, Franz-Josef; Siontis, Konstantinos C M; Ioannidis, John P A

2011-01-01

An invasive approach is superior to medical management for the treatment of patients with acute coronary syndromes without ST-segment elevation (NSTE-ACS), but the optimal timing of coronary angiography and subsequent intervention, if indicated, has not been settled. We conducted a meta-analysis of randomized trials addressing the optimal timing (early vs. delayed) of coronary angiography in NSTE-ACS. Four trials with 4013 patients were eligible (ABOARD, ELISA, ISAR-COOL, TIMACS), and data for longer follow-up periods than those published became available for this meta-analysis by the ELISA and ISAR-COOL investigators. The median time from admission or randomization to coronary angiography ranged from 1.16 to 14 h in the early and 20.8-86 h in the delayed strategy group. No statistically significant difference of risk of death [random effects risk ratio (RR) 0.85, 95% confidence interval (CI) 0.64-1.11] or myocardial infarction (MI) (RR 0.94, 95% CI 0.61-1.45) was detected between the two strategies. Early intervention significantly reduced the risk for recurrent ischaemia (RR 0.59, 95% CI 0.38-0.92, P = 0.02) and the duration of hospital stay (by 28%, 95% CI 22-35%, P < 0.001). Furthermore, decreased major bleeding events (RR 0.78, 95% CI 0.57-1.07, P = 0.13), and less major events (death, MI, or stroke) (RR 0.91, 95% CI 0.82-1.01, P = 0.09) were observed with the early strategy but these differences were not nominally significant. Early coronary angiography and potential intervention reduces the risk of recurrent ischaemia, and shortens hospital stay in patients with NSTE-ACS.

Comparison of Two Types of Warm-Up Upon Repeated-Sprint Performance in Experienced Soccer Players.

PubMed

van den Tillaar, Roland; von Heimburg, Erna

2016-08-01

van den Tillaar, R and von Heimburg, E. Comparison of two types of warm-up upon repeated-sprint performance in experienced soccer players. J Strength Cond Res 30(8): 2258-2265, 2016-The aim of the study was to compare the effects of a long warm-up and a short warm-up upon repeated-sprint performance in soccer players. Ten male soccer players (age, 21.9 ± 1.9 years; body mass, 77.7 ± 8.3 kg; body height, 1.85 ± 0.03 m) conducted 2 types of warm-ups with 1 week in between: a long warm-up (20 minutes: LWup) and a short warm-up (10 minutes: SWup). Each warm-up was followed by a repeated-sprint test consisting of 8 × 30 m sprints with a new start every 30th second. The best sprint time, total sprinting time, and % decrease in time together with heart rate, lactate, and rate of perceived exertion (RPE) were measured. No significant differences in performance were found for the repeated-sprint test parameters (total sprint time: 35.99 ± 1.32 seconds [LWup] and 36.12 ± 0.96 seconds [SWup]; best sprint time: 4.32 ± 0.13 seconds [LWup] and 4.30 ± 0.10 seconds [SWup]; and % sprint decrease: 4.16 ± 2.15% [LWup] and 5.02 ± 2.07% [SWup]). No differences in lactate concentration after the warm-up and after the repeated-sprint test were found. However, RPE and heart rate were significantly higher after the long warm-up and the repeated-sprint test compared with the short warm-up. It was concluded that a short warm-up is as effective as a long warm-up for repeated sprints in soccer. Therefore, in regular training, less warm-up time is needed; the extra time could be used for important soccer skill training.

The hyperventilation-induced ischaemia model in human neuropharmacology: neurophysiological and psychometric studies of aniracetam and 3-OH aniracetam.

PubMed

Kraaier, V; van Huffelen, A C; Wieneke, G H

1989-01-01

Standardized hyperventilation in young subjects induces changes in the EEG, a decrease in the velocity of the cerebral blood flow and a decline in cognitive performance, which are comparable to those occurring in patients with cerebral ischaemia. The anti-ischaemic properties of aniracetam and 3-OH aniracetam were tested in this model. A single oral dose of 3-OH aniracetam 1500 mg appeared to have the most pronounced effect on hyperventilation-induced EEG changes and cognitive deterioration. The test drugs had no effect on the heart rate or blood flow velocity. The effects agree with those of other drugs classified as noötropics.

Effects of in situ climate warming on monarch caterpillar (Danaus plexippus) development.

PubMed

Lemoine, Nathan P; Capdevielle, Jillian N; Parker, John D

2015-01-01

Climate warming will fundamentally alter basic life history strategies of many ectothermic insects. In the lab, rising temperatures increase growth rates of lepidopteran larvae but also reduce final pupal mass and increase mortality. Using in situ field warming experiments on their natural host plants, we assessed the impact of climate warming on development of monarch (Danaus plexippus) larvae. Monarchs were reared on Asclepias tuberosa grown under 'Ambient' and 'Warmed' conditions. We quantified time to pupation, final pupal mass, and survivorship. Warming significantly decreased time to pupation, such that an increase of 1 °C corresponded to a 0.5 day decrease in pupation time. In contrast, survivorship and pupal mass were not affected by warming. Our results indicate that climate warming will speed the developmental rate of monarchs, influencing their ecological and evolutionary dynamics. However, the effects of climate warming on larval development in other monarch populations and at different times of year should be investigated.

Respiratory muscle specific warm-up and elite swimming performance.

PubMed

Wilson, Emma E; McKeever, Tricia M; Lobb, Claire; Sherriff, Tom; Gupta, Luke; Hearson, Glenn; Martin, Neil; Lindley, Martin R; Shaw, Dominick E

2014-05-01

Inspiratory muscle training has been shown to improve performance in elite swimmers, when used as part of routine training, but its use as a respiratory warm-up has yet to be investigated. To determine the influence of inspiratory muscle exercise (IME) as a respiratory muscle warm-up in a randomised controlled cross-over trial. A total of 15 elite swimmers were assigned to four different warm-up protocols and the effects of IME on 100 m freestyle swimming times were assessed.Each swimmer completed four different IME warm-up protocols across four separate study visits: swimming-only warm-up; swimming warm-up plus IME warm-up (2 sets of 30 breaths with a 40% maximum inspiratory mouth pressure load using the Powerbreathe inspiratory muscle trainer); swimming warm-up plus sham IME warm-up (2 sets of 30 breaths with a 15% maximum inspiratory mouth pressure load using the Powerbreathe inspiratory muscle trainer); and IME-only warm-up. Swimmers performed a series of physiological tests and scales of perception (rate of perceived exertion and dyspnoea) at three time points (pre warm-up, post warm-up and post time trial). The combined standard swimming warm-up and IME warm-up were the fastest of the four protocols with a 100 m time of 57.05 s. This was significantly faster than the IME-only warm-up (mean difference=1.18 s, 95% CI 0.44 to 1.92, p<0.01) and the swim-only warm-up (mean difference=0.62 s, 95% CI 0.001 to 1.23, p=0.05). Using IME combined with a standard swimming warm-up significantly improves 100 m freestyle swimming performance in elite swimmers.

Effect of pre-warming on perioperative hypothermia and anesthetic recovery in small breed dogs undergoing ovariohysterectomy.

PubMed

Aarnes, Turi K; Bednarski, Richard M; Lerche, Phillip; Hubbell, John A E

2017-02-01

This study compared perianesthetic body temperatures and times to recovery from general anesthesia in small dogs that were either warmed for 20 minutes prior to anesthesia or not warmed. Twenty-eight client-owned dogs that were presented for ovariohysterectomy were included in the study. Small (<10 kg body weight) dogs with normal circulatory status were randomly assigned to receive pre-warming for 20 minutes or no treatment. Body temperature was measured during the procedure using a calibrated rectal probe. Duration of anesthesia and surgery, time to rescue warming, time to extubation, presence and duration of shivering, and time to return to normal temperature were recorded. Temperature at the end of surgery was significantly higher in the control group than the pre-warmed group. There was no difference in time to extubation or duration of postoperative shivering between groups. Pre-warming did not result in improved temperature or recovery from anesthesia.

Prevalence of silent myocardial ischaemia during exercise stress testing. Its relation to effort tolerance and myocardial perfusion abnormalities.

PubMed

Fragasso, G; Sciammarella, M G; Rossetti, E E; Xuereb, R G; Xuereb, M; Bonetti, F; Carandente, O M; Margonato, A; Chierchia, S L

1992-07-01

The number of underperfused myocardial segments, the extent of coronary artery disease and the severity of impairment of coronary flow reserve were compared in 147 consecutive patients exhibiting painful or painless ischaemic ST segment depression on exercise testing. Of 147 patients, only 61 (41%) experienced angina (group 1) whilst 86 (59%) did not (group 2). In the two groups coronary disease was comparable for both extent and distribution, and neither the location of transient perfusion defects nor their relation to areas of old myocardial necrosis appeared to influence the presence or absence of chest pain. However, exercise duration, exercise time and rate-pressure product at the beginning of ischaemia were lower in group 1. Furthermore, a greater proportion of asymptomatic patients had only one ischaemic segment on 99mTc-MIBI perfusion scintigraphy. We conclude that: (1) in patients with effort angina and coronary disease, the incidence of electrocardiographic silent ischaemic events induced by exercise is similar to that observed in studies based on continuous ECG monitoring. (2) Exertional angina is more frequently associated with greater ischaemic areas and with more severe degrees of impairment of residual coronary flow reserve. (3) The presence of an old myocardial infarction does not appear to influence the incidence of ischaemic cardiac pain.

Periprocedural ischaemia during recanalisation of chronic total coronary occlusions: the influence of the transcollateral retrograde approach.

PubMed

Werner, Gerald S; Coenen, Anja; Tischer, Karl-Heinz

2014-11-01

Percutaneous coronary intervention for chronic total coronary occlusions (CTO) becomes increasingly more complex with the transcollateral retrograde approach. This study assesses the effect of the retrograde approach on markers of ischaemia and clinical events. Four hundred and ninety-two consecutive procedures in 392 patients were prospectively evaluated. Before and within 18-24 hours after the PCI creatine kinase (CK) and cardiac troponin I (cTnI) were obtained. A CK increase of greater than three times the upper limit of normal (ULN) was considered a periprocedural MI. Patients with initially elevated cTnI were excluded. In 106 patients with a retrograde wire passage of the septal collaterals, the incidence of a CK or TnI increase was higher as compared to the antegrade group. Patients with septal dilatation or passage of a dilatation catheter (Corsair) showed the highest cTnI. There was no difference in cardiac death or cerebral complications between the groups with antegrade and retrograde approach within the first 30 days. Complex retrograde recanalisation procedures for CTOs lead to an increased periprocedural ischaemic burden, most likely due to obstruction of the collateral pathway, and to the increased plaque burden of complex lesions treated with the retrograde approach.

Macrophage skewing by Phd2 haplodeficiency prevents ischaemia by inducing arteriogenesis

PubMed Central

Takeda, Yukiji; Costa, Sandra; Delamarre, Estelle; Roncal, Carmen; de Oliveira, Rodrigo Leite; Squadrito, Mario Leonardo; Finisguerra, Veronica; Deschoemaeker, Sofie; Bruyére, Françoise; Wenes, Mathias; Hamm, Alexander; Serneels, Jens; Magat, Julie; Bhattacharyya, Tapan; Anisimov, Andrey; Jordan, Benedicte F.; Alitalo, Kari; Maxwell, Patrick; Gallez, Bernard; Zhuang, Zhen W.; Saito, Yoshihiko; Simons, Michael; De Palma, Michele; Mazzone, Massimiliano

2015-01-01

PHD2 serves as an oxygen sensor that rescues blood supply by regulating vessel formation and shape in case of oxygen shortage1–5. However, it is unknown whether PHD2 can influence arteriogenesis. Here we studied the role of PHD2 in collateral artery growth by using hindlimb ischaemia as a model, a process that compensates for the lack of blood flow in case of major arterial occlusion6–8. We show that Phd2 (also known as Egln1) haplodeficient (Phd2+/−) mice displayed preformed collateral arteries that preserved limb perfusion and prevented tissue necrosis in ischaemia. Improved arteriogenesis in Phd2+/− mice was due to an expansion of tissue-resident, M2-like macrophages9,10 and their increased release of arteriogenic factors, leading to enhanced smooth muscle cell (SMC) recruitment and growth. Both chronic and acute deletion of one Phd2 allele in macrophages was sufficient to skew their polarization towards a proarteriogenic phenotype. Mechanistically, collateral vessel preconditioning relied on the activation of canonical NF-κB pathway in Phd2+/− macrophages. These results unravel how PHD2 regulates arteriogenesis and artery homeostasis by controlling a specific differentiation state in macrophages and suggest new treatment options for ischaemic disorders. PMID:21983962

Lack of ecto-5'-nucleotidase (CD73) promotes arteriogenesis.

PubMed

Böring, Yang Chul; Flögel, Ulrich; Jacoby, Christoph; Heil, Matthias; Schaper, Wolfgang; Schrader, Jürgen

2013-01-01

Adenosine can stimulate angiogenesis, but its role in the distinct process of arteriogenesis is unknown. We have previously reported that mice lacking ecto-5'-nucleotidase (CD73-/-) show enhanced monocyte adhesion to the endothelium after ischaemia, which is considered to be an important trigger for arteriogenesis. Hindlimb ischaemia was induced in wild-type (WT) and CD73-/- mice to study the role of extracellularly formed adenosine in arteriogenesis. Magnetic resonance angiography (MRA) was performed for serial visualization of newly developed vessels at a spatial resolution of 1 nL, and high-energy phosphates (HEP) were quantified by (31)P MR spectroscopy (MRS). MRA of CD73-/- mice revealed substantially enhanced collateral artery conductance at day 7 [CD73-/-: 0.73 ± 0.11 a.u. (arbitrary units); WT: 0.44 ± 0.13 a.u.; P < 0.01, n = 6], and MRS of the affected hindlimb showed a faster restoration of HEP in correlation with enhanced functional recovery in the mutant. Additionally, histology showed no differences in capillary density between the groups but showed an increased monocyte infiltration in hindlimbs of CD73-/- mice. Serial assessment of dynamic changes of vessel growth and metabolism in the process of arteriogenesis demonstrate that the lack of CD73-derived adenosine importantly promotes arteriogenesis but does not alter angiogenesis in our model of hindlimb ischaemia.

Protective effect of Mangifera indica L. extract (Vimang) on the injury associated with hepatic ischaemia reperfusion.

PubMed

Sánchez, Gregorio Martínez; Rodríguez H, María A; Giuliani, Attilia; Núñez Sellés, Alberto J; Rodríguez, Niurka Pons; León Fernández, Olga Sonia; Re, L

2003-03-01

The effect of Mangifera indica L. extract (Vimang) on treatment of injury associated with hepatic ischaemia/reperfusion was tested. Vimang protects from the oxidative damage induced by oxygen-based free radicals as shown in several in vitro test systems conducted. The ability of Vimang to reduce liver damage was investigated in rats undergoing right-lobe blood fl ow occlusion for 45 min followed by 45 min of reperfusion. The ischaemia/reperfusion model leads to an increase of transaminase (ALT and AST), membrane lipid peroxidation, tissue neutrophil in filtration, DNA fragmentation, loss of protein -SH groups, cytosolic Ca2+ overload and a decrease of catalase activity. Oral administration of Vimang (50, 110 and 250 mg/kg, b.w.) 7 days before reperfusion, reduced transaminase levels and DNA fragmentation in a dose dependent manner (p < 0.05). Vimang also restored the cytosolic Ca2+ levels and inhibited polymorphonuclear migration at a dose of 250 mg/kg b.w., improved the oxidation of total and non protein sulfhydryl groups and prevented modification in catalase activity, uric acid and lipid peroxidation markers (p < 0.05). These data suggest that Vimang could be a useful new natural drug for preventing oxidative damage during hepatic injury associated with free radical generation. Copyright 2003 John Wiley & Sons, Ltd.

MicroRNA-125b protects against myocardial ischaemia/reperfusion injury via targeting p53-mediated apoptotic signalling and TRAF6

PubMed Central

Wang, Xiaohui; Ha, Tuanzhu; Zou, Jianghuan; Ren, Danyang; Liu, Li; Zhang, Xia; Kalbfleisch, John; Gao, Xiang; Williams, David; Li, Chuanfu

2014-01-01

Aims The present study examined the role of microRNA-125b (miR-125b) in myocardial ischaemia/reperfusion (I/R) injury. We constructed lentivirus-expressing miR-125b (LmiR-125b) and developed transgenic mice with overexpression of miR-125b. Methods and results LmiR-125b was transfected into mouse hearts through the right common carotid artery. Lentivirus vector (LmiR-Con) served as vector control. Untreated mice served as I/R control. Sham operation served as sham control. Seven days after transfection, the hearts were subjected to ischaemia (45 min) followed by reperfusion (4 h). Myocardial infarct size was analysed by 2,3,5-triphenyltetrazolium chloride staining. In separate experiments, hearts were subjected to ischaemia (45 min) followed by reperfusion for up to 7 days. Cardiac function was measured by echocardiography before, as well as 3 and 7 days after myocardial I/R. Increased expression of miR-125b significantly decreased I/R-induced myocardial infarct size by 60% and prevented I/R-induced decreases in ejection fraction (EF%) and fractional shortening (%FS). Transgenic mice with overexpression of miR-125b also showed the protection against myocardial I/R injury. Increased expression of miR-125b attenuated I/R-induced myocardial apoptosis and caspase-3/7 and -8 activities. Western blot showed that increased expression of miR-125b suppresses p53 and Bak1 expression in the myocardium. In addition, transfection of LmiR-125b decreased the levels of TNF receptor-associated factor 6 (TRAF6) and prevented I/R-induced NF-κB activation. Conclusion miR-125 protects the myocardium from I/R injury by preventing p53-mediated apoptotic signalling and suppressing TRAF6-mediated NF-κB activation. PMID:24576954

Activation of G protein‐coupled oestrogen receptor 1 at the onset of reperfusion protects the myocardium against ischemia/reperfusion injury by reducing mitochondrial dysfunction and mitophagy

PubMed Central

Feng, Yansheng; Madungwe, Ngonidzashe B; da Cruz Junho, Carolina Victoria

2017-01-01

Background and Purpose Recent evidence indicates that GPER (G protein‐coupled oestrogen receptor 1) mediates acute pre‐ischaemic oestrogen‐induced protection of the myocardium from ischaemia/reperfusion injury via a signalling cascade that includes PKC translocation, ERK1/2/ GSK‐3β phosphorylation and inhibition of the mitochondrial permeability transition pore (mPTP) opening. Here, we investigated the impact and mechanism involved in post‐ischaemic GPER activation in ischaemia/reperfusion injury. We determined whether GPER activation at the onset of reperfusion confers cardioprotective effects by protecting against mitochondrial impairment and mitophagy. Experimental Approach In vivo rat hearts were subjected to ischaemia followed by reperfusion with oestrogen (17β‐oestradiol, E2), E2 + G15, a GPER antagonist, or vehicle. Myocardial infarct size, the threshold for the opening of mPTP, mitophagy, mitochondrial membrane potential, ROS production, proteins ubiquitinated including cyclophilin D, and phosphorylation levels of ERK and GSK‐3β were measured. Results We found that post‐ischaemic E2 administration to both male and female ovariectomized‐rats reduced myocardial infarct size. Post‐ischaemic E2 administration preserved mitochondrial structural integrity and this was associated with a decrease in ROS production and increased mitochondrial membrane potential, as well as an increase in the mitochondrial Ca2+ load required to induce mPTP opening via activation of the MEK/ERK/GSK‐3β axis. Moreover, E2 reduced mitophagy via the PINK1/Parkin pathway involving LC3I, LC3II and p62 proteins. All these post‐ischaemic effects of E2 were abolished by G15 suggesting a GPER‐dependent mechanism. Conclusion These results indicate that post‐ischaemic GPER activation induces cardioprotective effects against ischaemia/reperfusion injury in males and females by protecting mitochondrial structural integrity and function and reducing mitophagy. PMID:28906548

[Significance of the level of implantation of the 'E-vita open plus' hybrid stent graft into the descending aorta in the development of spinal ischaemic complications].

PubMed

Kozlov, B N; Panfilov, D S; Saushkin, V V; Kuznetsov, M S; Nasrashvili, G G; Andriianova, A V; Shipulin, V M

Spinal ischaemia in patients after reconstruction of the thoracic aorta is referred to the category of the most severe postoperative complications, especially in hybrid interventions. The present study was aimed at assessing the risks for the development of spinal ischaemia in patients after implantation of the 'E-vita open plus' stent graft into the descending portion of the thoracic aorta during hybrid reconstruction. The 'E-vita open plus' hybrid stent graft (Jotec, Germany) was implanted to 18 patients presenting with various pathology of the thoracic aorta (dissection, aneurysms). All operations were carried out in the conditions of moderate hypothermia, circulatory arrest and antegrade perfusion of the brain through the brachiocephalic trunk. It was determined that the distal end of the stent graft was located at the level of Th7-Th12. In 12 (66.7%) cases the 'lower' edge of the stent graft was located at the level of thoracic vertebrae Th8-Th9. Before the operation the number of open pairs of intercostal arteries amounted to 10 [9, 11]. After the operation, the number of the open pairs of the segmental arteries amounted to 3 [1; 4], they were all in the lower thoracic portion; the above-located intercostal arteries were shut by the stent graft. In 17 (94.5%) cases in the early postoperative period there were no signs of spinal ischaemia. Only one (5.5%) patient was clinically diagnosed to have developed transient spinal ischaemia noted to disappear spontaneously within the first 24 hours. A conclusion was made that using the 'E-vita open plus' stent graft in the course of hybrid reconstruction of the thoracic aorta was accompanied by the minimal risk for spinal ischaemic complications. The level of the location of the distal edge of the stent graft is not the determining factor in the risks of spinal complications in of such similar operations.

B‐type natriuretic peptide release in the coronary effluent after acute transient ischaemia in humans

PubMed Central

Pascual‐Figal, Domingo A; Antolinos, María J; Bayes‐Genis, Antoni; Casas, Teresa; Nicolas, Francisco; Valdés, Mariano

2007-01-01

Background The association between B‐type natriuretic peptide (BNP) and coronary artery disease is not fully understood. Objective To assess whether ischaemia per se is a stimulus for BNP secretion. Setting University tertiary hospital, Spain (Virgen de la Arrixaca). Design Prospective interventional study. Patients 11 patients (55 (9) years, left ventricular ejection fraction (LVEF) 45% (7%) with a non‐complicated anterior myocardial infarction (MI) and isolated stenosis of the left anterior descending (LAD) coronary artery, successfully treated by primary angioplasty. Interventions 11.0 (0.9) days after MI, the LAD was occluded (20 min) for intracoronary infusion of progenitor cells. Blood samples were obtained from the femoral artery (peripheral circulation (PC)) and the coronary sinus (coronary circulation (CC)) immediately before and after coronary occlusion. Main outcome measures BNP (pg/ml) was measured and ischaemia biomarkers were monitored. Results During coronary occlusion, all patients experienced transitory chest pain and ST‐segment dynamic changes. After coronary occlusion, lactic acid levels rose in CC (1.42 (0.63) –1.78 (0.68) ng/ml, p = 0.003). Myoglobin and cardiac troponin T did not differ in CC or PC at 24 h. No differences were found in LVEF (+0.18% (2.4)%, p = 0.86) and motion score index (–0.02 (0.06), p = 0.37). Before occlusion, BNP levels did not differ significantly in CC versus PC (253 (56) vs 179 (34), p = 0.093). After occlusion, BNP showed a significant increase in CC (vs 332 (61), p = 0.004), but no change occurred in PC (vs 177 (23), p = 0.93), and circulating BNP levels were higher in CC versus PC (p = 0.008). Conclusions In response to acute ischaemia, BNP levels immediately increase in coronary sinus but not at the peripheral level. BNP release in the coronary effluent may exert local beneficial effects. PMID:17395669

MicroRNA-125b protects against myocardial ischaemia/reperfusion injury via targeting p53-mediated apoptotic signalling and TRAF6.

PubMed

Wang, Xiaohui; Ha, Tuanzhu; Zou, Jianghuan; Ren, Danyang; Liu, Li; Zhang, Xia; Kalbfleisch, John; Gao, Xiang; Williams, David; Li, Chuanfu

2014-06-01

The present study examined the role of microRNA-125b (miR-125b) in myocardial ischaemia/reperfusion (I/R) injury. We constructed lentivirus-expressing miR-125b (LmiR-125b) and developed transgenic mice with overexpression of miR-125b. LmiR-125b was transfected into mouse hearts through the right common carotid artery. Lentivirus vector (LmiR-Con) served as vector control. Untreated mice served as I/R control. Sham operation served as sham control. Seven days after transfection, the hearts were subjected to ischaemia (45 min) followed by reperfusion (4 h). Myocardial infarct size was analysed by 2,3,5-triphenyltetrazolium chloride staining. In separate experiments, hearts were subjected to ischaemia (45 min) followed by reperfusion for up to 7 days. Cardiac function was measured by echocardiography before, as well as 3 and 7 days after myocardial I/R. Increased expression of miR-125b significantly decreased I/R-induced myocardial infarct size by 60% and prevented I/R-induced decreases in ejection fraction (EF%) and fractional shortening (%FS). Transgenic mice with overexpression of miR-125b also showed the protection against myocardial I/R injury. Increased expression of miR-125b attenuated I/R-induced myocardial apoptosis and caspase-3/7 and -8 activities. Western blot showed that increased expression of miR-125b suppresses p53 and Bak1 expression in the myocardium. In addition, transfection of LmiR-125b decreased the levels of TNF receptor-associated factor 6 (TRAF6) and prevented I/R-induced NF-κB activation. miR-125 protects the myocardium from I/R injury by preventing p53-mediated apoptotic signalling and suppressing TRAF6-mediated NF-κB activation. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

AM1-receptor-dependent protection by intermedin of human vascular and cardiac non-vascular cells from ischaemia–reperfusion injury

PubMed Central

Bell, David; Campbell, Malcolm; Ferguson, Matthew; Sayers, Leah; Donaghy, Liz; O'Regan, Anna; Jewhurst, Victoria; Harbinson, Mark

2012-01-01

Intermedin (IMD) protects rodent heart and vasculature from oxidative stress and ischaemia. Less is known about distribution of IMD and its receptors and the potential for similar protection in man. Expression of IMD and receptor components were studied in human aortic endothelium cells (HAECs), smooth muscle cells (HASMCs), cardiac microvascular endothelium cells (HMVECs) and fibroblasts (v-HCFs). Receptor subtype involvement in protection by IMD against injury by hydrogen peroxide (H2O2, 1 mmol l−1) and simulated ischaemia and reperfusion were investigated using receptor component-specific siRNAs. IMD and CRLR, RAMP1, RAMP2 and RAMP3 were expressed in all cell types. When cells were treated with 1 nmol l−1 IMD during exposure to 1 mmol l−1 H2O2 for 4 h, viability was greater vs. H2O2 alone (P < 0.05 for all cell types). Viabilities under 6 h simulated ischaemia differed (P < 0.05) in the absence and presence of 1 nmol l−1 IMD: HAECs 63% and 85%; HMVECs 51% and 68%; v-HCFs 42% and 96%. IMD 1 nmol l−1 present throughout ischaemia (3 h) and reperfusion (1 h) attenuated injury (P < 0.05): viabilities were 95%, 74% and 82% for HAECs, HMVECs and v-HCFs, respectively, relative to those in the absence of IMD (62%, 35%, 32%, respectively). When IMD 1 nmol l−1 was present during reperfusion only, protection was still evident (P < 0.05, 79%, 55%, 48%, respectively). Cytoskeletal disruption and protein carbonyl formation followed similar patterns. Pre-treatment (4 days) of HAECs with CRLR or RAMP2, but not RAMP1 or RAMP3, siRNAs abolished protection by IMD (1 nmol l−1) against ischaemia–reperfusion injury. IMD protects human vascular and cardiac non-vascular cells from oxidative stress and ischaemia–reperfusion, predominantly via AM1 receptors. PMID:22183724

Women with dysmenorrhoea are hypersensitive to experimentally induced forearm ischaemia during painful menstruation and during the pain-free follicular phase.

PubMed

Iacovides, S; Avidon, I; Baker, F C

2015-07-01

Monthly primary dysmenorrhoeic pain is associated with increased sensitivity to painful stimuli, particularly in deep tissue. We investigated whether women with dysmenorrhoea, compared with controls, have increased sensitivity to experimentally induced deep-tissue muscle ischaemia in a body area distant from that of referred menstrual pain. The sub-maximal effort tourniquet test was used to induce forearm ischaemia in 11 women with severe dysmenorrhoea and in nine control women both during menstruation and in the follicular phase of the menstrual cycle. Von Frey hair assessments confirmed the presence of experimental ischaemia. Women rated the intensity of menstrual and ischaemic pain on a 100-mm visual analogue scale. Women with dysmenorrhoea [mean (SD): 68 (20) mm] reported significantly greater menstrual pain compared with controls [mean (SD): 2 (6) mm; p = 0.0001] during the menstruation phase. They also rated their forearm ischaemic pain as significantly greater than the controls during the menstruation [dysmenorrhoeics vs. controls mean (SD): 58 (19) mm vs. 31 (21) mm, p < 0.01] and follicular [dysmenorrhoeics vs. controls mean (SD): 60 (18) mm vs. 40 (14) mm, p < 0.01] phases of the menstrual cycle. These data show that compared with controls, women who experience severe recurrent dysmenorrhoea have deep-tissue hyperalgesia to ischaemic pain in muscles outside of the referred area of menstrual pain both during the painful menstruation phase and pain-free follicular phase. These findings suggest the presence of long-lasting changes in muscle pain sensitivity in women with dysmenorrhoea. Our findings that dysmenorrhoeic women are hyperalgesic to a clinically relevant, deep-muscle ischaemic pain in areas outside of referred menstrual pain confirm other studies showing long-lasting changes in pain sensitivity outside of the painful period during menstruation. © 2014 European Pain Federation - EFIC®

Transmyocardial laser revascularization in the acute ischaemic heart: no improvement of acute myocardial perfusion or prevention of myocardial infarction.

PubMed

Eckstein, F S; Scheule, A M; Vogel, U; Schmid, S T; Miller, S; Jurmann, M J; Ziemer, G

1999-05-01

Transmyocardial laser revascularization (TMLR) has been used to provide enhanced myocardial perfusion in patients not suitable for coronary revascularization or angioplasty. This study investigates the acute changes in myocardial perfusion after TMLR with a Holmium:Yttrium-Aluminium-Garnet (YAG) laser with a thermal imaging camera in a model of acute ischaemia, and confirms its midterm effects by post-mortem investigation of magnetic resonance imaging and histopathological examination. Acute myocardial ischaemia was induced by occlusion of the dominant diagonal branch in ten sheep. Perfusion measurements were undertaken first in the unaffected myocardium, then after temporary occlusion of the coronary to obtain a control measurement for ischaemic myocardium. Myocardial perfusion was then evaluated during reperfusion after release of coronary occlusion. Then the coronary was permanently occluded and 20.5+/-2 channels were drilled with the Holmium:YAG laser and perfusion was measured again. The other four sheep served as control with untreated ischaemia. All animals were sacrificed after 28 days following administration of gadolinium i.v. to serve as contrast medium for magnetic resonance tomography. The hearts were subjected to magnetic resonance tomography and histopathological examination. Intraoperative perfusion measurements revealed a decreased perfusion after temporary occlusion and an increased perfusion in reperfused myocardium. After TMLR, no improvement of myocardial perfusion above the ischaemic level could be shown. Magnetic resonance images could neither confirm patent laser channels nor viable myocardium within ischaemic areas. On histology no patent endocardial laser channel could be detected. The transmural features were myocardial infarct with scar tissue. In the presented sheep model with acute ischaemia, TMLR with a Holmium:YAG laser did not provide acute improvement of myocardial perfusion as assessed by a thermal imaging camera. This would suggest no direct contribution of newly created laser channels to myocardial perfusion. As chronic effects are concerned, no perfused laser channels could be identified by later magnetic resonance imaging or histology.

Elective frozen elephant trunk procedure using the E-Vita Open Plus prosthesis in 94 patients: a multicentre French registry.

PubMed

Verhoye, Jean-Philippe; Belhaj Soulami, Reda; Fouquet, Olivier; Ruggieri, Vito Giovanni; Kaladji, Adrien; Tomasi, Jacques; Sellin, Michel; Farhat, Fadi; Anselmi, Amedeo

2017-10-01

Our goal was to evaluate the operative outcomes of the frozen elephant trunk technique using the E-Vita Open Plus® hybrid prosthesis in chronic aortic arch diseases and report clinical and radiological outcomes at the 1-year follow-up. As determined from a prospective multicentre registry, 94 patients underwent frozen elephant trunk procedures using the E-Vita Open Plus hybrid device for the treatment of chronic aortic conditions, including 50% chronic aortic dissections, 40% degenerative aneurysms and 10% miscellaneous indications. Fifty percent of the cases were reoperations. The perioperative mortality rate was 11.7%. Spinal cord ischaemia and stroke rates were 4% and 9.6%, respectively. The mean cardiopulmonary bypass time was 252 ± 97 min, cardiac ischaemia time was 152 ± 53 min and cerebral perfusion time was 82 ± 22 min. Concomitant procedures were observed in 15% of patients. Among the 83 surviving patients, the survival rate after the 1-year follow-up was 98%. Eleven percent of patients underwent endovascular completion, whereas 4% of patients required aortic reintervention at 1 year. The E-Vita Open Plus hybrid device confirms the favourable short- and mid-term outcomes offered by its predecessor in frozen elephant trunk procedures in patients with chronic aortic arch disease. Implantation of the E-Vita Open Plus is associated with good 1-year survival rates, good rates of favourable aortic remodelling in both chronic dissection and degenerative aneurysms and a reproducible technique in a multicentre registry. Continued follow-up is required due to the risk of evolution at the downstream aorta. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Distinct cytoprotective roles of pyruvate and ATP by glucose metabolism on epithelial necroptosis and crypt proliferation in ischaemic gut

PubMed Central

Huang, Ching‐Ying; Kuo, Wei‐Ting; Huang, Chung‐Yen; Lee, Tsung‐Chun; Chen, Chin‐Tin; Peng, Wei‐Hao; Lu, Kuo‐Shyan; Yang, Chung‐Yi

2016-01-01

Key points Intestinal ischaemia causes epithelial death and crypt dysfunction, leading to barrier defects and gut bacteria‐derived septic complications.Enteral glucose protects against ischaemic injury; however, the roles played by glucose metabolites such as pyruvate and ATP on epithelial death and crypt dysfunction remain elusive.A novel form of necrotic death that involves the assembly and phosphorylation of receptor interacting protein kinase 1/3 complex was found in ischaemic enterocytes.Pyruvate suppressed epithelial cell death in an ATP‐independent manner and failed to maintain crypt function. Conversely, replenishment of ATP partly restored crypt proliferation but had no effect on epithelial necroptosis in ischaemic gut.Our data argue against the traditional view of ATP as the main cytoprotective factor by glucose metabolism, and indicate a novel anti‐necroptotic role of glycolytic pyruvate under ischaemic stress. Abstract Mesenteric ischaemia/reperfusion induces epithelial death in both forms of apoptosis and necrosis, leading to villus denudation and gut barrier damage. It remains unclear whether programmed cell necrosis [i.e. receptor‐interacting protein kinase (RIP)‐dependent necroptosis] is involved in ischaemic injury. Previous studies have demonstrated that enteral glucose uptake by sodium‐glucose transporter 1 ameliorated ischaemia/reperfusion‐induced epithelial injury, partly via anti‐apoptotic signalling and maintenance of crypt proliferation. Glucose metabolism is generally assumed to be cytoprotective; however, the roles played by glucose metabolites (e.g. pyruvate and ATP) on epithelial cell death and crypt dysfunction remain elusive. The present study aimed to investigate the cytoprotective effects exerted by distinct glycolytic metabolites in ischaemic gut. Wistar rats subjected to mesenteric ischaemia were enterally instilled glucose, pyruvate or liposomal ATP. The results showed that intestinal ischaemia caused RIP1‐dependent epithelial necroptosis and villus destruction accompanied by a reduction in crypt proliferation. Enteral glucose uptake decreased epithelial cell death and increased crypt proliferation, and ameliorated mucosal histological damage. Instillation of cell‐permeable pyruvate suppressed epithelial cell death in an ATP‐independent manner and improved the villus morphology but failed to maintain crypt function. Conversely, the administration of liposomal ATP partly restored crypt proliferation but did not reduce epithelial necroptosis and histopathological injury. Lastly, glucose and pyruvate attenuated mucosal‐to‐serosal macromolecular flux and prevented enteric bacterial translocation upon blood reperfusion. In conclusion, glucose metabolites protect against ischaemic injury through distinct modes and sites, including inhibition of epithelial necroptosis by pyruvate and the promotion of crypt proliferation by ATP. PMID:27121603

Prehospital aspirin administration for acute coronary syndrome (ACS) in the USA: an EMS quality assessment using the NEMSIS 2011 database.

PubMed

Tataris, Katie L; Mercer, Mary P; Govindarajan, Prasanthi

2015-11-01

National practice guidelines recommend early aspirin administration to reduce mortality in acute coronary syndrome (ACS). Although timely administration of aspirin has been shown to reduce mortality in ACS by 23%, prior regional Emergency Medical Service (EMS) data have shown inadequate prehospital administration of aspirin in patients with suspected cardiac ischaemia. Using the National EMS Information System (NEMSIS) database, we sought to determine (1) the proportion of patients with suspected cardiac ischaemia who received aspirin and (2) patient and prehospital characteristics that independently predicted administration of aspirin. Analysis of the 2011 NEMSIS database targeted patients aged ≥40 years with a paramedic primary impression of 'chest pain'. To identify patients with chest pain of suspected cardiac aetiology, we included those for whom an ECG or cardiac monitoring had been performed. Trauma-related chest pain and basic life support transports were excluded. The primary outcome was presence of aspirin administration. Patient (age, sex, race/ethnicity and insurance status) and regional characteristics where the EMS transport occurred were also obtained. Multivariate logistic regression was used to assess the independent association of patient and regional factors with aspirin administration for suspected cardiac ischaemia. Of the total 14,371,941 EMS incidents in the 2011 database, 198,231 patients met our inclusion criteria (1.3%). Of those, 45.4% received aspirin from the EMS provider. When compared with non-Hispanic white patients, several groups had greater odds of aspirin administration by EMS: non-Hispanic black patients (OR 1.49, 95% CI 1.44 to 1.55), non-Hispanic Asians (OR 1.62, 95% CI 1.21 to 2.18), Hispanics (OR 1.71, 95% CI 1.54 to 1.91) and other non-Hispanics (OR 1.27, 95% CI 1.07 to 1.51). Patients living in the Southern region of the USA (OR 0.59, 95% CI 0.57 to 0.62) and patients with governmental (federally administered such as Veteran's Health Care, but not Medicare or Medicaid) insurance (OR 0.67, 95% CI 0.57 to 0.78) had the lowest odds of receiving aspirin. Age and sex (OR 1.00, 95% CI 1.00 to 1.00) were not associated with aspirin administration. It is likely that prehospital aspirin administration for patients with suspected cardiac ischaemia remains low nationally and could be improved. Reasons for disparities among the various groups should be explored. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Donor characteristics and risk of hepatocellular carcinoma recurrence after liver transplantation.

PubMed

Orci, L A; Berney, T; Majno, P E; Lacotte, S; Oldani, G; Morel, P; Mentha, G; Toso, C

2015-09-01

To date, studies assessing the risk of post-transplant hepatocellular carcinoma (HCC) recurrence have focused on tumour characteristics. This study investigated the impact of donor characteristics and graft quality on post-transplant HCC recurrence. Using the Scientific Registry of Transplant Recipients patients with HCC who received a liver transplant between 2004 and 2011 were included, and post-transplant HCC recurrence was assessed. A multivariable competing risk regression model was fitted, adjusting for confounders such as recipient sex, age, tumour volume, α-fetoprotein, time on the waiting list and transplant centre. A total of 9724 liver transplant recipients were included. Patients receiving a graft procured from a donor older than 60 years (adjusted hazard ratio (HR) 1.38, 95 per cent c.i. 1.10 to 1.73; P = 0.006), a donor with a history of diabetes (adjusted HR 1.43, 1.11 to 1.83; P = 0.006) and a donor with a body mass index of 35 kg/m(2) or more (adjusted HR 1.36, 1.04 to 1.77; P = 0.023) had an increased rate of post-transplant HCC recurrence. In 3007 patients with documented steatosis, severe graft steatosis (more than 60 per cent) was also linked to an increased risk of recurrence (adjusted HR 1.65, 1.03 to 2.64; P = 0.037). Recipients of organs from donation after cardiac death donors with prolonged warm ischaemia had higher recurrence rates (adjusted HR 4.26, 1.20 to 15.1; P = 0.025). Donor-related factors such as donor age, body mass index, diabetes and steatosis are associated with an increased rate of HCC recurrence after liver transplantation. © 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.

Effect of pre-warming on perioperative hypothermia and anesthetic recovery in small breed dogs undergoing ovariohysterectomy

PubMed Central

Aarnes, Turi K.; Bednarski, Richard M.; Lerche, Phillip; Hubbell, John A.E.

2017-01-01

This study compared perianesthetic body temperatures and times to recovery from general anesthesia in small dogs that were either warmed for 20 minutes prior to anesthesia or not warmed. Twenty-eight client-owned dogs that were presented for ovariohysterectomy were included in the study. Small (<10 kg body weight) dogs with normal circulatory status were randomly assigned to receive pre-warming for 20 minutes or no treatment. Body temperature was measured during the procedure using a calibrated rectal probe. Duration of anesthesia and surgery, time to rescue warming, time to extubation, presence and duration of shivering, and time to return to normal temperature were recorded. Temperature at the end of surgery was significantly higher in the control group than the pre-warmed group. There was no difference in time to extubation or duration of postoperative shivering between groups. Pre-warming did not result in improved temperature or recovery from anesthesia. PMID:28216687

Technical aspects and limitations of fractional flow reserve measurement.

PubMed

Jerabek, Stepan; Kovarnik, Tomas

2018-02-27

The only indication for coronary revascularization is elimination of ischaemia. Invasive hemodynamic methods (fractional flow reserve - FFR and instantaneous wave-free ratio (iFR) are superior to coronary angiography in detection of lesions causing myocardial ischaemia. Current European guidelines for myocardial revascularization recommend using of FFR for detection of functional assessment of lesions severity in category IA and number of these procedures increases. However, routine usage of these methods requires knowledge of technical requirements and limitations. The aim of the study is to summarise good clinical practice for FFR and iFR measurements with explanation of possible technical challenges, that are necessary for increasing of measurement accuracy. Authors describe frequent technical mistakes and malpractice during invasive assessment of lesion severity in coronary arteries.

Weak Links in the Early Chain of Care of Acute Lower Limb Ischaemia in Terms of Recognition and Emergency Management.

PubMed

Langenskiöld, M; Smidfelt, K; Karlsson, A; Bohm, C; Herlitz, J; Nordanstig, J

2017-08-01

Acute lower limb ischaemia (ALLI) is a potentially fatal, limb threatening medical emergency. Early treatment is essential for a good outcome. The aim was to describe the early chain of care in ALLI focusing on lead times and emergency management in order to identify weak links for improvement. This was a retrospective, descriptive case study. This study analysed the medical records of all patients with a main discharge diagnosis of ALLI between January 2009 and December 2014. Predetermined emergency care data on lead times, diagnosis recognition, presenting symptoms, emergency care treatment and outcome were collected for patients who were transported by the Emergency Medical Service (EMS) and those who were not. In total, 552 medical records were audited of which 195 patients fulfilled the inclusion criteria and were analysed. Among them were 117 (60%) transported by the EMS. The median time from symptom onset to revascularisation was 23 (interquartile range [IQR] 10-55; EMS transported) and 93 (IQR 42-152, not EMS transported) hours (p < .01). The time from symptom onset to arrival in hospital was 5 (IQR 2-26; EMS transported) and 48 (IQR 6-108; not EMS transported) hours. After arrival in hospital, the median time to first doctor evaluation was 51 (IQR 28-90; EMS transported) and 80 (IQR 44-169; not EMS transported) minutes, p = .01. Low molecular weight heparin (LMWH) was given to 72% of patients in the emergency department (ED) and a multivariate analysis showed that the use of LMWH was associated with a more favourable outcome. Both the time spent in the ED and the time from the onset of symptoms to revascularisation were considerably longer than optimal. Time delays in the early treatment chain can mainly be attributed to "patient delay" and a considerable time spent in hospital before revascularisation. The use of LMWH as an integral part of ED management was associated with a better outcome. Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Independent effects of warming and nitrogen addition on plant phenology in the Inner Mongolian steppe.

PubMed

Xia, Jianyang; Wan, Shiqiang

2013-06-01

Phenology is one of most sensitive traits of plants in response to regional climate warming. Better understanding of the interactive effects between warming and other environmental change factors, such as increasing atmosphere nitrogen (N) deposition, is critical for projection of future plant phenology. A 4-year field experiment manipulating temperature and N has been conducted in a temperate steppe in northern China. Phenology, including flowering and fruiting date as well as reproductive duration, of eight plant species was monitored and calculated from 2006 to 2009. Across all the species and years, warming significantly advanced flowering and fruiting time by 0·64 and 0·72 d per season, respectively, which were mainly driven by the earliest species (Potentilla acaulis). Although N addition showed no impact on phenological times across the eight species, it significantly delayed flowering time of Heteropappus altaicus and fruiting time of Agropyron cristatum. The responses of flowering and fruiting times to warming or N addition are coupled, leading to no response of reproductive duration to warming or N addition for most species. Warming shortened reproductive duration of Potentilla bifurca but extended that of Allium bidentatum, whereas N addition shortened that of A. bidentatum. No interactive effect between warming and N addition was found on any phenological event. Such additive effects could be ascribed to the species-specific responses of plant phenology to warming and N addition. The results suggest that the warming response of plant phenology is larger in earlier than later flowering species in temperate grassland systems. The effects of warming and N addition on plant phenology are independent of each other. These findings can help to better understand and predict the response of plant phenology to climate warming concurrent with other global change driving factors.

Essential role of interleukin-6 in post-stroke angiogenesis

PubMed Central

Gertz, Karen; Kronenberg, Golo; Kälin, Roland E.; Baldinger, Tina; Werner, Christian; Balkaya, Mustafa; Eom, Gina D.; Hellmann-Regen, Julian; Kröber, Jan; Miller, Kelly R.; Lindauer, Ute; Laufs, Ulrich; Dirnagl, Ulrich; Heppner, Frank L.

2012-01-01

Ambivalent effects of interleukin-6 on the pathogenesis of ischaemic stroke have been reported. However, to date, the long-term actions of interleukin-6 after stroke have not been investigated. Here, we subjected interleukin-6 knockout (IL-6−/−) and wild-type control mice to mild brain ischaemia by 30-min filamentous middle cerebral artery occlusion/reperfusion. While ischaemic tissue damage was comparable at early time points, IL-6−/− mice showed significantly increased chronic lesion volumes as well as worse long-term functional outcome. In particular, IL-6−/− mice displayed an impaired angiogenic response to brain ischaemia with reduced numbers of newly generated endothelial cells and decreased density of perfused microvessels along with lower absolute regional cerebral blood flow and reduced vessel responsivity in ischaemic striatum at 4 weeks. Similarly, the early genomic activation of angiogenesis-related gene networks was strongly reduced and the ischaemia-induced signal transducer and activator of transcription 3 activation observed in wild-type mice was almost absent in IL-6−/− mice. In addition, systemic neoangiogenesis was impaired in IL-6−/− mice. Transplantation of interleukin-6 competent bone marrow into IL-6−/− mice (IL-6chi) did not rescue interleukin-6 messenger RNA expression or the early transcriptional activation of angiogenesis after stroke. Accordingly, chronic stroke outcome in IL-6chi mice recapitulated the major effects of interleukin-6 deficiency on post-stroke regeneration with significantly enhanced lesion volumes and reduced vessel densities. Additional in vitro experiments yielded complementary evidence, which showed that after stroke resident brain cells serve as the major source of interleukin-6 in a self-amplifying network. Treatment of primary cortical neurons, mixed glial cultures or immortalized brain endothelia with interleukin 6-induced robust interleukin-6 messenger RNA transcription in each case, whereas oxygen–glucose deprivation did not. However, oxygen–glucose deprivation of organotypic brain slices resulted in strong upregulation of interleukin-6 messenger RNA along with increased transcription of key angiogenesis-associated genes. In conclusion, interleukin-6 produced locally by resident brain cells promotes post-stroke angiogenesis and thereby affords long-term histological and functional protection. PMID:22492561

Retrospective analysis of case series of patients with vascular war injury treated in a district hospital.

PubMed

Salamon, Tal; Lerner, Alexander; Rothem, David; Altshuler, Alexander; Karmeli, Ron; Solomonov, Evgeny; Biswas, Seema

2016-04-01

As the Syrian civil war continues, medical care of the injured remains a priority for health facilities receiving casualties. Ziv Medical Centre, the closest hospital in Israel to the Syrian border, has received 500 casualties since February 2013. Seventeen of these patients had vascular injuries. This research reports the care of these seventeen patients and explores the challenges of treatment in patients with little antecedent clinical history and improvised initial care that may be complicated by delay to definitive care, sepsis and limb ischaemia. Electronic and paper patient records were examined. Descriptive case series data are presented. Fifteen of the 17 patients were male. The mean age was 20 years (range 8-30 years). Causes of injury included gunshot wounds (4 patients), shrapnel (multi-fragment) injury (12 patients), and 1 patient was run over and dragged behind a car. The time from injury to transfer to definitive care ranged from 5h to 7 days (mean 43 h). All but one patient had associated non-vascular multiple-trauma. Thirteen patients presented with limb ischaemia. Four patients had arterio-venous fistula (AVF) or pseudoaneurysm. There were 5 upper and 10 lower limb major vascular injuries. Three patients had neck vessel injuries. All patients were investigated with CT angiography and underwent surgical or endovascular intervention. In 12 patients, 4 vessels were debrided and re-anastomosed and 13 vessels bypassed. Endovascular repair was performed in 4 patients. After initial revascularisation, 4 patients went on to amputation. There were no deaths. The injuries treated are heterogeneous, and reflect the range of high energy vascular trauma expected in conflict. The broad range of vascular solutions required to optimise outcomes, in particular, limb salvage, in turn, reflect the challenges of dealing with such injuries, especially within the context of sepsis, ischaemia and delay. As war continues, there is a pressing need to address the needs of patients with high energy injuries in austere environments where there is a dearth of health resources and where definitive care may be days away. Copyright © 2016 Elsevier Ltd. All rights reserved.

APpropriAteness of percutaneous Coronary interventions in patients with ischaemic HEart disease in Italy: the APACHE pilot study

PubMed Central

Marino, Marcello; Crimi, Gabriele; Maiorana, Florinda; Rizzotti, Diego; Lettieri, Corrado; Bettari, Luca; Zuccari, Marco; Sganzerla, Paolo; Tresoldi, Simone; Adamo, Marianna; Ghiringhelli, Sergio; Sponzilli, Carlo; Pasquetto, Giampaolo; Pavei, Andrea; Pedon, Luigi; Bassan, Luciano; Bollati, Mario; Camisasca, Paola; Trabattoni, Daniela; Brancati, Marta; Poli, Arnaldo; Panciroli, Claudio; Lettino, Maddalena; Tarelli, Giuseppe; Tarantini, Giuseppe; De Luca, Leonardo; Varbella, Ferdinando; Musumeci, Giuseppe; De Servi, Stefano

2017-01-01

Objectives To first explore in Italy appropriateness of indication, adherence to guideline recommendations and mode of selection for coronary revascularisation. Design Retrospective, pilot study. Setting 22 percutaneous coronary intervention (PCI)-performing hospitals (20 patients per site), 13 (59%) with on-site cardiac surgery. Participants 440 patients who received PCI for stable coronary artery disease (CAD) or non-ST elevation acute coronary syndrome were independently selected in a 4:1 ratio with half diabetics. Primary and secondary outcome measures Proportion of patients who received appropriate PCI using validated appropriate use scores (ie, AUS≥7). Also, in patients with stable CAD, we examined adherence to the following European Society of Cardiology recommendations: (A) per cent of patients with complex coronary anatomy treated after heart team discussion; (B) per cent of fractional flow reserve-guided PCI for borderline stenoses in patients without documented ischaemia; (C) per cent of patients receiving guideline-directed medical therapy at the time of PCI as well as use of provocative test of ischaemia according to pretest probability (PTP) of CAD. Results Of the 401 mappable PCIs (91%), 38.7% (95% CI 33.9 to 43.6) were classified as appropriate, 47.6% (95% CI 42.7 to 52.6) as uncertain and 13.7% (95% CI 10.5% to 17.5%) as inappropriate. Median PTP in patients with stable CAD without known coronary anatomy was 69% (78% intermediate PTP, 22% high PTP). Ischaemia testing use was similar (p=0.71) in patients with intermediate (n=140, 63%) and with high PTP (n=40, 66%). In patients with stable CAD (n=352) guideline adherence to the three recommendations explored was: (A) 11%; (B) 25%; (C) 23%. AUS was higher in patients evaluated by the heart team as compared with patients who were not (7 (6.8) vs 5 (4.7); p=0.001). Conclusions Use of heart team approaches and adherence to guideline recommendations on coronary revascularisation in a real-world setting is limited. This pilot study documents the feasibility of measuring appropriateness and guideline adherence in clinical practice and identifies substantial opportunities for quality improvement. Trial registration number NCT02748603. PMID:28877948

Tumour ischaemia by interferon-γ resembles physiological blood vessel regression.

PubMed

Kammertoens, Thomas; Friese, Christian; Arina, Ainhoa; Idel, Christian; Briesemeister, Dana; Rothe, Michael; Ivanov, Andranik; Szymborska, Anna; Patone, Giannino; Kunz, Severine; Sommermeyer, Daniel; Engels, Boris; Leisegang, Matthias; Textor, Ana; Fehling, Hans Joerg; Fruttiger, Marcus; Lohoff, Michael; Herrmann, Andreas; Yu, Hua; Weichselbaum, Ralph; Uckert, Wolfgang; Hübner, Norbert; Gerhardt, Holger; Beule, Dieter; Schreiber, Hans; Blankenstein, Thomas

2017-05-04

The relative contribution of the effector molecules produced by T cells to tumour rejection is unclear, but interferon-γ (IFNγ) is critical in most of the analysed models. Although IFNγ can impede tumour growth by acting directly on cancer cells, it must also act on the tumour stroma for effective rejection of large, established tumours. However, which stroma cells respond to IFNγ and by which mechanism IFNγ contributes to tumour rejection through stromal targeting have remained unknown. Here we use a model of IFNγ induction and an IFNγ-GFP fusion protein in large, vascularized tumours growing in mice that express the IFNγ receptor exclusively in defined cell types. Responsiveness to IFNγ by myeloid cells and other haematopoietic cells, including T cells or fibroblasts, was not sufficient for IFNγ-induced tumour regression, whereas responsiveness of endothelial cells to IFNγ was necessary and sufficient. Intravital microscopy revealed IFNγ-induced regression of the tumour vasculature, resulting in arrest of blood flow and subsequent collapse of tumours, similar to non-haemorrhagic necrosis in ischaemia and unlike haemorrhagic necrosis induced by tumour necrosis factor. The early events of IFNγ-induced tumour ischaemia resemble non-apoptotic blood vessel regression during development, wound healing or IFNγ-mediated, pregnancy-induced remodelling of uterine arteries. A better mechanistic understanding of how solid tumours are rejected may aid the design of more effective protocols for adoptive T-cell therapy.

Sodium transport through the cerebral sodium-glucose transporter exacerbates neuron damage during cerebral ischaemia.

PubMed

Yamazaki, Yui; Harada, Shinichi; Wada, Tetsuyuki; Yoshida, Shigeru; Tokuyama, Shogo

2016-07-01

We recently demonstrated that the cerebral sodium-glucose transporter (SGLT) is involved in postischaemic hyperglycaemia-induced exacerbation of cerebral ischaemia. However, the associated SGLT-mediated mechanisms remain unclear. Thus, we examined the involvement of cerebral SGLT-induced excessive sodium ion influx in the development of cerebral ischaemic neuronal damage. [Na+]i was estimated according to sodium-binding benzofuran isophthalate fluorescence. In the in vitro study, primary cortical neurons were prepared from fetuses of ddY mice. Primary cortical neurons were cultured for 5 days before each treatment with reagents, and these survival rates were assessed using biochemical assays. In in vivo study, a mouse model of focal ischaemia was generated using middle cerebral artery occlusion (MCAO). In these experiments, treatment with high concentrations of glucose induced increment in [Na+]i, and this phenomenon was suppressed by the SGLT-specific inhibitor phlorizin. SGLT-specific sodium ion influx was induced using a-methyl-D-glucopyranoside (a-MG) treatments, which led to significant concentration-dependent declines in neuronal survival rates and exacerbated hydrogen peroxide-induced neuronal cell death. Moreover, phlorizin ameliorated these effects. Finally, intracerebroventricular administration of a-MG exacerbated the development of neuronal damage induced by MCAO, and these effects were ameliorated by the administration of phlorizin. Hence, excessive influx of sodium ions into neuronal cells through cerebral SGLT may exacerbate the development of cerebral ischaemic neuronal damage. © 2016 Royal Pharmaceutical Society.

Acupuncture elicits neuroprotective effect by inhibiting NAPDH oxidase-mediated reactive oxygen species production in cerebral ischaemia.

PubMed

Shi, Guang-Xia; Wang, Xue-Rui; Yan, Chao-Qun; He, Tian; Yang, Jing-Wen; Zeng, Xiang-Hong; Xu, Qian; Zhu, Wen; Du, Si-Qi; Liu, Cun-Zhi

2015-12-10

In the current study, we aimed to investigate whether NADPH oxidase, a major ROS-producing enzyme, was involved in the antioxidant effect of acupuncture on cognitive impairment after cerebral ischaemia. The cognitive function, infract size, neuron cell loss, level of superoxide anion and expression of NADPH oxidase subunit in hippocampus of two-vessel occlusion (2VO) rats were determined after 2-week acupuncture. Furthermore, the cognitive function and production of O2(-) were determined in the presence and absence of NADPH oxidase agonist (TBCA) and antagonist (Apocynin). The effect of acupuncture on cognitive function after cerebral ischaemia in gp91phox-KO mice was evaluated by Morris water maze. Acupuncture reduced infarct size, attenuated overproduction of O2(-), and reversed consequential cognitive impairment and neuron cell loss in 2VO rats. The elevations of gp91phox and p47phox after 2VO were significantly decreased after acupuncture treatment. However, no differences of gp91phox mRNA were found among any experimental groups. Furthermore, these beneficial effects were reversed by TBCA, whereas apocynin mimicked the effect of acupuncture by improving cognitive function and decreasing O2(-) generation. Acupuncture failed to improve the memory impairment in gp91phox KO mice. Full function of the NADPH oxidase enzyme plays an important role in neuroprotective effects against cognitive impairment via inhibition of NAPDH oxidase-mediated oxidative stress.

Delayed post-ischaemic administration of xenon reduces brain damage in a rat model of global ischaemia.

PubMed

Metaxa, V; Lagoudaki, R; Meditskou, S; Thomareis, O; Oikonomou, L; Sakadamis, A

2014-01-01

Xenon and nitrous oxide have been shown to be neuroprotective in vivo and in vitro, but mainly in models of focal cerebral ischaemia. This study aimed to investigate whether the two gases are able to attenuate cerebral injury after global cerebral ischaemia. Adult male Wistar rats underwent bilateral common carotid artery occlusion and were ventilated for 1 hour with 21% O₂/78% N₂. They were then randomized to three groups which continued to receive atmospheric air, 50% N2O/50% O₂ and 50% Xe/50% O₂ for an additional period of 45 minutes. The number of ischaemic neurons, the cortical volume loss and the immunochemical and molecular expression of c-fos and MMP-9 were evaluated. Xenon reduced the number of ischaemic neurons in the cortex and CA1 hippocampal region (p < 0.001) and decreased the cortical volume loss (p < 0.01). Immunochemical induction of c-fos in the cortex was significantly suppressed (p < 0.01) after administration of xenon. The molecular analysis revealed significant effects of N2O and xenon administration on c-fos and MMP-9 expression. The data indicate that N2O and xenon administration is neuroprotective 1 hour after bilateral common carotid artery occlusion. These findings provide valuable evidence on the beneficial role of N2O and xenon in global cerebral injury.

Vertigo and nystagmus in orthostatic hypotension.

PubMed

Choi, J-H; Seo, J-D; Kim, M-J; Choi, B-Y; Choi, Y R; Cho, B M; Kim, J S; Choi, K-D

2015-04-01

Generalized cerebral ischaemia from cardiovascular dysfunction usually leads to presyncopal dizziness, but several studies reported a higher frequency of rotatory vertigo in cardiovascular patients. Whether generalized cerebral ischaemia due to cardiovascular disorders may produce objective vestibular dysfunction was investigated. Thirty-three patients with orthostatic dizziness/vertigo due to profound orthostatic hypotension and 30 controls were recruited. All participants underwent recording of eye movements during two orthostatic challenging tests: the Schellong and the squatting-standing tests. Most patients had neuroimaging, and patients with abnormal eye movements were subjected to follow-up evaluations. Symptoms associated with orthostatic dizziness/vertigo included blurred vision, fainting and tinnitus. Ten (30%) of 33 patients developed rotatory vertigo and nystagmus during the Schellong (n = 5) or squatting-standing test (n = 5). Four of them showed pure downbeat nystagmus whilst five had downbeat and horizontal nystagmus with or without torsional component. Patients with orthostatic nystagmus had shorter duration of orthostatic intolerance than those without nystagmus (1.0 ± 1.6 vs. 11.0 ± 9.7 months, P < 0.001). In two patients, orthostatic nystagmus disappeared during follow-up despite the persistence of profound orthostatic hypotension. Generalized cerebral ischaemia caused by orthostatic hypotension induces rotatory vertigo due to objective vestibular dysfunction. The presence of orthostatic vertigo and nystagmus has an association with the duration of orthostatic intolerance. © 2014 EAN.

Effects of electroacupuncture on the cortical extracellular signal regulated kinase pathway in rats with cerebral ischaemia/reperfusion.

PubMed

Wu, Chunxiao; Li, Chun; Zhou, Guoping; Yang, Lu; Jiang, Guimei; Chen, Jing; Li, Qiushi; Zhan, Zhulian; Xu, Xiuhong; Zhang, Xin

2017-12-01

To explore the effects of electroacupuncture (EA) on the phosphorylated extracellular signal regulated kinase (p-ERK) pathway of the cerebral cortex in a rat model of focal cerebral ischaemia/reperfusion (I/R). 160 adult Sprague-Dawley rats underwent middle carotid artery occlusion (MCAO) to establish I/R injury and were randomly divided into four groups (n=40 each) that remained untreated (I/R group) or received EA at LU5, LI4, ST36 and SP6 (I/R+EA group), the ERK inhibitor PD98059 (I/R+PD group), or both interventions (I/R+PD+EA groups). An additional 40 rats undergoing sham surgery formed a healthy control group. Eight rats from each group were sacrificed at the following time points: 2 hours, 6 hours, 1 day, 3 days and 1 week. Neurological function was assessed using neurological deficit scores, morphological examination was performed following haematoxylin-eosin staining of cortical tissues, and apoptotic indices were calculated after terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labelling. Cortical protein and mRNA expression of p-ERK and ERK were measured by immunohistochemistry and real-time quantitative PCR, respectively. Compared with the I/R group, neurological deficit scores and apoptotic indices were lower in the I/R+EA group at 1 and 3 days, whereas mRNA/protein expression of ERK/p-ERK was higher in the EA group at all time points studied. Our results suggest that EA can alleviate neurological deficits and reduce cortical apoptosis in rats with I/R injury. These anti-apoptotic effects may be due to upregulation of p-ERK. Moreover, apoptosis appeared to peak at 1 day after I/R injury, which might therefore represent the optimal time point for targeting of EA. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Cardiac CT for myocardial ischaemia detection and characterization--comparative analysis.

PubMed

Bucher, A M; De Cecco, C N; Schoepf, U J; Wang, R; Meinel, F G; Binukrishnan, S R; Spearman, J V; Vogl, T J; Ruzsics, B

2014-11-01

The assessment of patients presenting with symptoms of myocardial ischaemia remains one of the most common and challenging clinical scenarios faced by physicians. Current imaging modalities are capable of three-dimensional, functional and anatomical views of the heart and as such offer a unique contribution to understanding and managing the pathology involved. Evidence has accumulated that visual anatomical coronary evaluation does not adequately predict haemodynamic relevance and should be complemented by physiological evaluation, highlighting the importance of functional assessment. Technical advances in CT technology over the past decade have progressively moved cardiac CT imaging into the clinical workflow. In addition to anatomical evaluation, cardiac CT is capable of providing myocardial perfusion parameters. A variety of CT techniques can be used to assess the myocardial perfusion. The single energy first-pass CT and dual energy first-pass CT allow static assessment of myocardial blood pool. Dynamic cardiac CT imaging allows quantification of myocardial perfusion through time-resolved attenuation data. CT-based myocardial perfusion imaging (MPI) is showing promising diagnostic accuracy compared with the current reference modalities. The aim of this review is to present currently available myocardial perfusion techniques with a focus on CT imaging in light of recent clinical investigations. This article provides a comprehensive overview of currently available CT approaches of static and dynamic MPI and presents the results of corresponding clinical trials.

Cardioprotective effect of hyperthyroidism on the stunned rat heart during ischaemia-reperfusion: energetics and role of mitochondria.

PubMed

Ragone, María Inés; Bonazzola, Patricia; Colareda, Germán A; Consolini, Alicia E

2015-06-01

What is the central question of this study? Hyperthyroidism is a cardiac risk factor, but thyroid therapy is used on myocardial stunning. What is the consequence of hyperthyroidism for mitochondrial metabolism and Ca(2+) handling of the postischaemic stunned heart? What is the main finding and its importance? Hyperthyroidism reduced stunning and improved muscle economy of the postischaemic rat heart. The activities of the mitochondrial sodium-calcium exchanger and mitochondrial K(+) channel in hyperthyroid rat hearts were different from those in the euthyroid rat hearts. These findings contribute to the understanding of mitochondrial bioenergetics in pathology and support thyroid therapy in the stunning induced by ischaemia. Transient ischaemia and hyperthyroidism are cardiovascular risk factors. Nevertheless, 3,5,3'-triiodothyronine/thyroxine therapy has been used to revert myocardial stunning. We studied the influence of hyperthyroidism on the role played by mitochondria in myocardial stunning consequent to ischaemia-reperfusion. Rats were injected s.c. daily with 20 μg kg(-1) triiodothyronine for 15 days (HpT group). Isolated ventricles from either HpT or euthyroid (EuT) rats were perfused in a calorimeter, and left intraventricular pressure (in millimetres of mercury) and heat release (Ht; in milliwatts per gram) were measured. Stunning was evoked by 20 min of no-flow ischaemia and 45 min reperfusion. The HpT hearts developed higher postischaemic contractile recovery (PICR) and improved total muscle economy (P/Ht) with lower diastolic contracture (ΔLVEDP) than EuT hearts. Release of Ca(2+) from the sarcoplasmic reticulum during reperfusion with 10 mm caffeine in low-[Na(+) ] Krebs solution evoked a higher contracture in EuT than in HpT hearts. Blockade of the mitochondrial sodium-calcium exchanger with clonazepam increased ΔLVEDP and reduced P/Ht and PICR in HpT but not in EuT hearts. The clonazepam-induced dysfunction in HpT hearts was reduced by ciclosporin, suggesting a dependance on activation of the mitochondrial permeability transition pore. Blockade of the mitochondrial Ca(2+) uniporter with Ru360 reduced P/Ht and PICR to ∼10% in both HpT and EuT hearts. Blockade of mitochondrial K(+) channels with 5-hydroxydecanoate increased LVEDP and reduced PICR and P/Ht in HpT hearts, while it only increased LVEDP in EuT hearts. The results suggest that hyperthyroidism prevents the stunning with high dependence on the mitochondrial sodium-calcium exchanger and mitochondrial K(+) channels. Both HpT and EuT hearts showed a similar and critical role of the uniporter. The HpT hearts have a slow sarcoplasmic reticulum Ca(2+) loss and low mitochondrial Ca(2+) uptake. © 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.

5 A study analysing the diagnostic performance of ECG interpretation for 30-day major cardiac events in the emergency department.

PubMed

Morris, Niall; Body, Rick

2017-12-01

This study evaluates the diagnostic accuracy of an Emergency Medicine (EM) clinician at identifying ischaemia on an ECG using 30-day major adverse cardiac events (MACE) as the primary outcome. This is a secondary analysis of a prospective, multi-centre, observational cohort at 14 centres: the Bedside Evaluation of Sensitive Troponin study. All fourteen Emergency Departments were based in the United Kingdom. Emergency physicians' assessments of the ECG were collected using a standardised form. Clinicians were asked to judge whether the ECG demonstrated ischaemia, the presence of ST depression (STD) and if there was abnormal T wave inversion (ATWI). Patients provided written informed consent and underwent serial high sensitivity troponin testing. 30 day follow-up was performed by research nurses using a standardised form via telephone. The primary outcome was 30-day major adverse cardiac events, defined as acute myocardial infarction, any cause of death and coronary revascularisation. In total, 756 patients were included in the analysis. Clinicians' ECG diagnosis of ischaemia for 30-day MACE: ECG ischaemia produces a sensitivity (Sn) of 19.54% (95% CI:11.81% to 29.43%), specificity (Sp) of 93.27% (95% CI:91.10% to 95.05%), positive predictive value (PPV) of 27.42% (95% CI:18.47% to 38.65%) and negative predictive value (NPV) of 89.91% (95%CI 88.92% to 90.83%). ECG ST depression produces Sn of 16.09% (9.09% to 25.52%), Sp of 89.69% (87.13% to 91.89%), PPV 16.87 (10.68% to 25.62%), and NPV 89.15% (88.19% to 90.04%). ECG ATWI produces Sn of 4.60% (1.27% to 11.36%), Sp of 91.63% (89.27% to 93.62%), PPV of 6.67% (2.59% to 16.12%) and NPV of 88.07% (87.52% to 88.6). This is the first prospective, multi-centre cohort study, that assess the diagnostic performance of EM clinician's ECG interpretation, with 30-day MACE as the primary outcome. The findings are highly relevant to EM as they represent the ECG terms used by popular acute coronary syndrome clinical decision rules. In this study a clinician's overall judgement of ischaemia has a better diagnostic performance compared to simple STD and ATWI. This may be due to an appreciation of morphology and the amount of deviation; future work should explore the effect of measuring deviation and analysing morphology. © 2017, Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Clinical Trial Research on Mongolian Medical Warm Acupuncture in Treating Insomnia.

PubMed

Bo, Agula; Si, Lengge; Wang, Yuehong; Xiu, Lan; Wu, Rihan; Li, Yutang; Mu, Rigenjiya; Ga, Latai; Miao, Mei; Shuang, Fu; Wu, Yunhua; Jin, Qiu; Tong, Suocai; Wuyun, Gerile; Guan, Wurihan; Mo, Rigen; Hu, Sileng; Zhang, Lixia; Peng, Rui; Bao, Lidao

2016-01-01

Objective. Insomnia is one of the most common sleep disorders. Hypnotics have poor long-term efficacy. Mongolian medical warm acupuncture has significant efficacy in treating insomnia. The paper evaluates the role of Mongolian medical warm acupuncture in treating insomnia by investigating the Mongolian medicine syndromes and conditions, Pittsburgh sleep quality index, and polysomnography indexes. Method. The patients were diagnosed in accordance with International Classification of Sleep Disorders (ICSD-2). The insomnia patients were divided into the acupuncture group (40 cases) and the estazolam group (40 cases). The patients underwent intervention of Mongolian medical warm acupuncture and estazolam. The indicators of the Mongolian medicine syndromes and conditions, Pittsburgh sleep quality index (PSQI), and polysomnography indexes (PSG) have been detected. Result. Based on the comparison of the Mongolian medicine syndrome scores between the warm acupuncture group and the drug treatment group, the result indicated P < 0.01. The clinical efficacy result showed that the effective rate (85%) in the warm acupuncture group was higher than that (70%) in the drug group. The total scores of PSQI of both groups were approximated. The sleep quality indexes of both groups decreased significantly ( P < 0.05). The sleep quality index in the Mongolian medical warm acupuncture group decreased significantly ( P < 0.01) and was better than that in the estazolam group. The sleep efficiency and daytime functions of the patients in the Mongolian medical warm acupuncture group improved significantly ( P < 0.01). The sleep time was significantly extended ( P < 0.01) in the Mongolian medical warm acupuncture group following PSG intervention. The sleep time during NREM in the Mongolian warm acupuncture group increased significantly ( P < 0.01). The sleep time exhibited a decreasing trend during REM and it decreased significantly in the Mongolian warm acupuncture group ( P < 0.01). The percentage of sleep time in the total sleep time during NREM3+4 in the Mongolian medical warm acupuncture group increased significantly. Conclusion. Mongolian medical warm acupuncture is efficient and safe in treating insomnia. It is able to better improve the patients' sleep time and daytime functions. It is better than that in the estazolam group following drug withdrawal in terms of improving the sleep time. It is more effective in helping the insomnia patients than hypnotics.

Robot-assisted partial nephrectomy: continued refinement of outcomes beyond the initial learning curve.

PubMed

Paulucci, David J; Abaza, Ronney; Eun, Daniel D; Hemal, Ashok K; Badani, Ketan K

2017-05-01

To evaluate trends in peri-operative outcomes of 250 consecutive cases beyond the initial learning curve (LC) of robot-assisted partial nephrectomy (RAPN) among multiple surgeons. A multi-institutional database was used to evaluate trends in patient demographics (e.g. age, gender, comorbidities), tumour characteristics (e.g. size, complexity) and peri-operative outcomes (e.g. warm ischaemia time [WIT], operating time, complications, estimated blood loss [EBL], trifecta achievement) in consecutive cases 50-300 (n = 960) from 2008 to 2016 among four experienced surgeons. Trends in outcomes were assessed using multivariable regression models adjusted for demographic and tumour-specific variables. Outcomes for cases 50-99 were compared with those for cases 250-300. In the study period RAPN was increasingly performed in patients with larger tumours (β = 0.001, P = 0.048), hypertension (odds ratio [OR] 1.003; P = 0.008) diabetes (OR 1.003; P = 0.025) and previous abdominal surgery (OR 1.003; P = 0.006). Surgeon experience was associated with more trifecta achievement (OR 1.006; P < 0.001), shorter WIT (β = -0.036, P < 0.001), less EBL (β = -0.154, P = 0.009), fewer blood transfusions (OR 0.989, P = 0.024) and a reduced length of hospital stay (β = -0.002, P = 0.002), but not with operating time (P = 0.243), complications (P = 0.587) or surgical margin status (P = 0.102). Tumour size and WIT in cases 50-99 vs 250-300 were 2.7 vs 3.2 cm (P = 0.001) and 21.4 vs 16.2 min (P < 0.001), respectively. Refinement of RAPN outcomes, concomitant with the treatment of a patient population with larger tumours and more comorbidities, occurs after the initial LC is reached. Although RAPN can consistently be performed safely with acceptable outcomes after a small number of cases, improvement in trifecta achievement, WIT, EBL, blood transfusions and a shorter hospitalization continues to occur up to 300 procedures. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Classification and outcomes of extended arch repair for acute Type A aortic dissection: a systematic review and meta-analysis.

PubMed

Smith, Holly N; Boodhwani, Munir; Ouzounian, Maral; Saczkowski, Richard; Gregory, Alexander J; Herget, Eric J; Appoo, Jehangir J

2017-03-01

Distal extent of repair in patients undergoing surgery for acute Type A aortic dissection (ATAAD) is controversial. Emerging hybrid techniques involving open and endovascular surgery have been reported in small numbers by select individual centres. A systematic review and meta-analysis was performed to investigate the outcomes following extended arch repair for ATAAD. A classification system is proposed of the different techniques to facilitate discussion and further investigation. Using Ovid MEDLINE, 38 studies were identified reporting outcomes for 2140 patients. Studies were categorized into four groups on the basis of extent of surgical aortic resection and the method of descending thoracic aortic stent graft deployment; during circulatory arrest (frozen stented elephant trunk) or with normothermic perfusion and use of fluoroscopy (warm stent graft): (I) surgical total arch replacement, (II) total arch and frozen stented elephant trunk, (III) hemiarch and frozen stented elephant trunk and (IV) total arch and warm stent graft. Perioperative event rates were obtained for each of the four groups and the entire cohort using pooled summary estimates. Linearized rates of late mortality and reoperation were calculated. Overall pooled hospital mortality for extended arch techniques was 8.6% (95% CI 7.2-10.0). Pooled data categorized by surgical technique resulted in hospital mortality of 11.9% for total arch, 8.6% total arch and frozen stented elephant trunk, 6.3% hemiarch and frozen stented elephant trunk and 5.5% total arch and 'warm stent graft'. Overall incidence of stroke for the entire cohort was 5.7% (95% CI 3.6-8.2). Rate of spinal cord ischaemia was 2.0% (95% CI 1.2-3.0). Pooled linearized rate of late mortality was 1.66%/pt-yr (95% CI 1.34-2.07) with linearized rate of re-operation of 1.62%/pt-yr (95% CI 1.24-2.05). Perioperative results of extended arch procedures are encouraging. Further follow-up is required to see if long-term complications are reduced with these emerging techniques. The proposed classification system will facilitate future comparison of short- and long-term results of different techniques of extended arch repair for ATAAD. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Independent effects of warming and nitrogen addition on plant phenology in the Inner Mongolian steppe

PubMed Central

Xia, Jianyang; Wan, Shiqiang

2013-01-01

Background and Aims Phenology is one of most sensitive traits of plants in response to regional climate warming. Better understanding of the interactive effects between warming and other environmental change factors, such as increasing atmosphere nitrogen (N) deposition, is critical for projection of future plant phenology. Methods A 4-year field experiment manipulating temperature and N has been conducted in a temperate steppe in northern China. Phenology, including flowering and fruiting date as well as reproductive duration, of eight plant species was monitored and calculated from 2006 to 2009. Key Results Across all the species and years, warming significantly advanced flowering and fruiting time by 0·64 and 0·72 d per season, respectively, which were mainly driven by the earliest species (Potentilla acaulis). Although N addition showed no impact on phenological times across the eight species, it significantly delayed flowering time of Heteropappus altaicus and fruiting time of Agropyron cristatum. The responses of flowering and fruiting times to warming or N addition are coupled, leading to no response of reproductive duration to warming or N addition for most species. Warming shortened reproductive duration of Potentilla bifurca but extended that of Allium bidentatum, whereas N addition shortened that of A. bidentatum. No interactive effect between warming and N addition was found on any phenological event. Such additive effects could be ascribed to the species-specific responses of plant phenology to warming and N addition. Conclusions The results suggest that the warming response of plant phenology is larger in earlier than later flowering species in temperate grassland systems. The effects of warming and N addition on plant phenology are independent of each other. These findings can help to better understand and predict the response of plant phenology to climate warming concurrent with other global change driving factors. PMID:23585496

The role of mitochondria in protection of the heart by preconditioning

PubMed Central

Halestrap, Andrew P.; Clarke, Samantha J.; Khaliulin, Igor

2007-01-01

A prolonged period of ischaemia followed by reperfusion irreversibly damages the heart. Such reperfusion injury (RI) involves opening of the mitochondrial permeability transition pore (MPTP) under the conditions of calcium overload and oxidative stress that accompany reperfusion. Protection from MPTP opening and hence RI can be mediated by ischaemic preconditioning (IP) where the prolonged ischaemic period is preceded by one or more brief (2–5 min) cycles of ischaemia and reperfusion. Following a brief overview of the molecular characterisation and regulation of the MPTP, the proposed mechanisms by which IP reduces pore opening are reviewed including the potential roles for reactive oxygen species (ROS), protein kinase cascades, and mitochondrial potassium channels. It is proposed that IP-mediated inhibition of MPTP opening at reperfusion does not involve direct phosphorylation of mitochondrial proteins, but rather reflects diminished oxidative stress during prolonged ischaemia and reperfusion. This causes less oxidation of critical thiol groups on the MPTP that are known to sensitise pore opening to calcium. The mechanisms by which ROS levels are decreased in the IP hearts during prolonged ischaemia and reperfusion are not known, but appear to require activation of protein kinase Cε, either by receptor-mediated events or through transient increases in ROS during the IP protocol. Other signalling pathways may show cross-talk with this primary mechanism, but we suggest that a role for mitochondrial potassium channels is unlikely. The evidence for their activity in isolated mitochondria and cardiac myocytes is reviewed and the lack of specificity of the pharmacological agents used to implicate them in IP is noted. Some K+ channel openers uncouple mitochondria and others inhibit respiratory chain complexes, and their ability to produce ROS and precondition hearts is mimicked by bona fide uncouplers and respiratory chain inhibitors. IP may also provide continuing protection during reperfusion by preventing a cascade of MPTP-induced ROS production followed by further MPTP opening. This phase of protection may involve survival kinase pathways such as Akt and glycogen synthase kinase 3 (GSK3) either increasing ROS removal or reducing mitochondrial ROS production. PMID:17631856

The clinical impact of contemporary stress echocardiography in morbid obesity for the assessment of coronary artery disease.

PubMed

Shah, Benoy N; Zacharias, Konstantinos; Pabla, Jatinder S; Karogiannis, Nikolaos; Calicchio, Francesca; Balaji, Gothandaraman; Alhajiri, Abdalla; Ramzy, Ihab S; Elghamaz, Ahmed; Gurunathan, Sothinathan; Khattar, Rajdeep S; Senior, Roxy

2016-03-01

Non-invasive cardiac imaging may suffer from poor image quality in morbidly obese individuals. This study aimed to determine the clinical value of contemporary stress echocardiography (SE) in morbidly obese patients referred for assessment of suspected coronary artery disease (CAD). This prospective, multicentre observational study was conducted in two district hospitals and one tertiary centre in London, UK. Individuals with body mass index ≥35 kg/m(2) referred for SE were evaluated. The percentage of patients with obstructive CAD on coronary angiography, following abnormal SE, was assessed. Patient outcomes were determined with follow-up for the composite end-point of all-cause mortality, myocardial infarction and late revascularisation. Over a 13-month period, 209 morbidly obese patients underwent SE, and contrast agent was used in 96% of patients. A diagnostic result was obtained in 200/209 (96%) patients. Of 32 (15%) patients with inducible ischaemia, 25 underwent angiography, 22 (88%) had corresponding significant CAD and, of these, 16 (77%) underwent revascularisation. Conversely, only 2/157 patients (1.3%) with normal SE underwent angiography, and none underwent revascularisation. Over a mean follow-up period of 17.8±5.4 months, there were nine events. The annualised cardiac event rate after a normal SE was 0.95%. Events were more frequent in patients with inducible ischaemia versus those without ischaemia (5/32 (15.6%) vs 4/153 (2.6%); p=0.002). Ejection fraction <50% (HR 9.5; 95% CI 2.4 to 38.0; p=0.002) and inducible ischaemia (HR 9.4; 95% CI 2.5 to 35.8; p=0.001) were predictors of outcome on univariable Cox regression analysis. Contemporary SE has excellent feasibility and positive predictive value and resulted in appropriate risk stratification of symptomatic patients with significant obesity. A normal SE portends an excellent outcome over the short-intermediate term in this high-risk patient population. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Warm Up to a Good Sound

ERIC Educational Resources Information Center

Tovey, David C.

1977-01-01

Most choral directors in schools today have been exposed to a variety of warm-up procedures. Yet, many do not use the warm-up time effectively as possible. Considers the factors appropriate to a warm-up exercise and three basic warm-up categories. (Author/RK)

The negative ultraslow potential, electrophysiological correlate of infarction in the human cortex

PubMed Central

Lückl, Janos; Lemale, Coline L; Kola, Vasilis; Horst, Viktor; Khojasteh, Uldus; Oliveira-Ferreira, Ana I; Major, Sebastian; Winkler, Maren K L; Kang, Eun-Jeung; Schoknecht, Karl; Martus, Peter; Hartings, Jed A; Woitzik, Johannes

2018-01-01

Abstract Spreading depolarizations are characterized by abrupt, near-complete breakdown of the transmembrane ion gradients, neuronal oedema, mitochondrial depolarization, glutamate excitotoxicity and activity loss (depression). Spreading depolarization induces either transient hyperperfusion in normal tissue; or hypoperfusion (inverse coupling = spreading ischaemia) in tissue at risk for progressive injury. The concept of the spreading depolarization continuum is critical since many spreading depolarizations have intermediate characteristics, as opposed to the two extremes of spreading depolarization in either severely ischaemic or normal tissue. In animals, the spreading depolarization extreme in ischaemic tissue is characterized by prolonged depolarization durations, in addition to a slow baseline variation termed the negative ultraslow potential. The negative ultraslow potential is initiated by spreading depolarization and similar to the negative direct current (DC) shift of prolonged spreading depolarization, but specifically refers to a negative potential component during progressive recruitment of neurons into cell death in the wake of spreading depolarization. We here first quantified the spreading depolarization-initiated negative ultraslow potential in the electrocorticographic DC range and the activity depression in the alternate current range after middle cerebral artery occlusion in rats. Relevance of these variables to the injury was supported by significant correlations with the cortical infarct volume and neurological outcome after 72 h of survival. We then identified negative ultraslow potential-containing clusters of spreading depolarizations in 11 patients with aneurysmal subarachnoid haemorrhage. The human platinum/iridium-recorded negative ultraslow potential showed a tent-like shape. Its amplitude of 45.0 (39.0, 69.4) mV [median (first, third quartile)] was 6.6 times larger and its duration of 3.7 (3.3, 5.3) h was 34.9 times longer than the negative DC shift of spreading depolarizations in less compromised tissue. Using Generalized Estimating Equations applied to a logistic regression model, we found that negative ultraslow potential displaying electrodes were significantly more likely to overlie a developing ischaemic lesion (90.0%, 27/30) than those not displaying a negative ultraslow potential (0.0%, 0/20) (P = 0.004). Based on serial neuroimages, the lesions under the electrodes developed within a time window of 72 (56, 134) h. The negative ultraslow potential occurred in this time window in 9/10 patients. It was often preceded by a spreading depolarization cluster with increasingly persistent spreading depressions and progressively prolonged DC shifts and spreading ischaemias. During the negative ultraslow potential, spreading ischaemia lasted for 40.0 (28.0, 76.5) min, cerebral blood flow fell from 57 (53, 65) % to 26 (16, 42) % (n = 4) and tissue partial pressure of oxygen from 12.5 (9.2, 15.2) to 3.3 (2.4, 7.4) mmHg (n = 5). Our data suggest that the negative ultraslow potential is the electrophysiological correlate of infarction in human cerebral cortex and a neuromonitoring-detected medical emergency. PMID:29668855

The negative ultraslow potential, electrophysiological correlate of infarction in the human cortex.

PubMed

Lückl, Janos; Lemale, Coline L; Kola, Vasilis; Horst, Viktor; Khojasteh, Uldus; Oliveira-Ferreira, Ana I; Major, Sebastian; Winkler, Maren K L; Kang, Eun-Jeung; Schoknecht, Karl; Martus, Peter; Hartings, Jed A; Woitzik, Johannes; Dreier, Jens P

2018-06-01

Spreading depolarizations are characterized by abrupt, near-complete breakdown of the transmembrane ion gradients, neuronal oedema, mitochondrial depolarization, glutamate excitotoxicity and activity loss (depression). Spreading depolarization induces either transient hyperperfusion in normal tissue; or hypoperfusion (inverse coupling = spreading ischaemia) in tissue at risk for progressive injury. The concept of the spreading depolarization continuum is critical since many spreading depolarizations have intermediate characteristics, as opposed to the two extremes of spreading depolarization in either severely ischaemic or normal tissue. In animals, the spreading depolarization extreme in ischaemic tissue is characterized by prolonged depolarization durations, in addition to a slow baseline variation termed the negative ultraslow potential. The negative ultraslow potential is initiated by spreading depolarization and similar to the negative direct current (DC) shift of prolonged spreading depolarization, but specifically refers to a negative potential component during progressive recruitment of neurons into cell death in the wake of spreading depolarization. We here first quantified the spreading depolarization-initiated negative ultraslow potential in the electrocorticographic DC range and the activity depression in the alternate current range after middle cerebral artery occlusion in rats. Relevance of these variables to the injury was supported by significant correlations with the cortical infarct volume and neurological outcome after 72 h of survival. We then identified negative ultraslow potential-containing clusters of spreading depolarizations in 11 patients with aneurysmal subarachnoid haemorrhage. The human platinum/iridium-recorded negative ultraslow potential showed a tent-like shape. Its amplitude of 45.0 (39.0, 69.4) mV [median (first, third quartile)] was 6.6 times larger and its duration of 3.7 (3.3, 5.3) h was 34.9 times longer than the negative DC shift of spreading depolarizations in less compromised tissue. Using Generalized Estimating Equations applied to a logistic regression model, we found that negative ultraslow potential displaying electrodes were significantly more likely to overlie a developing ischaemic lesion (90.0%, 27/30) than those not displaying a negative ultraslow potential (0.0%, 0/20) (P = 0.004). Based on serial neuroimages, the lesions under the electrodes developed within a time window of 72 (56, 134) h. The negative ultraslow potential occurred in this time window in 9/10 patients. It was often preceded by a spreading depolarization cluster with increasingly persistent spreading depressions and progressively prolonged DC shifts and spreading ischaemias. During the negative ultraslow potential, spreading ischaemia lasted for 40.0 (28.0, 76.5) min, cerebral blood flow fell from 57 (53, 65) % to 26 (16, 42) % (n = 4) and tissue partial pressure of oxygen from 12.5 (9.2, 15.2) to 3.3 (2.4, 7.4) mmHg (n = 5). Our data suggest that the negative ultraslow potential is the electrophysiological correlate of infarction in human cerebral cortex and a neuromonitoring-detected medical emergency.awy102media15775596049001.

Effects of spinal cord stimulation in angina pectoris induced by pacing and possible mechanisms of action.

PubMed Central

Mannheimer, C; Eliasson, T; Andersson, B; Bergh, C H; Augustinsson, L E; Emanuelsson, H; Waagstein, F

1993-01-01

OBJECTIVE--To investigate the effects of spinal cord stimulation on myocardial ischaemia, coronary blood flow, and myocardial oxygen consumption in angina pectoris induced by atrial pacing. DESIGN--The heart was paced to angina during a control phase and treatment with spinal cord stimulation. Blood samples were drawn from a peripheral artery and the coronary sinus. SETTING--Multidisciplinary pain centre, department of medicine, Ostra Hospital, and Wallenberg Research Laboratory, Sahlgrenska Hospital, Gothenburg, Sweden. SUBJECTS--Twenty patients with intractable angina pectoris, all with a spinal cord stimulator implanted before the study. RESULTS--Spinal cord stimulation increased patients' tolerance to pacing (p < 0.001). At the pacing rate comparable to that producing angina during the control recording, myocardial lactate production during control session turned into extraction (p = 0.003) and, on the electrocardiogram, ST segment depression decreased, time to ST depression increased, and time to recovery from ST depression decreased (p = 0.01; p < 0.05, and p < 0.05, respectively). Spinal cord stimulation also reduced coronary sinus blood flow (p = 0.01) and myocardial oxygen consumption (p = 0.02). At the maximum pacing rate during treatment, all patients experienced anginal pain. Myocardial lactate extraction reverted to production (p < 0.01) and the magnitude and duration of ST segment depression increased to the same values as during control pacing, indicating that myocardial ischaemia during treatment with spinal cord stimulation gives rise to anginal pain. CONCLUSIONS--Spinal cord stimulation has an anti-anginal and anti-ischaemic effect in severe coronary artery disease. These effects seem to be secondary to a decrease in myocardial oxygen consumption. Furthermore, myocardial ischemia during treatment gives rise to anginal pain. Thus, spinal cord stimulation does not deprive the patient of a warning signal. PMID:8400930

Utility of the RENAL index -Radius; Exophytic/endophytic; Nearness to sinus; Anterior/posterior; Location relative to polar lines- in the management of renal masses.

PubMed

Konstantinidis, C; Trilla, E; Lorente, D; Morote, J

2016-12-01

The growing incidence of renal masses and the wide range of available treatments require predictive tools that support the decision making process. The RENAL index -Radius; Exophytic/endophytic; Nearness to sinus; Anterior/posterior; Location relative to polar lines- helps standardise the anatomy of a renal mass by differentiating 3 groups of complexity. Since the introduction of the index, there have been a growing number of studies, some of which have been conflicting, that have evaluated the clinical utility of its implementation. To analyse the scientific evidence on the relationship between the RENAL index and the main strategies for managing renal masses. A search was conducted in the Medline database, which found 576 references on the RENAL index. In keeping with the PRISM Declaration, we selected 100 abstracts and ultimately reviewed 96 articles. The RENAL index has a high degree of interobserver correlation and has been validated as a predictive nomogram of histological results. In active surveillance, the index has been related to the tumour growth rate and probability of nephrectomy. In ablative therapy, the index has been associated with therapeutic efficacy, complications and tumour recurrence. In partial nephrectomy, the index has been related to the rate of complications, conversion to radical surgery, ischaemia time, function preservation and tumour recurrence, a finding also observed in radical nephrectomy. The RENAL index is an objective, reproducible and useful system as a predictive tool of highly relevant clinical parameters such as the rate of complications, ischaemia time, renal function and oncological results in the various currently accepted treatments for the management of renal masses. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

The prognostic value of dobutamine stress echocardiography amongst British Indian Asian and Afro-Caribbean patients: a comparison with European white patients.

PubMed

O'Driscoll, Jamie M; Rossato, Claire; Gargallo-Fernandez, Paula; Araco, Marco; Giannoglou, Dimitrios; Sharma, Sanjay; Sharma, Rajan

2015-08-06

The incidence of cardiovascular disease is considerably disparate among different racial and ethnic populations. While dobutamine stress echocardiography (DSE) has been shown to be useful in Caucasian patients, its role among ethnic minority groups remains unclear. This study aimed to investigate the prognostic importance of DSE in three ethnic groups in the UK. DSE was performed on 6231 consecutive patients. After exclusions, 5329 patients formed the study (2676 [50.2%] Indian Asian, 2219 [41.6%] European white and 434 [8.1%] Afro-Caribbean). Study outcome measures were non-fatal cardiac events (NFCE) and all-cause mortality. There were 849 (15.9%) NFCE and 1365 (25.6%) deaths over a median follow-up period of 4.6 years. In total 1174 (22%) patients had inducible myocardial ischaemia during DSE, 859 (16.1%) had fixed wall motion abnormalities and 3645 (68.4%) patients had a normal study. Ethnicity did not predict events. Among the three ethnic groups, ischaemia on DSE was associated with 2 to 2.5 times the risk of non-fatal cardiac events and 1.2 to 1.4 times the risk of all-cause mortality. Peak wall motion score index was the strongest independent predictor of non-fatal cardiac events and all-cause mortality in all groups. The C statistic for the prediction of NFCE and all-cause mortality were significantly higher when DSE parameters were added to the standard risk factors for all ethnic groups. DSE is a strong predictor of NFCE and all-cause mortality and provides predictive information beyond that provided by standard risk factors in three major racial and ethnic groups. No major differences among racial and ethnic groups in the predictive value of DSE was detected.

Triggered by asphyxia neurogenesis seems not to be an endogenous repair mechanism, gliogenesis more like it.

PubMed

Keilhoff, G; John, R; Langnaese, K; Schweizer, H; Ebmeyer, U

2010-12-15

We analyzed the long-term consequences of asphyxial cardiac arrest for hippocampal cell proliferation in rats to evaluate if the ischaemia-induced degenerated CA1 region may be repopulated by endogenous (stem) cells. Studies were performed in an asphyxial cardiac arrest model with 5 minutes of asphyxiation and three different survival times: 7, 21, and 90 days. Sham-operated non-asphyxiated rats served as control. Cell proliferation was studied by labeling dividing cells with 5-bromo-2'-deoxy-uridine (BrdU). The neurodegenerative/regenerative pattern at single cell levels was monitored by immunohistochemistry. Alterations of gene expression were analyzed by real-time quantitative RT-PCR. Analysis of BrdU-incorporation demonstrated an increase at 7, 21 as well as 90 days after global ischaemia in the hippocampal CA1 pyramidal cell layer. Similar results were found in the dentate gyrus. Differentiation of BrdU-positive cells, investigated by cell phenotype-specific double fluorescent labeling, showed increased neurogenesis only in the dentate gyrus of animals surviving the cardiac arrest for 7 days. The majority of newcomers, especially in the damaged CA1 region, consisted of glial cells. Moreover, asphyxia seemed to be able to induce the migration of microglia and astroglia from adjacent areas into the damaged area and/or the activation of resident cells. In addition, we show microglia proliferation/activation even 90 days after cardiac arrest. This morphological finding was confirmed by PCR analysis. The results indicate that asphyxia triggers cell proliferation in general and gliogenesis in particular - a possible pro-reparative event. Furthermore, from the finding of microglia proliferation up to 90 days after insult we conclude that delayed cell death processes take place which should be considered for further therapy strategies. Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Timing of xenon-induced delayed postconditioning to protect against spinal cord ischaemia-reperfusion injury in rats.

PubMed

Yang, Y W; Cheng, W P; Lu, J K; Dong, X H; Wang, C B; Zhang, J; Zhao, L Y; Gao, Z F

2014-07-01

This study was designed to assess the neuroprotective effect of xenon-induced delayed postconditioning on spinal cord ischaemia-reperfusion injury (IRI) and to determine the time of administration for best neuroprotection in a rat model of spinal cord IRI. Fifty male rats were randomly divided equally into a sham group, control group, and three xenon postconditioning groups (n=10 per group). The control group underwent spinal cord IRI and immediately inhaled 50% nitrogen/50% oxygen for 3 h at the initiation of reperfusion. The three xenon postconditioning groups underwent the same surgical procedure and immediately inhaled 50% xenon/50% oxygen for 3 h at the initiation of reperfusion or 1 and 2 h after reperfusion. The sham operation group underwent the same surgical procedure without aortic occlusion, and inhaled 50% nitrogen/50% oxygen. Neurological function was assessed using the Basso, Beattie, and Bresnahan score at 4, 24, and 48 h of reperfusion. Histological examination was performed using Nissl staining and immunohistochemistry, and apoptosis was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling staining. Compared with the control group, the three xenon postconditioning groups showed improvements in neurological outcomes, and had more morphologically normal neurones at 48 h of reperfusion. Apoptotic cell death was reduced and the ratio of Bcl-2/Bax immunoreactivity increased in xenon-treated rats compared with controls. Xenon postconditioning up to 2 h after reperfusion provided protection against spinal cord IRI in rats, but the greatest neuroprotection occurred with administration of xenon for 1 h at reperfusion. © The Author [2013]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Lower limb ischaemia in patients with diabetic foot ulcers and gangrene: recognition, anatomic patterns and revascularization strategies.

PubMed

Mills, Joseph L

2016-01-01

The confluence of several chronic conditions--in particular ageing, peripheral artery disease, diabetes, and chronic kidney disease--has created a global wave of lower limbs at risk for major amputation. While frequently asymptomatic or not lifestyle limiting, at least 1% of the population has peripheral artery disease of sufficient severity to be limb threatening. To avoid the critical error of failing to diagnose ischaemia, all patients with diabetic foot ulcers and gangrene should routinely undergo physiologic evaluation of foot perfusion. Ankle brachial index is useful when measurable, but may be falsely elevated or not obtainable in as many as 30% of patients with diabetic foot ulcers primarily because of medial calcinosis. Toe pressures and skin perfusion pressures are applicable to such patients. Copyright © 2016 John Wiley & Sons, Ltd.

A randomised study of perioperative esmolol infusion for haemodynamic stability during major vascular surgery; rationale and design of DECREASE-XIII.

PubMed

Bakker, E J; Ravensbergen, N J; Voute, M T; Hoeks, S E; Chonchol, M; Klimek, M; Poldermans, D

2011-09-01

This article describes the rationale and design of the DECREASE-XIII trial, which aims to evaluate the potential of esmolol infusion, an ultra-short-acting beta-blocker, during surgery as an add-on to chronic low-dose beta-blocker therapy to maintain perioperative haemodynamic stability during major vascular surgery. A double-blind, placebo-controlled, randomised trial. A total of 260 vascular surgery patients will be randomised to esmolol or placebo as an add-on to standard medical care, including chronic low-dose beta-blockers. Esmolol is titrated to maintain a heart rate within a target window of 60-80 beats per minute for 24 h from the induction of anaesthesia. Heart rate and ischaemia are assessed by continuous 12-lead electrocardiographic monitoring for 72 h, starting 1 day prior to surgery. The primary outcome measure is duration of heart rate outside the target window during infusion of the study drug. Secondary outcome measures will be the efficacy parameters of occurrence of cardiac ischaemia, troponin T release, myocardial infarction and cardiac death within 30 days after surgery and safety parameters such as the occurrence of stroke and hypotension. This study will provide data on the efficacy of esmolol titration in chronic beta-blocker users for tight heart-rate control and reduction of ischaemia in patients undergoing vascular surgery as well as data on safety parameters. Copyright © 2011 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Heparin binding epidermal growth factor in renal ischaemia/reperfusion injury.

PubMed

Mulder, Gemma M; Nijboer, Willemijn N; Seelen, Marc A; Sandovici, Maria; Bos, Eelke M; Melenhorst, Wynand B W H; Trzpis, Monika; Kloosterhuis, Niels J; Visser, Lydia; Henning, Rob H; Leuvenink, Henri G D; Ploeg, Rutger J; Sunnarborg, Susan W; van Goor, Harry

2010-06-01

The epidermal growth factor (EGF) receptor and its ligands are crucially involved in the renal response to ischaemia. We studied the heparin binding-epidermal growth factor (HB-EGF), a major ligand for the EGF receptor, in experimental and human ischaemia/reperfusion injury (IRI). HB-EGF mRNA and protein expression was studied in rat kidneys and cultured human tubular (HK-2) cells that were subjected to IRI and in human donor kidneys during transplantation. The effect of EGF receptor inhibition was investigated in vivo and in vitro. Furthermore, urinary HB-EGF protein excretion was studied after renal transplantation. Finally, HB-EGF KO and WT mice were subjected to IRI to study the role of HB-EGF in renal injury. HB-EGF mRNA was significantly up-regulated in the early phase of IRI in rats, cells, and human donor biopsies. Treatment with PKI-166 reduces macrophage accumulation and interstitial alpha-SMA in the early phase of IRI in rats. In vitro, PKI-166 causes a marked reduction in HB-EGF-induced cellular proliferation. Urinary HB-EGF is increased after transplantation compared with control urines from healthy subjects. HB-EGF KO mice subjected to IRI revealed significantly less morphological damage after IRI, compared with WT mice. We conclude that IRI results in early induction of HB-EGF mRNA and protein in vivo and in vitro. Absence of HB-EGF and inhibition of the EGF receptor in the early phase of IRI has protective effects, suggesting a modulating role for HB-EGF.

Preservation of the gut by preoperative carbohydrate loading improves postoperative food intake.

PubMed

Luttikhold, Joanna; Oosting, Annemarie; van den Braak, Claudia C M; van Norren, Klaske; Rijna, Herman; van Leeuwen, Paul A M; Bouritius, Hetty

2013-08-01

A carbohydrate (CHO) drink given preoperatively changes the fasted state into a fed state. The ESPEN guidelines for perioperative care include preoperative CHO loading and re-establishment of oral feeding as early as possible after surgery. An intestinal ischaemia reperfusion (IR) animal model was used to investigate whether preoperative CHO loading increases spontaneous postoperative food intake, intestinal barrier function and the catabolic response. Male Wistar rats (n = 65) were subjected to 16 h fasting with ad libitum water and: A) sham laparotomy (Sham fasted, n = 24); B) intestinal ischaemia (IR fasted, n = 27); and C) intestinal ischaemia with preoperatively access to a CHO drink (IR CHO, n = 14). Spontaneous food intake, intestinal barrier function, insulin sensitivity, intestinal motility and plasma amino acids were measured after surgery. The IR CHO animals started eating significantly earlier and also ate significantly more than the IR fasted animals. Furthermore, preoperative CHO loading improved the intestinal barrier function, functional enterocyte metabolic mass measured by citrulline and reduced muscle protein catabolism, as indicated by normalization of the biomarker 3-methylhistidine. Preoperative CHO loading improves food intake, preserves the GI function and reduces the catabolic response in an IR animal model. These findings suggest that preoperative CHO loading preserves the intestinal function in order to accelerate recovery and food intake. If this effect is caused by overcoming the fasted state or CHO loading remains unclear. Copyright © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Defibrotide reduces infarct size in a rabbit model of experimental myocardial ischaemia and reperfusion.

PubMed Central

Thiemermann, C.; Thomas, G. R.; Vane, J. R.

1989-01-01

1. Defibrotide, a single-stranded polydeoxyribonucleotide obtained from bovine lungs, has significant anti-thrombotic, pro-fibrinolytic and prostacyclin-stimulating properties. 2. The present study was designed to evaluate the effects of defibrotide on infarct size and regional myocardial blood flow in a rabbit model of myocardial ischaemia and reperfusion. 3. Defibrotide (32 mg kg-1 bolus + 32 mg kg-1 h-1, i.v.) either with or without co-administration of indomethacin (5 mg kg-1 x 2, i.v.) was administered 5 min after occlusion of the left anterior-lateral coronary artery and continued during the 60 min occlusion and subsequent 3 h reperfusion periods. 4. Defibrotide significantly attenuated the ischaemia-induced ST-segment elevation and abolished the reperfusion-related changes (R-wave reduction and Q-wave development) in the electrocardiogram. In addition, defibrotide significantly improved myocardial blood flow in normal and in ischaemic, but not in infarcted sections of the heart. The improvement in blood flow in normal perfused myocardium, but not in the ischaemic area was prevented by indomethacin. 5. Although the area at risk was similar in all animal groups studied, defibrotide treatment resulted in a 51% reduction of infarct size. Indomethacin treatment abolished the reduction of infarct size seen with defibrotide alone. 6. The data demonstrate a considerable cardioprotective effect of defibrotide in the reperfused ischaemic rabbit myocardium. This effect may be related, at least in part, to a stimulation of endogenous prostaglandin formation. Other possible mechanisms are discussed. PMID:2758223

Assessment of myeloperoxidase activity in renal tissue after ischemia/reperfusion.

PubMed

Laight, D W; Lad, N; Woodward, B; Waterfall, J F

1994-11-01

We have shown that a photometric assay of myeloperoxidase derived from rat blood polymorphonucleocytes employing 3,3',5,5'-tetramethylbenzidine as substrate is more sensitive than an established assay employing o-dianisidine. We went on to demonstrate that rat renal tissue is capable of inhibiting peroxidase activity. This activity approached 100% when the rat renal supernate was incubated at 60 degree C for 2 h and the assay was conducted in the presence of a 10-fold higher concentration of hydrogen peroxide (H2O2). Rat kidneys undergoing 45 min ischaemia and 1,3 and 6 h reperfusion in vivo, exhibited significant increases in myeloperoxidase activity, indicating tissue polymorphonucleocyte accumulation. Monoclonal antibodies against rat intercellular adhesion molecule 1 (ICAM-1) and CD18 of beta 2-integrins administered both 5 min before a period of 45 min renal ischaemia (20 micrograms/kg i.v.) and at the commencement of 1 h reperfusion (20 micrograms/kg i.v.) reduced renal tissue polymorphonucleocyte accumulation. However, similar treatment with the parent murine antibody immunoglobulin G1 (IgG1) and an unrelated murine antibody, IgG2a, also significantly reduced renal tissue polymorphonucleocyte accumulation. In conclusion, we demonstrate that the rat renal suppression of peroxidase activity can be overcome by a combination of heat inactivation and the provision of excess assay H2O2. In addition, the available evidence suggests that murine monoclonal antibodies against rat adhesion molecules may exert non-specific actions in our model of renal ischaemia/reperfusion in vivo.

Usefulness of warm water and oil assistance in colonoscopy by trainees.

PubMed

Park, Sung Chul; Keum, Bora; Kim, Eun Sun; Jung, Eun Suk; Lee, Sehe Dong; Park, Sanghoon; Seo, Yeon Seok; Kim, Yong Sik; Jeen, Yoon Tae; Chun, Hoon Jai; Um, Soon Ho; Kim, Chang Duck; Ryu, Ho Sang

2010-10-01

Success rate of cecal intubation, endoscopist's difficulty, and procedure-related patient pain are still problems for beginners performing colonoscopy. New methods to aid colonoscopic insertion such as warm water instillation and oil lubrication have been proposed. The aim of this study is to evaluate the feasibility of using warm water or oil in colonoscopy. Colonoscopy was performed in 117 unsedated patients by three endoscopists-in-training. Patients were randomly allocated to three groups, using a conventional method with administration of antispasmodics, warm water instillation, and oil lubrication, respectively. Success rate of total intubation within time limit (15 min), cecal intubation time, degree of endoscopist's difficulty, and level of patient discomfort were compared among the three groups. Cecal intubation time was shorter in the warm water group than in the conventional and oil groups. Degree of procedural difficulty was lower in the warm water group, and patient pain score was higher in the oil lubrication group, compared with the other groups. However, there was no significant difference in success rate of intubation within time limit among the three groups. The warm water method is a simple, safe, and feasible method for beginners. Oil lubrication may not be a useful method compared with conventional and warm water method.

IMMEDIATE EFFECTS OF A DYNAMIC ROTATION-SPECIFIC WARM-UP ON X-FACTOR AND X-FACTOR STRETCH IN THE AMATEUR GOLFER.

PubMed

Henry, Elizabeth; Berglund, Kathy; Millar, Lynn; Locke, Frederick

2015-12-01

Recent evidence suggests performing a warm-up prior to golf can improve performance and reduce injuries. While some characteristics of effective golf warm-ups have been determined, no studies have explored the immediate effects of a rotational-specific warm-up with elements of motor control on the biomechanical aspects of the full X-Factor and X-Factor Stretch during the golf swing. Thirty-six amateur golfers (mean ± SD age: 64 ± 8 years old; 75% male) were randomized into a Dynamic Rotation-Specific Warm-up group (n=20), or a Sham Warm-up group (n=16). X-Factor and X-Factor Stretch were measured at baseline and immediately following the warm-up. Mixed model ANCOVAs were used to determine if a Group*Time interaction existed for each variable with group as the between-subjects variable and time as the within-subjects variable. The mixed model ANCOVAs did not reveal a statistically significant group*time interaction for X-Factor or X-Factor Stretch. There was not a significant main effect for time for X-Factor but there was for X-Factor Stretch. These results indicate that neither group had a significant effect on improving X-Factor, however performing either warm-up increased X-Factor Stretch without significant difference between the two. The results of this study suggest that performing the Dynamic Rotation-Specific Warm-up did not increase X-Factor or X-Factor Stretch when controlled for age compared to the Sham Warm-up. Further study is needed to determine the long-term effects of the Dynamic Rotation-Specific Warm-up on performance factors of the golf swing while examining across all ages. 2b.

Prolonged warm ischemia time is associated with graft failure and mortality after kidney transplantation.

PubMed

Tennankore, Karthik K; Kim, S Joseph; Alwayn, Ian P J; Kiberd, Bryce A

2016-03-01

Warm ischemia time is a potentially modifiable insult to transplanted kidneys, but little is known about its effect on long-term outcomes. Here we conducted a study of United States kidney transplant recipients (years 2000-2013) to determine the association between warm ischemia time (the time from organ removal from cold storage to reperfusion with warm blood) and death/graft failure. Times under 10 minutes were potentially attributed to coding error. Therefore, the 10-to-under-20-minute interval was chosen as the reference group. The primary outcome was mortality and graft failure (return to chronic dialysis or preemptive retransplantation) adjusted for recipient, donor, immunologic, and surgical factors. The study included 131,677 patients with 35,901 events. Relative to the reference patients, times of 10 to under 20, 20 to under 30, 30 to under 40, 40 to under 50, 50 to under 60, and 60 and more minutes were associated with hazard ratios of 1.07 (95% confidence interval, 0.99-1.15), 1.13 (1.06-1.22), 1.17 (1.09-1.26), 1.20 (1.12-1.30), and 1.23 (1.15-1.33) for the composite event, respectively. Association between prolonged warm ischemia time and death/graft failure persisted after stratification by donor type (living vs. deceased donor) and delayed graft function status. Thus, warm ischemia time is associated with adverse long-term patient and graft survival after kidney transplantation. Identifying strategies to reduce warm ischemia time is an important consideration for future study. Copyright © 2015 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Efficient Warm-ups: Creating a Warm-up That Works.

ERIC Educational Resources Information Center

Lauffenburger, Sandra Kay

1992-01-01

Proper warm-up is important for any activity, but designing an effective warm-up can be time consuming. An alternative approach is to take a cue from Laban Movement Analysis (LMA) and consider movement design from the perspective of space and planes of motion. Efficient warm-up exercises using LMA are described. (SM)

Cocaine, a risk factor for myocardial infarction.

PubMed

Galasko, G I

1997-06-01

Cocaine usage goes back thousands of years, to the times of the Incas. Over the past 20 years, its use has increased dramatically, especially in America, and adverse cardiovascular reactions to the drug have begun to be reported. The first report of myocardial infarction temporally related to the recreational use of cocaine appeared in 1982. Since then, myocardial infarction has become recognized as the drug's most common cardiovascular consequence, with over 250 cases now documented in the literature. This review discusses the history of cocaine use, its pharmacology, the possible pathological mechanisms underlying the pathogenesis of myocardial ischaemia and infarction, and current ideas on the management of cocaine-induced myocardial infarction.

Shengmai injection reduces apoptosis and enhances angiogenesis after myocardial ischaemia and reperfusion injury in rats.

PubMed

Liu, Xuan; Tan, Wangxiao; Yang, Fengwen; Wang, Yu; Yue, Shaoqian; Wang, Ting; Wang, Xiaoying

2018-08-01

To investigate whether Shengmai injection (SMI) helps to improve cardiac function and enhances angiogenesis after myocardial ischaemia reperfusion injury (MIRI). A rat model of MIRI was created via occlusion of the left anterior descending coronary artery for 30 min, followed by 3 days or 7 days of reperfusion (n = 6 each group). SMI is widely used for the treatment of myocardial infarction. The mechanism underlying the effect on cardiac function is not known and whether SMI has any effects on angiogenesis during treatment of MIRI is not clear. Echocardiography showed that SMI improved the left ventricular ejection fraction (LVEF) in the rat model of MIRI. TUNEL staining indicated that SMI decreased the myocardial apoptosis rate after MIRI. This result may be related to the increase of Bcl-2 expression in the SMI group and a reduction in Bax and caspase 3 expression, as determined by immunohistochemical staining. Small vessels (<60 μm in diameter) of the heart of rats in the group treated with SMI were denser (more numerous) than those in the heart of rats in the other groups. Real-time PCR indicated that the SMI-driven reduction in apoptosis was associated with a change in the ratio of Bcl-2 to Bax expression, and treatment-induced angiogenesis was associated with enhanced vascular endothelial growth factor A (VEGF) expression. We elucidated that SMI promotes angiogenesis, which is important for the development of cardiac remodelling after MIRI. Copyright © 2018. Published by Elsevier Masson SAS.

Cardiomyocyte-expressed farnesoid-X-receptor is a novel apoptosis mediator and contributes to myocardial ischaemia/reperfusion injury

PubMed Central

Pu, Jun; Yuan, Ancai; Shan, Peiren; Gao, Erhe; Wang, Xiaoliang; Wang, Yajing; Lau, Wayne Bond; Koch, Walter; Ma, Xin-Liang; He, Ben

2013-01-01

Aims Emerging evidence indicates that nuclear receptors play a critical regulatory role in cardiovascular physiology/pathology. Recently, farnesoid-X-receptor (FXR), a member of the metabolic nuclear receptor superfamily, has been demonstrated to be expressed in vascular cells, with important roles in vascular physiology/pathology. However, the potential cardiac function of FXR remains unclear. We investigated the cardiac expression and biological function of FXR. Methods and results Farnesoid-X-receptor was detected in both isolated neonatal rat cardiac myocytes and fibroblasts. Natural and synthetic FXR agonists upregulated cardiac FXR expression, stimulated myocyte apoptosis, and reduced myocyte viability dose- and time-dependently. Mechanistic studies demonstrated that FXR agonists disrupted mitochondria, characterized by mitochondrial permeability transition pores activation, mitochondrial potential dissipation, cytochrome c release, and both caspase-9 and -3 activation. Such mitochondrial apoptotic responses were abolished by siRNA-mediated silencing of endogenous FXR or pharmacological inhibition of mitochondrial death signalling. Furthermore, low levels of FXR were detected in the adult mouse heart, with significant (∼2.0-fold) upregulation after myocardial ischaemia/reperfusion (MI/R). Pharmacological inhibition or genetic ablation of FXR significantly reduced myocardial apoptosis by 29.0–53.4%, decreased infarct size by 23.4–49.7%, and improved cardiac function in ischaemic/reperfused myocardium. Conclusion These results demonstrate that nuclear receptor FXR acts as a novel functional receptor in cardiac tissue, regulates apoptosis in cardiomyocytes, and contributes to MI/R injury. PMID:22307460

Animal models of ischaemic stroke and characterisation of the ischaemic penumbra.

PubMed

McCabe, Christopher; Arroja, Mariana M; Reid, Emma; Macrae, I Mhairi

2018-05-15

Over the past forty years, animal models of focal cerebral ischaemia have allowed us to identify the critical cerebral blood flow thresholds responsible for irreversible cell death, electrical failure, inhibition of protein synthesis, energy depletion and thereby the lifespan of the potentially salvageable penumbra. They have allowed us to understand the intricate biochemical and molecular mechanisms within the 'ischaemic cascade' that initiate cell death in the first minutes, hours and days following stroke. Models of permanent, transient middle cerebral artery occlusion and embolic stroke have been developed each with advantages and limitations when trying to model the complex heterogeneous nature of stroke in humans. Yet despite these advances in understanding the pathophysiological mechanisms of stroke-induced cell death with numerous targets identified and drugs tested, a lack of translation to the clinic has hampered pre-clinical stroke research. With recent positive clinical trials of endovascular thrombectomy in acute ischaemic stroke the stroke community has been reinvigorated, opening up the potential for future translation of adjunctive treatments that can be given alongside thrombectomy/thrombolysis. This review discusses the major animal models of focal cerebral ischaemia highlighting their advantages and limitations. Acute imaging is crucial in longitudinal pre-clinical stroke studies in order to identify the influence of acute therapies on tissue salvage over time. Therefore, the methods of identifying potentially salvageable ischaemic penumbra are discussed. This article is part of the Special Issue entitled 'Cerebral Ischemia'. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Neonatal Hypoxia Ischaemia: Mechanisms, Models, and Therapeutic Challenges

PubMed Central

Millar, Lancelot J.; Shi, Lei; Hoerder-Suabedissen, Anna; Molnár, Zoltán

2017-01-01

Neonatal hypoxia-ischaemia (HI) is the most common cause of death and disability in human neonates, and is often associated with persistent motor, sensory, and cognitive impairment. Improved intensive care technology has increased survival without preventing neurological disorder, increasing morbidity throughout the adult population. Early preventative or neuroprotective interventions have the potential to rescue brain development in neonates, yet only one therapeutic intervention is currently licensed for use in developed countries. Recent investigations of the transient cortical layer known as subplate, especially regarding subplate’s secretory role, opens up a novel set of potential molecular modulators of neonatal HI injury. This review examines the biological mechanisms of human neonatal HI, discusses evidence for the relevance of subplate-secreted molecules to this condition, and evaluates available animal models. Neuroserpin, a neuronally released neuroprotective factor, is discussed as a case study for developing new potential pharmacological interventions for use post-ischaemic injury. PMID:28533743

Lymphangioma of the jejunal mesentery and jejunal polyps presenting as an acute abdomen in a teenager.

PubMed

Jayasundara, Jasb; Perera, E; Chandu de Silva, M V; Pathirana, A A

2017-03-01

Cystic lymphangioma of the small bowel mesentery is a rare clinical entity, especially after childhood. Medical literature reveals a limited number of such cases presenting as acute abdomen due to bowel obstruction, small bowel volvulus and bleeding into the tumour. We present the management experience of an 18-year-old woman who presented with rapid onset diffuse peritonism and raised inflammatory markers. Computed tomography showed a mass in the small bowel mesentery with suspicion of segmental bowel ischaemia. Emergency laparotomy revealed a mass in the mid-jejunal mesentery close to the bowel wall with no bowel ischaemia. The patient made an uncomplicated recovery after segmental bowel resection and end-to-end anastomosis. Histology confirmed the mass as a cystic lymphangioma involving the jejunal mesentery and two small jejunal polyps. Lymphangioma could be considered in the differential diagnosis of an acute abdomen in a young adult when the presentation is atypical.

A novel microwave sensor to detect specific biomarkers in human cerebrospinal fluid and their relationship to cellular ischemia during thoracoabdominal aortic aneurysm repair.

PubMed

Fok, M; Bashir, M; Fraser, H; Strouther, N; Mason, A

2015-04-01

Thoraco-abdominal aneurysms (TAAA) represents a particularly lethal vascular disease that without surgical repair carries a dismal prognosis. However, there is an inherent risk from surgical repair of spinal cord ischaemia that can result in paraplegia. One method of reducing this risk is cerebrospinal fluid (CSF) drainage. We believe that the CSF contains clinically significant biomarkers that can indicate impending spinal cord ischaemia. This work therefore presents a novel measurement method for proteins, namely albumin, as a precursor to further work in this area. The work uses an interdigitated electrode (IDE) sensor and shows that it is capable of detecting various concentrations of albumin (from 0 to 100 g/L) with a high degree of repeatability at 200 MHz (R(2) = 0.991) and 4 GHz (R(2) = 0.975).

Lidocaine effect on flotillin-2 distribution in detergent-resistant membranes of equine jejunal smooth muscle in vitro.

PubMed

Tappenbeck, Karen; Schmidt, Sonja; Feige, Karsten; Naim, Hassan Y; Huber, Korinna

2014-05-01

Lidocaine is the most commonly chosen prokinetic for treating postoperative ileus in horses, a motility disorder associated with ischaemia-reperfusion injury of intestinal tissues. Despite the frequent use of lidocaine, the mechanism underlying its prokinetic effects is still unclear. Previous studies suggested that lidocaine altered cell membrane characteristics of smooth muscle cells. Therefore, the present study aimed to elucidate effects of lidocaine administration on characteristics of detergent-resistant membranes in equine jejunal smooth muscle. Lidocaine administration caused significant redistribution of flotillin-2, a protein marker of detergent-resistant membranes, in fractions of sucrose-density-gradients obtained from ischaemia-reperfusion injured smooth muscle solubilised with Triton X-100. It was concluded that lidocaine induced disruption of detergent-resistant membranes which might affect ion channel activity and therefore enhance smooth muscle contractility. Copyright © 2014 Elsevier Ltd. All rights reserved.

Spatio-temporal Organization During Ventricular Fibrillation in the Human Heart.

PubMed

Robson, Jinny; Aram, Parham; Nash, Martyn P; Bradley, Chris P; Hayward, Martin; Paterson, David J; Taggart, Peter; Clayton, Richard H; Kadirkamanathan, Visakan

2018-06-01

In this paper, we present a novel approach to quantify the spatio-temporal organization of electrical activation during human ventricular fibrillation (VF). We propose three different methods based on correlation analysis, graph theoretical measures and hierarchical clustering. Using the proposed approach, we quantified the level of spatio-temporal organization during three episodes of VF in ten patients, recorded using multi-electrode epicardial recordings with 30 s coronary perfusion, 150 s global myocardial ischaemia and 30 s reflow. Our findings show a steady decline in spatio-temporal organization from the onset of VF with coronary perfusion. We observed transient increases in spatio-temporal organization during global myocardial ischaemia. However, the decline in spatio-temporal organization continued during reflow. Our results were consistent across all patients, and were consistent with the numbers of phase singularities. Our findings show that the complex spatio-temporal patterns can be studied using complex network analysis.

Limb salvage following iatrogenic arterial injury: complications of cardiac support using intra-aortic balloon pumps.

PubMed

Hunt, Adam; Waldin, Owen; Slim, Hani; Brar, Ranjeet

2016-06-06

This is a unique case report describing complex limb salvage in a patient who experienced acute limb ischaemia due to a complication of intra-aortic balloon pump (IABP) counterpulsation. This case focuses on a patient who had an IABP counterpulsation device inserted following myocardial infarction, requiring urgent coronary artery bypass grafting for acute coronary syndrome. Postoperatively, the IABP could not be removed, with consequent iliac thrombosis and acute limb ischaemia. Emergency femoral-to-femoral crossover bypass was performed using a polytetrafluoroethylene graft. A portion of the IABP balloon tip was entrapped and retained, however, and became the focus of delayed septicaemia, resulting in graft infection and wound breakdown 6 weeks later. Explantation of the residual balloon tip, ligation of the right external iliac artery and redo femoral-femoral crossover using the great saphenous vein were successfully performed. 2016 BMJ Publishing Group Ltd.

Modelling blood flow and metabolism in the piglet brain during hypoxia-ischaemia: simulating brain energetics.

PubMed

Moroz, Tracy; Hapuarachchi, Tharindi; Bainbridge, Alan; Price, David; Cady, Ernest; Baer, Ether; Broad, Kevin; Ezzati, Mojgan; Thomas, David; Golay, Xavier; Robertson, Nicola J; Cooper, Chris E; Tachtsidis, Ilias

2013-01-01

We have developed a computational model to simulate hypoxia-ischaemia (HI) in the neonatal piglet brain. It has been extended from a previous model by adding the simulation of carotid artery occlusion and including pH changes in the cytoplasm. Here, simulations from the model are compared with near-infrared spectroscopy (NIRS) and phosphorus magnetic resonance spectroscopy (MRS) measurements from two piglets during HI and short-term recovery. One of these piglets showed incomplete recovery after HI, and this is modelled by considering some of the cells to be dead. This is consistent with the results from MRS and the redox state of cytochrome-c-oxidase as measured by NIRS. However, the simulations do not match the NIRS haemoglobin measurements. The model therefore predicts that further physiological changes must also be taking place if the hypothesis of dead cells is correct.

Ischaemia-reperfusion injury in central retinal artery occlusion.

PubMed

Saxena, Sandeep; Mishra, Nibha; Meyer, Carsten H; Akduman, Levent

2013-10-21

A 53-year-old man presented with sudden painless diminution of vision in his right eye for 3 days. His fundus examination showed diffuse whitening of the retina with a cherry red spot at the fovea with cilioretinal artery sparing. On fluorescein angiography delayed arteriovenous transit was observed. Three-dimensional spectral domain optical coherence tomography was used to assess retinal nerve fibre layer thickness and average macular central subfield thickness on days 3, 7, 30 and 90. Marked retinal oedema due to ischaemia was observed on day 3 of occurrence of central retinal artery occlusion. On day 7, significant decrease in retinal nerve fibre thickness and macular thickness was noted suggestive of acute reperfusion injury. Retinal nerve fibre layer thickness and macular thickness returned to near normal on day 30 due to restoration of blood supply with wash out of stress mediators. Retinal atrophy was observed on day 90.

Ischaemia-reperfusion injury in central retinal artery occlusion

PubMed Central

Saxena, Sandeep; Mishra, Nibha; Meyer, Carsten H; Akduman, Levent

2013-01-01

A 53-year-old man presented with sudden painless diminution of vision in his right eye for 3 days. His fundus examination showed diffuse whitening of the retina with a cherry red spot at the fovea with cilioretinal artery sparing. On fluorescein angiography delayed arteriovenous transit was observed. Three-dimensional spectral domain optical coherence tomography was used to assess retinal nerve fibre layer thickness and average macular central subfield thickness on days 3, 7, 30 and 90. Marked retinal oedema due to ischaemia was observed on day 3 of occurrence of central retinal artery occlusion. On day 7, significant decrease in retinal nerve fibre thickness and macular thickness was noted suggestive of acute reperfusion injury. Retinal nerve fibre layer thickness and macular thickness returned to near normal on day 30 due to restoration of blood supply with wash out of stress mediators. Retinal atrophy was observed on day 90. PMID:24145508

An unexpected cause of small bowel obstruction in an adult patient: midgut volvulus

PubMed Central

Söker, Gökhan; Yılmaz, Cengiz; Karateke, Faruk; Gülek, Bozkurt

2014-01-01

The most important complication of intestinal malrotation is midgut volvulus because it may lead to intestinal ischaemia and necrosis. A 29-year-old male patient was admitted to the emergency department with abdominal pain. Ultrasonography (US), colour Doppler ultrasonography (CDUS), CT and barium studies were carried out. On US and CDUS, twisting of intestinal segments around the superior mesenteric artery (SMA) and superior mesenteric vein (SMV) and alteration of the SMA–SMV relationship were detected. CT demonstrated that the small intestine was making a rotation around the SMA and SMV, which amounted to more than 360°. The upper gastrointestinal barium series revealed a corkscrew appearance of the duodenum and proximal jejunum, which is a pathognomonic finding of midgut volvulus. Prior knowledge of characteristic imaging findings of midgut volvulus is essential in order to reach proper diagnosis and establish proper treatment before the development of intestinal ischaemia and necrosis. PMID:24811563

A randomized comparison of intraoperative PerfecTemp and forced-air warming during open abdominal surgery.

PubMed

Egan, Cameron; Bernstein, Ethan; Reddy, Desigen; Ali, Madi; Paul, James; Yang, Dongsheng; Sessler, Daniel I

2011-11-01

The PerfecTemp is an underbody resistive warming system that combines servocontrolled underbody warming with viscoelastic foam pressure relief. Clinical efficacy of the system has yet to be formally evaluated. We therefore tested the hypothesis that intraoperative distal esophageal (core) temperatures with the PerfecTemp (underbody resistive) warming system are noninferior to upper-body forced-air warming in patients undergoing major open abdominal surgery under general anesthesia. Adults scheduled for elective major open abdominal surgery (liver, pancreas, gynecological, and colorectal surgery) under general anesthesia were enrolled at 2 centers. Patients were randomly assigned to underbody resistive or forced-air warming. Resistive heating started when patients were transferred to the operating room table; forced-air warming started after patients were draped. The primary outcome was noninferiority of intraoperative time-weighted average core temperature, adjusted for baseline characteristics and using a buffer of 0.5°C. Thirty-six patients were randomly assigned to underbody resistive heating and 34 to forced-air warming. Baseline and surgical characteristics were generally similar. We had sufficient evidence (P=0.018) to conclude that underbody resistive warming is not worse than (i.e., noninferior to) upper-body forced-air warming in the time-weighted average intraoperative temperature, with a mean difference of -0.12°C [95% confidence interval (CI) -0.37 to 0.14]. Core temperatures at the end of surgery averaged 36.3°C [95% CI 36 to 36.5] in the resistive warming patients and 36.6°C [95% CI 36.4 to 36.8] in those assigned to forced-air warming for a mean difference of -0.34°C [95% CI -0.69 to 0.01]. Mean intraoperative time-weighted average core temperatures were no different, and significantly noninferior, with underbody resistive heating in comparison with upper-body forced-air warming. Underbody resistive heating may be an alternative to forced-air warming.

The relationship between renal warm ischemia time and glomerular loss. An experimental study in a pig model.

PubMed

Damasceno-Ferreira, José Aurelino; Bechara, Gustavo Ruschi; Costa, Waldemar Silva; Pereira-Sampaio, Marco Aurélio; Sampaio, Francisco José Barcellos; Souza, Diogo Benchimol De

2017-05-01

To investigate the glomerular number after different warm ischemia times. Thirty two pigs were assigned into four groups. Three groups (G10, G20, and G30) were treated with 10, 20, and 30 minutes of left renal warm ischemia. The sham group underwent the same surgery without renal ischemia. The animals were euthanized after 3 weeks, and the kidneys were collected. Right kidneys were used as controls. The kidney weight, volume, cortical-medullar ratio, glomerular volumetric density, volume-weighted mean glomerular volume, and the total number of glomeruli per kidney were obtained. Serum creatinine levels were assessed pre and postoperatively. Serum creatinine levels did not differ among the groups. All parameters were similar for the sham, G10, and G20 groups upon comparison of the right and left organs. The G30 group pigs' left kidneys had lower weight, volume, and cortical-medullar ratio and 24.6% less glomeruli compared to the right kidney. A negative correlation was found between warm ischemia time and glomerular number. About one quarter of glomeruli was lost after 30 minutes of renal warm ischemia. No glomeruli loss was detected before 20 minutes of warm ischemia. However, progressive glomerular loss was associated with increasing warm ischemia time.

No effect of a homoeopathic combination of Arnica montana and Bryonia alba on bleeding, inflammation, and ischaemia after aortic valve surgery.

PubMed

Cornu, Catherine; Joseph, Pierre; Gaillard, Ségolène; Bauer, Christian; Vedrinne, Catherine; Bissery, Alvine; Melot, Ghislaine; Bossard, Nadine; Belon, Philippe; Lehot, Jean-Jacques

2010-02-01

" Arnica montana is a popular homoeopathic treatment with potential haemostatic and anti-inflammatory properties. A homoeopathic combination of A. montana and Bryonia alba was used in aortic valve surgery to evaluate its effectiveness in reducing bleeding, inflammation, pain and myocardial ischaemia. One day before surgery, 92 adult patients were randomly assigned to a double-blind parallel trial with either homoeopathic granules or a matching placebo until 4 days after surgery. The primary outcome was the volume of blood/liquid in the drains at their removal. The secondary outcomes included postoperative blood/liquid losses at 12 and 24 h as well as C-reactive protein (CRP), pain, temperature and plasma troponin Ic. At 12 h and 24 h after surgery, then at drain removal, blood losses in homoeopathy and placebo groups were not statistically significant (362 +/- 218, 520 +/- 269 and 640 +/- 297 ml vs. 456 +/- 440, 620 +/- 477 and 796 +/- 717 ml; P= 0.19, 0.23 and 0.35, respectively). The statistical modelling did not show significantly different patterns of CRP, troponin and body temperature changes or of pain perception. The number of transfused packed red cells was not significantly different either (P= 0.58). Two patients from each group died during the study period and the number of serious adverse events was not statistically different (six in homoeopathy vs. 10 in placebo groups; Fisher's exact test P= 0.41). In the study setting, there was no evidence of effects of A. montana and B. alba combination on bleeding, inflammation, pain or myocardial ischaemia.

McConnell's sign in intra-operative acute right ventricle ischaemia: An under-recognized aetiology.

PubMed

Longo, S A; Echegaray, A; Acosta, C M; Rinaldi, L I; Cabrera Schulmeyer, M C; Olavide Goya, I

2016-11-01

Transoesophageal echocardiography (TEE) has become a fundamental tool in modern cardiothoracic anaesthesia. It has an indisputable role in coronary valve surgery and revascularisations with severe impairment of ventricle function. It helps in making diagnoses that can optimise the surgical strategy and to minimal invasively dynamically monitor volaemia and cardiac function during the post-operative period, detecting complications unobservable by other methods. The McConnell sign, visualised using TEE as an akinesis of the right ventricular free wall, with a normal apex motility and enlargement of the right cavities, is characteristic of right ventricular (RV) dysfunction. This sign has a 77% sensitivity and 94% specificity for the diagnosis of acute pulmonary embolism (APE). The case is presented of a 53-year-old man scheduled for aortic valve and ascending aorta replacement surgery, with a history of severe valve aortic stenosis, aortic root and arch aneurysm, and with normal coronary arteries. Post-cardiopulmonary bypass (CBP), the patient presented with haemodynamic instability, with the TEE showing a typical image of the McConnell sign, with no pulmonary hypertension. This enabled making an early diagnosis of acute RV ischaemia, that led to a change in the surgical plan, the performing of coronary revascularisation surgery. As a result, the McConnell sign, which describes the characteristics of RV dysfunction, led to making a differential diagnosis between APE, RV infarction and acute myocardial ischaemia. Copyright © 2016 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Topical application of recombinant platelet-derived growth factor increases the rate of healing and the level of proteins that regulate this response.

PubMed

Gowda, Santosh; Weinstein, David A; Blalock, Timothy D; Gandhi, Kavita; Mast, Bruce A; Chin, Gloria; Schultz, Gregory S

2015-10-01

A bipedicle ischaemic rat skin flap model was used to study the effects of daily topical applications of platelet-derived growth factor (PDGF) on the healing of ischaemic wounds. Levels of tumour necrosis factor-alpha (TNFA), interleukin 1-beta (IL1B) and both the latent and active forms of matrix metalloproteinase 2 (MMP2) and 9 (MMP9) were measured. Full-thickness wounds were made on a total of 72 adult male Sprague-Dawley rats. Each group of 18 rats with normal and ischaemic wounds received either vehicle or 0·01% recombinant PDGF-BB. Additional applications were made on the wounds on a daily basis. Wound areas were measured at 0, 1, 3, 5, 7 9 and 13 days after wounding. Ischaemia caused a delay in wound healing as well as an increase in TNFA, IL1B and both the pro and active forms of MMP2 and MMP9. PDGF accelerated the rate of wound healing in both normal and ischaemic wounds and negated the effect of ischaemia. PDGF reduced the TNFA concentration in both normal and ischaemic wounds, and the rate of wound healing closely resembled the pattern of TNFA protein expression. PDGF also reduced both the magnitude and duration of the increases in IL1B and both the pro and active forms of MMP2 and MMP9 induced by ischaemia. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Consecutive pharmacological activation of PKA and PKC mimics the potent cardioprotection of temperature preconditioning

PubMed Central

Khaliulin, Igor; Parker, Joanna E.; Halestrap, Andrew P.

2010-01-01

Aims Temperature preconditioning (TP) provides very powerful protection against ischaemia/reperfusion. Understanding the signalling pathways involved may enable the development of effective pharmacological cardioprotection. We investigated the interrelationship between activation of protein kinase A (PKA) and protein kinase C (PKC) in the signalling mechanisms of TP and developed a potent pharmacological intervention based on this mechanism. Methods and results Isolated rat hearts were subjected to TP, 30 min global ischaemia, and 60 min reperfusion. Other control and TP hearts were perfused with either sotalol (β-adrenergic blocker) or H-89 (PKA inhibitor). Some hearts were pre-treated with either isoproterenol (β-adrenergic agonist) or adenosine (PKC activator) that were given alone, simultaneously, or sequentially. Pre-treatment with isoproterenol, adenosine, and the consecutive isoproterenol/adenosine treatment was also combined with the PKC inhibitor chelerythrine. Cardioprotection was evaluated by haemodynamic function recovery, lactate dehydrogenase release, measurement of mitochondrial permeability transition pore opening, and protein carbonylation during reperfusion. Cyclic AMP and PKA activity were increased in TP hearts. H-89 and sotalol blocked the cardioprotective effect of TP and TP-induced PKC activation. Isoproterenol, adenosine, and the consecutive treatment increased PKC activity during pre-ischaemia. Isoproterenol significantly reduced myocardial glycogen content. Isoproterenol and adenosine, alone or simultaneously, protected hearts but the consecutive treatment gave the highest protection. Cardioprotective effects of adenosine were completely blocked by chelerythrine but those of the consecutive treatment only attenuated. Conclusion The signal transduction pathway of TP involves PKA activation that precedes PKC activation. Pharmacologically induced consecutive PKA/PKC activation mimics TP and induces extremely potent cardioprotection. PMID:20558443

Transitory Activation of AMPK at Reperfusion Protects the Ischaemic-Reperfused Rat Myocardium Against Infarction

PubMed Central

Paiva, Marta A.; Gonçalves, Lino M.; Providência, Luis A.; Davidson, Sean M.; Yellon, Derek M.; Mocanu, Mihaela M.

2010-01-01

Purpose AMPK plays a crucial role in the regulation of the energy metabolism of the heart. During ischaemia, AMPK activation is a known adaptative prosurvival mechanism that helps to maintain the energy levels of the myocardium. However, it still remains unclear if activation of AMPK during reperfusion is beneficial for the heart. Two known AMPK activators (metformin and AICAR) were used to verify the hypothesis that a transitory activation of AMPK at reperfusion may exert cardioprotection, as reflected in a reduction in myocardial infarct size. Methods Perfused rat hearts were subjected to 35 min ischaemia and 120 min reperfusion. Metformin (50 μM) or AICAR (0.5 mM) were added for 15 min at the onset of reperfusion alone or with Compound C (CC, 10 μM), an AMPK inhibitor. Infarct size and α-AMPK phosphorylation were measured. Results Metformin significantly reduced infarct size from 47.8±1.7% in control to 31.4±2.9%, an effect abolished by CC when the drugs were given concomitantly. Similarly, AICAR also induced a significant reduction in infarct size to 32.3±4.8%, an effect also abrogated by CC. However, metformin's protection was not abolished if CC was administered later in reperfusion. In addition, α-AMPK phosphorylation was significantly increased in the metformin treated group during the initial 30 min of reperfusion. Conclusions Our data demonstrated that, in our ex vivo model of myocardial ischaemia-reperfusion injury, AMPK activation in early reperfusion is associated with a reduction in infarct size. PMID:20229055

Ischaemia-reperfusion injury in orthotopic mouse lung transplants – a scanning electron microscopy study

PubMed Central

Draenert, Alice; Marquardt, Klaus; Inci, Ilhan; Soltermann, Alex; Weder, Walter; Jungraithmayr, Wolfgang

2011-01-01

Lung ischaemia-reperfusion (I/R) injury remains a major cause of graft failure in lung transplantation (Tx). With the implementation of orthotopic lung Tx in mice, a physiological model on the base of a perfused and ventilated graft became available for the investigation of I/R injury. Using the scanning electron microscopy (SEM) technique, we here present an analysis of early and late morphological changes of pulmonary I/R injury. Syngeneic lungs were orthotopically transplanted between C57BL/6 mice. Grafts were exposed to 2 h of cold ischaemia. Transplants and right lungs were examined by SEM with corresponding haematoxylin–eosin histology 30 min and 4 h after reperfusion. Thirty minutes after reperfusion, the alveolar surface of transplants showed a discontinued lining of surfactant, while the lining of the non-transplanted lung was normal. Within the graft, leucocytes displayed an irregular surface with development of pseudopodia, and microvilli were detected on the membrane of pneumocytes. At 4 h after reperfusion, leucocytes significantly increased in numbers within the alveolar space. Also, the number of microvilli on pneumocytes increased significantly. Similar to these, the endothelium of vessels increasingly developed microvilli from 30 min towards 4 h after reperfusion. The airways of transplanted grafts showed mild changes with thickening of the bronchial epithelium and a destruction of kinocilia. Taken together, SEM detects pathological events of I/R that are previously not described in normal histology. These findings may influence the interpretation of studies investigating the I/R injury in the mouse model of lung Tx. PMID:21272104

Patent foramen ovale is not associated with an increased risk of stroke recurrence.

PubMed

Feurer, R; Sadikovic, S; Sepp, D; Esposito, L; Schleef, M; Bockelbrink, A; Schwarze, J; Hemmer, B; Sander, D; Poppert, H

2010-11-01

Despite numerous studies suggesting a relationship between paradoxical embolism from a patent foramen ovale (PFO) and stroke, the role of PFO as a risk factor for cerebral ischaemia remains controversial. We therefore sought to determine the association between a RLS detected by contrast-enhanced transcranial Doppler ultrasonography (c-TCD) and recurrent stroke in an unselected population sample. We analyzed the records of 763 patients with diagnosis of cerebral ischaemia at our institution. All patients had undergone TCD-based detection of RLS. Embolic signals have been measured both under resting conditions and after performing a Valsalva maneuver. For follow-up, all patients were contacted by mail, which included a standardized questionnaire. Endpoints of follow-up were defined as recurrence of cerebral ischaemia, occurrence of myocardial infarction or death from any cause. Follow-up data were available in 639 patients (83.7%). At baseline, a RLS was detected in 140 (28%) men and in 114 (42%) women. Ten shunt-carriers (1.6%) and 32 patients (5.0%) without RLS had suffered a recurrent stroke. After adjustment for age, sex, and atrial fibrillation, the hazard ratio of RLS for stroke recurrence was 0.86 (95% CI 0.41-1.79). The condition of RLS at rest adjusted for age, sex, stroke subtype, and cardiovascular risk factors was not found to increase the risk of stroke substantially (HR 1.16 [95% CI 0.41-3.29]) Our data suggest that the risk of recurrent stroke in subjects with PFO is not significantly increased in comparison with subject without it. © 2010 The Author(s). Journal compilation © 2010 EFNS.

123I-BMIPP fatty acid analogue imaging is a novel diagnostic and prognostic approach following acute myocardial infarction.

PubMed

Biswas, S K; Sarai, M; Hishida, H; Ozaki, Y

2009-10-01

Fatty acid oxidation is the most efficient mode of myocardial energy production which requires a large amount of oxygen. Thus, alteration of fatty acid oxidation is considered to be a sensitive marker of ischaemia and myocardial damage. (123)I-BMIPP ([123]I-beta-methyl-p-iodophenylpentadecanoic acid) is a newly-investigated single-photon branching free fatty acid radiopharmaceutical with slow metabolism; thus, it is well-suited for single-photon emission computed tomography (SPECT). Assessment of fatty acid metabolism by radionuclide techniques has a potential role for the early detection of myocardial ischaemia and the assessment of the severity of ischaemic heart disease. Although stable patients with a healed myocardial infarction may have a relatively good prognosis, risk stratification in the predischarge period should be valuable for deciding upon appropriate management. In this respect, the presence of discordant BMIPP uptake relative to (201)Tl perfusion appears to be the best predictor of future cardiac events among all other cardiovascular imaging modalities. Since discordant BMIPP uptake correlates well with redistribution on stress (201)Tl imaging and perfusion-metabolism mismatch on positron emission tomography, it is considered that such BMIPP and (201)Tl discordance may identify a high-risk subgroup among patients with acute myocardial infarction. A BMIPP scan may reflect prior severe ischaemia after recovery of perfusion, the so-called "ischaemic memory". Gated BMIPP SPECT has been recently introduced for simultaneous assessment of myocardial metabolism and ventricular function. Such a new technique seems to be valuable for a better understanding of the pathophysiological state of heart failure and cardiomyopathy.

40 CFR Table A-1 to Subpart A of... - Global Warming Potentials

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 22 2013-07-01 2013-07-01 false Global Warming Potentials A Table A-1... A-1 to Subpart A of Part 98—Global Warming Potentials Global Warming Potentials [100-Year Time Horizon] Name CAS No. Chemical formula Global warming potential(100 yr.) Carbon dioxide 124-38-9 CO2 1...

40 CFR Table A-1 to Subpart A of... - Global Warming Potentials

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 21 2014-07-01 2014-07-01 false Global Warming Potentials A Table A-1... A-1 to Subpart A of Part 98—Global Warming Potentials Global Warming Potentials [100-Year Time Horizon] Name CAS No. Chemical formula Global warming potential(100 yr.) Carbon dioxide 124-38-9 CO2 1...

75 FR 81179 - Approval and Promulgation of Implementation Plans; Nebraska: Prevention of Significant...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-27

... Global Warming Potential (GWP) was developed to compare the heat- trapping capacity and atmospheric... CH 4 emissions would have 21 times as much impact on global warming over a 100-year time horizon as 1... emissions contribution to global warming based on a single metric. B. What are the general requirements of...

The tropical Pacific as a key pacemaker of the variable rates of global warming

NASA Astrophysics Data System (ADS)

Kosaka, Yu; Xie, Shang-Ping

2016-09-01

Global mean surface temperature change over the past 120 years resembles a rising staircase: the overall warming trend was interrupted by the mid-twentieth-century big hiatus and the warming slowdown since about 1998. The Interdecadal Pacific Oscillation has been implicated in modulations of global mean surface temperatures, but which part of the mode drives the variability in warming rates is unclear. Here we present a successful simulation of the global warming staircase since 1900 with a global ocean-atmosphere coupled model where tropical Pacific sea surface temperatures are forced to follow the observed evolution. Without prescribed tropical Pacific variability, the same model, on average, produces a continual warming trend that accelerates after the 1960s. We identify four events where the tropical Pacific decadal cooling markedly slowed down the warming trend. Matching the observed spatial and seasonal fingerprints we identify the tropical Pacific as a key pacemaker of the warming staircase, with radiative forcing driving the overall warming trend. Specifically, tropical Pacific variability amplifies the first warming epoch of the 1910s-1940s and determines the timing when the big hiatus starts and ends. Our method of removing internal variability from the observed record can be used for real-time monitoring of anthropogenic warming.

Amiodarone. Haemodynamic profile during intravenous administration and effect on pacing-induced ischaemia in man.

PubMed

Remme, W J; van Hoogenhuyze, D C; Kruyssen, D A; Krauss, X H; Storm, C J

1985-03-01

The haemodynamic changes during intravenous amiodarone administration in laboratory animals and human studies are reviewed and compared with the results from our investigations. While the results of previous human studies have been rather variable, our investigations suggest that the cardiovascular changes following intravenous amiodarone include an early and usually short reduction of systemic and coronary vascular resistance, which may be partially due to the vasodilating properties of the solvent, polysorbate 80. As a result, a decrease in afterload and cardiac work and increases in cardiac output and coronary blood flow occur. Contrary to the observations in the animal experiments, heart rate increases in man, presumably as a result of the relatively greater fall in afterload which occurs. However, in spite of this increase in heart rate, contractility is reduced at the end of amiodarone administration and remains depressed after the infusion, resulting in a significant increase in left ventricular filling pressure. Neither myocardial oxygen demand nor consumption change during amiodarone administration. Although the intrinsic negative inotropic effects of amiodarone warrant a cautious approach in patients with left ventricular dysfunction, worsening of heart failure or the occurrence of myocardial ischaemia has been reported in only very few cases so far. In contrast, the drug was demonstrated to protect against pacing-induced myocardial ischaemia, in patients with both normal and depressed left ventricular function. These anti-ischaemic properties of amiodarone were investigated in a second study using a double pacing stress test protocol. Overall myocardial oxygen consumption did not change during pacing after amiodarone, but it clearly reduced (regional) myocardial ischaemia, as demonstrated by a reduction of ST-segment changes and anginal pain, and in particular by the absence of myocardial lactate production during pacing after amiodarone. These anti-ischaemic properties are mainly based on a reduction of myocardial oxygen demand, rather than on an improvement in coronary flow. It is concluded then, that amiodarone has significant haemodynamic effects as manifested by an early reduction in vascular resistance and a late negative inotropic effect. Although vasodilatation of short duration caused by its solvent, polysorbate 80, also occurs, the overall cardiovascular changes are caused by the direct, intrinsic haemodynamic effects of amiodarone alone. The important anti-ischaemic properties of amiodarone appear to result primarily from these cardiovascular actions and the inherent reduction in myocardial oxygen demand.

Preconditioning Shields Against Vascular Events in Surgery (SAVES), a multicentre feasibility trial of preconditioning against adverse events in major vascular surgery: study protocol for a randomised control trial.

PubMed

Healy, Donagh; Clarke-Moloney, Mary; Gaughan, Brendan; O'Daly, Siobhan; Hausenloy, Derek; Sharif, Faisal; Newell, John; O'Donnell, Martin; Grace, Pierce; Forbes, John F; Cullen, Walter; Kavanagh, Eamon; Burke, Paul; Cross, Simon; Dowdall, Joseph; McMonagle, Morgan; Fulton, Greg; Manning, Brian J; Kheirelseid, Elrasheid A H; Leahy, Austin; Moneley, Daragh; Naughton, Peter; Boyle, Emily; McHugh, Seamus; Madhaven, Prakash; O'Neill, Sean; Martin, Zenia; Courtney, Donal; Tubassam, Muhammed; Sultan, Sherif; McCartan, Damian; Medani, Mekki; Walsh, Stewart

2015-04-23

Patients undergoing vascular surgery procedures constitute a 'high-risk' group. Fatal and disabling perioperative complications are common. Complications arise via multiple aetiological pathways. This mechanistic redundancy limits techniques to reduce complications that target individual mechanisms, for example, anti-platelet agents. Remote ischaemic preconditioning (RIPC) induces a protective phenotype in at-risk tissue, conferring protection against ischaemia-reperfusion injury regardless of the trigger. RIPC is induced by repeated periods of upper limb ischaemia-reperfusion produced using a blood pressure cuff. RIPC confers some protection against cardiac and renal injury during major vascular surgery in proof-of-concept trials. Similar trials suggest benefit during cardiac surgery. Several uncertainties remain in advance of a full-scale trial to evaluate clinical efficacy. We propose a feasibility trial to fully evaluate arm-induced RIPC's ability to confer protection in major vascular surgery, assess the incidence of a proposed composite primary efficacy endpoint and evaluate the intervention's acceptability to patients and staff. Four hundred major vascular surgery patients in five Irish vascular centres will be randomised (stratified for centre and procedure) to undergo RIPC or not immediately before surgery. RIPC will be induced using a blood pressure cuff with four cycles of 5 minutes of ischaemia followed by 5 minutes of reperfusion immediately before the start of operations. There is no sham intervention. Participants will undergo serum troponin measurements pre-operatively and 1, 2, and 3 days post-operatively. Participants will undergo 12-lead electrocardiograms pre-operatively and on the second post-operative day. Predefined complications within one year of surgery will be recorded. Patient and staff experiences will be explored using qualitative techniques. The primary outcome measure is the proportion of patients who develop elevated serum troponin levels in the first 3 days post-operatively. Secondary outcome measures include length of hospital and critical care stay, unplanned critical care admissions, death, myocardial infarction, stroke, mesenteric ischaemia and need for renal replacement therapy (within 30 days of surgery). RIPC is novel intervention with the potential to significantly improve perioperative outcomes. This trial will provide the first evaluation of RIPC's ability to reduce adverse clinical events following major vascular surgery. www.clinicaltrials.gov NCT02097186 Date Registered: 24 March 2014.

A new cannabinoid CB2 receptor agonist HU-910 attenuates oxidative stress, inflammation and cell death associated with hepatic ischaemia/reperfusion injury

PubMed Central

Horváth, Bėla; Magid, Lital; Mukhopadhyay, Partha; Bátkai, Sándor; Rajesh, Mohanraj; Park, Ogyi; Tanchian, Galin; Gao, Rachel Y; Goodfellow, Catherine E; Glass, Michelle; Mechoulam, Raphael; Pacher, Pál

2012-01-01

BACKGROUND AND PURPOSE Cannabinoid CB2 receptor activation has been reported to attenuate myocardial, cerebral and hepatic ischaemia-reperfusion (I/R) injury. EXPERIMENTAL APPROACH We have investigated the effects of a novel CB2 receptor agonist ((1S,4R)-2-(2,6-dimethoxy-4-(2-methyloctan-2-yl)phenyl)-7,7-dimethylbicyclo[2.2.1]hept-2-en-1-yl)methanol (HU-910) on liver injury induced by 1 h of ischaemia followed by 2, 6 or 24 h of reperfusion, using a well-established mouse model of segmental hepatic I/R. KEY RESULTS Displacement of [3H]CP55940 by HU-910 from specific binding sites in CHO cell membranes transfected with human CB2 or CB1 receptors (hCB1/2) yielded Ki values of 6 nM and 1.4 µM respectively. HU-910 inhibited forskolin-stimulated cyclic AMP production by hCB2 CHO cells (EC50= 162 nM) and yielded EC50 of 26.4 nM in [35S]GTPγS binding assays using hCB2 expressing CHO membranes. HU-910 given before ischaemia significantly attenuated levels of I/R-induced hepatic pro-inflammatory chemokines (CCL3 and CXCL2), TNF-α, inter-cellular adhesion molecule-1, neutrophil infiltration, oxidative stress and cell death. Some of the beneficial effect of HU-910 also persisted when given at the beginning of the reperfusion or 1 h after the ischaemic episode. Furthermore, HU-910 attenuated the bacterial endotoxin-triggered TNF-α production in isolated Kupffer cells and expression of adhesion molecules in primary human liver sinusoidal endothelial cells stimulated with TNF-α. Pretreatment with a CB2 receptor antagonist attenuated the protective effects of HU-910, while pretreatment with a CB1 antagonist tended to enhance them. CONCLUSION AND IMPLICATIONS HU-910 is a potent CB2 receptor agonist which may exert protective effects in various diseases associated with inflammation and tissue injury. LINKED ARTICLES This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7 PMID:21449982

Histological, morphometric, protein and gene expression analyses of rat retinas with ischaemia-reperfusion injury model treated with sildenafil citrate.

PubMed

Zanoni, Diogo S; Da Silva, Germana A; Ezra-Elia, Raaya; Carvalho, Márcio; Quitzan, Juliany G; Ofri, Ron; Laus, José L; Laufer-Amorim, Renee

2017-06-01

The aim of this study was to better understand the role of apoptosis in a retinal ischaemia-reperfusion injury model and to determine whether sildenafil citrate treatment can prevent retinal cell apoptosis. Thirty-six rats were divided into a control group (n = 6) and two experimentally induced ischaemia-reperfusion groups (7 and 21 days; n = 15 per group). The induced ischaemia-reperfusion groups were treated with sildenafil for 7 and 21 days (n = 10 per group), and 10 animals were treated with a placebo for the same period (n = 5 per group). Paracentesis of the anterior chamber was performed with a 30-G needle attached to a saline solution (0.9%) bag positioned at a height of 150 cm above the eye for 60 min. Intraocular pressure was measured by rebound tonometer (TonoVet ® ). The eyes were analysed by histology and morphometry, and by immunohistochemistry and qRT-PCR for expression of Caspase-7, Caspase-6, Caspase-9, Tnf-r2, Fas-l, Bcl-2 and Bax. Sildenafil-treated animals showed lower levels of histopathological changes (inflammatory, cellular and tissue) than their placebo-treated counterparts at both 7 and 21 days. The retinal ganglion cell layer (RGC) was preserved in the sildenafil groups (SG), with a cell count closer to control than in the placebo groups (PG). Caspase-7 expression was significantly higher in both treated groups at 7 days compared to controls. Gene expression levels in both treatment groups differed from the controls, but in SG Bax and Caspase-6 expression levels were similar to control animals. These results suggest that the main mechanism of retinal cell death in this model is apoptosis, as there is an increase in pro-apoptotic factors and decrease in the anti-apoptotic ones. Also, sildenafil seems to protect the retinal ganglion cell layer from apoptosis. Cell survival was evident in the histological and morphometric analyses, and sildenafil treatment had a protective effect in the apoptosis pathways, with gene expression levels in SG similar to the controls. © 2017 The Authors. International Journal of Experimental Pathology © 2017 International Journal of Experimental Pathology.

Assessing the magnitude and timing of anthropogenic warming of a shallow aquifer: example from Virginia Beach, USA

USGS Publications Warehouse

Eggleston, John R.; McCoy, Kurt J.

2015-01-01

Groundwater temperature measurements in a shallow coastal aquifer in Virginia Beach, Virginia, USA, suggest groundwater warming of +4.1 °C relative to deeper geothermal gradients. Observed warming is related to timing and depth of influence of two potential thermal drivers—atmospheric temperature increases and urbanization. Results indicate that up to 30 % of groundwater warming at the water table can be attributed to atmospheric warming while up to 70 % of warming can be attributed to urbanization. Groundwater temperature readings to 30-m depth correlate positively with percentage of impervious cover and negatively with percentage of tree canopy cover; thus, these two land-use metrics explain up to 70 % of warming at the water table. Analytical and numerical modeling results indicate that an average vertical groundwater temperature profile for the study area, constructed from repeat measurement at 11 locations over 15 months, is consistent with the timing of land-use change over the past century in Virginia Beach. The magnitude of human-induced warming at the water table (+4.1 °C) is twice the current seasonal temperature variation, indicating the potential for ecological impacts on wetlands and estuaries receiving groundwater discharge from shallow aquifers.

Warming trends: Adapting to nonlinear change

DOE PAGES

Jonko, Alexandra K.

2015-01-28

As atmospheric carbon dioxide concentrations rise, some regions are expected to warm more than others. Research suggests that whether warming will intensify or slow down over time also depends on location.

Enhanced decomposition of stable soil organic carbon and microbial catabolic potentials by long-term field warming

DOE PAGES

Feng, Wenting; Liang, Junyi; Hale, Lauren E.; ...

2017-06-09

Quantifying soil organic carbon (SOC) decomposition under warming is critical to predict carbon–climate feedbacks. According to the substrate regulating principle, SOC decomposition would decrease as labile SOC declines under field warming, but observations of SOC decomposition under warming do not always support this prediction. This discrepancy could result from varying changes in SOC components and soil microbial communities under warming. This study aimed to determine the decomposition of SOC components with different turnover times after subjected to long-term field warming and/or root exclusion to limit C input, and to test whether SOC decomposition is driven by substrate lability under warming.more » Taking advantage of a 12-year field warming experiment in a prairie, we assessed the decomposition of SOC components by incubating soils from control and warmed plots, with and without root exclusion for 3 years. We assayed SOC decomposition from these incubations by combining inverse modeling and microbial functional genes during decomposition with a metagenomic technique (GeoChip). The decomposition of SOC components with turnover times of years and decades, which contributed to 95% of total cumulative CO 2 respiration, was greater in soils from warmed plots. But the decomposition of labile SOC was similar in warmed plots compared to the control. The diversity of C-degradation microbial genes generally declined with time during the incubation in all treatments, suggesting shifts of microbial functional groups as substrate composition was changing. Compared to the control, soils from warmed plots showed significant increase in the signal intensities of microbial genes involved in degrading complex organic compounds, implying enhanced potential abilities of microbial catabolism. These are likely responsible for accelerated decomposition of SOC components with slow turnover rates. Overall, the shifted microbial community induced by long-term warming accelerates the decomposition of SOC components with slow turnover rates and thus amplify the positive feedback to climate change.« less

Enhanced decomposition of stable soil organic carbon and microbial catabolic potentials by long-term field warming

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feng, Wenting; Liang, Junyi; Hale, Lauren E.

Quantifying soil organic carbon (SOC) decomposition under warming is critical to predict carbon–climate feedbacks. According to the substrate regulating principle, SOC decomposition would decrease as labile SOC declines under field warming, but observations of SOC decomposition under warming do not always support this prediction. This discrepancy could result from varying changes in SOC components and soil microbial communities under warming. This study aimed to determine the decomposition of SOC components with different turnover times after subjected to long-term field warming and/or root exclusion to limit C input, and to test whether SOC decomposition is driven by substrate lability under warming.more » Taking advantage of a 12-year field warming experiment in a prairie, we assessed the decomposition of SOC components by incubating soils from control and warmed plots, with and without root exclusion for 3 years. We assayed SOC decomposition from these incubations by combining inverse modeling and microbial functional genes during decomposition with a metagenomic technique (GeoChip). The decomposition of SOC components with turnover times of years and decades, which contributed to 95% of total cumulative CO 2 respiration, was greater in soils from warmed plots. But the decomposition of labile SOC was similar in warmed plots compared to the control. The diversity of C-degradation microbial genes generally declined with time during the incubation in all treatments, suggesting shifts of microbial functional groups as substrate composition was changing. Compared to the control, soils from warmed plots showed significant increase in the signal intensities of microbial genes involved in degrading complex organic compounds, implying enhanced potential abilities of microbial catabolism. These are likely responsible for accelerated decomposition of SOC components with slow turnover rates. Overall, the shifted microbial community induced by long-term warming accelerates the decomposition of SOC components with slow turnover rates and thus amplify the positive feedback to climate change.« less

Enhanced decomposition of stable soil organic carbon and microbial catabolic potentials by long-term field warming.

PubMed

Feng, Wenting; Liang, Junyi; Hale, Lauren E; Jung, Chang Gyo; Chen, Ji; Zhou, Jizhong; Xu, Minggang; Yuan, Mengting; Wu, Liyou; Bracho, Rosvel; Pegoraro, Elaine; Schuur, Edward A G; Luo, Yiqi

2017-11-01

Quantifying soil organic carbon (SOC) decomposition under warming is critical to predict carbon-climate feedbacks. According to the substrate regulating principle, SOC decomposition would decrease as labile SOC declines under field warming, but observations of SOC decomposition under warming do not always support this prediction. This discrepancy could result from varying changes in SOC components and soil microbial communities under warming. This study aimed to determine the decomposition of SOC components with different turnover times after subjected to long-term field warming and/or root exclusion to limit C input, and to test whether SOC decomposition is driven by substrate lability under warming. Taking advantage of a 12-year field warming experiment in a prairie, we assessed the decomposition of SOC components by incubating soils from control and warmed plots, with and without root exclusion for 3 years. We assayed SOC decomposition from these incubations by combining inverse modeling and microbial functional genes during decomposition with a metagenomic technique (GeoChip). The decomposition of SOC components with turnover times of years and decades, which contributed to 95% of total cumulative CO 2 respiration, was greater in soils from warmed plots. But the decomposition of labile SOC was similar in warmed plots compared to the control. The diversity of C-degradation microbial genes generally declined with time during the incubation in all treatments, suggesting shifts of microbial functional groups as substrate composition was changing. Compared to the control, soils from warmed plots showed significant increase in the signal intensities of microbial genes involved in degrading complex organic compounds, implying enhanced potential abilities of microbial catabolism. These are likely responsible for accelerated decomposition of SOC components with slow turnover rates. Overall, the shifted microbial community induced by long-term warming accelerates the decomposition of SOC components with slow turnover rates and thus amplify the positive feedback to climate change. © 2017 John Wiley & Sons Ltd.

Warming and elevated CO2 lead to longer growing season in temperate grassland

USDA-ARS?s Scientific Manuscript database

Observational data over time suggest that as climate has warmed the growing season has lengthened, although experimental warming shortens early-growing species’ life cycles. Are other plant species living longer? We found that experimental warming in a temperate, semi-arid grassland led to earlier l...

Observed variations in U.S. frost timing linked to atmospheric circulation patterns

NASA Astrophysics Data System (ADS)

Strong, Courtenay; McCabe, Gregory J.

2017-05-01

Several studies document lengthening of the frost-free season within the conterminous United States (U.S.) over the past century, and report trends in spring and fall frost timing that could stem from hemispheric warming. In the absence of warming, theory and case studies link anomalous frost timing to atmospheric circulation anomalies. However, recent efforts to relate a century of observed changes in U.S. frost timing to various atmospheric circulations yielded only modest correlations, leaving the relative importance of circulation and warming unclear. Here, we objectively partition the U.S. into four regions and uncover atmospheric circulations that account for 25-48% of spring and fall-frost timing. These circulations appear responsive to historical warming, and they consistently account for more frost timing variability than hemispheric or regional temperature indices. Reliable projections of future variations in growing season length depend on the fidelity of these circulation patterns in global climate models.

Observed variations in U.S. frost timing linked to atmospheric circulation patterns

USGS Publications Warehouse

Strong, Courtenay; McCabe, Gregory J.

2017-01-01

Several studies document lengthening of the frost-free season within the conterminous United States (U.S.) over the past century, and report trends in spring and fall frost timing that could stem from hemispheric warming. In the absence of warming, theory and case studies link anomalous frost timing to atmospheric circulation anomalies. However, recent efforts to relate a century of observed changes in U.S. frost timing to various atmospheric circulations yielded only modest correlations, leaving the relative importance of circulation and warming unclear. Here, we objectively partition the U.S. into four regions and uncover atmospheric circulations that account for 25–48% of spring and fall-frost timing. These circulations appear responsive to historical warming, and they consistently account for more frost timing variability than hemispheric or regional temperature indices. Reliable projections of future variations in growing season length depend on the fidelity of these circulation patterns in global climate models.

Observed variations in U.S. frost timing linked to atmospheric circulation patterns.

PubMed

Strong, Courtenay; McCabe, Gregory J

2017-05-23

Several studies document lengthening of the frost-free season within the conterminous United States (U.S.) over the past century, and report trends in spring and fall frost timing that could stem from hemispheric warming. In the absence of warming, theory and case studies link anomalous frost timing to atmospheric circulation anomalies. However, recent efforts to relate a century of observed changes in U.S. frost timing to various atmospheric circulations yielded only modest correlations, leaving the relative importance of circulation and warming unclear. Here, we objectively partition the U.S. into four regions and uncover atmospheric circulations that account for 25-48% of spring and fall-frost timing. These circulations appear responsive to historical warming, and they consistently account for more frost timing variability than hemispheric or regional temperature indices. Reliable projections of future variations in growing season length depend on the fidelity of these circulation patterns in global climate models.

Adult mortality probability and nest predation rates explain parental effort in warming eggs with consequences for embryonic development time

USGS Publications Warehouse

Martin, Thomas E.; Oteyza, Juan C.; Boyce, Andy J.; Lloyd, Penn; Ton, Riccardo

2015-01-01

Parental behavior and effort vary extensively among species. Life-history theory suggests that age-specific mortality could cause this interspecific variation, but past tests have focused on fecundity as the measure of parental effort. Fecundity can cause costs of reproduction that confuse whether mortality is the cause or the consequence of parental effort. We focus on a trait, parental allocation of time and effort in warming embryos, that varies widely among species of diverse taxa and is not tied to fecundity. We conducted studies on songbirds of four continents and show that time spent warming eggs varies widely among species and latitudes and is not correlated with clutch size. Adult and offspring (nest) mortality explained most of the interspecific variation in time and effort that parents spend warming eggs, measured by average egg temperatures. Parental effort in warming eggs is important because embryonic temperature can influence embryonic development period and hence exposure time to predation risk. We show through correlative evidence and experimental swapping of embryos between species that parentally induced egg temperatures cause interspecific variation in embryonic development period. The strong association of age-specific mortality with parental effort in warming eggs and the subsequent effects on embryonic development time are unique results that can advance understanding of broad geographic patterns of life-history variation.

Robot-assisted partial nephrectomy (RAPN) for completely endophytic renal masses: a single institution experience.

PubMed

Autorino, Riccardo; Khalifeh, Ali; Laydner, Humberto; Samarasekera, Dinesh; Rizkala, Emad; Eyraud, Remi; Stein, Robert J; Haber, Georges-Pascal; Kaouk, Jihad H

2014-05-01

To analyse the outcomes of robot-assisted partial nephrectomy (RAPN) for completely endophytic renal tumours. Medical records of patients who had undergone RAPN for a completely endophytic (i.e. 3 points for the 'E' domain of the R.E.N.A.L. nephrometry score) enhancing renal mass at our Centre from 2006 to 2012 were retrieved from our prospectively maintained RAPN database and used for this analysis. Demographics, surgical and early postoperative outcomes were compared with those of patients with exophytic masses (i.e. 1 point for the 'E' domain) and those of patients with mesophytic masses (i.e. 2 points for the 'E' domain). In all, 65 patients (mean age 56 years; mean body mass index 29.4 kg/m(2) ; mean Charlson comorbidity index 3.2) were included in the study group, accounting for 16.7% of RAPN cases over the study period. The main surgical outcomes were: mean operative time 175 min, mean estimated blood loss 225 mL, and mean warm ischaemia time 21.7 min. Pathology showed a malignant histology in 48 cases (74%), mostly clear cell renal cell carcinoma. Two positive margins (3%) were found. Patients with a completely endophytic mass had smaller tumours on preoperative imaging (mean 2.6 vs 3.3 for mesophytic vs 3.7 cm for exophytic; P < 0.001), and higher overall R.E.N.A.L. score (mean 8.7 vs 7.6 vs 6.4; P < 0.001). There was a lower rate of unclamped cases in the endophytic group (3.1% vs 4.8% vs 18%; P < 0.001). There were no differences in intraoperative complications, length of hospital stay, positive margin rate, postoperative change in estimated glomerular filtration rate, given a similar length of follow-up (mean 12.6 vs 15.7 vs 14.5 months; P = 0.3). RAPN for completely intraparenchymal renal tumours can be safely and effectively performed in centres with significant robotic expertise, with surgical outcomes resembling those obtained in the general RAPN population. © 2013 The Authors. BJU International © 2013 BJU International.

Designing a warm-up protocol for elite bob-skeleton athletes.

PubMed

Cook, Christian; Holdcroft, Danny; Drawer, Scott; Kilduff, Liam P

2013-03-01

To investigate how different warm-ups influenced subsequent sled-pull sprint performance in Olympic-level bob-skeleton athletes as part of their preparation for the 2010 Winter Olympics. Three female and 3 male athletes performed 5 different randomized warm-ups of differing intensities, durations, and timing relative to subsequent testing, each 2 days apart, all repeated twice. After warm-ups, testing on a sled-pull sprint over 20 m, 3 repeats 3 min apart, took place. Performance testing showed improvement (P < .001, ES > 1.2) with both increasing intensity of warm-up and closeness of completion to testing, with 20-m sled sprinting being 0.1-0.25 s faster in higher-intensity protocols performed near testing In addition, supplementing the warm-ups by wearing of a light survival coat resulted in further performance improvement (P = .000, ES 1.8). Changing timing and intensity of warm-up and using an ancillary passive heat-retention device improved sprint performance in Olympic-level bob-skeleton athletes. Subsequent adoption of these on the competitive circuit was associated with a seasonal improvement in push times and was ultimately implemented in the 2010 Winter Olympics.

Core temperature changes and sprint performance of elite female soccer players after a 15-minute warm-up in a hot-humid environment.

PubMed

Somboonwong, Juraiporn; Chutimakul, Ladawan; Sanguanrungsirikul, Sompol

2015-01-01

Warm-up session should be modified according to the environmental conditions. However, there is limited evidence regarding the proper soccer warm-up time for female players in the heat. The purpose of this study was to examine the rise in core body temperature and the sprint performance after a 15-minute warm-up in a hot-humid environment using female soccer players during the different phases of their menstrual cycle. Thirteen eumenorrheic national female soccer players (aged 18.8 ± 1.3 years, (Equation is included in full-text article.)53.05 ± 6.66 ml·kg·min) performed a 15-minute warm-up protocol at an ambient temperature of 32.5 ± 1.6° C with a relative humidity of 53.6 ± 10.2% during their early follicular and midluteal phases of their cycle. The warm-up protocol is composed of jogging, skipping by moving the legs in various directions, and sprinting alternated with jogging, followed by a 45-minute recovery period. Rectal temperatures were recorded during the rest period and every 5 minutes throughout the warm-up and recovery phases of the study. Heart rate was monitored at rest and every 5 minutes during the warm-up. Forty-yard sprint time was assessed immediately after the completion of warm-up, which was later compared with the time at baseline. The value for the baseline was obtained at least 2 days before the experiment. During the early follicular and midluteal phases, the rectal temperatures obtained at the end of the warm-up period were significantly (p < 0.05) higher by 1.26° C (95% confidence interval [CI] = +0.46 to +2.06° C) and 1.18° C (95% CI = +0.53 to +1.83° C), whereas the heart rates increased to 153.67 ± 20.34 and 158.38 ± 15.19 b·min, respectively. After 20 minutes of the recovery period, the rectal temperature decreased by approximately 50%. The sprint times were significantly (p < 0.05) faster post-warm-up during both the early follicular (5.52 seconds; 95% CI = 5.43-5.60 seconds) and midluteal phases (5.51 seconds; 95% CI = 5.41-5.60 seconds) compared with the baseline time (5.66 seconds; 95% CI = 5.58-5.74 seconds). There were no significant differences in any parameters assessed after warm-up between the 2 phases. In conclusion, a 15-minute warm-up increased the core temperature by approximately 1° C and improved the 40-yd sprint time for elite female soccer players in a hot environment regardless of menstrual phase.

The effects of warmed intravenous fluids, combined warming (warmed intravenous fluids with humid-warm oxygen), and pethidine on the severity of shivering in general anesthesia patients in the recovery room

PubMed Central

Nasiri, Ahmad; Akbari, Ayob; Sharifzade, GholamReza; Derakhshan, Pooya

2015-01-01

Background: Shivering is a common complication of general and epidural anesthesia. Warming methods and many drugs are used for control of shivering in the recovery room. The present study is a randomized clinical trial aimed to investigate the effects of two interventions in comparison with pethidine which is the routine treatment on shivering in patients undergoing abdominal surgery with general anesthesia. Materials and Methods: Eighty-seven patients undergoing abdominal surgery by general anesthesia were randomly assigned to three groups (two intervention groups in comparison with pethidine as routine). Patients in warmed intravenous fluids group received pre-warmed Ringer serum (38°C), patients in combined warming group received pre-warmed Ringer serum (38°C) accompanied by humid-warm oxygen, and patients in pethidine group received intravenous pethidine routinely. The elapsed time of shivering and some hemodynamic parameters of the participants were assessed for 20 min postoperatively in the recovery room. Then the collected data were analyzed by software SPSS (v. 16) with the significance level being P < 0.05. Results: The mean of elapsed time in the warmed intravenous serum group, the combined warming group, and the pethidine group were 7 (1.5) min, 6 (1.5) min, and 2.8 (0.7) min, respectively, which was statistically significant (P < 0.05). The body temperatures in both combined warming and pethidine groups were increased significantly (P < 0.05). Conclusions: Combined warming can be effective in controlling postoperative shivering and body temperature increase. PMID:26793258

Effect of the timing of ice slurry ingestion for precooling on endurance exercise capacity in a warm environment.

PubMed

Takeshima, Keisuke; Onitsuka, Sumire; Xinyan, Zheng; Hasegawa, Hiroshi

2017-04-01

It has been demonstrated that precooling with ice slurry ingestion enhances endurance exercise capacity in the heat. However, no studies have yet evaluated the optimal timing of ice slurry ingestion for precooling. This study aimed to investigate the effects of varying the timing of ice slurry ingestion for precooling on endurance exercise capacity in a warm environment. Ten active male participants completed 3 experimental cycling trials to exhaustion at 55% peak power output (PPO) after 15min of warm-up at 30% PPO at 30°C and 80% relative humidity. Three experimental conditions were set: no ice slurry ingestion (CON), pre-warm-up ice slurry ingestion (-1°C; 7.5gkg -1 ) (PRE), and post-warm-up ice slurry ingestion (POST). Rectal and mean skin temperatures at the beginning of exercise in the POST condition (37.1±0.2°C, 33.8±0.9°C, respectively) were lower than those in the CON (37.5±0.3°C; P<0.001, 34.8±0.8°C; P<0.01, respectively) and PRE (37.4±0.2°C; P<0.01, 34.6±0.7°C; P<0.01, respectively) conditions. These reductions increased heat storage capacity and resulted in improved exercise capacity in the POST condition (60.2±8.7min) compared to that in the CON (52.0±11.9min; effect size [ES]=0.78) and PRE (56.9±10.4min; ES=0.34) conditions. Ice slurry ingestion after warm-up effectively reduced both rectal and skin temperatures and increased cycling time to exhaustion in a warm environment. Timing ice slurry ingestion to occur after warm-up may be effective for precooling in a warm environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

The rise of global warming skepticism: exploring affective image associations in the United States over time.

PubMed

Smith, Nicholas; Leiserowitz, Anthony

2012-06-01

This article explores how affective image associations to global warming have changed over time. Four nationally representative surveys of the American public were conducted between 2002 and 2010 to assess public global warming risk perceptions, policy preferences, and behavior. Affective images (positive or negative feelings and cognitive representations) were collected and content analyzed. The results demonstrate a large increase in "naysayer" associations, indicating extreme skepticism about the issue of climate change. Multiple regression analyses found that holistic affect and "naysayer" associations were more significant predictors of global warming risk perceptions than cultural worldviews or sociodemographic variables, including political party and ideology. The results demonstrate the important role affective imagery plays in judgment and decision-making processes, how these variables change over time, and how global warming is currently perceived by the American public. © 2012 Society for Risk Analysis.

Ipsilateral renal function preservation after robot-assisted partial nephrectomy (RAPN): an objective analysis using mercapto-acetyltriglycine (MAG3) renal scan data and volumetric assessment.

PubMed

Zargar, Homayoun; Akca, Oktay; Autorino, Riccardo; Brandao, Luis Felipe; Laydner, Humberto; Krishnan, Jayram; Samarasekera, Dinesh; Stein, Robert J; Kaouk, Jihad H

2015-05-01

To objectively assess ipsilateral renal function (IRF) preservation and factors influencing it after robot-assisted partial nephrectomy (RAPN). Our database was queried to identify patients who had undergone RAPN from 2007 to 2013 and had complete pre- and postoperative mercapto-acetyltriglycine (MAG3) renal scan assessment. The estimated glomerular filtration rate (eGFR) for the operated kidney was calculated by multiplying the percentage of contribution from the renal scan by the total eGFR. IRF preservation was defined as a ratio of the postoperative eGFR for the operated kidney to the preoperative eGFR for the operated kidney. The percentage of total eGFR preservation was calculated in the same manner (postoperative eGFR/preoperative eGFR × 100). The amount of healthy rim of renal parenchyma removed was assessed by deducting the volume of tumour from the volume of the PN specimen assessed on pathology. Multivariable linear regression was used for analysis. In all, 99 patients were included in the analysis. The overall median (interquartile range) total eGFR preservation and IRF preservation for the operated kidney was 83.83 (75.2-94.1)% and 72 (60.3-81)%, respectively (P < 0.01). On multivariable analysis, volume of healthy rim of renal parenchyma removed, warm ischaemia time (WIT) > 30 min, body mass index (BMI) and operated kidney preoperative eGFR were predictive of IRF preservation. Using total eGFR tends to overestimate the degree of renal function preservation after RAPN. This is particularly relevant when studying factors affecting functional outcomes after nephron-sparing surgery. IRF may be a more precise assessment method in this setting. Operated kidney baseline renal function, BMI, WIT >30 min, and amount of resected healthy renal parenchyma represent the factors with a significant impact on the IRF preservation. RAPN provides significant preservation of renal function as shown by objective assessment criteria. © 2014 The Authors. BJU International © 2014 BJU International.

Analysis of data from spacecraft (stratospheric warmings)

NASA Technical Reports Server (NTRS)

1974-01-01

The details of the stratospheric warming processes as to time, area, and intensity were established, and the warmings with other terrestrial and solar phenomena occurring at satellite platform altitudes, or observable from satellite platforms, were correlated. Links were sought between the perturbed upper atmosphere (mesosphere and thermosphere) and the stratosphere that might explain stratospheric warmings.

Predominant role of water in regulating the tree-growth response to diurnal asymmetric warmin

NASA Astrophysics Data System (ADS)

Chen, Z.; Xia, J.; Cui, E.

2017-12-01

Growth of the Northern Hemisphere trees is affected by diurnal asymmetric warming, which is generally considered to touch off carbon assimilation and increment of carbon storage. Asymmetric effects of diurnal warming on vegetation greenness were validated in previous researches, however, the effect of diurnal warming on wood tissue which stores most carbon of a whole plant is still unknown. Here, we combined ring-width index (RWI), remote sensing-based normalized difference vegetation index (NDVI) and climate datasets to detect the effects of daytime and night-time warming on vegetation growth, respectively. Our results indicate that daytime warming enhances NDVI but has neutral effect on tree woody growth over the Northern Hemisphere. Response of wood growth to daytime warming is linearly regulated by soil water availability. The underlying mechanism of different response of canopy and wood growth to daytime warming may attribute to the biomass change, that is, allocation to foliage tissues increased at the expense of wood tissue under warming and water-limited conditions. Night-time warming show neutral effects on NDVI and RWI over the Northern Hemisphere, and the neutral Tmin-NDVI correlations result from the non-linear mediation of soil water availability. Our results highlight the current greening trend under daytime warming does not mean higher carbon sink capacity, the warming-drying climate may impair the large carbon sink of global forests.

Simulated climate warming alters phenological synchrony between an outbreak insect herbivore and host trees.

PubMed

Schwartzberg, Ezra G; Jamieson, Mary A; Raffa, Kenneth F; Reich, Peter B; Montgomery, Rebecca A; Lindroth, Richard L

2014-07-01

As the world's climate warms, the phenologies of interacting organisms in seasonally cold environments may advance at differing rates, leading to alterations in phenological synchrony that can have important ecological consequences. For temperate and boreal species, the timing of early spring development plays a key role in plant-herbivore interactions and can influence insect performance, outbreak dynamics, and plant damage. We used a field-based, meso-scale free-air forest warming experiment (B4WarmED) to examine the effects of elevated temperature on the phenology and performance of forest tent caterpillar (Malacosoma disstria) in relation to the phenology of two host trees, aspen (Populus tremuloides) and birch (Betula papyrifera). Results of our 2-year study demonstrated that spring phenology advanced for both insects and trees, with experimentally manipulated increases in temperature of 1.7 and 3.4 °C. However, tree phenology advanced more than insect phenology, resulting in altered phenological synchrony. Specifically, we observed a decrease in the time interval between herbivore egg hatch and budbreak of aspen in both years and birch in one year. Moreover, warming decreased larval development time from egg hatch to pupation, but did not affect pupal mass. Larvae developed more quickly on aspen than birch, but pupal mass was not affected by host species. Our study reveals that warming-induced phenological shifts can alter the timing of ecological interactions across trophic levels. These findings illustrate one mechanism by which climate warming could mediate insect herbivore outbreaks, and also highlights the importance of climate change effects on trophic interactions.

Exploration of warm-up period in conceptual hydrological modelling

NASA Astrophysics Data System (ADS)

Kim, Kue Bum; Kwon, Hyun-Han; Han, Dawei

2018-01-01

One of the important issues in hydrological modelling is to specify the initial conditions of the catchment since it has a major impact on the response of the model. Although this issue should be a high priority among modelers, it has remained unaddressed by the community. The typical suggested warm-up period for the hydrological models has ranged from one to several years, which may lead to an underuse of data. The model warm-up is an adjustment process for the model to reach an 'optimal' state, where internal stores (e.g., soil moisture) move from the estimated initial condition to an 'optimal' state. This study explores the warm-up period of two conceptual hydrological models, HYMOD and IHACRES, in a southwestern England catchment. A series of hydrologic simulations were performed for different initial soil moisture conditions and different rainfall amounts to evaluate the sensitivity of the warm-up period. Evaluation of the results indicates that both initial wetness and rainfall amount affect the time required for model warm up, although it depends on the structure of the hydrological model. Approximately one and a half months are required for the model to warm up in HYMOD for our study catchment and climatic conditions. In addition, it requires less time to warm up under wetter initial conditions (i.e., saturated initial conditions). On the other hand, approximately six months is required for warm-up in IHACRES, and the wet or dry initial conditions have little effect on the warm-up period. Instead, the initial values that are close to the optimal value result in less warm-up time. These findings have implications for hydrologic model development, specifically in determining soil moisture initial conditions and warm-up periods to make full use of the available data, which is very important for catchments with short hydrological records.

Are patient specific meshes required for EIT head imaging?

PubMed

Jehl, Markus; Aristovich, Kirill; Faulkner, Mayo; Holder, David

2016-06-01

Head imaging with electrical impedance tomography (EIT) is usually done with time-differential measurements, to reduce time-invariant modelling errors. Previous research suggested that more accurate head models improved image quality, but no thorough analysis has been done on the required accuracy. We propose a novel pipeline for creation of precise head meshes from magnetic resonance imaging and computed tomography scans, which was applied to four different heads. Voltages were simulated on all four heads for perturbations of different magnitude, haemorrhage and ischaemia, in five different positions and for three levels of instrumentation noise. Statistical analysis showed that reconstructions on the correct mesh were on average 25% better than on the other meshes. However, the stroke detection rates were not improved. We conclude that a generic head mesh is sufficient for monitoring patients for secondary strokes following head trauma.

The impact of winter and spring temperatures on temperate tree budburst dates: results from an experimental climate manipulation.

PubMed

Fu, Yongshuo H; Campioli, Matteo; Deckmyn, Gaby; Janssens, Ivan A

2012-01-01

Budburst phenology is a key driver of ecosystem structure and functioning, and it is sensitive to global change. Both cold winter temperatures (chilling) and spring warming (forcing) are important for budburst. Future climate warming is expected to have a contrasting effect on chilling and forcing, and subsequently to have a non-linear effect on budburst timing. To clarify the different effects of warming during chilling and forcing phases of budburst phenology in deciduous trees, (i) we conducted a temperature manipulation experiment, with separate winter and spring warming treatments on well irrigated and fertilized saplings of beech, birch and oak, and (ii) we analyzed the observations with five temperature-based budburst models (Thermal Time model, Parallel model, Sequential model, Alternating model, and Unified model). The results show that both winter warming and spring warming significantly advanced budburst date, with the combination of winter plus spring warming accelerating budburst most. As expected, all three species were more sensitive to spring warming than to winter warming. Although the different chilling requirement, the warming sensitivity was not significantly different among the studied species. Model evaluation showed that both one- and two- phase models (without and with chilling, respectively) are able to accurately predict budburst. For beech, the Sequential model reproduced budburst dates best. For oak and birch, both Sequential model and the Thermal Time model yielded good fit with the data but the latter was slightly better in case of high parameter uncertainty. However, for late-flushing species, the Sequential model is likely be the most appropriate to predict budburst data in a future warmer climate.

Curcumin promotes cardiac repair and ameliorates cardiac dysfunction following myocardial infarction

PubMed Central

Wang, Ning-Ping; Wang, Zhang-Feng; Tootle, Stephanie; Philip, Tiji; Zhao, Zhi-Qing

2012-01-01

BACKGROUND AND PURPOSE Curcumin, the natural yellow pigment extracted from the rhizomes of the plant curcuma longa, has been demonstrated to exhibit a variety of potent beneficial effects, acting as an antioxidant, anti-inflammatory and anti-fibrotic. In this study we tested the hypothesis that curcumin attenuates maladaptive cardiac repair and improves cardiac function after ischaemia and reperfusion by reducing degradation of extracellular matrix (ECM) and inhibiting synthesis of collagens via TGFβ/Smad-mediated signalling pathway. EXPERIMENTAL APPROACH Sprague-Dawley rats were subjected to 45 min of ischaemia followed by 7, 21 and 42 days of reperfusion respectively. Curcumin was fed orally at a dose of 150 mg·kg−1·day−1 only during reperfusion. KEY RESULTS Curcumin reduced the level of malondialdehyde, inhibited activity of MMPs, preserved ECM from degradation and attenuated collagen deposition, as it reduced the extent of collagen-rich scar and increased mass of viable myocardium. In addition to reducing collagen synthesis and fibrosis in the ischaemic/reperfused myocardium, curcumin significantly down-regulated the expression of TGFβ1 and phospho-Smad2/3, and up-regulated Smad7 and also increased the population of α-smooth muscle actin expressing myofibroblasts within the infarcted myocardium relative to the control. Echocardiography showed it significantly improved left ventricular end-diastolic volume, stroke volume and ejection fraction. The wall thickness of the infarcted middle anterior septum in the curcumin group was also greater than that in the control group. CONCLUSION AND IMPLICATIONS Dietary curcumin is effective at inhibiting maladaptive cardiac repair and preserving cardiac function after ischaemia and reperfusion. Curcumin has potential as a treatment for patients who have had a heart attack. PMID:22823335

The impact of a focused vascular lower limb arterial duplex (F-VLAD) scan in management decisions for acute limb ischaemia.

PubMed

Normahani, Pasha; Aslam, Mohammed; Standfield, Nigel J; Jaffer, Usman

2017-01-01

To establish the diagnostic accuracy of a 'focused vascular lower limb arterial duplex scan (F-VLAD)' developed to facilitate rapid decision-making for acute limb ischaemia (ALI). Ten cases of ALI were identified from our patient database; clinical details, history and examination findings were extracted from the clinical notes. Original 'full' duplex ultrasound (DUS) pictorial reports were 're-formatted' to include only anatomical segments included in the 'F-VLAD' scan. The series of 10 reports were emailed to 1741 vascular surgeons. Each recipient received a random mixture of full and F-VLAD scans. Participants were asked regarding next step in management and confidence in decision-making (Likert scale; 1 strongly disagree, 5 strongly agree). The cases were again sent out to the same database and respondents were asked as to the cause of ischaemia (embolic or thrombosis). Eighty-one participants responded to the first survey and 43 participants to the second survey. Participants felt more confident making decisions regarding management using the full duplex report compared to the F-VLAD report (4 (3-4) vs 3 (2-4), median (IQR); p<0.001). However, there was no significant difference in diagnostic accuracy (differentiating embolus from thrombosis) when comparing the F-VLAD and full DUS reports (85.4% vs 88.3%; p=0.461). F-VLAD and 'full' DUS reports had comparable sensitivity (85.1% vs 86.8%), specificity (85.6% vs 89.2%),positive predictive value (PPV) (80.4% vs 81.9%) and negative predictive value (NPV) (89.2% vs 92.2%), respectively. The F-VLAD scan has comparable accuracy to a traditional full DUS in diagnosing the underlying aetiology of ALI. This may facilitate surgeon-performed point-of-care DUS.

Depressant effects of hypoxia and hypoglycaemia on neuro-effector transmission of guinea-pig intestine studied in vitro with a pharmacological model

PubMed Central

Corbett, A D; Lees, G M

1996-01-01

Since intermittent ischaemia may play an important role in the ætiology of Inflammatory Bowel Disease, particularly Crohn's Disease, a pharmacological model of neuronal ischaemia was applied to guinea-pig isolated intestinal preparations to mimic the acute effects of reduced blood flow on intestinal motility.Neuro-effector transmission and smooth muscle performance were examined in myenteric plexus-longitudinal muscle preparations of guinea-pig ileum exposed to sodium cyanide (NaCN), in order to inhibit oxidative phosphorylation, or to iodoacetic acid (IAA), to block glycolysis. Comparisons were made with the effects due to simple deprivation of oxygen or glucose.Depressions of cholinergic neuro-effector transmission induced by hypoxia or NaCN (effective concentration range 0.1–3 mM), given as separate treatments, singly or repetitively over 60–90 min, were apparent within 30 s and were reversible. The maximum inhibition was 90% and the IC50 for NaCN was 0.3 mM. A conspicuous component of these inhibitions was prejunctional.Non-cholinergic neuro-effector contractions were inhibited by up to 90% by anoxia or NaCN but recovery was incomplete and slower than with cholinergic contractions.Glucose-free solutions also caused a reversible failure of cholinergic neuro-effector transmission but of slower onset. In contrast, IAA (0.06–1 mM) abolished contractions irreversibly, apparently by a direct depressant effect on smooth muscle contraction. Unlike NaCN, IAA caused an initial potentiation of electrically-induced contractions, partly by a prejunctional potentiation of cholinergic neuro-effector transmission.It is concluded that a disruption of intestinal activity in pathological conditions associated with intestinal ischaemia may result from disturbances in the function of enteric neurones. PMID:9117084

No effect of a homoeopathic combination of Arnica montana and Bryonia alba on bleeding, inflammation, and ischaemia after aortic valve surgery

PubMed Central

Cornu, Catherine; Joseph, Pierre; Gaillard, Ségolène; Bauer, Christian; Vedrinne, Catherine; Bissery, Alvine; Melot, Ghislaine; Bossard, Nadine; Belon, Philippe; Lehot, Jean-Jacques

2010-01-01

AIMS Arnica montana is a popular homoeopathic treatment with potential haemostatic and anti-inflammatory properties. A homoeopathic combination of A. montana and Bryonia alba was used in aortic valve surgery to evaluate its effectiveness in reducing bleeding, inflammation, pain and myocardial ischaemia. METHODS One day before surgery, 92 adult patients were randomly assigned to a double-blind parallel trial with either homoeopathic granules or a matching placebo until 4 days after surgery. The primary outcome was the volume of blood/liquid in the drains at their removal. The secondary outcomes included postoperative blood/liquid losses at 12 and 24 h as well as C-reactive protein (CRP), pain, temperature and plasma troponin Ic. RESULTS At 12 h and 24 h after surgery, then at drain removal, blood losses in homoeopathy and placebo groups were not statistically significant (362 ± 218, 520 ± 269 and 640 ± 297 ml vs. 456 ± 440, 620 ± 477 and 796 ± 717 ml; P= 0.19, 0.23 and 0.35, respectively). The statistical modelling did not show significantly different patterns of CRP, troponin and body temperature changes or of pain perception. The number of transfused packed red cells was not significantly different either (P= 0.58). Two patients from each group died during the study period and the number of serious adverse events was not statistically different (six in homoeopathy vs. 10 in placebo groups; Fisher's exact test P= 0.41). CONCLUSIONS In the study setting, there was no evidence of effects of A. montana and B. alba combination on bleeding, inflammation, pain or myocardial ischaemia. PMID:20233176

The inhibitor of 20-HETE synthesis, TS-011, improves cerebral microcirculatory autoregulation impaired by middle cerebral artery occlusion in mice.

PubMed

Marumo, Toshiyuki; Eto, Kei; Wake, Hiroaki; Omura, Tomohiro; Nabekura, Junichi

2010-11-01

20-Hydroxyeicosatetraenoic acid is a potent vasoconstrictor that contributes to cerebral ischaemia. An inhibitor of 20-Hydroxyeicosatetraenoic acid synthesis, TS-011, reduces infarct volume and improves neurological deficits in animal stroke models. However, little is known about how TS-011 affects the microvessels in ischaemic brain. Here, we investigated the effect of TS-011 on microvessels after cerebral ischaemia. TS-011 (0.3 mg·kg(-1) ) or a vehicle was infused intravenously for 1 h every 6 h in a mouse model of stroke, induced by transient occlusion of the middle cerebral artery occlusion following photothrombosis. The cerebral blood flow velocity and the vascular perfusion area of the peri-infarct microvessels were measured using in vivo two-photon imaging. The cerebral blood flow velocities in the peri-infarct microvessels decreased at 1 and 7 h after reperfusion, followed by an increase at 24 h after reperfusion in the vehicle-treated mice. We found that TS-011 significantly inhibited both the decrease and the increase in the blood flow velocities in the peri-infarct microvessels seen in the vehicle-treated mice after reperfusion. In addition, TS-011 significantly inhibited the reduction in the microvascular perfusion area after reperfusion, compared with the vehicle-treated group. Moreover, TS-011 significantly reduced the infarct volume by 40% at 72 h after middle cerebral artery occlusion. These findings demonstrated that infusion of TS-011 improved defects in the autoregulation of peri-infarct microcirculation and reduced the infarct volume. Our results could be relevant to the treatment of cerebral ischaemia. © 2010 The Authors. British Journal of Pharmacology © 2010 The British Pharmacological Society.

[Mesenteric flow in an experimental model of ischaemia-reperfusion in rats].

PubMed

Cáceres, F; Castañon, M; Lerena, J; Cusi, V; Badosa, J; Morales, L

2014-03-01

Maintained acute occlusion followed by reperfusion of the superior mesenteric artery (SMA) in a few hours can trigger irreversible bowel damage. The aim of the study was to determine the changes in mesenteric flow measured by colour Doppler Ultrasound and correlating with histological lesions in an experimental model of ischaemia-reperfusion. Three groups of Sprague-Dawley 17 day-old rats were studied (control, ischemia and reperfusion). The model used was ischaemia-reperfusion over the SMA. Intra-abdominal ultrasound was then performed. The parameters recorded were: Maximum systolic velocity (MSV), pulsatility index (PI), resistance (RI) and systole-diastole (S/D). The histological variables were: intestinal lesion (Wallace/Keenan-Chiu scale), morphometrics (mean villus height [MVH]), and goblet cells. The Spearman (rs) correlation was used. The MSV in the reperfusion group was 74.3 cm/s, the PI 7.33 and S/D 25.75 in the SMA, which were higher than the controls (41.35 cm/s; 3.12 and 12.45, respectively). A direct association (P<.01) was found between MSV, PI and S/D regarding: Wallace/Kennan scoring system (rs = 0.655; rs = 0.593; rs = 0.63) and the Chiu (rs = 0.569; rs = 0.522; rs = 0.47). While the correlation was the reverse (P<.01) when associated with the MVH (rs = -0,495; rs = -0,452; rs = -0,459) and goblet cells of the colon (rs = -0,525; rs = -0,45; rs = -0,518). The reperfusion phase increased mesenteric flow expressed by the MSV and PI and could significantly predict the potential bowel damage at macroscopic and microscopic level. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Ischaemia-reperfusion injury in orthotopic mouse lung transplants - a scanning electron microscopy study.

PubMed

Draenert, Alice; Marquardt, Klaus; Inci, Ilhan; Soltermann, Alex; Weder, Walter; Jungraithmayr, Wolfgang

2011-02-01

Lung ischaemia-reperfusion (I/R) injury remains a major cause of graft failure in lung transplantation (Tx). With the implementation of orthotopic lung Tx in mice, a physiological model on the base of a perfused and ventilated graft became available for the investigation of I/R injury. Using the scanning electron microscopy (SEM) technique, we here present an analysis of early and late morphological changes of pulmonary I/R injury. Syngeneic lungs were orthotopically transplanted between C57BL/6 mice. Grafts were exposed to 2 h of cold ischaemia. Transplants and right lungs were examined by SEM with corresponding haematoxylin-eosin histology 30 min and 4 h after reperfusion. Thirty minutes after reperfusion, the alveolar surface of transplants showed a discontinued lining of surfactant, while the lining of the non-transplanted lung was normal. Within the graft, leucocytes displayed an irregular surface with development of pseudopodia, and microvilli were detected on the membrane of pneumocytes. At 4 h after reperfusion, leucocytes significantly increased in numbers within the alveolar space. Also, the number of microvilli on pneumocytes increased significantly. Similar to these, the endothelium of vessels increasingly developed microvilli from 30 min towards 4 h after reperfusion. The airways of transplanted grafts showed mild changes with thickening of the bronchial epithelium and a destruction of kinocilia. Taken together, SEM detects pathological events of I/R that are previously not described in normal histology. These findings may influence the interpretation of studies investigating the I/R injury in the mouse model of lung Tx. © 2011 The Authors. International Journal of Experimental Pathology © 2011 International Journal of Experimental Pathology.

Controlled lung reperfusion to reduce pulmonary ischaemia/reperfusion injury after cardiopulmonary bypass in a porcine model.

PubMed

Slottosch, Ingo; Liakopoulos, Oliver; Kuhn, Elmar; Deppe, Antje; Lopez-Pastorini, Alberto; Schwarz, David; Neef, Klaus; Choi, Yeong-Hoon; Sterner-Kock, Anja; Jung, Kristina; Mühlfeld, Christian; Wahlers, Thorsten

2014-12-01

Ischaemia/reperfusion (I/R) injury of the lungs contributes to pulmonary dysfunction after cardiac surgery with cardiopulmonary bypass (CPB), leading to increased morbidity and mortality of patients. This study investigated the value of controlled lung reperfusion strategies on lung ischaemia-reperfusion injury in a porcine CPB model. Pigs were subjected to routine CPB for 120 min with 60 min of blood cardioplegic cardiac arrest (CCA). Following CCA, the uncontrolled reperfusion (UR, n = 6) group was conventionally weaned from CPB. Two groups underwent controlled lung reperfusion strategies (CR group: controlled reperfusion conditions, n = 6; MR group: controlled reperfusion conditions and modified reperfusate, n = 6) via the pulmonary artery before CPB weaning. Sham-operated pigs (n = 7) served as controls. Animals were followed up until 4 h after CPB. Pulmonary function, haemodynamics, markers of inflammation, endothelial injury and oxidative stress as well as morphological lung alterations were analysed. CPB (UR group) induced deterioration of pulmonary function (lung mechanics, oxygenation index and lung oedema). Also, controlled lung reperfusion groups (CR and MR) presented with pulmonary dysfunction after CPB. However, compared with UR, controlled lung reperfusion strategies (CR and MR) improved lung mechanics and reduced markers of oxidative stress, but without alteration of haemodynamics, oxygenation, inflammation, endothelial injury and lung morphology. Both controlled reperfusion groups were similar without relevant differences. Controlled lung reperfusion strategies attenuated a decrease in lung mechanics and an increase in oxidative stress, indicating an influence on CPB-related pulmonary injury. However, they failed to avoid completely CPB-related lung injury, implying the need for additional strategies given the multifactorial pathophysiology of postoperative pulmonary dysfunction. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Effects and interaction, of cariporide and preconditioning on cardiac arrhythmias and infarction in rat in vivo

PubMed Central

Aye, Nu Nu; Komori, Sadayoshi; Hashimoto, Keitaro

1999-01-01

Although Na+-H+ exchange (NHE) inhibitors are reported to protect the myocardium against ischaemic injury, NHE activation has also been proposed as a potential mechanism of ischaemic preconditioning-induced protection. This study was performed to test any modifiable effect of cariporide, an NHE inhibitor, on cardioprotective effects of preconditioning.Anaesthetized rats were subjected to 30 min of coronary artery occlusion and 150 min of reperfusion. The preconditioning (PC) was induced by 3 min of ischaemia and 10 min of reperfusion (1PC) or three episodes of 3 min ischaemia and 5 min reperfusion (3PC). Cariporide (0.3 mg kg−1) an NHE inhibitor, was administered 30 min (cari(30)) or 45 min (cari(45)) before coronary ligation (n=8–11 for each group).Ventricular arrhythmias during 30 min ischaemia and infarct size (measured by triphenyltetrazolium (TTC) and expressed as a per cent area at risk (%AAR)) were determined. Cari(30) reduced ventricular fibrillation (VF) incidence and infarct size (from 45 to 0% and 34±4 to 9±2%; each P<0.05), whereas cari(45) did not. Likewise, 3PC reduced these variables (to 0% and 10±2%; P<0.05 in each case) whereas 1PC did not. Moreover, subthreshold preconditioning (1PC) and cariporide (cari(45)), when combined, reduced VF incidence and infarct size (to 0% and 15+3%; each P<0.05).In conclusion, changes in NHE activity do not seem to be responsible for the cardioprotective action of ischaemic preconditioning. Protective effects of NHE inhibition and subthreshold preconditioning appear to act additively. PMID:10433514

Neuroprotective and anticonvulsant effects of EGIS-8332, a non-competitive AMPA receptor antagonist, in a range of animal models

PubMed Central

Gigler, G; Móricz, K; ágoston, M; Simó, A; Albert, M; Benedek, A; Kapus, G; Kertész, S; Vegh, M; Barkóczy, J; Markó, B; Szabó, G; Matucz, É; Gacsályi, I; Lévay, G; Hársing, L G; Szénási, G

2007-01-01

Background and purpose: Blockade of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors is a good treatment option for a variety of central nervous system disorders. The present study evaluated the neuroprotective and anticonvulsant effects of EGIS-8332, a non-competitive AMPA receptor antagonist, as a potential drug candidate. Experimental approach: AMPA antagonist effects of EGIS-8332 were measured using patch-clamp techniques. Neuroprotective and anticonvulsant effects of EGIS-8332 were evaluated in various experimental models, relative to those of GYKI 53405. Key results: EGIS-8332 inhibited AMPA currents in rat cerebellar Purkinje cells and inhibited the AMPA- and quisqualate-induced excitotoxicity in primary cultures of telencephalon neurons (IC50=5.1-9.0 μM), in vitro. Good anticonvulsant actions were obtained in maximal electroshock-, sound- and chemically-induced seizures (range of ED50=1.4-14.0 mg kg−1 i.p.) in mice. Four days after transient global cerebral ischaemia, EGIS-8332 decreased neuronal loss in the hippocampal CA1 area in gerbils and rats. EGIS-8332 dose-dependently reduced cerebral infarct size after permanent middle cerebral artery occlusion in mice and rats (minimum effective dose=3 mg kg−1 i.p.). Side effects of EGIS-8332 emerged much above its pharmacologically active doses. A tendency for better efficacy of GYKI 53405 than that of EGIS-8332 was observed in anticonvulsant tests that reached statistical significance in few cases, while the contrary was perceived in cerebral ischaemia tests. Conclusions and implications: EGIS-8332 seems suitable for further development for the treatment of epilepsy, ischaemia and stroke based on its efficacy in a variety of experimental disease models, and on its low side effect potential. PMID:17603549

Polydeoxyribonucleotides and nitric oxide release from guinea-pig hearts during ischaemia and reperfusion.

PubMed Central

Masini, E.; Lupini, M.; Mugnai, L.; Raspanti, S.; Mannaioni, P. F.

1995-01-01

1. Two polydeoxyribonucleotides, produced by the controlled hydrolysis of DNA of mammalian lung (defibrotide and its lower molecular weight fraction, P.O. 085 DV), were studied for their ability to modify the release of nitrite and the coronary flow in perfusates collected from isolated, normally perfused hearts of guinea-pigs and from hearts subjected to regional ischaemia and reperfusion. 2. In guinea-pig normally perfused hearts, both defibrotide (DFT) and its fraction, P.O. 085 DV, increase the amount of nitrite appearing in perfusates in a concentration-dependent fashion. At the highest concentration studied (10(-6) M), P.O. 085 DV was more effective than DFT. A concomitant increase in the coronary flow was observed. 3. The increase in nitrite in perfusates and the increase in coronary flow induced by both DFT and P.O. 085 DV were significantly reduced by NG-monomethyl-L-arginine (L-NMMA, 10(-4) M), an inhibitor of nitric oxide synthase (NOS). 4. The endothelium-dependent vasodilator, acetylcholine (ACh), enhances the formation of nitrite and the coronary flow. Both the increase in coronary flow and in the formation of nitrite were significantly reduced by L-NMMA (10(-4) M). 5. In guinea-pig hearts subjected to ischaemia and reperfusion, the effect of both compounds in increasing the amount of nitrite in perfusates was more evident and more pronounced with P.O. 085 DV. 6. Reperfusion-induced arrhythmias were significantly reduced by both compounds to the extent of complete protection afforded by compound P.O. 085 DV. 7. The cardioprotective and antiarrhythmic effects of DFT and P.O. 085 DV are discussed. PMID:7582482

Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS

PubMed Central

Gaude, Edoardo; Aksentijević, Dunja; Sundier, Stephanie Y.; Robb, Ellen L.; Logan, Angela; Nadtochiy, Sergiy M.; Ord, Emily N. J.; Smith, Anthony C.; Eyassu, Filmon; Shirley, Rachel; Hu, Chou-Hui; Dare, Anna J.; James, Andrew M.; Rogatti, Sebastian; Hartley, Richard C.; Eaton, Simon; Costa, Ana S.H.; Brookes, Paul S.; Davidson, Sean M.; Duchen, Michael R.; Saeb-Parsy, Kourosh; Shattock, Michael J.; Robinson, Alan J.; Work, Lorraine M.; Frezza, Christian; Krieg, Thomas; Murphy, Michael P.

2014-01-01

Ischaemia-reperfusion (IR) injury occurs when blood supply to an organ is disrupted and then restored, and underlies many disorders, notably heart attack and stroke. While reperfusion of ischaemic tissue is essential for survival, it also initiates oxidative damage, cell death, and aberrant immune responses through generation of mitochondrial reactive oxygen species (ROS)1-5. Although mitochondrial ROS production in IR is established, it has generally been considered a non-specific response to reperfusion1,3. Here, we developed a comparative in vivo metabolomic analysis and unexpectedly identified widely conserved metabolic pathways responsible for mitochondrial ROS production during IR. We showed that selective accumulation of the citric acid cycle (CAC) intermediate succinate is a universal metabolic signature of ischaemia in a range of tissues and is responsible for mitochondrial ROS production during reperfusion. Ischaemic succinate accumulation arises from reversal of succinate dehydrogenase (SDH), which in turn is driven by fumarate overflow from purine nucleotide breakdown and partial reversal of the malate/aspartate shuttle. Upon reperfusion, the accumulated succinate is rapidly re-oxidised by SDH, driving extensive ROS generation by reverse electron transport (RET) at mitochondrial complex I. Decreasing ischaemic succinate accumulation by pharmacological inhibition is sufficient to ameliorate in vivo IR injury in murine models of heart attack and stroke. Thus, we have identified a conserved metabolic response of tissues to ischaemia and reperfusion that unifies many hitherto unconnected aspects of IR injury. Furthermore, these findings reveal a novel pathway for metabolic control of ROS production in vivo, while demonstrating that inhibition of ischaemic succinate accumulation and its oxidation upon subsequent reperfusion is a potential therapeutic target to decrease IR injury in a range of pathologies. PMID:25383517

Revascularization with percutaneous coronary intervention does not affect androgen status in males with chronic stable angina pectoris.

PubMed

Gosai, J N; Charalampidis, P; Nikolaidou, T; Parviz, Y; Morris, P D; Channer, K S; Jones, T H; Grech, E D

2016-05-01

There is a clear association between low serum testosterone and coronary artery disease (CAD) in men. Hypotestosteronaemia is associated with accelerated atherosclerosis and a quarter of men with CAD are biochemically hypogonadal. Amongst those with CAD, hypotestosteronaemia is associated with increased mortality. Testosterone vasodilates coronary arteries, and exogenous testosterone reduces ischaemia. Whether hypotestosteronaemia is a cause or a consequence of CAD remains unanswered. The aim of this prospective observational study was to investigate whether coronary revascularization affected androgen status in men with stable angina pectoris. Twenty five men (mean age 62.7, SD 9.18) with angiographically significant CAD and symptomatic angina underwent full coronary revascularization by percutaneous coronary intervention. Androgen status and symptoms of angina, stress, depression and sexual function were assessed before, and at one and 6 months after the coronary revascularization. All patients underwent complete revascularization which was associated with a significant reduction in angina symptoms and ischaemia. No significant difference was seen in total testosterone (11.33 nmol/L baseline; 12.56, 1 month post; 13.04 at 6 months; p = 0.08). A significant and sustained rise in sex hormone-binding globulin was seen (33.99 nm/L baseline; 36.11 nm/L 1 month post PCI; 37.94 nm/L at 6 months; p = 0.03) Overall, there was no significant alteration in any other marker of androgen status including free testosterone or bioavailable testosterone. There was no change in symptoms of anxiety, depression or sexual function. Coronary revascularization has no sustained effect on androgen status. This supports the hypothesis that hypotestosteronaemia is not a consequence of angina pectoris or myocardial ischaemia. © 2016 American Society of Andrology and European Academy of Andrology.

Effect of spinal cord stimulation on myocardial perfusion reserve in patients with refractory angina pectoris.

PubMed

Saraste, Antti; Ukkonen, Heikki; Varis, Antti; Vasankari, Tuija; Tunturi, Satu; Taittonen, Markku; Rautakorpi, Pirkka; Luotolahti, Matti; Airaksinen, K E Juhani; Knuuti, Juhani

2015-04-01

Epidural spinal cord stimulation (SCS) provides symptom relief in refractory angina pectoris, but its mechanism of action remains incompletely understood. We studied effects of short-term SCS therapy on myocardial ischaemia tolerance, myocardial perfusion reserve (MPR), and endothelium-mediated vasodilatation induced by cold pressor test (CPT) in patients with refractory angina pectoris. We prospectively recruited 18 patients with refractory angina pectoris and studied them after implantation of SCS device at baseline before starting the therapy and after 3 weeks of continuous SCS therapy. Myocardial ischaemia was evaluated by dobutamine stress echocardiography. Global and regional myocardial blood flow (MBF) were measured using positron emission tomography and (15)O-water at rest, during adenosine stress, and in response to CPT. Systemic haemodynamics were comparable before and after 3 weeks of SCS at rest, during adenosine stress and during CPT. Appearance of angina pectoris induced by dobutamine stress was delayed after SCS therapy. Global MPR increased (P = 0.02) from 1.7 ± 0.6 at baseline to 2.0 ± 0.6 after 3-week SCS therapy. This was associated with a significant reduction in global MBF at rest and increase in MBF induced by adenosine in the ischaemic regions. Global MBF response to CPT was improved after SCS (0.27 ± 0.20 vs. 0.40 ± 0.15, P = 0.03). Short-term SCS therapy improved myocardial ischaemia tolerance, absolute MPR, and endothelium-mediated vasomotor function in refractory angina pectoris, indicating that this therapy can alleviate myocardial perfusion abnormalities in advanced CAD. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

NDUFA4L2 protects against ischaemia/reperfusion-induced cardiomyocyte apoptosis and mitochondrial dysfunction by inhibiting complex I.

PubMed

Li, Jianhua; Bai, Caiyan; Guo, Junxia; Liang, Wanqian; Long, Jingning

2017-07-01

Myocardial ischaemia/reperfusion (I/R) injury may cause the apoptosis of cardiomyocytes as well as mitochondrial dysfunction. The aims of the present study were to investigate whether NADH dehydrogenase 1 alpha subcomplex subunit 4-like 2 (NDUFA4L2) on myocardial ischaemia-reperfusion (I/R) injury and the underlying molecular mechanism. The hypoxia-reperfusion (H/R) model was established in vitro using H9c2 cells to simulate I/R injury. NDUFA4L2 and complex I expression levels were detected using RT-PCR and western blot. The apoptosis of H9c2 cells was evaluated by flow cytometry and the expression of Bax and Bcl-2 was detected by western blot. The mitochondrial function was assessed by ATP concentration, mPTP opening and cytochrome c (cyto C) expression. Our data indicated that NDUFA4L2 expression was significantly down-regulated in myocardial H/R injury. Overexpression of NDUFA4L2 led to a dramatic prevention of H/R-induced apoptosis accompanied by a decrease in the expression of Bax and an increase in the expression of Bcl-2. Meanwhile, augmentation of NDUFA4L2 dramatically prevented mitochondrial dysfunction caused by H/R as reflecting in the increased ATP concentration, delayed mPTP opening, as well as down-regulated cyto C expression. Moreover, complex I activation was heightened and negatively regulated by NDUFA4L2. Silencing complex I conspicuously attenuated cell apoptosis and mitochondrial dysfunction. Taken together, our findings demonstrated that NDUFA4L2 protects against H/R injury by preventing myocardium apoptosis and mitochondrial dysfunction via the complex I, and may be a potential therapeutic approach for attenuating myocardial I/R injury. © 2017 John Wiley & Sons Australia, Ltd.

Amelioration of renal ischaemia-reperfusion injury by liposomal delivery of curcumin to renal tubular epithelial and antigen-presenting cells.

PubMed

Rogers, N M; Stephenson, M D; Kitching, A R; Horowitz, J D; Coates, P T H

2012-05-01

Renal ischaemia-reperfusion (IR) injury is an inevitable consequence of renal transplantation, causing significant graft injury, increasing the risk of rejection and contributing to poor long-term graft outcome. Renal injury is mediated by cytokine and chemokine synthesis, inflammation and oxidative stress resulting from activation of the NF-κB pathway. We utilized liposomal incorporation of a potent inhibitor of the NF-κB pathway, curcumin, to target delivery to renal tubular epithelial and antigen-presenting cells. Liposomes containing curcumin were administered before bilateral renal ischaemia in C57/B6 mice, with subsequent reperfusion. Renal function was assessed from plasma levels of urea and creatinine, 4 and 24 h after reperfusion. Renal tissue was examined for NF-κB activity and oxidative stress (histology, immunostaining) and for apoptosis (TUNEL). Cytokines and chemokines were measured by RT-PCR and Western blotting. Liposomal curcumin significantly improved serum creatinine, reduced histological injury and cellular apoptosis and lowered Toll-like receptor-4, heat shock protein-70 and TNF-α mRNA expression. Liposomal curcumin also reduced neutrophil infiltration and diminished inflammatory chemokine expression. Curcumin liposomes reduced intracellular superoxide generation and increased superoxide dismutase levels, decreased inducible NOS mRNA expression and 3-nitrotyrosine staining consistent with limitations in nitrosative stress and inhibited renal tubular mRNA and protein expression of thioredoxin-interacting protein. These actions of curcumin were mediated by inhibition of NF-κB, MAPK and phospho-S6 ribosomal protein. Liposomal delivery of curcumin promoted effective, targeted delivery of this non-toxic compound that provided cytoprotection via anti-inflammatory and multiple antioxidant mechanisms following renal IR injury. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Epigenomic and transcriptomic approaches in the post-genomic era: path to novel targets for diagnosis and therapy of the ischaemic heart? Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart

PubMed Central

Perrino, Cinzia; Barabási, Albert-Laszló; Condorelli, Gianluigi; Davidson, Sean Michael; De Windt, Leon; Dimmeler, Stefanie; Engel, Felix Benedikt; Hausenloy, Derek John; Hill, Joseph Addison; Van Laake, Linda Wilhelmina; Lecour, Sandrine; Leor, Jonathan; Madonna, Rosalinda; Mayr, Manuel; Prunier, Fabrice; Sluijter, Joost Petrus Geradus; Schulz, Rainer; Thum, Thomas; Ytrehus, Kirsti

2017-01-01

Despite advances in myocardial reperfusion therapies, acute myocardial ischaemia/reperfusion injury and consequent ischaemic heart failure represent the number one cause of morbidity and mortality in industrialized societies. Although different therapeutic interventions have been shown beneficial in preclinical settings, an effective cardioprotective or regenerative therapy has yet to be successfully introduced in the clinical arena. Given the complex pathophysiology of the ischaemic heart, large scale, unbiased, global approaches capable of identifying multiple branches of the signalling networks activated in the ischaemic/reperfused heart might be more successful in the search for novel diagnostic or therapeutic targets. High-throughput techniques allow high-resolution, genome-wide investigation of genetic variants, epigenetic modifications, and associated gene expression profiles. Platforms such as proteomics and metabolomics (not described here in detail) also offer simultaneous readouts of hundreds of proteins and metabolites. Isolated omics analyses usually provide Big Data requiring large data storage, advanced computational resources and complex bioinformatics tools. The possibility of integrating different omics approaches gives new hope to better understand the molecular circuitry activated by myocardial ischaemia, putting it in the context of the human ‘diseasome’. Since modifications of cardiac gene expression have been consistently linked to pathophysiology of the ischaemic heart, the integration of epigenomic and transcriptomic data seems a promising approach to identify crucial disease networks. Thus, the scope of this Position Paper will be to highlight potentials and limitations of these approaches, and to provide recommendations to optimize the search for novel diagnostic or therapeutic targets for acute ischaemia/reperfusion injury and ischaemic heart failure in the post-genomic era. PMID:28460026

Combined therapy for critical limb ischaemia: Biomimetic PLGA microcarriers potentiates the pro-angiogenic effect of adipose tissue stromal vascular fraction cells.

PubMed

Hoareau, Laurence; Fouchet, Florian; Planesse, Cynthia; Mirbeau, Sophie; Sindji, Laurence; Delay, Emmanuel; Roche, Régis; Montero-Menei, Claudia N; Festy, Franck

2018-06-01

We propose a regenerative solution in the treatment of critical limb ischaemia (CLI). Poly-lactic/glycolic acid microcarriers were prepared and coated with laminin to be sterilized through γ-irradiation of 25 kGy at low temperature. Stromal vascular fraction (SVF) cells were extracted through enzymatic digestion of adipose tissue. Streptozotocin-induced diabetic mice underwent arteriotomy and received an administration of SVF cells combined or not with biomimetic microcarriers. Functional evaluation of the ischaemic limb was then reported, and tissue reperfusion was evaluated through fluorescence molecular tomography. Microcarriers were stable and functional after γ-irradiation until at least 12 months of storage. Mice that received an injection of SVF cells in the ischaemic limb have 22% of supplementary blood supply within this limb 7 days after surgery compared with vehicle, whereas no difference was observed at Day 14. With the combined therapy, the improvement of blood flow is significantly higher compared with vehicle, of about 31% at Day 7 and of about 11% at Day 14. Injection of SVF cells induces a significant 27% decrease of necrosis compared with vehicle. This effect is more important when SVF cells were mixed with biomimetic microcarriers: -37% compared with control. Although SVF cells injection leads to a non-significant 22% proprioception recovery, the combined therapy induces a significant recovery of about 27% compared with vehicle. We show that the combination of SVF cells from adipose tissue with laminin-coated poly-lactic/glycolic acid microcarriers is efficient for critical limb ischaemia therapy in a diabetic mouse model. Copyright © 2018 John Wiley & Sons, Ltd.

Serum ischemia modified albumin level and its relationship with the thiol/disulfide balance in placenta percreta patients.

PubMed

Uyanikoglu, Hacer; Sak, Muhammet Erdal; Tatli, Faik; Hilali, Nese Gul; Sak, Sibel; Incebiyik, Adnan; Barut, Mert Ulas; Erel, Ozcan; Gonel, Ataman

2018-06-08

The pathogenesis of placenta percreta (PP) is not very well known. This study was designed to analyse the oxidative stress (OS), the thiol/disulphide balance, and ischaemia-modified albumin (IMA) the women with PP. The study included 38 pregnant women with PP and 40 similarly aged healthy pregnant women in their third trimester of gestation. We measured the IMA, native and total thiols, and disulphide concentrations in the maternal sera of all of the participating women. The IMA levels were higher and the native and total thiols were lower in the PP group than in the control group. However, there was no statistical significance with respect to the thiol/disulphide balance between the two groups. The results of this study suggest that an increase in the ischaemia and OS and a decrease in the antioxidant status may contribute to the pathogenesis of PP. Impact statement What is already known on this subject? Placenta percreta (PP) is a serious complication of pregnancy. Although there are several studies investigating the pathophysiological mechanism of PP, whether the pathology results from a lack of decidua or from the over-invasiveness of trophoblasts remains controversial. The pathology of PP is poorly understood. What do the results of this study add? This prospective study has shown an increased ischaemia modified albumin (IMA) and a decreased antioxidant capacity in the patients with placenta percreta. The results from 38 women with PP suggest that the serum concentrations of IMA and the oxidative stress parameters may be able to predict PP in cases of uncertainty. What are the implications of these findings for clinical practice and/or further research? The implication of these findings shed light on understanding the pathogenesis of PP for further research.

Improved recovery from limb ischaemia by delivery of an affinity-isolated heparan sulphate.

PubMed

Poon, Selina; Lu, Xiaohua; Smith, Raymond A A; Ho, Pei; Bhakoo, Kishore; Nurcombe, Victor; Cool, Simon M

2018-05-18

Peripheral arterial disease is a major cause of limb loss and its prevalence is increasing worldwide. As most standard-of-care therapies yield only unsatisfactory outcomes, more options are needed. Recent cell- and molecular-based therapies that have aimed to modulate vascular endothelial growth factor-165 (VEGF 165 ) levels have not yet been approved for clinical use due to their uncertain side effects. We have previously reported a heparan sulphate (termed HS7) tuned to avidly bind VEGF 165 . Here, we investigated the ability of HS7 to promote vascular recovery in a murine hindlimb vascular ischaemia model. HS7 stabilised VEGF 165 against thermal and enzyme degradation in vitro, and isolated VEGF 165 from serum via affinity-chromatography. C57BL6 mice subjected to unilateral hindlimb ischaemia injury received daily intramuscular injections of respective treatments (n = 8) and were assessed over 3 weeks by laser Doppler perfusion, magnetic resonance angiography, histology and the regain of function. Mice receiving HS7 showed improved blood reperfusion in the footpad by day 7. In addition, they recovered hindlimb blood volume two- to fourfold faster compared to the saline group; the greatest rate of recovery was observed in the first week. Notably, 17% of HS7-treated animals recovered full hindlimb function by day 7, a number that grew to 58% and 100% by days 14 and 21, respectively. This was in contrast to only 38% in the control animals. These results highlight the potential of purified glycosaminoglycan fractions for clinical use following vascular insult, and confirm the importance of harnessing the activity of endogenous pro-healing factors generated at injury sites.

Effect of black tea consumption on brachial artery flow-mediated dilation and ischaemia-reperfusion in humans.

PubMed

Schreuder, Tim H A; Eijsvogels, Thijs M H; Greyling, Arno; Draijer, Richard; Hopman, Maria T E; Thijssen, Dick H J

2014-02-01

Tea consumption is associated with reduced cardiovascular risk. Previous studies found that tea flavonoids work through direct effects on the vasculature, leading to dose-dependent improvements in endothelial function. Cardioprotective effects of regular tea consumption may relate to the prevention of endothelial ischaemia-reperfusion (IR) injury. Therefore, we examined the effect of black tea consumption on endothelial function and the ability of tea to prevent IR injury. In a randomized, crossover study, 20 healthy subjects underwent 7 days of tea consumption (3 cups per day) or abstinence from tea. We examined brachial artery (BA) endothelial function via flow-mediated dilation (FMD), using high resolution echo-Doppler, before and 90 min after tea or hot water consumption. Subsequently, we followed a 20-min ischaemia and 20-min reperfusion protocol of the BA after which we measured FMD to examine the potential of tea consumption to protect against IR injury. Tea consumption resulted in an immediate increase in FMD% (pre-consumption: 5.8 ± 2.5; post-consumption: 7.2 ± 3.2; p < 0.01), whilst no such change occurred after ingestion of hot water. The IR protocol resulted in a significant decrease in FMD (p < 0.005), which was also present after tea consumption (p < 0.001). This decline was accompanied by an increase in the post-IR baseline diameter. In conclusion, these data indicate that tea ingestion improves BA FMD. However, the impact of the IR protocol on FMD was not influenced by tea consumption. Therefore, the cardioprotective association of tea ingestion relates to a direct effect of tea on the endothelium in humans in vivo.

[Behavior of late ventricular potentials in acute experimental myocardial ischemia].

PubMed

Duck, H J; Pankau, H; Köhler, H

1985-06-01

Locally retarded depolarizations of the ischaemic myocardium are regarded as frequent trigger mechanisms of dangerous ventricular arrhythmias. Up to now, however, there are scarcely systematic investigations concerning their concrete developmental conditions in man, since late potentials can be made evident only by means of expensive invasive methods or signal mediation techniques. Therefore, an animal model should be built, which is suitable for the control of new therapy conceptions with antiarrhythmic drugs. The investigations were performed on 22 pigs in whom under insufflation anaesthesia altogether 10 pressure, flow and contractility parameters as well as 6 epicardial ECG signals were continuously recorded. The episodes of ischaemia were caused by LAD occlusions of different duration and intensity. Typical late potentials could be registered in 5 animals who all had survived complete interruptions of the coronary blood flow of longer than 10 min. The mean duration of the late potentials was 20 +/- 9.2 ms, their amplitudes reached from 150 to 600 microV. Also with regard to time and cycle constancy, the delay of the late Q-potential and the morphology they corresponded to the homogeneous phenomenon, known from man. They always could be derived only from electrodes outside the immediate zone of ischaemia. Neither partial occlusions nor complete interruption of the coronary blood flow in intervals shorter than 10 minutes led to the development of a late potential. The animal model used altogether appears very suitable to investigate the medicamentous influencibility of arrhythmogenic areas of the myocardium under direct control of the dynamic behaviour of ventricular late potentials.

Diagnostic performance of a Lattice Boltzmann-based method for CT-based fractional flow reserve.

PubMed

Giannopoulos, Andreas A; Tang, Anji; Ge, Yin; Cheezum, Michael K; Steigner, Michael L; Fujimoto, Shinichiro; Kumamaru, Kanako K; Chiappino, Dante; Della Latta, Daniele; Berti, Sergio; Chiappino, Sara; Rybicki, Frank J; Melchionna, Simone; Mitsouras, Dimitrios

2018-02-20

Fractional flow reserve (FFR) estimated from coronary computed tomography angiography (CT-FFR) offers non-invasive detection of lesion-specific ischaemia. We aimed to develop and validate a fast CT-FFR algorithm utilising the Lattice Boltzmann method for blood flow simulation (LBM CT-FFR). Sixty-four patients with clinically indicated CTA and invasive FFR measurement from three institutions were retrospectively analysed. CT-FFR was performed using an onsite tool interfacing with a commercial Lattice Boltzmann fluid dynamics cloud-based platform. Diagnostic accuracy of LBM CT-FFR ≤0.8 and percent diameter stenosis >50% by CTA to detect invasive FFR ≤0.8 were compared using area under the receiver operating characteristic curve (AUC). Sixty patients successfully underwent LBM CT-FFR analysis; 29 of 73 lesions in 69 vessels had invasive FFR ≤0.8. Total time to perform LBM CT-FFR was 40±10 min. Compared to invasive FFR, LBM CT-FFR had good correlation (r=0.64), small bias (0.009) and good limits of agreement (-0.223 to 0.206). The AUC of LBM CT-FFR (AUC=0.894, 95% confidence interval [CI]: 0.792-0.996) was significantly higher than CTA (AUC=0.685, 95% CI: 0.576-0.794) to detect FFR ≤0.8 (p=0.0021). Per-lesion specificity, sensitivity, and accuracy of LBM CT-FFR were 97.7%, 79.3%, and 90.4%, respectively. LBM CT-FFR has very good diagnostic accuracy to detect lesion-specific ischaemia (FFR ≤0.8) and can be performed in less than one hour.

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

PubMed

Kisu, Iori; Umene, Kiyoko; Adachi, Masataka; Emoto, Katsura; Nogami, Yuya; Banno, Kouji; Itagaki, Iori; Kawamoto, Ikuo; Nakagawa, Takahiro; Narita, Hayato; Yoshida, Atsushi; Tsuchiya, Hideaki; Ogasawara, Kazumasa; Aoki, Daisuke

2017-10-01

How long is the allowable warm ischemic time of the uterus and what morphological and biochemical changes are caused by uterine ischemia/reperfusion injury in cynomolgus macaques? Warm ischemia in the uterus of cynomolgus macaques is tolerated for up to 4 h and reperfusion after uterine ischemia caused no further morphological and biochemical changes. Uterus transplantation is a potential option for women with uterine factor infertility. The allowable warm ischemic time and ischemia/reperfusion injury of the uterus in humans and non-human primates is unknown. This experimental study included 18 female cynomolgus macaques with periodic menstruation. Animals were divided into six groups of three monkeys each: a control group and groups with uterine ischemia for 0.5, 1, 2, 4 and 8 h. Biopsies of uterine tissues were performed before blood flow blockage, after each blockage time, and after reperfusion for 3 h. Blood sampling was performed after each blockage time, and after reperfusion for 5, 15 and 30 min for measurement of biochemical data. Resumption of menstruation was monitored after the surgical procedure. Morphological, physiological and biochemical changes after ischemia and reperfusion were evaluated. Mild muscle degeneration and zonal degeneration were observed in all animals subjected to warm ischemia for 4 or 8 h, but there were no marked differences in the appearance of specimens immediately after ischemia and after reperfusion for 3 h in animals subjected to 4 or 8 h of warm ischemia. There were no significant changes in any biochemical parameters at any time point in each group. Periodical menstruation resumed in all animals with warm ischemia up to 4 h, but did not recover in animals with warm ischemia for 8 h with atrophic uteri. Warm ischemia in actual transplantation was not exactly mimicked in this study because uteri were not perfused, cooled, transplanted or reanastomosed with vessels. Results in non-human primates cannot always be extrapolated to humans. The findings suggest that the tolerable warm ischemia time in the uterus is expected to be longer than that in other vital organs. This study was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Number 26713050. None of the authors has a conflict of interest to declare. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Precompetition warm-up in elite and subelite rhythmic gymnastics.

PubMed

Guidetti, Laura; Di Cagno, Alessandra; Gallotta, Maria Chiara; Battaglia, Claudia; Piazza, Marina; Baldari, Carlo

2009-09-01

The aim of this study was to investigate which precompetition warm-up methodologies resulted in the best overall performance in rhythmic gymnastics. The coaches of national and international clubs (60 elite and 90 subelite) were interviewed. The relationship between sport performance and precompetition warm-up routines was examined. A total of 49% of the coaches interviewed spent more than 1 hour to prepare their athletes for the competition, including 45 minutes dedicated to warm-up exercises. In spite of previous studies' suggestions, the time between the end of warm-up and the beginning of competition was more than 5 minutes for 68% of those interviewed. A slow run was the activity of choice used to begin the warm-up (96%). Significant differences between elite and subelite gymnasts were found concerning the total duration of warm-up, duration of slow running, utilization of rhythmic steps and leaps during the warm-up, the use of dynamic flexibility exercises, competition performances repetition (p < 0.01), and utilization of imagery (p < 0.05). A precompetition warm-up in rhythmic gymnastics would include static stretching exercises at least 60 minutes prior to the competition starting time and the active stretching exercises alternated with analytic muscle strengthening aimed at increasing muscle temperature. Rhythmic gymnastics coaches at all levels can use this data as a review of precompetition warm-up practices and a possible source of new ideas.

Does Vibration Warm-up Enhance Kinetic and Temporal Sprint Parameters?

PubMed

Cochrane, D J; Cronin, M J; Fink, P W

2015-08-01

The aim of this study was to investigate the efficacy of vibration warm-up to enhance sprint performance. 12 males involved in representative team sports performed 4 warm-up conditions in a randomised order performed at least 24 h apart; VbX warm-up (VbX-WU); Neural activation warm-up (Neu-WU); Dynamic warm-up (Dyn-WU) and Control (No VbX). Participants completed 5 m sprint at 30 s, 2:30 min and 5 min post warm-up where sprint time, kinetics, and temporal components were recorded. There was no significant (p>0.05) main effect or interaction effect between the split sprint times of 1 m, 2.5 m, and 5 m. There was a condition effect where vertical mean force was significantly higher (p<0.05) in Dyn-WU and Control compared to Neu-WU. No other significant (p>0.05) main and interaction effects in sprint kinetic and temporal parameters existed. Overall, all 4 warm-up conditions produced comparable results for sprint performance, and there was no detrimental effect on short-duration sprint performance using VbX-WU. Therefore, VbX could be useful for adding variety to the training warm-up or be included into the main warm-up routine as a supplementary modality. © Georg Thieme Verlag KG Stuttgart · New York.

Snf1-related kinase improves cardiac mitochondrial efficiency and decreases mitochondrial uncoupling

PubMed Central

Rines, Amy K.; Chang, Hsiang-Chun; Wu, Rongxue; Sato, Tatsuya; Khechaduri, Arineh; Kouzu, Hidemichi; Shapiro, Jason; Shang, Meng; Burke, Michael A.; Abdelwahid, Eltyeb; Jiang, Xinghang; Chen, Chunlei; Rawlings, Tenley A.; Lopaschuk, Gary D.; Schumacker, Paul T.; Abel, E. Dale; Ardehali, Hossein

2017-01-01

Ischaemic heart disease limits oxygen and metabolic substrate availability to the heart, resulting in tissue death. Here, we demonstrate that the AMP-activated protein kinase (AMPK)-related protein Snf1-related kinase (SNRK) decreases cardiac metabolic substrate usage and mitochondrial uncoupling, and protects against ischaemia/reperfusion. Hearts from transgenic mice overexpressing SNRK have decreased glucose and palmitate metabolism and oxygen consumption, but maintained power and function. They also exhibit decreased uncoupling protein 3 (UCP3) and mitochondrial uncoupling. Conversely, Snrk knockout mouse hearts have increased glucose and palmitate oxidation and UCP3. SNRK knockdown in cardiac cells decreases mitochondrial efficiency, which is abolished with UCP3 knockdown. We show that Tribbles homologue 3 (Trib3) binds to SNRK, and downregulates UCP3 through PPARα. Finally, SNRK is increased in cardiomyopathy patients, and SNRK reduces infarct size after ischaemia/reperfusion. SNRK also decreases cardiac cell death in a UCP3-dependent manner. Our results suggest that SNRK improves cardiac mitochondrial efficiency and ischaemic protection. PMID:28117339

Comparison of cardiogoniometry and electrocardiography with perfusion cardiac magnetic resonance imaging and late gadolinium enhancement.

PubMed

Birkemeyer, Ralf; Toelg, Ralph; Zeymer, Uwe; Wessely, Rainer; Jäckle, Sebastian; Hairedini, Bajram; Lübke, Mike; Aßfalg, Manfred; Jung, Werner

2012-12-01

Cardiogoniometry (CGM) is a spatio-temporal five-lead resting electrocardiographic method utilizing automated analysis. The purpose of this study was to determine CGM's and electrocardiography (ECG)'s accuracy for detecting myocardial ischaemia and/or lesions in comparison with perfusion cardiac magnetic resonance imaging (CMRI) and late gadolinium enhancement (LGE). Forty (n= 40) patients with suspected or known stable coronary artery disease were examined by CGM and resting ECG directly prior to CMRI including adenosine stress perfusion (ASP) and LGE. The investigators visually reading the CMRI were blinded to the CGM and ECG results. Half of the patients (n= 20) had a normal CMRI while the other half presented with either abnormal ASP and/or detectable LGE. Cardiogoniometry yielded an accuracy of 83% (sensitivity 70%) and ECG of 63% (sensitivity 35%) compared with CMRI. In this pilot study CGM compares more favourably than ECG with the detection of ischaemia and/or structural myocardial lesions on CMRI.

Hypoglycaemia and hypoxic-ischaemic encephalopathy.

PubMed

Boardman, James P; Hawdon, Jane M

2015-04-01

The transition from fetal to neonatal life requires metabolic adaptation to ensure that energy supply to vital organs and systems is maintained after separation from the placental circulation. Under normal conditions, this is achieved through the mobilization and use of alternative cerebral fuels (fatty acids, ketone bodies, and lactate) when blood glucose concentration falls. Severe hypoxia-ischaemia is associated with impaired metabolic adaptation, and animal and human data suggest that levels of hypoglycaemia that are tolerated under normal conditions can be harmful in association with hypoxia-ischaemia. The optimal target blood glucose level for ensuring adequate energy provision in hypoxic-ischaemic encephalopathy (HIE) remains unknown. However, recent data support guidance to maintain a blood glucose concentration of 2.5 mmol/L or more in neonates with signs of acute neurological dysfunction, which includes those with HIE, and this is higher than the accepted threshold of 2 mmol/L in infants without signs of neurological dysfunction or hyperinsulinism. © The Authors. Journal compilation © 2015 Mac Keith Press.

Studies on possibility for alleviation of lifestyle diseases by low-dose irradiation or radon inhalation.

PubMed

Kataoka, Takahiro; Sakoda, Akihiro; Yoshimoto, Masaaki; Nakagawa, Shinya; Toyota, Teruaki; Nishiyama, Yuichi; Yamato, Keiko; Ishimori, Yuu; Kawabe, Atsushi; Hanamoto, Katsumi; Taguchi, Takehito; Yamaoka, Kiyonori

2011-07-01

Our previous studies showed the possibility that activation of the antioxidative function alleviates various oxidative damages, which are related to lifestyle diseases. Results showed that, low-dose X-ray irradiation activated superoxide dismutase and inhibits oedema following ischaemia-reperfusion. To alleviate ischaemia-reperfusion injury with transplantation, the changes of the antioxidative function in liver graft using low-dose X-ray irradiation immediately after exenteration were examined. Results showed that liver grafts activate the antioxidative function as a result of irradiation. In addition, radon inhalation enhances the antioxidative function in some organs, and alleviates alcohol-induced oxidative damage of mouse liver. Moreover, in order to determine the most effective condition of radon inhalation, mice inhaled radon before or after carbon tetrachloride (CCl(4)) administration. Results showed that radon inhalation alleviates CCl(4)-induced hepatopathy, especially prior inhalation. It is highly possible that adequate activation of antioxidative functions induced by low-dose irradiation can contribute to preventing or reducing oxidative damages, which are related to lifestyle diseases.

Myocardial ischaemia and cardiac pain – a mysterious relationship

PubMed Central

Fisher, Mike

2013-01-01

Pain related to cardiac disease has been recognised for centuries. However, the precise mechanisms of angina pectoris remain bafflingly obscure. Conventional cardiological angina management concentrates on methods to improve oxygen delivery to cardiac myocytes as our understanding of cardiac muscle cells’ response to hypoxia increases. In common with other chronic visceral pain syndromes, little is understood about how pain signals are generated and propagated by visceral nerves. Improved imaging and other physiological assessments have demonstrated important central nervous system (CNS) responses to myocardial ischaemia, including activation of CNS areas known to be ‘key players’ in chronic pain syndromes. Patients with stable angina usually have an excellent prognosis, especially if left ventricular function is preserved. Educating patients about their condition, teaching simple techniques known to help chronic pain patients and introducing targeted pain treatments specific to angina can be extremely helpful adjuncts to conventional cardiological treatments and will often bring about significant improvements in quality of life. PMID:26516494

The time of day effects of warm temperature on flowering time involve PIF4 and PIF5

PubMed Central

Thines, Bryan C.; Duarte, Maritza I.; Harmon, Frank G.

2014-01-01

Warm temperature promotes flowering in Arabidopsis thaliana and this response involves multiple signalling pathways. To understand the temporal dynamics of temperature perception, tests were carried out to determine if there was a daily window of enhanced sensitivity to warm temperature (28 °C). Warm temperature applied during daytime, night-time, or continuously elicited earlier flowering, but the effects of each treatment were unequal. Plants exposed to warm night (WN) conditions flowered nearly as early as those in constant warm (CW) conditions, while treatment with warm days (WD) caused later flowering than either WN or CW. Flowering in each condition relied to varying degrees on the activity of CO , FT , PIF4 , and PIF5 , as well as the action of unknown genes. The combination of signalling pathways involved in flowering depended on the time of the temperature cue. WN treatments caused a significant advance in the rhythmic expression waveform of CO, which correlated with pronounced up-regulation of FT expression, while WD caused limited changes in CO expression and no stimulation of FT expression. WN- and WD-induced flowering was partially CO independent and, unexpectedly, dependent on PIF4 and PIF5 . pif4-2, pif5-3, and pif4-2 pif5-3 mutants had delayed flowering under all three warm conditions. The double mutant was also late flowering in control conditions. In addition, WN conditions alone imposed selective changes to PIF4 and PIF5 expression. Thus, the PIF4 and PIF5 transcription factors promote flowering by at least two means: inducing FT expression in WN and acting outside of FT by an unknown mechanism in WD. PMID:24574484

Spring Temperatures Alone Cannot Explain Timing of Budburst of Boreal-Temperate Tree Species under Experimental Warming

NASA Astrophysics Data System (ADS)

Montgomery, R. A.; Reich, P. B.; Rich, R. L.; Stefanski, A.

2011-12-01

Phenology, the timing of seasonal biological events such as budburst, blossom dates, bird migration and insect development, is critical to understanding species interactions (e.g. pollination, herbivory); determines growing season length in many (i.e. seasonal) terrestrial ecosystems; and can play a role in determining species range limits. There is ample evidence that plant and animal phenology has changed in recent decades. For trees in seasonally cold climates, change is most commonly manifested as earlier budburst, likely caused by earlier onset of warming temperatures in spring. Indeed, it is often assumed that one of the major phenological responses of temperate and boreal forest ecosystems to climate change will be earlier leafing and concomitantly, a longer growing season. However, spring warming interacts with other factors such as winter chilling and photoperiod to determine timing of spring leafing. For example, warmer winters could reduce the duration and amount of chilling experienced by dormant buds and lead to delayed budburst. Despite knowledge that such interactions exist, we know little about the interactive mechanisms by which various cues influence budburst in forest tree species or whether species differ in sensitivity to those cues. This gap hinders our ability to predict phenological responses and their ecological impacts under future climate scenarios. Over the past three years, we have conducted studies of leafing phenology, germination, photosynthesis, respiration, and growth of seedlings of ten boreal-temperate tree species subjected to experimental warming using infrared heat lamps and soil heating cables. Seedlings were planted into plots receiving ambient, +1.8°C or +3.6°C temperature treatments in open, aspen forest at the Cloquet Forestry Center, Cloquet, MN, USA (46°31' N, 92°30' W, 386 m a.s.l.; 4.5°C MAT, 807 mm MAP). While all species responded to warming by advancing the absolute date of budburst, several lines of evidence support the role of other factors, namely photoperiod or chilling, in co-determining observed responses. First, a number of species showed non-linear responses in absolute day of year of budburst across levels of warming: specifically, some species did not advance the date of budburst in +3.6°C compared to +1.8°C treatments. Second, if warming was the only cue for budburst, then one would expect that the plants would break bud after the same amount of warming regardless of treatment (i.e. at the same thermal time) and thus they would reach that threshold earlier in the warmed treatments (i.e. earlier absolute time). This was not observed. Instead, using thermal time to budburst rather than absolute date of budburst, we found that all species required more warming to break bud in warmed compared to unwarmed treatments. Lastly, when we examined the relationship between thermal time to budburst and chill days, we found that longer thermal time to budburst was associated with reduced chilling. Taken together, these three lines of evidence suggest that spring warming is not the only cue for budburst. Future research and modelling must recognize the role of other cues.

Bimodal Modulation of Ipsilateral Spinal-Coeruleo-Spinal Pathway in CRPS: A Novel Model for Explaining Different Clinical Features of the Syndrome.

PubMed

Carcamo, Cesar R

2015-08-01

The objective is to present a hypothesis to explain the sensory, autonomic, and motor disturbances associated with complex regional pain syndrome (CRPS) syndrome. The author reviewed the available and relevant literature, which was supplemented with research on experimental animal models, with a focus on how they may translate into humans, particularly in areas about pathophysiologic mechanisms of CRPS. We propose that different CRPS subtypes may result from facilitative or inhibitory influences exerted by the spinal-coeruleo-spinal pathway in three sites at the spinal cord: the dorsal horn (DH), intermediolateral cell column (IML) and ventral horn (VH). A facilitatory influence over DH may have a pronociceptive effect that explains exacerbated pain, sensory disturbances, and spreading sensitization and neuroinflammation. Conversely, a facilitatory influence over preganglionic neurons located in IML cell column may increase sympathetic outflow with peripheral vasoconstriction, which leads to cold skin, ipsilateral limb ischaemia, and sympathetically maintained pain (SMP). For patients presenting with these symptoms, a descending inhibitory influence would be predicted to result in decreased sympathetic outflow and warm skin, as well as impairment of peripheral vasoconstrictor reflexes. Finally, a descending inhibitory influence over VH could explain muscle weakness and decreased active range of motion, while also facilitating motor reflexes, tremor and dystonia. The proposed model provides a mechanistically based diagnostic scheme for classifying and explaining the sensory, autonomic and motor disturbances associated with CRPS syndrome. Wiley Periodicals, Inc.

The depletion of donor macrophages reduces ischaemia-reperfusion injury after mouse lung transplantation.

PubMed

Tsushima, Yukio; Jang, Jae-Hwi; Yamada, Yoshito; Schwendener, Reto; Suzuki, Kenji; Weder, Walter; Jungraithmayr, Wolfgang

2014-04-01

Macrophages (M) are one of the most important cells of the innate immune system for first line defense. Upon transplantation (Tx), M play a prominent role during lung ischaemia reperfusion (I/R) injury. Here, we hypothesize that the depletion of donor M ameliorates the post-transplant lung I/R injury. Orthotopic single-lung Tx was performed between syngeneic BALB/c mice after a cold ischaemic time of 8 h and a reperfusion time of 10 h. Prior to graft implantation, alveolar macrophages of donor lungs were selectively depleted applying the 'suicide technique' by intratracheal application of clodronate liposomes (experimental, n = 6) vs the application of empty liposomes (control, n = 6). Cell count (number of F4/80(+)-macrophages) and graft injury were evaluated by histology and immunohistochemistry, and levels of lactat dehydrogenase (LDH) (apoptosis assay), enzyme linked immunosorbent assay for nuclear protein high-mobility-group-protein B1 (HMGB1), tumor necrosis factor alpha (TNF-α) and transforming growth factor beta1 (TGF-β1) in plasma were analysed. Clodronate liposomes successfully reduced 70% of M from donor lungs when compared with grafts treated with empty liposome only. M-depleted transplants showed improved histology and revealed considerably less graft damage when compared with control recipients (LDH, P = 0.03; HMGB1, P = 0.3). Oxygenation capacity was ameliorated in M-depleted transplants, if not significant (P = 0.114); however, wet/dry ratio did not differ between groups (P = 0.629). The inflammatory response was significantly reduced in M-depleted mice when compared with control recipients (TNF-α, P = 0.042; TGF-β1, P = 0.039). The selective depletion of M in donor lung transplants can be successfully performed and results in a sustained anti-inflammatory response upon I/R-injury. The beneficial effect of this preconditioning method should be further evaluated as a promising tool for the attenuation of I/R prior to graft implantation in clinical Tx.

Feasibility Study of a Novel Thoraco-abdominal Aortic Hybrid Device (SPIDER-graft) in a Translational Pig Model.

PubMed

Debus, Eike S; Kölbel, Tilo; Duprée, Anna; Daum, Günter; Sandhu, Harleen K; Manzoni, Daniel; Wipper, Sabine H

2018-02-01

The hybrid SPIDER-graft consists of a proximal descending aortic stent graft and a conventional six branched Dacron graft for open abdominal aortic repair. Technical feasibility with regard to avoiding thoracotomy and extracorporeal circulation (ECC) during thoraco-abdominal aortic hybrid repair and peri-procedural safety of this novel device are unknown. This was a feasibility and safety study in domestic pigs (75-85 kg). The abdominal aorta including iliac bifurcation, left renal artery, and visceral arteries were exposed via retroperitoneal access. The right iliac branch was first temporarily anastomosed end to side to the distal aorta via partial clamping. During inflow reduction and infra-coeliac cross-clamping, the coeliac trunk (CT) was divided and the proximal stent graft portion of the SPIDER-graft was deployed into the descending aorta via the CT ostium. Retrograde visceral and antegrade aorto-iliac blood flow was maintained via the iliac side branch. The visceral, renal, and iliac arteries were sequentially anastomosed, finally replacing the first iliac end to side anastomosis. Technical success, blood flow, periods of ischaemia, and peri-procedural complications were evaluated after intra-operative completion angiography and post-operative computed tomography angiography. Six animals underwent successful thoracic stent graft deployment and distal open reconstruction without peri-operative death. The median thoracic graft implantation time was 4.5 min, and the median ischaemia times before reperfusion were 10 min for the CT, 8 min for the superior mesenteric artery, 13 min for the right renal artery, and 22 min for the left renal artery. Angiography demonstrated appropriate graft implantation and blood flow measurements confirmed sufficient blood flow through all side branches. In this translational pig model, thoraco-abdominal hybrid repair using the novel SPIDER-graft was successful in avoiding thoracotomy and ECC. Technical feasibility and safety appear promising, but need to be reassessed in humans. Copyright © 2017. Published by Elsevier Ltd.

Terrestrial carbon cycle affected by non-uniform climate warming

NASA Astrophysics Data System (ADS)

Xia, Jianyang; Chen, Jiquan; Piao, Shilong; Ciais, Philippe; Luo, Yiqi; Wan, Shiqiang

2014-03-01

Feedbacks between the terrestrial carbon cycle and climate change could affect many ecosystem functions and services, such as food production, carbon sequestration and climate regulation. The rate of climate warming varies on diurnal and seasonal timescales. A synthesis of global air temperature data reveals a greater rate of warming in winter than in summer in northern mid and high latitudes, and the inverse pattern in some tropical regions. The data also reveal a decline in the diurnal temperature range over 51% of the global land area and an increase over only 13%, because night-time temperatures in most locations have risen faster than daytime temperatures. Analyses of satellite data, model simulations and in situ observations suggest that the impact of seasonal warming varies between regions. For example, spring warming has largely stimulated ecosystem productivity at latitudes between 30° and 90° N, but suppressed productivity in other regions. Contrasting impacts of day- and night-time warming on plant carbon gain and loss are apparent in many regions. We argue that ascertaining the effects of non-uniform climate warming on terrestrial ecosystems is a key challenge in carbon cycle research.

Thermal comfort and safety of cotton blankets warmed at 130°F and 200°F.

PubMed

Kelly, Patricia A; Cooper, Susan K; Krogh, Mary L; Morse, Elizabeth C; Crandall, Craig G; Winslow, Elizabeth H; Balluck, Julie P

2013-12-01

In 2009, the ECRI Institute recommended warming cotton blankets in cabinets set at 130°F or less. However, there is limited research to support the use of this cabinet temperature. To measure skin temperatures and thermal comfort in healthy volunteers before and after application of blankets warmed in cabinets set at 130 and 200°F, respectively, and to determine the time-dependent cooling of cotton blankets after removal from warming cabinets set at the two temperatures. Prospective, comparative, descriptive. Participants (n = 20) received one or two blankets warmed in 130 or 200°F cabinets. First, skin temperatures were measured, and thermal comfort reports were obtained at fixed timed intervals. Second, blanket temperatures (n = 10) were measured at fixed intervals after removal from the cabinets. No skin temperatures approached levels reported in the literature that cause epidermal damage. Thermal comfort reports supported using blankets from the 200°F cabinet, and blankets lost heat quickly over time. We recommend warming cotton blankets in cabinets set at 200°F or less to improve thermal comfort without compromising patient safety. Copyright © 2013 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

Stochastic Modeling and Global Warming Trend Extraction For Ocean Acoustic Travel Times.

DTIC Science & Technology

1995-01-06

consideration and that these models can not currently be relied upon by themselves to predict global warming . Experimental data is most certainly needed, not...only to measure global warming itself, but to help improve the ocean model themselves. (AN)

The influence of subchondral vascularisation on chondromalacia patellae.

PubMed

Neusel, E; Graf, J

1996-01-01

An experiment was carried out on 40 rabbits in which the blood supply to the patella was interrupted for periods from 2 weeks to 6 months. With prolonged ischaemia, there were clear changes in the articular cartilage which were comparable with those seen in chondromalacia patellae.

The whole-soil carbon flux in response to warming

NASA Astrophysics Data System (ADS)

Hicks Pries, Caitlin E.; Castanha, C.; Porras, R. C.; Torn, M. S.

2017-03-01

Soil organic carbon harbors three times as much carbon as Earth’s atmosphere, and its decomposition is a potentially large climate change feedback and major source of uncertainty in climate projections. The response of whole-soil profiles to warming has not been tested in situ. In a deep warming experiment in mineral soil, we found that CO2 production from all soil depths increased with 4°C warming; annual soil respiration increased by 34 to 37%. All depths responded to warming with similar temperature sensitivities, driven by decomposition of decadal-aged carbon. Whole-soil warming reveals a larger soil respiration response than many in situ experiments (most of which only warm the surface soil) and models.

New evidence of neuroprotection by lactate after transient focal cerebral ischaemia: extended benefit after intracerebroventricular injection and efficacy of intravenous administration.

PubMed

Berthet, Carole; Castillo, Ximena; Magistretti, Pierre J; Hirt, Lorenz

2012-01-01

Lactate protects mice against the ischaemic damage resulting from transient middle cerebral artery occlusion (MCAO) when administered intracerebroventricularly at reperfusion, yielding smaller lesion sizes and a better neurological outcome 48 h after ischaemia. We have now tested whether the beneficial effect of lactate is long-lasting and if lactate can be administered intravenously. Male ICR-CD1 mice were subjected to 15-min suture MCAO under xylazine + ketamine anaesthesia. Na L-lactate (2 µl of 100 mmol/l) or vehicle was administered intracerebroventricularly at reperfusion. The neurological deficit was evaluated using a composite deficit score based on the neurological score, the rotarod test and the beam walking test. Mice were sacrificed at 14 days. In a second set of experiments, Na L-lactate (1 µmol/g body weight) was administered intravenously into the tail vein at reperfusion. The neurological deficit and the lesion volume were measured at 48 h. Intracerebroventricularly injected lactate induced sustained neuroprotection shown by smaller neurological deficits at 7 days (median = 0, min = 0, max = 3, n = 7 vs. median = 2, min = 1, max = 4.5, n = 5, p < 0.05) and 14 days after ischaemia (median = 0, min = 0, max = 3, n = 7 vs. median = 3, min = 0.5, max = 3, n = 7, p = 0.05). Reduced tissue damage was demonstrated by attenuated hemispheric atrophy at 14 days (1.3 ± 4.0 mm(3), n = 7 vs. 12.1 ± 3.8 mm(3), n = 5, p < 0.05) in lactate-treated animals. Systemic intravenous lactate administration was also neuroprotective and attenuated the deficit (median = 1, min = 0, max = 2.5, n = 12) compared to vehicle treatment (median = 1.5, min = 1, max = 8, n = 12, p < 0.05) as well as the lesion volume at 48 h (13.7 ± 12.2 mm(3), n = 12 vs. 29.6 ± 25.4 mm(3), n = 12, p < 0.05). The beneficial effect of lactate is long-lasting: lactate protects the mouse brain against ischaemic damage when supplied intracerebroventricularly during reperfusion with behavioural and histological benefits persisting 2 weeks after ischaemia. Importantly, lactate also protects after systemic intravenous administration, a more suitable route of administration in a clinical emergency setting. These findings provide further steps to bring this physiological, commonly available and inexpensive neuroprotectant closer to clinical translation for stroke. Copyright © 2012 S. Karger AG, Basel.

Clinically-relevant consecutive treatment with isoproterenol and adenosine protects the failing heart against ischaemia and reperfusion

PubMed Central

2014-01-01

Background Consecutive treatment of normal heart with a high dose of isoproterenol and adenosine (Iso/Ade treatment), confers strong protection against ischaemia/reperfusion injury. In preparation for translation of this cardioprotective strategy into clinical practice during heart surgery, we further optimised conditions for this intervention using a clinically-relevant dose of Iso and determined its cardioprotective efficacy in hearts isolated from a model of surgically-induced heart failure. Methods Isolated Langendorff-perfused rat hearts were treated sequentially with 5 nM Iso and 30 μM Ade followed by different durations of washout prior to 30 min global ischaemia and 2 hrs reperfusion. Reperfusion injury was assessed by measuring haemodynamic function, lactate dehydrogenase (LDH) release and infarct size. Protein kinase C (PKC) activity and glycogen content were measured in hearts after the treatment. In a separate group of hearts, Cyclosporine A (CsA), a mitochondria permeability transition pore (MPTP) inhibitor, was added with Iso/Ade. Failing hearts extracted after 16 weeks of ligation of left coronary artery in 2 months old rats were also subjected to Iso/Ade treatment followed by ischaemia/reperfusion. Results Recovery of the rate pressure product (RPP) in Iso/Ade-treated hearts was significantly higher than in controls. Thus in Iso/Ade treated hearts with 5 nM Iso and no washout period, RPP recovery was 76.3 ± 6.9% of initial value vs. 28.5 ± 5.2% in controls. This was associated with a 3 fold reduction in LDH release irrespective to the duration of the washout period. Hearts with no washout of the drugs (Ade) had least infarct size, highest PKC activity and also showed reduced glycogen content. Cardioprotection with CsA was not additive to the effect of Iso/Ade treatment. Iso/Ade treatment conferred significant protection to failing hearts. Thus, RPP recovery in failing hearts subjected to the treatment was 69.0 ± 16.3% while in Control hearts 19.7 ± 4.0%. LDH release in these hearts was also 3 fold lower compared to Control. Conclusions Consecutive Iso/Ade treatment of normal heart can be effective at clinically-relevant doses and this effect appears to be mediated by glycogen depletion and inhibition of MPTP. This intervention protects clinically relevant failing heart model making it a promising candidate for clinical use. PMID:24885907

A new cannabinoid CB2 receptor agonist HU-910 attenuates oxidative stress, inflammation and cell death associated with hepatic ischaemia/reperfusion injury.

PubMed

Horváth, Bėla; Magid, Lital; Mukhopadhyay, Partha; Bátkai, Sándor; Rajesh, Mohanraj; Park, Ogyi; Tanchian, Galin; Gao, Rachel Y; Goodfellow, Catherine E; Glass, Michelle; Mechoulam, Raphael; Pacher, Pál

2012-04-01

Cannabinoid CB(2) receptor activation has been reported to attenuate myocardial, cerebral and hepatic ischaemia-reperfusion (I/R) injury. We have investigated the effects of a novel CB(2) receptor agonist ((1S,4R)-2-(2,6-dimethoxy-4-(2-methyloctan-2-yl)phenyl)-7,7-dimethylbicyclo[2.2.1]hept-2-en-1-yl)methanol (HU-910) on liver injury induced by 1 h of ischaemia followed by 2, 6 or 24 h of reperfusion, using a well-established mouse model of segmental hepatic I/R. Displacement of [(3) H]CP55940 by HU-910 from specific binding sites in CHO cell membranes transfected with human CB(2) or CB(1) receptors (hCB(1/2) ) yielded K(i) values of 6 nM and 1.4 µM respectively. HU-910 inhibited forskolin-stimulated cyclic AMP production by hCB(2) CHO cells (EC(50) = 162 nM) and yielded EC(50) of 26.4 nM in [(35) S]GTPγS binding assays using hCB(2) expressing CHO membranes. HU-910 given before ischaemia significantly attenuated levels of I/R-induced hepatic pro-inflammatory chemokines (CCL3 and CXCL2), TNF-α, inter-cellular adhesion molecule-1, neutrophil infiltration, oxidative stress and cell death. Some of the beneficial effect of HU-910 also persisted when given at the beginning of the reperfusion or 1 h after the ischaemic episode. Furthermore, HU-910 attenuated the bacterial endotoxin-triggered TNF-α production in isolated Kupffer cells and expression of adhesion molecules in primary human liver sinusoidal endothelial cells stimulated with TNF-α. Pretreatment with a CB(2) receptor antagonist attenuated the protective effects of HU-910, while pretreatment with a CB(1) antagonist tended to enhance them. HU-910 is a potent CB(2) receptor agonist which may exert protective effects in various diseases associated with inflammation and tissue injury. This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7. Published 2011. This article is a U.S. Government work and is in the public domain in the USA.

Reliability and sensitivity analysis of a system with multiple unreliable service stations and standby switching failures

NASA Astrophysics Data System (ADS)

Ke, Jyh-Bin; Lee, Wen-Chiung; Wang, Kuo-Hsiung

2007-07-01

This paper presents the reliability and sensitivity analysis of a system with M primary units, W warm standby units, and R unreliable service stations where warm standby units switching to the primary state might fail. Failure times of primary and warm standby units are assumed to have exponential distributions, and service times of the failed units are exponentially distributed. In addition, breakdown times and repair times of the service stations also follow exponential distributions. Expressions for system reliability, RY(t), and mean time to system failure, MTTF are derived. Sensitivity analysis, relative sensitivity analysis of the system reliability and the mean time to failure, with respect to system parameters are also investigated.

40 CFR Table A-1 to Subpart A of... - Global Warming Potentials

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Global Warming Potentials A Table A-1... A-1 to Subpart A of Part 98—Global Warming Potentials [100-Year Time Horizon] Name CAS No. Chemical formula Global warming potential(100 yr.) Carbon dioxide 124-38-9 CO2 1 Methane 74-82-8 CH4 21 Nitrous...

40 CFR Table A-1 to Subpart A of... - Global Warming Potentials

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 21 2011-07-01 2011-07-01 false Global Warming Potentials A Table A-1... A-1 to Subpart A of Part 98—Global Warming Potentials [100-Year Time Horizon] Name CAS No. Chemical formula Global warming potential(100 yr.) Carbon dioxide 124-38-9 CO2 1 Methane 74-82-8 CH4 21 Nitrous...

40 CFR Table A-1 to Subpart A of... - Global Warming Potentials

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 22 2012-07-01 2012-07-01 false Global Warming Potentials A Table A-1... A-1 to Subpart A of Part 98—Global Warming Potentials [100-Year Time Horizon] Name CAS No. Chemical formula Global warming potential(100 yr.) Carbon dioxide 124-38-9 CO2 1 Methane 74-82-8 CH4 21 Nitrous...

Effects of different warming patterns on the translocations of cadmium and copper in a soil-rice seedling system.

PubMed

Ge, Liqiang; Cang, Long; Liu, Hui; Zhou, Dongmei

2015-10-01

Heavy-metal-polluted rice poses potential threats to food security and has received great attention in recent years, while how elevated temperature affects the translocation of heavy metals in soil-rice system is unclear. In this study, potting experiments were conducted in plant growth chambers for 24 days to evaluate the effects of different warming patterns on cadmium (Cd) and copper (Cu) migrations in soil-rice seedling system. Rice seedlings were cultivated under four different day/night temperature patterns: 25/18 °C (CK), 25/23 °C (N5), 30/18 °C (D5), and 30/23 °C (DN5), respectively. Non-contaminated soil (CS), Cd/Cu lightly polluted soil (LS), and highly polluted soil (HS) were chosen for experiments. The results showed that different warming patterns decreased soil pH and elevated available soil Cd/Cu concentrations. The shoot and root biomass were increased by 39.0-320 and 28.6-348 %, respectively. Warming induced significant (p < 0.05) increase of Cd/Cu uptake and translocation in rice seedlings, especially for the Cd concentration in shoot. The Cd concentrations of shoot increased by 5-12 times and up to 8 times for LS and HS, respectively. Meanwhile, the Cd concentration of shoot increased with warming while that of root kept unchanged, indicating that warming promoted cadmium translocation from root to shoot (about -four to nine times of CK), while warming changed the Cu concentration of shoot similarly to that of root and had no significant effects on Cu translocations in rice seedlings. Our study may provide improved understanding for Cd/Cu fates in soil-rice system by warming and imply that heavy metals had the higher environmental risk under the future global warming.

Unabated global surface temperature warming: evaluating the evidence

NASA Astrophysics Data System (ADS)

Karl, T. R.; Arguez, A.

2015-12-01

New insights related to time-dependent bias corrections in global surface temperatures have led to higher rates of warming over the past few decades than previously reported in the IPCC Fifth Assessment Report (2014). Record high global temperatures in the past few years have also contributed to larger trends. The combination of these factors and new analyses of the rate of temperature change show unabated global warming since at least the mid-Twentieth Century. New time-dependent bias corrections account for: (1) differences in temperatures measured from ships and drifting buoys; (2) improved corrections to ship measured temperatures; and (3) the larger rates of warming in polar regions (particularly the Arctic). Since 1951, the period over which IPCC (2014) attributes over half of the observed global warming to human causes, it is shown that there has been a remarkably robust and sustained warming, punctuated with inter-annual and decadal variability. This finding is confirmed through simple trend analysis and Empirical Mode Decomposition (EMD). Trend analysis however, especially for decadal trends, is sensitive to selection bias of beginning and ending dates. EMD has no selection bias. Additionally, it can highlight both short- and long-term processes affecting the global temperature times series since it addresses both non-linear and non-stationary processes. For the new NOAA global temperature data set, our analyses do not support the notion of a hiatus or slowing of long-term global warming. However, sub-decadal periods of little (or no warming) and rapid warming can also be found, clearly showing the impact of inter-annual and decadal variability that previously has been attributed to both natural and human-induced non-greenhouse forcings.

Three times greater weight of daytime than of night-time temperature on leaf unfolding phenology in temperate trees.

PubMed

Fu, Yongshuo H; Liu, Yongjie; De Boeck, Hans J; Menzel, Annette; Nijs, Ivan; Peaucelle, Marc; Peñuelas, Josep; Piao, Shilong; Janssens, Ivan A

2016-11-01

The phenology of spring leaf unfolding plays a key role in the structure and functioning of ecosystems. The classical concept of heat requirement (growing degree days) for leaf unfolding was developed hundreds of years ago, but this model does not include the recently reported greater importance of daytime than night-time temperature. A manipulative experiment on daytime vs night-time warming with saplings of three species of temperate deciduous trees was conducted and a Bayesian method was applied to explore the different effects of daytime and night-time temperatures on spring phenology. We found that both daytime and night-time warming significantly advanced leaf unfolding, but the sensitivities to increased daytime and night-time temperatures differed significantly. Trees were most sensitive to daytime warming (7.4 ± 0.9, 4.8 ± 0.3 and 4.8 ± 0.2 d advancement per degree Celsius warming (d °C -1 ) for birch, oak and beech, respectively) and least sensitive to night-time warming (5.5 ± 0.9, 3.3 ± 0.3 and 2.1 ± 0.9 d °C -1 ). Interestingly, a Bayesian analysis found that the impact of daytime temperature on leaf unfolding was approximately three times higher than that of night-time temperatures. Night-time global temperature is increasing faster than daytime temperature, so model projections of future spring phenology should incorporate the effects of these different temperatures. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Time-dependent postural control adaptations following a neuromuscular warm-up in female handball players: a randomized controlled trial.

PubMed

Steib, Simon; Zahn, Peter; Zu Eulenburg, Christine; Pfeifer, Klaus; Zech, Astrid

2016-01-01

Female handball athletes are at a particular risk of sustaining lower extremity injuries. The study examines time-dependent adaptations of static and dynamic balance as potential injury risk factors to a specific warm-up program focusing on neuromuscular control. Fourty one (24.0 ± 5.9 years) female handball athletes were randomized to an intervention or control group. The intervention group implemented a 15-min specific neuromuscular warm-up program, three times per week for eleven weeks, whereas the control group continued with their regular warm-up. Balance was assessed at five time points. Measures included the star excursion balance test (SEBT), and center of pressure (COP) sway velocity during single-leg standing. No baseline differences existed between groups in demographic data. Adherence to neuromuscular warm-up was 88.7 %. Mean COP sway velocity decreased significantly over time in the intervention group (-14.4 %; p  < .001), but not in the control group (-6.2 %; p  = 0.056). However, these effects did not differ significantly between groups ( p  = .098). Mean changes over time in the SEBT score were significantly greater ( p  = .014) in the intervention group (+5.48) compared to the control group (+3.45). Paired t-tests revealed that the first significant balance improvements were observed after 6 weeks of training. A neuromuscular warm-up positively influences balance variables associated with an increased risk of lower extremity injuries in female handball athletes. The course of adaptations suggests that a training volume of 15 min, three times weekly over at least six weeks produces measurable changes. Retrospectively registered on 4th October 2016. Registry: clinicaltrials.gov. Trial number: NCT02925377.

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial.

PubMed

Bath, Philip M; Woodhouse, Lisa J; Appleton, Jason P; Beridze, Maia; Christensen, Hanne; Dineen, Robert A; Duley, Lelia; England, Timothy J; Flaherty, Katie; Havard, Diane; Heptinstall, Stan; James, Marilyn; Krishnan, Kailash; Markus, Hugh S; Montgomery, Alan A; Pocock, Stuart J; Randall, Marc; Ranta, Annemarei; Robinson, Thompson G; Scutt, Polly; Venables, Graham S; Sprigg, Nikola

2018-03-03

Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67-1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05-3·16, p<0·0001). Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice. National Institutes of Health Research Health Technology Assessment Programme, British Heart Foundation. Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Germination shifts of C3 and C4 species under simulated global warming scenario.

PubMed

Zhang, Hongxiang; Yu, Qiang; Huang, Yingxin; Zheng, Wei; Tian, Yu; Song, Yantao; Li, Guangdi; Zhou, Daowei

2014-01-01

Research efforts around the world have been increasingly devoted to investigating changes in C3 and C4 species' abundance or distribution with global warming, as they provide important insight into carbon fluxes and linked biogeochemical cycles. However, changes in the early life stage (e.g. germination) of C3 and C4 species in response to global warming, particularly with respect to asymmetric warming, have received less attention. We investigated germination percentage and rate of C3 and C4 species under asymmetric (+3/+6°C at day/night) and symmetric warming (+5/+5°C at day/night), simulated by alternating temperatures. A thermal time model was used to calculate germination base temperature and thermal time constant. Two additional alternating temperature regimes were used to test temperature metrics effect. The germination percentage and rate increased continuously for C4 species, but increased and then decreased with temperature for C3 species under both symmetric and asymmetric warming. Compared to asymmetric warming, symmetric warming significantly overestimated the speed of germination percentage change with temperature for C4 species. Among the temperature metrics (minimum, maximum, diurnal temperature range and average temperature), maximum temperature was most correlated with germination of C4 species. Our results indicate that global warming may favour germination of C4 species, at least for the C4 species studied in this work. The divergent effects of asymmetric and symmetric warming on plant germination also deserve more attention in future studies.

Warm water and cool nests are best. How global warming might influence hatchling green turtle swimming performance.

PubMed

Booth, David T; Evans, Andrew

2011-01-01

For sea turtles nesting on beaches surrounded by coral reefs, the most important element of hatchling recruitment is escaping predation by fish as they swim across the fringing reef, and as a consequence hatchlings that minimize their exposure to fish predation by minimizing the time spent crossing the fringing reef have a greater chance of surviving the reef crossing. One way to decrease the time required to cross the fringing reef is to maximize swimming speed. We found that both water temperature and nest temperature influence swimming performance of hatchling green turtles, but in opposite directions. Warm water increases swimming ability, with hatchling turtles swimming in warm water having a faster stroke rate, while an increase in nest temperature decreases swimming ability with hatchlings from warm nests producing less thrust per stroke.

75 FR 70657 - Approval and Promulgation of Implementation Plans; Kansas: Prevention of Significant...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-18

... Global Warming Potential (GWP) was developed to compare the heat- trapping capacity and atmospheric... CH 4 emissions would have 21 times as much impact on global warming over a 100-year time horizon as 1...

76 FR 752 - Approval and Promulgation of Implementation Plans; Connecticut: Prevention of Significant...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-06

... Global Warming Potential (GWP) was developed to compare the heat- trapping capacity and atmospheric... CH 4 emissions would have 21 times as much impact on global warming over a 100-year time horizon as 1...

75 FR 68285 - Approval and Promulgation of Implementation Plans; Alabama: Prevention of Significant...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-05

... Global Warming Potential (GWP) was developed to compare the heat- trapping capacity and atmospheric... CH 4 emissions would have 21 times as much impact on global warming over a 100-year time horizon as 1...

75 FR 68272 - Approval and Promulgation of Implementation Plans; Kentucky: Prevention of Significant...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-05

... Global Warming Potential (GWP) was developed to compare the heat- trapping capacity and atmospheric... CH 4 emissions would have 21 times as much impact on global warming over a 100-year time horizon as 1...

Warm-up Practices in Elite Boxing Athletes: Impact on Power Output.

PubMed

Cunniffe, Brian; Ellison, Mark; Loosemore, Mike; Cardinale, Marco

2017-01-01

Cunniffe, B, Ellison, M, Loosemore, M, and Cardinale, M. Warm-up practices in elite boxing athletes: Iimpact on power output. J Strength Cond Res 31(1): 95-105, 2017-This study evaluated the performance impact of routine warm-up strategies in elite Olympic amateur boxing athletes and physiological implications of the time gap (GAP) between warm-up and boxing activity. Six male boxers were assessed while performing standardized prefight warm-up routines. Core and skin temperature measurements (Tcore and Tskin), heart rate, and upper- and lower-body power output (PO) were assessed before and after warm-up, during a 25-minutes GAP and after 3 × 2 minutes rounds of sparring. Reflected temperature (Tc) was also determined using high-resolution thermal images at fixed time-points to explore avenues for heat loss. Despite individual differences in warm-up duration (range 7.4-18.5 minutes), increases in Tcore and Tskin occurred (p ≤ 0.05). Corresponding increases (4.8%; p ≤ 0.05) in countermovement jump (CMJ) height and upward-rightward shifts in upper-body force-velocity and power-velocity curves were observed. Athletes remained inactive during the 25-minutes GAP with a gradual and significant increase in Tc occurring by the end of GAP suggesting the likelihood of heat loss. Decreases in CMJ height and upper-body PO were observed after 15 minutes and 25 minutes GAP (p ≤ 0.05). By the end of GAP period, all performance variables had returned to pre-warm-up values. Results suggest routine warm-ups undertaken by elite boxers have acute effects on power-generating capacity. Gradual decreases in performance variables are evident with inactivity and seem related to alterations in body temperature. Considering the constraints of major competitions and time spent in air conditioned holding areas before fights, practitioners should be aware of the potential of nullifying the warm-up effects.

40 CFR Appendix I to Subpart A of... - Global Warming Potentials (Mass Basis), Referenced to the Absolute GWP for the Adopted Carbon...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 17 2011-07-01 2011-07-01 false Global Warming Potentials (Mass Basis..., App. I Appendix I to Subpart A of Part 82—Global Warming Potentials (Mass Basis), Referenced to the... formula Global warming potential (time horizon) 20 years 100 years 500 years CFC-11 CFCl3 5000 4000 1400...

40 CFR Appendix I to Subpart A of... - Global Warming Potentials (Mass Basis), Referenced to the Absolute GWP for the Adopted Carbon...

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 18 2014-07-01 2014-07-01 false Global Warming Potentials (Mass Basis..., App. I Appendix I to Subpart A of Part 82—Global Warming Potentials (Mass Basis), Referenced to the... formula Global warming potential (time horizon) 20 years 100 years 500 years CFC-11 CFCl3 5000 4000 1400...

40 CFR Appendix I to Subpart A of... - Global Warming Potentials (Mass Basis), Referenced to the Absolute GWP for the Adopted Carbon...

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 18 2012-07-01 2012-07-01 false Global Warming Potentials (Mass Basis..., App. I Appendix I to Subpart A of Part 82—Global Warming Potentials (Mass Basis), Referenced to the... formula Global warming potential (time horizon) 20 years 100 years 500 years CFC-11 CFCl3 5000 4000 1400...

40 CFR Appendix I to Subpart A of... - Global Warming Potentials (Mass Basis), Referenced to the Absolute GWP for the Adopted Carbon...

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 18 2013-07-01 2013-07-01 false Global Warming Potentials (Mass Basis..., App. I Appendix I to Subpart A of Part 82—Global Warming Potentials (Mass Basis), Referenced to the... formula Global warming potential (time horizon) 20 years 100 years 500 years CFC-11 CFCl3 5000 4000 1400...

Research on trend of warm-humid climate in Central Asia

NASA Astrophysics Data System (ADS)

Gong, Zhi; Peng, Dailiang; Wen, Jingyi; Cai, Zhanqing; Wang, Tiantian; Hu, Yuekai; Ma, Yaxin; Xu, Junfeng

2017-07-01

Central Asia is a typical arid area, which is sensitive and vulnerable part of climate changes, at the same time, Central Asia is the Silk Road Economic Belt of the core district, the warm-humid climate change will affect the production and economic development of neighboring countries. The average annual precipitation, average anneal temperature and evapotranspiration are the important indexes to weigh the climate change. In this paper, the annual precipitation, annual average temperature and evapotranspiration data of every pixel point in Central Asia are analyzed by using long-time series remote sensing data to analyze the trend of warm and humid conditions. Finally, using the model to analyzed the distribution of warm-dry trend, the warm-wet trend, the cold-dry trend and the cold-wet trend in Central Asia and Xinjiang area. The results showed that most of the regions of Central Asia were warm-humid and warm-dry trends, but only a small number of regions showed warm-dry and cold-dry trends. It is of great significance to study the climatic change discipline and guarantee the ecological safety and improve the ability to cope with climate change in the region. It also provide scientific basis for the formulation of regional climate change program. The first section in your paper

Warming enhances old organic carbon decomposition through altering functional microbial communities

DOE PAGES

Cheng, Lei; Zhang, Naifang; Yuan, Mengting; ...

2017-04-21

Soil organic matter (SOM) stocks contain nearly three times as much carbon (C) as the atmosphere and changes in soil C stocks may have a major impact on future atmospheric carbon dioxide concentrations and climate. Over the past two decades, much research has been devoted to examining the influence of warming on SOM decomposition in topsoil. Most SOM, however, is old and stored in subsoil. The fate of subsoil SOM under future warming remains highly uncertain. Here, by combining a long-term field warming experiment and a meta-analysis study, we showed that warming significantly increased SOM decomposition in subsoil. We alsomore » showed that a decade of warming promoted decomposition of subsoil SOM with turnover times of decades to millennia in a tall grass prairie and this effect was largely associated with shifts in the functional gene structure of microbial communities. By coupling stable isotope probing with metagenomics, we found that microbial communities in warmed soils possessed a higher relative abundance of key functional genes involved in the degradation of organic materials with varying recalcitrance than those in control soils. These findings suggest warming may considerably alter the stability of the vast pool of old SOM in subsoil, contributing to the long-term positive feedback between the C cycle and climate.« less

Warming enhances old organic carbon decomposition through altering functional microbial communities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cheng, Lei; Zhang, Naifang; Yuan, Mengting

Soil organic matter (SOM) stocks contain nearly three times as much carbon (C) as the atmosphere and changes in soil C stocks may have a major impact on future atmospheric carbon dioxide concentrations and climate. Over the past two decades, much research has been devoted to examining the influence of warming on SOM decomposition in topsoil. Most SOM, however, is old and stored in subsoil. The fate of subsoil SOM under future warming remains highly uncertain. Here, by combining a long-term field warming experiment and a meta-analysis study, we showed that warming significantly increased SOM decomposition in subsoil. We alsomore » showed that a decade of warming promoted decomposition of subsoil SOM with turnover times of decades to millennia in a tall grass prairie and this effect was largely associated with shifts in the functional gene structure of microbial communities. By coupling stable isotope probing with metagenomics, we found that microbial communities in warmed soils possessed a higher relative abundance of key functional genes involved in the degradation of organic materials with varying recalcitrance than those in control soils. These findings suggest warming may considerably alter the stability of the vast pool of old SOM in subsoil, contributing to the long-term positive feedback between the C cycle and climate.« less

Global assessment of experimental climate warming on tundra vegetation: heterogeneity over space and time.

PubMed

Elmendorf, Sarah C; Henry, Gregory H R; Hollister, Robert D; Björk, Robert G; Bjorkman, Anne D; Callaghan, Terry V; Collier, Laura Siegwart; Cooper, Elisabeth J; Cornelissen, Johannes H C; Day, Thomas A; Fosaa, Anna Maria; Gould, William A; Grétarsdóttir, Járngerður; Harte, John; Hermanutz, Luise; Hik, David S; Hofgaard, Annika; Jarrad, Frith; Jónsdóttir, Ingibjörg Svala; Keuper, Frida; Klanderud, Kari; Klein, Julia A; Koh, Saewan; Kudo, Gaku; Lang, Simone I; Loewen, Val; May, Jeremy L; Mercado, Joel; Michelsen, Anders; Molau, Ulf; Myers-Smith, Isla H; Oberbauer, Steven F; Pieper, Sara; Post, Eric; Rixen, Christian; Robinson, Clare H; Schmidt, Niels Martin; Shaver, Gaius R; Stenström, Anna; Tolvanen, Anne; Totland, Orjan; Troxler, Tiffany; Wahren, Carl-Henrik; Webber, Patrick J; Welker, Jeffery M; Wookey, Philip A

2012-02-01

Understanding the sensitivity of tundra vegetation to climate warming is critical to forecasting future biodiversity and vegetation feedbacks to climate. In situ warming experiments accelerate climate change on a small scale to forecast responses of local plant communities. Limitations of this approach include the apparent site-specificity of results and uncertainty about the power of short-term studies to anticipate longer term change. We address these issues with a synthesis of 61 experimental warming studies, of up to 20 years duration, in tundra sites worldwide. The response of plant groups to warming often differed with ambient summer temperature, soil moisture and experimental duration. Shrubs increased with warming only where ambient temperature was high, whereas graminoids increased primarily in the coldest study sites. Linear increases in effect size over time were frequently observed. There was little indication of saturating or accelerating effects, as would be predicted if negative or positive vegetation feedbacks were common. These results indicate that tundra vegetation exhibits strong regional variation in response to warming, and that in vulnerable regions, cumulative effects of long-term warming on tundra vegetation - and associated ecosystem consequences - have the potential to be much greater than we have observed to date. © 2011 Blackwell Publishing Ltd/CNRS.

Warming enhances old organic carbon decomposition through altering functional microbial communities

PubMed Central

Cheng, Lei; Zhang, Naifang; Yuan, Mengting; Xiao, Jing; Qin, Yujia; Deng, Ye; Tu, Qichao; Xue, Kai; Van Nostrand, Joy D; Wu, Liyou; He, Zhili; Zhou, Xuhui; Leigh, Mary Beth; Konstantinidis, Konstantinos T; Schuur, Edward AG; Luo, Yiqi; Tiedje, James M; Zhou, Jizhong

2017-01-01

Soil organic matter (SOM) stocks contain nearly three times as much carbon (C) as the atmosphere and changes in soil C stocks may have a major impact on future atmospheric carbon dioxide concentrations and climate. Over the past two decades, much research has been devoted to examining the influence of warming on SOM decomposition in topsoil. Most SOM, however, is old and stored in subsoil. The fate of subsoil SOM under future warming remains highly uncertain. Here, by combining a long-term field warming experiment and a meta-analysis study, we showed that warming significantly increased SOM decomposition in subsoil. We also showed that a decade of warming promoted decomposition of subsoil SOM with turnover times of decades to millennia in a tall grass prairie and this effect was largely associated with shifts in the functional gene structure of microbial communities. By coupling stable isotope probing with metagenomics, we found that microbial communities in warmed soils possessed a higher relative abundance of key functional genes involved in the degradation of organic materials with varying recalcitrance than those in control soils. These findings suggest warming may considerably alter the stability of the vast pool of old SOM in subsoil, contributing to the long-term positive feedback between the C cycle and climate. PMID:28430189

Warming enhances old organic carbon decomposition through altering functional microbial communities.

PubMed

Cheng, Lei; Zhang, Naifang; Yuan, Mengting; Xiao, Jing; Qin, Yujia; Deng, Ye; Tu, Qichao; Xue, Kai; Van Nostrand, Joy D; Wu, Liyou; He, Zhili; Zhou, Xuhui; Leigh, Mary Beth; Konstantinidis, Konstantinos T; Schuur, Edward Ag; Luo, Yiqi; Tiedje, James M; Zhou, Jizhong

2017-08-01

Soil organic matter (SOM) stocks contain nearly three times as much carbon (C) as the atmosphere and changes in soil C stocks may have a major impact on future atmospheric carbon dioxide concentrations and climate. Over the past two decades, much research has been devoted to examining the influence of warming on SOM decomposition in topsoil. Most SOM, however, is old and stored in subsoil. The fate of subsoil SOM under future warming remains highly uncertain. Here, by combining a long-term field warming experiment and a meta-analysis study, we showed that warming significantly increased SOM decomposition in subsoil. We also showed that a decade of warming promoted decomposition of subsoil SOM with turnover times of decades to millennia in a tall grass prairie and this effect was largely associated with shifts in the functional gene structure of microbial communities. By coupling stable isotope probing with metagenomics, we found that microbial communities in warmed soils possessed a higher relative abundance of key functional genes involved in the degradation of organic materials with varying recalcitrance than those in control soils. These findings suggest warming may considerably alter the stability of the vast pool of old SOM in subsoil, contributing to the long-term positive feedback between the C cycle and climate.

Investigation of mechanisms and non-pharmacological therapy of cardiac arrhythmias

NASA Astrophysics Data System (ADS)

Vago, Hajnalka

Learning of mechanisms of arrhythmias may contribute substantially to the development of effective pharmacological and non-pharmacological therapeutic methods. Clinical relevance of endothelin-1 (ET-1), a strong vasoconstrictor and arrhythmogenic endogenous substrate, is not clarified yet. In our experimental studies, performed in the in situ canine heart, electrophysiological effects and the role in the pathomechanism of malignant ventricular tachyarrhythmias of endogenous and exogenous ET-1 was investigated. It has been proven in the in vivo ischaemia-reperfusion canine heart model, that during reperfusion ET-1 and big-ET levels increase in the coronary sinus, however there was no correlation between endothelin levels and electrophysiological changes. ET A-receptor antagonist darusentan does not prevent electrophysiological changes and development of ventricular tachyarrhythmias during ischaemia and reperfusion. On the contrary, during ischaemia endogenous ET-1 tends to show balancing effect. It has been proven that administration of high dose intracoronary ET-1 bolus has dual, ischaemic and direct, electrophysiological effect. It has been shown for the first time, that ET-1 causes monophasic action potential (MAP) and T-wave alternant. Our clinical study leads to the conclusion that previous atrial fibrillation, absence of preoperative beta-blocker treatment and combined heart surgery are strong predictors of atrial fibrillation following open heart surgery. The basis of new nonpharmacological therapies is the learning of pathomechanisms of arrhythmias and in some cases heart failure, which is an arrhythmogenic substrate. In our experimental study reliable MAP measurements, suitable for investigation of arrhythmogenesis, were performed for the first time using fractally coated ablation catheters during spontaneous rate and during stimulations. It has been proven that radiofrequency ablation affects significantly MAP parameters. In Hungary, we were the first to apply effectively biatrial pacemaker and biatrial cardioverter defibrillator for the prevention of paroxysmal atrial fibrillation. In the majority of patients frequency of paroxysmal atrial fibrillation decreased significantly due to biatrial stimulation or combined pharmacological and resynchronisation therapy. Parasymphathetic cardiac neurostimulation is a promising new non-pharmacological treatment option in certain types of arrhythmias. In our clinical study we were able to stimulate cardiac parasympathetic nerves innervating atrioventricular node achieving ventricular rate control during atrial tachyarrhythmias with chronically implanted coronary sinus lead. In our study biventricular pacemakers and cardioverter defibrillators were applied successfully in the treatment of drug refractory congestive heart failure combined with inter- and/or intraventricular conduction disturbances. AV sequential left sided chronic pacing using a single lead located in the coronary sinus has not been previously reported. Left sided DDD pacing was effective chronically in the improvement of the functional stage of patient suffering from congestive heart disease combined with left bundle branch block and binodal disease. Parallel with the investigation of pathomechanism of life-threatening ventricular tachyarrhythmias and the most common, clinically relevant atrial fibrillation due to recent technical development, we were able to support nonpharmacological therapeutic modalities, gaining popularity in clinical management, with novel observations.

[A pharmaceutical of the century will be 100. A historical vignette on the introduction of acetylsalicylic acid to the market in 1899].

PubMed

Kohl, F

1999-10-15

This article describes the historic roots of acetylsalicylic acid (ASA) from the first experiments at 1800 until the introduction into the pharmaceutical market in 1899. In 1869, Hermann Kolbe enlightened the chemical structure of salicylic acid, which was used at that time as an analgetic and antipyretic drug. Because of the side effects, for example the irritation of the stomach, analytical chemists and pharmacologists searched for chemical modifications. In August 1897 Felix Hoffmann (1868-1946) was successful in acetylizing the salicylic acid to acetylsalicylic acid (ASA). Between 1897 and 1899 Kurt Witthauer (1865-1911) collected clinical data and experiences on the efficiency of ASA as an analgetic and antipyretic drug. In 1899 ASA was introduced into the pharmaceutical market as Aspirin and became soon one of the most successful drugs of its time. The indication exceeds analgesia in the mean time and to prophylaxis of myocardial ischaemia or cerebral stroke, among others.

Combined effects of night warming and light pollution on predator-prey interactions.

PubMed

Miller, Colleen R; Barton, Brandon T; Zhu, Likai; Radeloff, Volker C; Oliver, Kerry M; Harmon, Jason P; Ives, Anthony R

2017-10-11

Interactions between multiple anthropogenic environmental changes can drive non-additive effects in ecological systems, and the non-additive effects can in turn be amplified or dampened by spatial covariation among environmental changes. We investigated the combined effects of night-time warming and light pollution on pea aphids and two predatory ladybeetle species. As expected, neither night-time warming nor light pollution changed the suppression of aphids by the ladybeetle species that forages effectively in darkness. However, for the more-visual predator, warming and light had non-additive effects in which together they caused much lower aphid abundances. These results are particularly relevant for agriculture near urban areas that experience both light pollution and warming from urban heat islands. Because warming and light pollution can have non-additive effects, predicting their possible combined consequences over broad spatial scales requires knowing how they co-occur. We found that night-time temperature change since 1949 covaried positively with light pollution, which has the potential to increase their non-additive effects on pea aphid control by 70% in US alfalfa. Our results highlight the importance of non-additive effects of multiple environmental factors on species and food webs, especially when these factors co-occur. © 2017 The Author(s).

Protein kinase A is activated by the n–3 polyunsaturated fatty acid eicosapentaenoic acid in rat ventricular muscle

PubMed Central

Szentandrássy, Norbert; Pérez-Bido, M R; Alonzo, E; Negretti, N; O'Neill, Stephen C

2007-01-01

During cardiac ischaemia antiarrhythmic n–3 polyunsaturated fatty acids (PUFAs) are released following activation of phospholipase A2, if they are in the diet prior to ischaemia. Here we show a positive lusitropic effect of one such PUFA, eicosapentaenoic acid (EPA) in the antiarrhythmic concentration range in Langendorff hearts and isolated rat ventricular myocytes due to activation of protein kinase A (PKA). Several different approaches indicated activation of PKA by EPA (5–10 μmol l−1): the time constant of decay of the systolic Ca2+ transient decreased to 65.3 ± 5.0% of control, Western blot analysis showed a fourfold increase in phospholamban phosphorylation, and PKA activity increased by 21.0 ± 7.3%. In addition myofilament Ca2+ sensitivity was reduced in EPA; this too may have resulted from PKA activation. We also found that EPA inhibited L-type Ca2+ current by 38.7 ± 3.9% but this increased to 63.3 ± 3.4% in 10 μmol l−1 H89 (to inhibit PKA), providing further evidence of activation of PKA by EPA. PKA inhibition also prevented the lusitropic effect of EPA on the systolic Ca2+ transient and contraction. Our measurements show, however, PKA activation in EPA cannot be explained by increased cAMP levels and alternative mechanisms for PKA activation are discussed. The combined lusitropic effect and inhibition of contraction by EPA may, respectively, combat diastolic dysfunction in ischaemic cardiac muscle and promote cell survival by preserving ATP. This is a further level of protection for the heart in addition to the well-documented antiarrhythmic qualities of these fatty acids. PMID:17510185

Effect of subconjunctival glucose on retinal ganglion cell survival in experimental retinal ischaemia and contrast sensitivity in human glaucoma.

PubMed

Shibeeb, O'Sam; Chidlow, Glyn; Han, Guoge; Wood, John P M; Casson, Robert J

2016-01-01

This study aims to evaluate the effect of subconjunctival glucose on the retinal ganglion cells (RGCs) in experimental retinal ischaemia and contrast sensitivity in humans with primary open-angle glaucoma (POAG). First, we measured the intravitreal concentration of glucose at various time points after a subconjunctival injection of 100 μl of 50% glucose to Sprague-Dawley rats. Next, treatment and control groups received 50% subconjunctival glucose and iso-osmotic (8%) saline, respectively, 1 h prior to a unilateral ischaemic retinal injury; 7 days later, the damage profiles were compared using RGC and axon counts. Subsequently, we conducted a double-blind, crossover, pilot clinical study in seven eyes of five pseudophakic subjects with severe POAG. Subjects received either 0.3 mL of 50% glucose subconjunctivally or iso-osmotic (8%) saline, then vice versa after a 2-3 week 'wash-out' period; change in contrast sensitivity from baseline was the primary outcome. Subconjunctival glucose preserved approximately 60% of Brn3a-positive RGCs in all retinal zones compared with an 80% loss in control retinas, and rescued approximately 40% of the axonal loss. In the human trial, the contrast sensitivity at 12 cycles/degree was 0.24 log units greater than baseline (95% confidence interval 0.12-0.36; P < 0.001). Subconjunctival glucose partially protects RGC somata and axons against an ischaemic insult and temporarily recovers contrast sensitivity in patients with severe POAG. Although an unlikely therapeutic strategy for POAG, the findings motivate further bioenergetic-based research in glaucoma and other optic nerve and retinal diseases, where energy failure may be part of the pathogenesis. © 2015 Royal Australian and New Zealand College of Ophthalmologists.

Long-lasting neuroprotection and neurological improvement in stroke models with new, potent and brain permeable inhibitors of poly(ADP-ribose) polymerase

PubMed Central

Moroni, F; Cozzi, A; Chiarugi, A; Formentini, L; Camaioni, E; Pellegrini-Giampietro, DE; Chen, Y; Liang, S; Zaleska, MM; Gonzales, C; Wood, A; Pellicciari, R

2012-01-01

BACKGROUND AND PURPOSES Thienyl-isoquinolone (TIQ-A) is a relatively potent PARP inhibitor able to reduce post-ischaemic neuronal death in vitro. Here we have studied, in different stroke models in vivo, the neuroprotective properties of DAMTIQ and HYDAMTIQ, two TIQ-A derivatives able to reach the brain and to inhibit PARP-1 and PARP-2. EXPERIMENTAL APPROACH Studies were carried out in (i) transient (2 h) middle cerebral artery occlusion (tMCAO), (ii) permanent MCAO (pMCAO) and (iii) electrocoagulation of the distal portion of MCA in conjunction with transient (90 min) bilateral carotid occlusion (focal cortical ischaemia). KEY RESULTS In male rats with tMCAO, HYDAMTIQ (0.1–10 mg·kg−1) injected i.p. three times, starting 4 h after MCAO, reduced infarct volumes by up to 70%, reduced the loss of body weight by up to 60% and attenuated the neurological impairment by up to 40%. In age-matched female rats, HYDAMTIQ also reduced brain damage. Protection, however, was less pronounced than in the male rats. In animals with pMCAO, HYDAMTIQ administered 30 min after MCAO reduced infarct volumes by approximately 40%. In animals with focal cortical ischaemia, HYDAMTIQ treatment decreased post-ischaemic accumulation of PAR (the product of PARP activity) and the presence of OX42-positive inflammatory cells in the ischaemic cortex. It also reduced sensorimotor deficits for up to 90 days after MCAO. CONCLUSION AND IMPLICATIONS Our results show that HYDAMTIQ is a potent PARP inhibitor that conferred robust neuroprotection and long-lasting improvement of post-stroke neurological deficits. PMID:21913897

Results of bypass graft surgery after prior angioplasty in critical limb ischaemia treatment.

PubMed

Cury, Marcus Vinícius Martins; Brochado-Neto, Francisco Cardoso; Matielo, Marcelo Fernando; de Athayde Soares, Rafael; Sarpe, Anna Karina Paiva; Sacilotto, Roberto

2016-01-01

The aim of this study was to determine the outcomes of primary bypass graft surgery (BGS) compared to BGS after failed angioplasty (PTA). Between January 2007 and January 2014, we performed 136 BGSs exclusively for the treatment of critical limb ischaemia. Two cohorts were identified: 1) primary BGS (n = 102; group I), and 2) BGS after prior PTA (n = 34; group II). Data were analysed retrospectively and the primary endpoints were the rates of secondary patency, amputation-free survival, freedom from major adverse outcomes (graft occlusion, amputation, or death), and overall survival, which were assessed with the Kaplan-Meier method. Both groups were comparable with a predominance of Rutherford's category 5 ischaemic lesions (73.3 %). Most patients had extensive TASC D athe-rosclerotic disease (83.6 %), and the main conduit was the greater saphenous vein (58.1 %). The mean follow-up time was 36.2 months. The 3-year secondary patency rates were better for group I (64.3 % vs 49.6 %; P = 0.04). During the same period, the amputation-free survival rates were similar between the groups (77.4 % vs 74.5 %; P = 0.59). For multivariate Cox regression analysis, BGS after prior PTA was the only factor associated with re-intervention for limb salvage (hazard ratio = 2.39; CI 95 % = 1.19 - 4.80; P = 0.02). At the 3-year point, there were no differences in the overall survival rates (72.6 % vs 70 %; P = 0.97), but the proportion of patients without adverse outcomes was higher in group I (37.3 % vs 13.4 %; P = 0.007). Although secondary patency was better after primary BGS, the amputation-free and overall survival rates support the use of BGS after prior PTA.

The influence of climate change and the timing of stratospheric warmings on Arctic ozone depletion

NASA Astrophysics Data System (ADS)

Austin, John; Butchart, Neal

1994-01-01

Satellite data are presented showing the timing of sudden warmings in the lower stratosphere during the winters 1979-1992. A three-dimensional dynamical-radiative-photochemical model is used to establish how Arctic ozone depletion will respond to a doubling of CO2 according to the timing of the warmings. In a series of idealized experiments the timing of the warmings is varied by specifying different geopotential wave amplitudes at the 316-mbar model lower boundary. Results from a "transient climate change experiment" show that the chosen wave amplitudes are appropriate for both the current and the doubled CO2 atmosphere. For doubled CO2 the experiments show that any significant risk of an Arctic ozone hole will be confined to those years with only a late stratospheric warming. In all other years the results suggest that springtime total ozone over the Arctic is more likely to increase by a small amount due to a combination of slower homogeneous chemistry and changes in transport. The predictions obtained from the idealized studies are then tested by prescribing at the model lower boundary the observed geopotential wave amplitudes from two specific years with late winter warmings. Doubling CO2 amounts produced no significant increase in ozone depletion with the 1989 wave amplitudes, but with 1990 wave amplitudes, an Arctic ozone hole occurred with minimum column of 187 Dobson Units. This contrasting response is attributed to the large midwinter pulse in the 1989 wave amplitudes compared to the less dramatic and shorter timescale fluctuations in the 1990 wave amplitudes. It is concluded that under doubled CO2 conditions an Arctic ozone hole is likely to occur in years with late stratospheric warmings following winters in which there were no significant pulses in the upper tropospheric planetary wave amplitudes.

Transition phase clothing strategies and their effect on body temperature and 100-m swimming performance.

PubMed

Galbraith, Andy; Willmott, Aimee

2018-03-01

Effective warm-ups are attributed to several temperature-related mechanisms. Strategies during the transition phase, preceding swimming competition, have been shown to prolong temperature-related warm-up effects. The purpose of this study was to evaluate the effects of two different clothing strategies during the transition phase, on subsequent 100-m maximal swimming performance. Nine competitive swimmers (3 female, 21 ± 3 yrs; 6 male 20 ± 2 yrs, mean performance standard 702 FINA Points, mean 100-m seasons best time 61.54 s) completed their own 30-min individual pool warm-up, followed by 7-min changing time and a 30-min transition phase, straight into a 100-m maximal effort time-trial. During the transition phase, swimmers remained seated, either wearing warm or limited clothing. Swimmers returned 1 week later, where clothing conditions were alternated. Post-transition phase skin and core temperature remained higher in the warm clothing condition compared to the limited clothing condition (Mean Core: 36.90 ± 0.17°C, 36.61 ± 0.15°C, P < .01; Mean Skin: 33.49 ± 0.59°C, 31.94 ± 0.59°C, P < .01). One hundred-metre finish times were 0.6% faster in the warm clothing condition compared to the limited clothing condition (62.63 ± 7.69 s, 63.00 ± 7.75 s, P < .01). Wearing warm clothing during a 30-min transition phase improved swimming performance by 0.6%, compared to limited clothing.

Warm-ups for military fitness testing: rapid evidence assessment of the literature.

PubMed

Zeno, Stacey A; Purvis, Dianna; Crawford, Cindy; Lee, Courtney; Lisman, Peter; Deuster, Patricia A

2013-07-01

Warm-up exercises are commonly used before exercise as a method to physiologically prepare for strenuous physical activity. Various warm-up exercises are often implemented but without scientific merit and, at times, may be detrimental to performance. To date, no systematic reviews have examined the effectiveness of warm-up exercises for military physical fitness test (PFT) or combat fitness test (CFT). The purpose of this rapid evidence assessment of the literature was to examine the quantity, quality, and effectiveness of warm-up exercises for PFT and identify those that might increase PFT and/or CFT scores, as reported in the literature. Literature searches of randomized controlled trials were performed across various databases from database inception to May 2011. Methodological quality of included studies was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) 50 criteria for randomized controlled trial designs, and studies were individually described. Subject matter experts summarized the results applicable or generalizable to military testing. The search yielded a total of 1177 citations, with 37 fitting our inclusion criteria. Cardiovascular warm-ups increased sprint/running time, but dynamic stretching and dynamic warm-ups had the most positive outcome for the various exercise tests examined. Systematically, static stretching had no beneficial or detrimental effect on exercise performance but did improve range of movement exercises. Selected warm-up exercise may increase PFT and possibly CFT scores. Further research is needed to investigate the efficacy of dynamic stretching and dynamic warm-ups.

Experimental ex vivo lung perfusion with sevoflurane: effects on damaged donor lung grafts.

PubMed

Wang, Xingyu; Parapanov, Roumen; Francioli, Cyril; Perentes, Jean Yannis; Letovanec, Igor; Gonzalez, Michel; Kern, Christian; Ris, Hans-Beat; Piquilloud, Lise; Marcucci, Carlo; Krueger, Thorsten; Liaudet, Lucas; Gronchi, Fabrizio

2018-06-01

Volatile anaesthetics can provide significant protection against reperfusion injury in various experimental settings. The aim of this study was to assess the potential of sevoflurane treatment, the most commonly used volatile anaesthetic in modern anaesthesia, in rat lungs donated after circulatory death and reconditioned in an ex vivo lung perfusion (EVLP) system. Fifteen rats were sacrificed and divided into 3 groups. In the control and sevoflurane groups, the heart-lung blocks were exposed to 1 h of warm ischaemia and 2 h of cold ischaemia and were mounted on an EVLP circuit for 3 h, in the absence or in the presence of 2% sevoflurane. In the baseline group, heart-lung blocks were harvested immediately after euthanasia. Physiological data, lung nitro-oxidative stress, lactate dehydrogenase (LDH), expression of cytokines, oedema and histopathological findings were assessed during or post-EVLP. The sevoflurane group showed significantly reduced LDH (8.82 ± 3.58 arbitrary unit vs 3.80 ± 3.02 arbitrary unit, P = 0.03), protein carbonyl (1.17 ± 0.44 nmol⋅mg-1 vs 0.55 ± 0.11 nmol⋅mg-1, P = 0.006), 3-nitrotyrosine (197.44 ± 18.47 pg⋅mg-1 vs 151.05 ± 23.54 pg⋅mg-1, P = 0.004), cytokine-induced neutrophil chemoattractant factor 1 (1.17 ± 0.32 ng⋅mg-1 vs 0.66 ± 0.28 ng⋅mg-1, P = 0.03) and tumour necrosis factor alpha (1.50 ± 0.59 vs 0.59 ± 0.38 ng⋅mg-1, P = 0.02) when compared with the control group. In addition, sevoflurane lungs gained significantly less weight (0.72 ± 0.09 g vs 0.72 ± 0.09 g, P = 0.044), had less perivascular oedema (0.58 ± 0.09 vs 0.47 ± 0.07, P = 0.036), and improved static pulmonary compliance (+0.215 ml⋅cmH2O-1, P = 0.003) and peak airways pressure (-1.33 cmH2O, P = 0.04) but similar oxygenation capacity (+1.61 mmHg, P = 0.77) and pulmonary vascular resistances (+0.078 mmHg⋅min⋅ml-1, P = 0.15) when compared with the control group. These findings suggest that the potential of sevoflurane in protecting the lungs donated after cardiac death and reconditioned using EVLP could improve the outcome of these lungs following subsequent transplantation.

Influences of spawning timing, water temperature, and climatic warming on early life history phenology in western Alaska sockeye salmon

USGS Publications Warehouse

Sparks, Morgan M.; Falke, Jeffrey A.; Quinn, Thomas P.; Adkison, Milo D.; Schindler, Daniel E.; Bartz, Krista K.; Young, Daniel B.; Westley, Peter A. H.

2018-01-01

We applied an empirical model to predict hatching and emergence timing for 25 western Alaska sockeye salmon (Oncorhynchus nerka) populations in four lake-nursery systems to explore current patterns and potential responses of early life history phenology to warming water temperatures. Given experienced temperature regimes during development, we predicted hatching to occur in as few as 58 d to as many as 260 d depending on spawning timing and temperature. For a focal lake spawning population, our climate-lake temperature model predicted a water temperature increase of 0.7 to 1.4 °C from 2015 to 2099 during the incubation period, which translated to a 16 d to 30 d earlier hatching timing. The most extreme scenarios of warming advanced development by approximately a week earlier than historical minima and thus climatic warming may lead to only modest shifts in phenology during the early life history stage of this population. The marked variation in the predicted timing of hatching and emergence among populations in close proximity on the landscape may serve to buffer this metapopulation from climate change.

Eutrophication and Warming Boost Cyanobacterial Biomass and Microcystins.

PubMed

Lürling, Miquel; van Oosterhout, Frank; Faassen, Elisabeth

2017-02-11

Eutrophication and warming are key drivers of cyanobacterial blooms, but their combined effects on microcystin (MC) concentrations are less studied. We tested the hypothesis that warming promotes cyanobacterial abundance in a natural plankton community and that eutrophication enhances cyanobacterial biomass and MC concentrations. We incubated natural seston from a eutrophic pond under normal, high, and extreme temperatures (i.e., 20, 25, and 30 °C) with and without additional nutrients added (eutrophication) mimicking a pulse as could be expected from projected summer storms under climate change. Eutrophication increased algal- and cyanobacterial biomass by 26 and 8 times, respectively, and led to 24 times higher MC concentrations. This effect was augmented with higher temperatures leading to 45 times higher MC concentrations at 25 °C, with 11 times more cyanobacterial chlorophyll- a and 25 times more eukaryote algal chlorophyll- a . At 30 °C, MC concentrations were 42 times higher, with cyanobacterial chlorophyll- a being 17 times and eukaryote algal chlorophyll- a being 24 times higher. In contrast, warming alone did not yield more cyanobacteria or MCs, because the in situ community had already depleted the available nutrient pool. MC per potential MC producing cell declined at higher temperatures under nutrient enrichments, which was confirmed by a controlled experiment with two laboratory strains of Microcystis aeruginosa. Nevertheless, MC concentrations were much higher at the increased temperature and nutrient treatment than under warming alone due to strongly promoted biomass, lifting N-imitation and promotion of potential MC producers like Microcystis . This study exemplifies the vulnerability of eutrophic urban waters to predicted future summer climate change effects that might aggravate cyanobacterial nuisance.

Warm-adapted microbial communities enhance their carbon-use efficiency in warmed soils

NASA Astrophysics Data System (ADS)

Rousk, Johannes; Frey, Serita

2017-04-01

Ecosystem models predict that climate warming will stimulate microbial decomposition of soil carbon (C), resulting in a positive feedback to increasing temperatures. The current generation of models assume that the temperature sensitivities of microbial processes do not respond to warming. However, recent studies have suggested that the ability of microbial communities to adapt to warming can lead both strengthened and weakened feedbacks. A further complication is that the balance between microbial C used for growth to that used for respiration - the microbial carbon-use efficiency (CUE) - also has been shown through both modelling and empirical study to respond to warming. In our study, we set out to assess how chronic warming (+5°C over ambient during 9 years) of a temperate hardwood forest floor (Harvard Forest LTER, USA) affected temperature sensitivities of microbial processes in soil. To do this, we first determined the temperature relationships for bacterial growth, fungal growth, and respiration in plots exposed to warmed or ambient conditions. Secondly, we parametrised the established temperature functions microbial growth and respiration with plot-specific measured soil temperature data at a hourly time-resolution over the course of 3 years to estimate the real-time variation of in situ microbial C production and respiration. To estimate the microbial CUE, we also divided the microbial C production with the sum of microbial C production and respiration as a proxy for substrate use. We found that warm-adapted bacterial and fungal communities both shifted their temperature relationships to grow at higher rates in warm conditions which coincided with reduced rates at cool conditions. As such, their optimal temperature (Topt), minimum temperature (Tmin) and temperature sensitivity (Q10) were all increased. The temperature relationship for temperature, in contrast, was only marginally shifted in the same direction, but at a much smaller effect size, with negligible changes in Topt, Tmin and Q10 for respiration. When these physiological changes were scaled with soil temperature data to estimate real-time variation in situ during three years, the warm-adaptation resulted in elevated microbial CUEs during summer temperatures in warm-adapted communities and reduced microbial CUEs during winter temperatures. By comparing simulated microbial CUEs in cold-adapted communities exposed to warmed conditions to microbial CUEs in the warm-adapted communities exposed to those temperatures, we could demonstrate that the shifts towards warm-adapted microbial communities had selected for elevated microbial CUEs for the full range of in situ soil temperatures during three years. Our results suggest that microbial adaptation to warming will enhance microbial CUEs, shifting their balance of C use from respiration to biomass production. If our estimates scale to ecosystem level, this would imply that warm-adapted microbial communities will ultimately have the potential to store more C in soil than their cold-adapted counter parts could when exposed to warmer temperatures.

Controlled warming effects on wheat growth and yield: field measurements and modeling

USDA-ARS?s Scientific Manuscript database

Climate warming may raise wheat yields in cooler climates and lower them in warmer. To understand these contrasting effects, infrared heating lamps were used to warm irrigated spring wheat by 1.5 'C (day) and 3.0 'C (night) above unheated controls during different times of the year at Maricopa, AZ. ...

Warm Rain Processes Over the Tropical Oceans and Implications on Climate Change

NASA Technical Reports Server (NTRS)

Lau, William K. M.; Wu, H. T.

2004-01-01

In this talk, we will first show results from TRMM regarding the characteristics of warm rains over the tropical oceans, and the dependence of rate of warm rain production on sea surface temperature. Results lead to the hypothesis that warm rain production efficiency, i.e., autoconversion, may be increased in a warm climate. We use the GEOS-II GCM to test this hypothesis. Our modeling results show that in a climate with increased rate of autoconversion, the total rain amount is increased, with warm rain contributing to a larger portion of the increase. The abundant rainout of warm precipitation at middle to low levels causes a reduction of high cloud cover due to the depletion of water available for ice-phase rain production. As a result, more isolated, but more intense penetrative convection develops. Results also show that increased autoconversion reduces the convective adjustment time scale tends, implying a faster recycling of atmospheric water. Most interestingly, the increased low level heating associated with warm rain leads to more energetic Madden and Julian oscillations in the tropics, with well-defined eastward propagation. While reducing the autoconversion leads to an abundant mix of westward and eastward tropical disturbance on daily to weekly time scales. The causes of the sensitivity of the dynamical regimes to the microphysics parameterization in the GCM will be discussed.

Changes in Concurrent Risk of Warm and Dry Years under Impact of Climate Change

NASA Astrophysics Data System (ADS)

Sarhadi, A.; Wiper, M.; Touma, D. E.; Ausín, M. C.; Diffenbaugh, N. S.

2017-12-01

Anthropogenic global warming has changed the nature and the risk of extreme climate phenomena. The changing concurrence of multiple climatic extremes (warm and dry years) may result in intensification of undesirable consequences for water resources, human and ecosystem health, and environmental equity. The present study assesses how global warming influences the probability that warm and dry years co-occur in a global scale. In the first step of the study a designed multivariate Mann-Kendall trend analysis is used to detect the areas in which the concurrence of warm and dry years has increased in the historical climate records and also climate models in the global scale. The next step investigates the concurrent risk of the extremes under dynamic nonstationary conditions. A fully generalized multivariate risk framework is designed to evolve through time under dynamic nonstationary conditions. In this methodology, Bayesian, dynamic copulas are developed to model the time-varying dependence structure between the two different climate extremes (warm and dry years). The results reveal an increasing trend in the concurrence risk of warm and dry years, which are in agreement with the multivariate trend analysis from historical and climate models. In addition to providing a novel quantification of the changing probability of compound extreme events, the results of this study can help decision makers develop short- and long-term strategies to prepare for climate stresses now and in the future.

Global Ocean Circulation During Cretaceous Time

NASA Astrophysics Data System (ADS)

Haupt, B. J.; Seidov, D.

2001-12-01

Present--day global thermohaline ocean circulation (TOC) is usually associated with high--latitude deep-water formation due to surface cooling. In this understanding of the TOC driven by the deep--water production, the warm deep ocean during Mesozoic--Cenozoic time is a challenge. It may be questioned whether warm deep--ocean water, which is direct geologic evidence, does reflect warm polar surface--ocean regions. For the warm Cretaceous, it is difficult to maintain strong poleward heat transport in the case of reduced oceanic thermal contrasts. Usually, atmospheric feedbacks, in conjunction with the increase of atmospheric concentrations of greenhouse gases, are employed in order to explain the warm equable Cretaceous--Eocene climate. However, there is no feasible physical mechanism that could maintain warm subpolar surface oceans in both hemispheres, an assumption often used in atmospheric modeling. Our numerical experiments indicate that having a relatively cool but saltier high--latitude sea surface in at least one hemisphere is sufficient for driving a strong meridional overturning. Thus freshwater impacts in the high latitudes may be responsible for a vigorous conveyor capable of maintaining sufficient poleward oceanic heat transport needed to keep the polar oceans ice--free. These results imply that evaporation-precipitation patterns during warm climates are especially important climatic factors that can redistribute freshwater to create hemispheric asymmetry of sea surface conditions capable of generating a sufficiently strong TOC, otherwise impossible in warm climates.

Transient global amnesia—a hippocampal phenomenon?

PubMed Central

Ponsford, J L; Donnan, G A

1980-01-01

A case of transient global amnesia of clear vascular aetiology is described. Results of neuropsychological testing carried out during the attack clarify the nature of the memory disorder and suggest that the critical region of ischaemia is the medial temporal area around the hippocampus. Follow-up testing suggests that no lasting memory impairment resulted. PMID:7373328

Excitatory amino acid receptors and disease.

PubMed

Meldrum, B S

1992-08-01

Recent advances in the molecular biology of excitatory amino acid receptors are reviewed. Evidence that drugs blocking the excitatory action of glutamate at the N-methyl-D-aspartate (NMDA) and non-NMDA receptors may be of clinical use in epilepsy, Parkinson's disease, cerebral ischaemia and trauma, acquired immune deficiency syndrome (AIDS) encephalopathy and neuropathic pain is summarized.

Consensus best practice pathway of the UK Scleroderma Study Group: digital vasculopathy in systemic sclerosis.

PubMed

Hughes, Michael; Ong, Voon H; Anderson, Marina E; Hall, Frances; Moinzadeh, Pia; Griffiths, Bridget; Baildam, Eileen; Denton, Christopher P; Herrick, Ariane L

2015-11-01

Digital vasculopathy (comprising RP, digital ulceration and critical digital ischaemia) is responsible for much of the pain and disability experienced by patients with SSc. However, there is a limited evidence base to guide clinicians in the management of SSc-related digital vasculopathy. Our aim was to produce recommendations that would be helpful for clinicians, especially for those managing patients outside specialist centres. The UK Scleroderma Study Group set up several working groups to develop a number of consensus best practice pathways for the management of SSc-specific complications, including digital vasculopathy. This overview presents the background and best practice consensus pathways for SSc-related RP, digital ulceration and critical ischaemia. Examples of drug therapies, including doses, are suggested in order to inform prescribing practice. A number of treatment algorithms are provided that are intended to provide the clinician with accessible reference tools for use in daily management. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

[Myocardial infarction. New universal definition and its implementation in clinical practice].

PubMed

Vafaie, M; Katus, H A

2013-12-01

The third version of the Universal Definition of Myocardial Infarction (MI) was published in 2012. The diagnosis of acute myocardial infarction (AMI) should only be made in a clinical setting consistent with acute myocardial ischaemia when evidence of myocardial necrosis is present. The diagnostic criteria for MI are fulfilled when a rise and/or fall of cardiac biomarkers (preferentially troponins) occurs with at least one value above the 99th percentile of the upper reference limit. In addition, there should be symptoms of ischaemia, new changes in electrocardiogram (ECG), imaging evidence of a new loss of viable myocardium or new regional wall motion abnormality, or the identification of an intracoronary thrombus by angiography or autopsy. This revised definition updates previous versions by including changes to diagnostic ECG criteria, placing a higher emphasis on cardiac imaging, modifying the criteria for subtypes of MI and implementing high sensitivity cardiac troponin (cTn) assays. A guideline-based algorithm for management of patients with suspected acute coronary syndrome allowing "early rule-in" and "rule-out" of non-STEMI with high sensitivity cTn assays is also presented.

cGMP signalling in pre- and post-conditioning: the role of mitochondria.

PubMed

Costa, Alexandre D T; Pierre, Sandrine V; Cohen, Michael V; Downey, James M; Garlid, Keith D

2008-01-15

Much of cell death from ischaemia/reperfusion in heart and other tissues is generally thought to arise from mitochondrial permeability transition (MPT) in the first minutes of reperfusion. In ischaemic pre-conditioning, agonist binding to G(i) protein-coupled receptors prior to ischaemia triggers a signalling cascade that protects the heart from MPT. We believe that the cytosolic component of this trigger pathway terminates in activation of guanylyl cyclase resulting in increased production of cGMP and subsequent activation of protein kinase G (PKG). PKG phosphorylates a protein on the mitochondrial outer membrane (MOM), which then causes the mitochondrial K(ATP) channel (mitoK(ATP)) on the mitochondrial inner membrane to open, leading to increased production of reactive oxygen species (ROS) by the mitochondria. This implies that the protective signal is somehow transmitted from the MOM to its inner membrane. This is accomplished by a series of intermembrane signalling steps that includes protein kinase C (PKCepsilon) activation. The resulting ROS then activate a second PKC pool which, through another signal transduction pathway termed the mediator pathway, causes inhibition of MPT and reduction in cell death.

Remote ischaemic preconditioning and prevention of cerebral injury.

PubMed

Rehni, Ashish K; Shri, Richa; Singh, Manjeet

2007-03-01

Bilateral carotid artery occlusion of 10 min followed by reperfusion for 24 hr was employed in present study to produce ischaemia and reperfusion induced cerebral injury in mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Short-term memory was evaluated using elevated plus maze. Inclined beam walking test was employed to assess motor incoordination. Bilateral carotid artery occlusion followed by reperfusion produced cerebral infarction and impaired short-term memory, motor co-ordination and lateral push response. A preceding episode of mesenteric artery occlusion for 15 min and reperfusion of 15 min (remote mesenteric ischaemic preconditioning) prevented markedly ischaemia-reperfusion-induced cerebral injury measured in terms of infarct size, loss of short-term memory, motor coordination and lateral push response. Glibenclamide (5 mg/kg, iv) a KATP channel blocker and caffeine (7 mg/kg, iv) an adenosine receptor blocker attenuated the neuroprotective effect of remote mesenteric ischaemic preconditioning. It may be concluded that neuroprotective effect of remote mesenteric ischaemic preconditioning may be due to activation of adenosine receptors and consequent activation of KATP channels in mice.

Thoracic Unilateral Spinal Cord Injury After Spinal Anaesthesia for Total Hip Replacement: Fate or Mistake?

PubMed Central

Fabio, Costa; Romualdo, Del Buono; Eugenio, Agrò Felice; Vittoradolfo, Tambone; Massimiliano, Vitali Andrea; Giovanna, Ricci

2017-01-01

Spinal anaesthesia is the most preffered anesthesia technique for total hip replacement, and its complications range from low entity (insignificant) to life threatening. The incidence of neurologic complications after neuraxial anaesthesia is not perfectly clear, although there are several described cases of spinal cord ischaemia. We present a case of unilateral T8–T11 spinal cord ischaemia following L2–L3 spinal anaesthesia for total hip replacement. Magnetic resonance imaging showed a hyperintense T8–T11 signal alteration on the leftside of paramedian spinal cord. A temporal epidemiologic linkage between the damage and the surgery seems to be present. The injury occurred without anatomical proximity between the injury site and the spinal needle entry site. This may be due to multiple contributing factors, each of them is probably not enough to determine the damage by itself; however, acting simultaneously, they could have been responsible for the complication. The result was unpredictable and unavoidable and was caused by unforeseeable circumstances and not by inadequate medical practice. PMID:28439446

Myocardial infarction increases progressive visual field defects in well treated early primary open angle glaucoma--a prospective case control study.

PubMed

Mondal, Lakshmikanta; Baidya, Krishnapada; Choudhury, Himadri; Roy, Rupam

2013-06-01

The purpose of the study was to evaluate the progression of glaucomatous field damage in patients with stable primary open angle glaucoma after an attack of myocardial infarction. In this case control study, 62 open angle glaucoma patients were selected and regularly followed up. Among 62 patients, 9 had an attack of myocardial infarction. The intra-ocular pressure and visual field progression of both the groups (myocardial infarction versus no myocardial infarction) were analysed. Three (33.3%) out of 9 patients who had suffered from myocardial infarction showed progressive visual field loss whereas only 9 (16.9%) out of 53 patients who did not suffer from myocardial infarction, showed progressive field changes. Both the groups had stable target intra-ocular pressure between 14 and 16 mm Hg. Myocardial infarction may adversely influence the progression of primary open angle glaucoma which is suspected to result from ischaemia induced neuronal loss and only control of intraocular pressure is not the only solution. We have to look for other drugs that prevents ischaemia induced neuronal damage.

Emerging molecular therapies targeting myocardial infarction-related arrhythmias.

PubMed

Driessen, Helen E; van Veen, Toon A B; Boink, Gerard J J

2017-04-01

Cardiac disease is the leading cause of death in the developed world. Ventricular arrhythmias associated with myocardial ischaemia and/or infarction are a major contributor to cardiovascular mortality, and require improved prevention and treatment. Drugs, devices, and radiofrequency catheter ablation have made important inroads, but have significant limitations ranging from incomplete success to undesired toxicities and major side effects. These limitations derive from the nature of the intervention. Drugs are frequently ineffective, target the entire heart, and often do not deal with the specific arrhythmia trigger or substrate. Devices can terminate rapid rhythms but at best indirectly affect the underlying disease, while ablation, even when appropriately targeted, induces additional tissue damage. In contrast, exploration of gene and cell therapies are expected to provide a targeted, non-destructive, and potentially regenerative approach to ischaemia- and infarction-related arrhythmias. Although these approaches are in the early stages of development, they carry substantial potential to advance arrhythmia prevention and treatment. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

How does warming affect carbon allocation, respiration and residence time in trees? An isotope tracer approach in a eucalypt

NASA Astrophysics Data System (ADS)

Pendall, E.; Drake, J. E.; Furze, M.; Barton, C. V.; Carillo, Y.; Richter, A.; Tjoelker, M. G.

2017-12-01

Climate warming has the potential to alter the balance between photosynthetic carbon assimilation and respiratory losses in forest trees, leading to uncertainty in predicting their future physiological functioning. In a previous experiment, warming decreased canopy CO2 assimilation (A) rates of Eucalyptus tereticornis trees, but respiration (R) rates were usually not significantly affected, due to physiological acclimation to temperature. This led to a slight increase in (R/A) and thus decrease in plant carbon use efficiency with climate warming. In contrast to carbon fluxes, the effect of warming on carbon allocation and residence time in trees has received less attention. We conducted a study to test the hypothesis that warming would decrease the allocation of C belowground owing to reduced cost of nutrient uptake. E. parramattensis trees were grown in the field in unique whole-tree chambers operated at ambient and ambient +3 °C temperature treatments (n=3 per treatment). We applied a 13CO2 pulse and followed the label in CO2 respired from leaves, roots, canopy and soil, in plant sugars, and in rhizosphere microbes over a 3-week period in conjunction with measurements of tree growth. The 9-m tall, 57 m3 whole-tree chambers were monitored for CO2 concentrations in independent canopy and below ground (root and soil) compartments; periodic monitoring of δ13C values in air in the compartments allowed us to quantify the amount of 13CO2 assimilated and respired by each tree. Warmed trees grew faster and assimilated more of the label than control trees, but the 13C allocation to canopy, root and soil respiration was not altered. However, warming appeared to reduce the residence time of carbon respired from leaves, and especially from roots and soil, indicating that autotrophic respiration has the potential to feedback to climate change. This experiment provides insights into how warming may affect the fate of assimilated carbon from the leaf to the ecosystem scale.

Comparison of the WarmCloud and Bair Hugger Warming Devices for the Prevention of Intraoperative Hypothermia in Patients Undergoing Orthotopic Liver Transplantation: A Randomized Clinical Trial

PubMed Central

Pearce, Brett; Mattheyse, Linda; Ellard, Louise; Desmond, Fiona; Pillai, Param; Weinberg, Laurence

2018-01-01

Background The avoidance of hypothermia is vital during prolonged and open surgery to improve patient outcomes. Hypothermia is particularly common during orthotopic liver transplantation (OLT) and associated with undesirable physiological effects that can adversely impact on perioperative morbidity. The KanMed WarmCloud (Bromma, Sweden) is a revolutionary, closed-loop, warm-air heating mattress developed to maintain normothermia and prevent pressure sores during major surgery. The clinical effectiveness of the WarmCloud device during OLT is unknown. Therefore, we conducted a randomized controlled trial to determine whether the WarmCloud device reduces hypothermia and prevents pressure injuries compared with the Bair Hugger underbody warming device. Methods Patients were randomly allocated to receive either the WarmCloud or Bair Hugger warming device. Both groups also received other routine standardized multimodal thermoregulatory strategies. Temperatures were recorded by nasopharyngeal temperature probe at set time points during surgery. The primary endpoint was nasopharyngeal temperature recorded 5 minutes before reperfusion. Secondary endpoints included changes in temperature over the predefined intraoperative time points, number of patients whose nadir temperature was below 35.5°C and the development of pressure injuries during surgery. Results Twenty-six patients were recruited with 13 patients randomized to each group. One patient from the WarmCloud group was excluded because of a protocol violation. Baseline characteristics were similar. The mean (standard deviation) temperature before reperfusion was 36.0°C (0.7) in the WarmCloud group versus 36.3°C (0.6) in the Bairhugger group (P = 0.25). There were no statistical differences between the groups for any of the secondary endpoints. Conclusions When combined with standardized multimodal thermoregulatory strategies, the WarmCloud device does not reduce hypothermia compared with the Bair Hugger device in patients undergoing OLT. PMID:29707629

A real-time Global Warming Index.

PubMed

Haustein, K; Allen, M R; Forster, P M; Otto, F E L; Mitchell, D M; Matthews, H D; Frame, D J

2017-11-13

We propose a simple real-time index of global human-induced warming and assess its robustness to uncertainties in climate forcing and short-term climate fluctuations. This index provides improved scientific context for temperature stabilisation targets and has the potential to decrease the volatility of climate policy. We quantify uncertainties arising from temperature observations, climate radiative forcings, internal variability and the model response. Our index and the associated rate of human-induced warming is compatible with a range of other more sophisticated methods to estimate the human contribution to observed global temperature change.

A Congeneric Comparison Shows That Experimental Warming Enhances the Growth of Invasive Eupatorium adenophorum

PubMed Central

He, Wei-Ming; Li, Jing-Ji; Peng, Pei-Hao

2012-01-01

Rising air temperatures may change the risks of invasive plants; however, little is known about how different warming timings affect the growth and stress-tolerance of invasive plants. We conducted an experiment with an invasive plant Eupatorium adenophorum and a native congener Eupatorium chinense, and contrasted their mortality, plant height, total biomass, and biomass allocation in ambient, day-, night-, and daily-warming treatments. The mortality of plants was significantly higher in E. chinense than E. adenophorum in four temperature regimes. Eupatorium adenophorum grew larger than E. chinense in the ambient climate, and this difference was amplified with warming. On the basis of the net effects of warming, daily-warming exhibited the strongest influence on E. adenophorum, followed by day-warming and night-warming. There was a positive correlation between total biomass and root weight ratio in E. adenophorum, but not in E. chinense. These findings suggest that climate warming may enhance E. adenophorum invasions through increasing its growth and stress-tolerance, and that day-, night- and daily-warming may play different roles in this facilitation. PMID:22536425

Effect of anthropogenic aerosol emissions on precipitation in warm conveyor belts in the western North Pacific in winter - a model study with ECHAM6-HAM

NASA Astrophysics Data System (ADS)

Joos, Hanna; Madonna, Erica; Witlox, Kasja; Ferrachat, Sylvaine; Wernli, Heini; Lohmann, Ulrike

2017-05-01

While there is a clear impact of aerosol particles on the radiation balance, whether and how aerosol particles influence precipitation is controversial. Here we use the ECHAM6-HAM global climate model coupled to an aerosol module to analyse whether an impact of anthropogenic aerosol particles on the timing and amount of precipitation can be detected in North Pacific warm conveyor belts. Warm conveyor belts are the strongest precipitation-producing airstreams in extratropical cyclones and are identified here with a Lagrangian technique, i.e. by objectively identifying the most strongly ascending trajectories in North Pacific cyclones. These conveyor belts have been identified separately in 10-year ECHAM6-HAM simulations with present-day and pre-industrial aerosol conditions. Then, the evolution of aerosols and cloud properties has been analysed in detail along the identified warm conveyor belt trajectories. The results show that, under present-day conditions, some warm conveyor belt trajectories are strongly polluted (i.e. high concentrations of black carbon and sulfur dioxide) due to horizontal transport from eastern Asia to the oceanic region where warm conveyor belts start their ascent. In these polluted trajectories a weak delay and reduction of precipitation formation occurs compared to clean warm conveyor belt trajectories. However, all warm conveyor belts consist of both polluted and clean trajectories at the time they start their ascent, and the typically more abundant clean trajectories strongly reduce the aerosol impact from the polluted trajectories. The main conclusion then is that the overall amount of precipitation is comparable in pre-industrial conditions, when all warm conveyor belt trajectories are clean, and in present-day conditions, when warm conveyor belts consist of a mixture of clean and polluted trajectories.

Warming by immersion or exercise affects initial cooling rate during subsequent cold water immersion.

PubMed

Scott, Chris G; Ducharme, Michel B; Haman, François; Kenny, Glen P

2004-11-01

We examined the effect of prior heating, by exercise and warm-water immersion, on core cooling rates in individuals rendered mildly hypothermic by immersion in cold water. There were seven male subjects who were randomly assigned to one of three groups: 1) seated rest for 15 min (control); 2) cycling ergometry for 15 min at 70% Vo2 peak (active warming); or 3) immersion in a circulated bath at 40 degrees C to an esophageal temperature (Tes) similar to that at the end of exercise (passive warming). Subjects were then immersed in 7 degrees C water to a Tes of 34.5 degrees C. Initial Tes cooling rates (initial approximately 6 min cooling) differed significantly among the treatment conditions (0.074 +/- 0.045, 0.129 +/- 0.076, and 0.348 +/- 0.117 degrees C x min(-1) for control, active, and passive warming conditions, respectively); however, secondary cooling rates (rates following initial approximately 6 min cooling to the end of immersion) were not different between treatments (average of 0.102 +/- 0.085 degrees C x min(-1)). Overall Tes cooling rates during the full immersion period differed significantly and were 0.067 +/- 0.047, 0.085 +/- 0.045, and 0.209 +/- 0.131 degrees C x min(-1) for control, active, and passive warming, respectively. These results suggest that prior warming by both active and, to a greater extent, passive warming, may predispose a person to greater heat loss and to experience a larger decline in core temperature when subsequently exposed to cold water. Thus, functional time and possibly survival time could be reduced when cold water immersion is preceded by whole-body passive warming, and to a lesser degree by active warming.

Impacts of different climate change regimes and extreme climatic events on an alpine meadow community

PubMed Central

Alatalo, Juha M.; Jägerbrand, Annika K.; Molau, Ulf

2016-01-01

Climate variability is expected to increase in future but there exist very few experimental studies that apply different warming regimes on plant communities over several years. We studied an alpine meadow community under three warming regimes over three years. Treatments consisted of (a) a constant level of warming with open-top chambers (ca. 1.9 °C above ambient), (b) yearly stepwise increases in warming (increases of ca. 1.0, 1.9 and 3.5 °C), and (c) pulse warming, a single first-year pulse event of warming (increase of ca. 3.5 °C). Pulse warming and stepwise warming was hypothesised to cause distinct first-year and third-year effects, respectively. We found support for both hypotheses; however, the responses varied among measurement levels (whole community, canopy, bottom layer, and plant functional groups), treatments, and time. Our study revealed complex responses of the alpine plant community to the different experimentally imposed climate warming regimes. Plant cover, height and biomass frequently responded distinctly to the constant level of warming, the stepwise increase in warming and the extreme pulse-warming event. Notably, we found that stepwise warming had an accumulating effect on biomass, the responses to the different warming regimes varied among functional groups, and the short-term perturbations had negative effect on species richness and diversity PMID:26888225

Repeated ischaemic preconditioning: a novel therapeutic intervention and potential underlying mechanisms.

PubMed

Thijssen, Dick H J; Maxwell, Joseph; Green, Daniel J; Cable, N Timothy; Jones, Helen

2016-06-01

What is the topic of this review? This review discusses the effects of repeated exposure of tissue to ischaemic preconditioning on cardiovascular function, the attendant adaptations and their potential clinical relevance. What advances does it highlight? We discuss the effects of episodic exposure to ischaemic preconditioning to prevent and/or attenuate ischaemic injury and summarize evidence pertaining to improvements in cardiovascular function and structure. Discussion is provided regarding the potential mechanisms that contribute to both local and systemic adaptation. Findings suggest that clinical benefits result from both the prevention of ischaemic events and the attenuation of their consequences. Ischaemic preconditioning (IPC) refers to the phenomenon whereby short periods of cyclical tissue ischaemia confer subsequent protection against ischaemia-induced injury. As a consequence, IPC can ameliorate the myocardial damage following infarction and can reduce infarct size. The ability of IPC to confer remote protection makes IPC a potentially feasible cardioprotective strategy. In this review, we discuss the concept that repeated exposure of tissue to IPC may increase the 'dose' of protection and subsequently lead to enhanced protection against ischaemia-induced myocardial injury. This may be relevant for clinical populations, who demonstrate attenuated efficacy of IPC to prevent or attenuate ischaemic injury (and therefore myocardial infarct size). Furthermore, episodic IPC facilitates repeated exposure to local (e.g. shear stress) and systemic stimuli (e.g. hormones, cytokines, blood-borne substances), which may induce improvement in vascular function and health. Such adaptation may contribute to prevention of cardio- and cerebrovascular events. The clinical benefits of repeated IPC may, therefore, result from both the prevention of ischaemic events and the attenuation of their consequences. We provide an overview of the literature pertaining to the impact of repeated IPC on cardiovascular function, related to both local and remote adaptation, as well as potential clinical implications. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

Ketamine and thiopental sodium: individual and combined neuroprotective effects on cortical cultures exposed to NMDA or nitric oxide.

PubMed

Shibuta, S; Varathan, S; Mashimo, T

2006-10-01

An N-methyl-D-aspartate (NMDA) blocker, ketamine, has been shown to be neuroprotective both in vivo and in vitro. However, ketamine is not commonly recommended for use in patients suffering from cerebral ischaemia because of its adverse neurological effects. We hypothesized that combined administration of ketamine and thiopental sodium (TPS) would be highly effective in protecting cerebral cortical neurones from ischaemia, with possibly reduced dosages. We examined the degree of neuroprotection provided by various concentrations of ketamine and TPS, alone and in combination, in cortical cultures exposed to NMDA or a nitric oxide-releasing compound (NOC-5) for 24 h. The survival rate (SR) of E16 Wistar rat cortical neurones was evaluated using photomicrographs before and after exposure to these compounds. The SRs of cortical neurones exposed to 30 microM NMDA or NOC-5 were 15.0 (3.8)%, 12.8 (3.1)%, respectively. Higher doses (5, 10 and 50 microM) but not lower doses (<1 microM) of ketamine improved SRs [57.9 (2.2)%, 61.1 (5.4)%, 76.7 (3.0)%, respectively] against NMDA but not NOC. Enhanced survival was observed with combined administration of 5 or 10 microM ketamine and 50 microM TPS [SR 71.3 (4.8)%, 74.7 (3.7)%, respectively, P<0.05 if ketamine alone, P<0.01 if TPS alone], against NMDA-induced neurotoxicity in vitro. Only the highest dose of TPS (50 microM) improved survival after NOC exposure. This neuroprotection was not influenced by ketamine. These data indicate that a low, clinically relevant dose of ketamine offer significant neuroprotection during prolonged exposure to NMDA but not to NOC. Combinations of reduced doses of ketamine and TPS exhibited enhanced neuroprotection against NMDA-induced neurotoxicity. Hence, combinations of these two common i.v. anaesthetics agents could be developed to protect the brain from ischaemia.

The threatened stomach: management of the acute gastric volvulus.

PubMed

Light, D; Links, D; Griffin, M

2016-05-01

Acute presentation of gastric volvulus is a rare condition with a high mortality for acute ischaemia. This study was undertaken to investigate the acute management, diagnosis, and long-term outcomes of patients presenting with acute gastric volvulus. Cases were reviewed retrospectively from 2004 to 2014. Patients presenting as an emergency admission with acute gastric volvulus were included. Thirty-six patients were included, five of whom had previous surgery. The mean age was 71 years old. All patients presented with vomiting and chest/epigastric pain. CT was diagnostic in all 26 patients. Barium swallow was diagnostic in two/four patients. OGD was diagnostic in 9 of 20 patients. All patients had an NG tube placed, and eight patients were treated conservatively and made a full recovery. Twenty-nine patients proceeded to surgery. Nine had a laparoscopic repair with two open conversions. Four patients had gastric necrosis, and all had open surgery with resection. Three patients had a mediastinal perforation, and one patient required an additional thoracotomy. All patients with viable stomach had a hiatal repair (where appropriate), 11 had a gastropexy, and 11 had a fundoplication. Mortality for gastric necrosis/perforation was 30 %. Mean postoperative stay was 4 days for laparoscopic repair and 8 days for uncomplicated open surgery. Nine of twenty-nine had transient dysphagia postoperatively. Three of eight patients treated conservatively had an elective procedure subsequently. Acute paraoesophageal hiatus hernia requires early resuscitation and diagnosis. CT should be favoured in assessment, and an NG tube placed promptly. A conservative management may be considered safely in stable patients. Surgical management should be prompt for unstable patients. Gastric ischaemia or perforation has a mortality of 30 %. Laparoscopic repair has a shorter postoperative stay, but has a higher recurrence rate. Surgery for patients without gastric ischaemia has good long-term outcomes with minimal morbidity.

Epigenomic and transcriptomic approaches in the post-genomic era: path to novel targets for diagnosis and therapy of the ischaemic heart? Position Paper of the European Society of Cardiology Working Group on Cellular Biology of the Heart.

PubMed

Perrino, Cinzia; Barabási, Albert-Laszló; Condorelli, Gianluigi; Davidson, Sean Michael; De Windt, Leon; Dimmeler, Stefanie; Engel, Felix Benedikt; Hausenloy, Derek John; Hill, Joseph Addison; Van Laake, Linda Wilhelmina; Lecour, Sandrine; Leor, Jonathan; Madonna, Rosalinda; Mayr, Manuel; Prunier, Fabrice; Sluijter, Joost Petrus Geradus; Schulz, Rainer; Thum, Thomas; Ytrehus, Kirsti; Ferdinandy, Péter

2017-06-01

Despite advances in myocardial reperfusion therapies, acute myocardial ischaemia/reperfusion injury and consequent ischaemic heart failure represent the number one cause of morbidity and mortality in industrialized societies. Although different therapeutic interventions have been shown beneficial in preclinical settings, an effective cardioprotective or regenerative therapy has yet to be successfully introduced in the clinical arena. Given the complex pathophysiology of the ischaemic heart, large scale, unbiased, global approaches capable of identifying multiple branches of the signalling networks activated in the ischaemic/reperfused heart might be more successful in the search for novel diagnostic or therapeutic targets. High-throughput techniques allow high-resolution, genome-wide investigation of genetic variants, epigenetic modifications, and associated gene expression profiles. Platforms such as proteomics and metabolomics (not described here in detail) also offer simultaneous readouts of hundreds of proteins and metabolites. Isolated omics analyses usually provide Big Data requiring large data storage, advanced computational resources and complex bioinformatics tools. The possibility of integrating different omics approaches gives new hope to better understand the molecular circuitry activated by myocardial ischaemia, putting it in the context of the human 'diseasome'. Since modifications of cardiac gene expression have been consistently linked to pathophysiology of the ischaemic heart, the integration of epigenomic and transcriptomic data seems a promising approach to identify crucial disease networks. Thus, the scope of this Position Paper will be to highlight potentials and limitations of these approaches, and to provide recommendations to optimize the search for novel diagnostic or therapeutic targets for acute ischaemia/reperfusion injury and ischaemic heart failure in the post-genomic era. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Cardiology.

AP39, a mitochondria‐targeting hydrogen sulfide (H2S) donor, protects against myocardial reperfusion injury independently of salvage kinase signalling

PubMed Central

Karwi, Qutuba G; Bornbaum, Julia; Boengler, Kerstin; Torregrossa, Roberta; Whiteman, Matthew; Wood, Mark E; Schulz, Rainer

2017-01-01

Background and Purpose H2S protects myocardium against ischaemia/reperfusion injury. This protection may involve the cytosolic reperfusion injury salvage kinase (RISK) pathway, but direct effects on mitochondrial function are possible. Here, we investigated the potential cardioprotective effect of a mitochondria‐specific H2S donor, AP39, at reperfusion against ischaemia/reperfusion injury. Experimental Approach Anaesthetized rats underwent myocardial ischaemia (30 min)/reperfusion (120 min) with randomization to receive interventions before reperfusion: vehicle, AP39 (0.01, 0.1, 1 μmol·kg−1), or control compounds AP219 and ADT‐OH (1 μmol·kg−1). LY294002, L‐NAME or ODQ were used to investigate the involvement of the RISK pathway. Myocardial samples harvested 5 min after reperfusion were analysed for RISK protein phosphorylation and isolated cardiac mitochondria were used to examine the direct mitochondrial effects of AP39. Key Results AP39, dose‐dependently, reduced infarct size. Inhibition of either PI3K/Akt, eNOS or sGC did not affect this effect of AP39. Western blot analysis confirmed that AP39 did not induce phosphorylation of Akt, eNOS, GSK‐3β or ERK1/2. In isolated subsarcolemmal and interfibrillar mitochondria, AP39 significantly attenuated mitochondrial ROS generation without affecting respiratory complexes I or II. Furthermore, AP39 inhibited mitochondrial permeability transition pore (PTP) opening and co‐incubation of mitochondria with AP39 and cyclosporine A induced an additive inhibitory effect on the PTP. Conclusion and Implications AP39 protects against reperfusion injury independently of the cytosolic RISK pathway. This cardioprotective effect could be mediated by inhibiting PTP via a cyclophilin D‐independent mechanism. Thus, selective delivery of H2S to mitochondria may be therapeutically applicable for employing the cardioprotective utility of H2S. PMID:27930802

Reduction of infarct size by gentle reperfusion without activation of reperfusion injury salvage kinases in pigs.

PubMed

Musiolik, Judith; van Caster, Patrick; Skyschally, Andreas; Boengler, Kerstin; Gres, Petra; Schulz, Rainer; Heusch, Gerd

2010-01-01

Reperfusion is mandatory to salvage ischaemic myocardium from infarction, but also induces additional reperfusion injury and contributes to infarct size (IS). Gentle reperfusion (GR) has been proposed to attenuate reperfusion injury, but this remains contentious. We now investigated whether (i) GR reduces IS and (ii) GR is associated with the activation of reperfusion injury salvage kinases (RISK). Anaesthetized pigs were subjected to 90 min left anterior descending coronary artery hypoperfusion and 120 min reperfusion. GR was induced by slowly increasing coronary inflow back to baseline over 30 min, using an exponential algorithm [F(t) = F(i)+e(-(0.1)(t)((min)-3)).(F(b)-F(i)); F(b), coronary inflow at baseline; F(i), coronary inflow during ischaemia; n = 12]. Pigs subjected to immediate full reperfusion (IFR; n = 13) served as controls. IS was determined by triphenyl tetrazolium chloride staining. The expression level of phosphorylated RISK proteins was determined by western blot analysis in myocardial biopsies taken at baseline, after 80-85 min ischaemia and at 10, 30, and 120 min reperfusion. In additional experiments with IFR (n = 3) and GR (n = 3), the PI3-AKT and MEK1/2-ERK1/2 pathways were pharmacologically blocked (BL). IS was 37 +/- 2% (mean +/- SEM) of the area at risk with IFR and 29 +/- 1% (P < 0.05) with GR. RISK phosphorylation was similar between GR and IFR at baseline and 85 min ischaemia. At 10 min reperfusion, RISK phosphorylation was increased with IFR, but not with GR. At 30 and 120 min reperfusion, RISK phosphorylation was still greater with IFR than GR. RISK blockade did not abolish the IS reduction by GR (BL-IFR: 27 +/- 4% of the area at risk; BL-GR: 42 +/- 5%; P < 0.05). Gentle reperfusion reduces infarct size in pigs, but RISK activation is not causally involved in this infarct size reduction.

TLR2 ligands induce cardioprotection against ischaemia/reperfusion injury through a PI3K/Akt-dependent mechanism

PubMed Central

Ha, Tuanzhu; Hu, Yulong; Liu, Li; Lu, Chen; McMullen, Julie R.; Kelley, Jim; Kao, Race L.; Williams, David L.; Gao, Xiang; Li, Chuanfu

2010-01-01

Aims Toll-like receptor (TLR)-mediated signalling pathways have been implicated in myocardial ischaemia/reperfusion (I/R) injury. Activation of the phosphoinositide 3-kinase (PI3K)/Akt pathway protects the myocardium from ischaemic injury. We hypothesized that the modulation of TLR2 would induce cardioprotection against I/R injury via activation of the PI3K/Akt signalling. Methods and results Mice were treated with TLR2 ligands, peptidoglycan (PGN) or Pam3CSK4, respectively, 1 h before the hearts were subjected to ischaemia (1 h), followed by reperfusion (4 h). Infarct size was determined by triphenyltetrazolium chloride staining. Cardiac function and haemodynamic performance were evaluated. Infarct size was significantly reduced in PGN- or Pam3CSK4-treated mice compared with untreated I/R mice. Administration of TLR2 ligands improved cardiac function following I/R. PGN treatment increased the levels of phospho-Akt and phospho-GSK-3β (glycogen synthase kinase-3β), compared with untreated I/R hearts. PGN stimulation increased TLR2 tyrosine phosphorylation and association of the p85 subunit of PI3K with TLR2. To investigate the role of PI3K/Akt signalling in PGN-induced cardioprotection, we administered the PI3K inhibitor, Wortmannin, to the mice 15 min before PGN treatment. We also administered PGN to kinase-deficient Akt (kdAkt) transgenic mice 1 h before myocardial I/R. Both PI3K inhibition and kdAkt mice abolished the cardioprotection induced by PGN. To examine the role of TLR2 in PGN-induced cardioprotection, we administrated PGN to TLR2 knockout mice 1 h before the hearts were subjected to I/R. PGN-induced cardioprotection was lost in TLR2-deficient mice. Conclusion These results demonstrate that TLR2 ligands induced cardioprotection, which is mediated through a TLR2/PI3K/Akt-dependent mechanism. PMID:20421349

Dissociation of nNOS from PSD-95 promotes functional recovery after cerebral ischaemia in mice through reducing excessive tonic GABA release from reactive astrocytes.

PubMed

Lin, Yu-Hui; Liang, Hai-Ying; Xu, Ke; Ni, Huan-Yu; Dong, Jian; Xiao, Hui; Chang, Lei; Wu, Hai-Yin; Li, Fei; Zhu, Dong-Ya; Luo, Chun-Xia

2018-02-01

Mechanisms underlying functional recovery after stroke are little known, and effective drug intervention during the delayed stage is desirable. One potential drug target, the protein-protein interaction between neuronal nitric oxide synthase (nNOS) and postsynaptic density protein 95 (PSD-95), is critical to acute ischaemic damage and neurogenesis. We show that nNOS-PSD-95 dissociation induced by microinjection of a recombinant fusion protein, Tat-nNOS-N 1-133 , or systemic administration of a small-molecule, ZL006, from day 4 to day 10 after photothrombotic ischaemia in mice reduced excessive tonic inhibition in the peri-infarct cortex and ameliorated motor functional outcome. We also demonstrated improved neuroplasticity including increased dendrite spine density and synaptogenesis after reducing excessive tonic inhibition by nNOS-PSD-95 dissociation. Levels of gamma-aminobutyric acid (GABA) and GABA transporter-3/4 (GAT-3/4) are increased in the reactive astrocytes in the peri-infarct cortex. The GAT-3/4-selective antagonist SNAP-5114 reduced tonic inhibition and promoted function recovery, suggesting that increased tonic inhibition in the peri-infarct cortex was due to GABA release from reversed GAT-3/4 in reactive astrocytes. Treatments with Tat-nNOS-N 1-133 or ZL006 after ischaemia inhibited astrocyte activation and GABA production, prevented the reversal of GAT-3/4, and consequently decreased excessive tonic inhibition and ameliorated functional outcome. The underlying molecular mechanisms were associated with epigenetic inhibition of glutamic acid decarboxylase 67 and monoamine oxidase B expression through reduced NO production. The nNOS-PSD-95 interaction is thus a potential target for functional restoration after stroke and ZL006, a small molecule inhibitor of this interaction, is a promising pharmacological lead compound. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Perioperative elafin for ischaemia-reperfusion injury during coronary artery bypass graft surgery: a randomised-controlled trial

PubMed Central

Alam, S R; Lewis, S C; Zamvar, V; Pessotto, R; Dweck, M R; Krishan, A; Goodman, K; Oatey, K; Harkess, R; Milne, L; Thomas, S; Mills, N M; Moore, C; Semple, S; Wiedow, O; Stirrat, C; Mirsadraee, S; Newby, D E; Henriksen, P A

2015-01-01

Background Elafin is a potent endogenous neutrophil elastase inhibitor that protects against myocardial inflammation and injury in preclinical models of ischaemic-reperfusion injury. We investigated whether elafin could inhibit myocardial ischaemia-reperfusion injury induced during coronary artery bypass graft (CABG) surgery. Methods and results In a randomised double-blind placebo-controlled parallel group clinical trial, 87 patients undergoing CABG surgery were randomised 1:1 to intravenous elafin 200 mg or saline placebo administered after induction of anaesthesia and prior to sternotomy. Myocardial injury was measured as cardiac troponin I release over 48 h (area under the curve (AUC)) and myocardial infarction identified with MRI. Postischaemic inflammation was measured by plasma markers including AUC high-sensitive C reactive protein (hs-CRP) and myeloperoxidase (MPO). Elafin infusion was safe and resulted in >3000-fold increase in plasma elafin concentrations and >50% inhibition of elastase activity in the first 24 h. This did not reduce myocardial injury over 48 h (ratio of geometric means (elafin/placebo) of AUC troponin I 0.74 (95% CI 0.47 to 1.15, p=0.18)) although post hoc analysis of the high-sensitive assay revealed lower troponin I concentrations at 6 h in elafin-treated patients (median 2.4 vs 4.1 μg/L, p=0.035). Elafin had no effect on myocardial infarction (elafin, 7/34 vs placebo, 5/35 patients) or on markers of inflammation: mean differences for AUC hs-CRP of 499 mg/L/48 h (95% CI −207 to 1205, p=0.16), and AUC MPO of 238 ng/mL/48 h (95% CI −235 to 711, p=0.320). Conclusions There was no strong evidence that neutrophil elastase inhibition with a single-dose elafin treatment reduced myocardial injury and inflammation following CABG-induced ischaemia-reperfusion injury. Trial registration number (EudraCT 2010-019527-58, ISRCTN82061264). PMID:26310261

Sulfiredoxin-1 protects against simulated ischaemia/reperfusion injury in cardiomyocyte by inhibiting PI3K/AKT-regulated mitochondrial apoptotic pathways.

PubMed

Zhang, Jiankai; He, Zhangyou; Guo, Jinhua; Li, Zhe; Wang, Xiaohong; Yang, Chun; Cui, Xiaojun

2016-01-01

Reactive oxygen species (ROS)-triggered cardiac cell injury is recognized as the major contributor for the pathogenesis progression of ischaemic cardiovascular diseases. Sulfiredoxin-1 (Srx-1) is an endogenous antioxidant and exerts the crucial neuroprotective effects in cerebral ischaemia. However, its function and the underlying mechanism in ischaemic heart diseases remain poorly defined. Here, a dramatical decrease in Srx-1 was validated in H9c2 cardiomyocytes upon simulated ischaemia-reperfusion (SI/R) injury. Moreover, Srx-1 protected H9c2 cells from SI/R-injured injury as the evidences that Srx-1 up-regulation attenuated the inhibitory effects on cell viability, lactate dehydrogenase (LDH) and cell apoptosis upon SI/R treatment. Knockdown of Srx-1 accelerated cell injury upon SI/R. Mechanism assay corroborated that SI/R treatment noticeably aggravated the loss of mitochondrial membrane potential (Δψm), which was remarkably abated in Ad-Srx-1 groups. Importantly, Srx-1 elevation substantially reduced cytochrome c release, the activity of caspase-9 and caspase-3, accompany with the subsequent decrease in the cleavage of poly (ADP ribose) polymerase (PARP). Concomitantly, overexpression of Srx-1 also decreased the expression of pro-apoptosis protein Bax and increased anti-apoptotic Bcl-2 expression. Further analysis substantiated that Srx-1 treatment remarkably induced the activation of PI3K/AKT signalling. Preconditioning with LY294002 dramatically decreased Srx-1-enhanced cell resistance to SI/R injury. Importantly, LY294002 mitigated the inhibitory effects of Srx-1 on Δψm loss, cytochrome c release, caspase-9/3 activity, and the expression of Bcl-2 family. Together, these results suggested that Srx-1 might protect cardiomyocyte injury upon SI/R by suppressing PI3K/AKT-mediated mitochondria dependent apoptosis, revealing a promising therapeutic agent against ischaemic cardiovascular diseases. © 2016 The Author(s).

Brain ischaemia induces shedding of a BDNF-scavenger ectodomain from TrkB receptors by excitotoxicity activation of metalloproteinases and γ-secretases.

PubMed

Tejeda, Gonzalo S; Ayuso-Dolado, Sara; Arbeteta, Raquel; Esteban-Ortega, Gema M; Vidaurre, Oscar G; Díaz-Guerra, Margarita

2016-04-01

Stroke remains a leading cause of death and disability in the world with limited therapies available to restrict brain damage or improve functional recovery after cerebral ischaemia. A promising strategy currently under investigation is the promotion of brain-derived neurotrophic factor (BDNF) signalling through tropomyosin-related kinase B (TrkB) receptors, a pathway essential for neuronal survival and function. However, TrkB and BDNF-signalling are impaired by excitotoxicity, a primary pathological process in stroke also associated with neurodegenerative diseases. Pathological imbalance of TrkB isoforms is critical in neurodegeneration and is caused by calpain processing of BDNF high affinity full-length receptor (TrkB-FL) and an inversion of the transcriptional pattern of the Ntrk2 gene, to favour expression of the truncated isoform TrkB-T1 over TrkB-FL. We report here that both TrkB-FL and neuronal TrkB-T1 also undergo ectodomain shedding by metalloproteinases activated after ischaemic injury or excitotoxic damage of cortical neurons. Subsequently, the remaining membrane-bound C-terminal fragments (CTFs) are cleaved by γ-secretases within the transmembrane region, releasing their intracellular domains (ICDs) into the cytosol. Therefore, we identify TrkB-FL and TrkB-T1 as new substrates of regulated intramembrane proteolysis (RIP), a mechanism that highly contributes to TrkB-T1 regulation in ischaemia but is minor for TrkB-FL which is mainly processed by calpain. However, since the secreted TrkB ectodomain acts as a BDNF scavenger and significantly alters BDNF/TrkB signalling, the mechanism of RIP could contribute to neuronal death in excitotoxicity. These results are highly relevant since they reveal new targets for the rational design of therapies to treat stroke and other pathologies with an excitotoxic component. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Role of peripheral sigma-1 receptors in ischaemic pain: Potential interactions with ASIC and P2X receptors.

PubMed

Kwon, S G; Roh, D H; Yoon, S Y; Choi, S R; Choi, H S; Moon, J Y; Kang, S Y; Kim, H W; Han, H J; Beitz, A J; Oh, S B; Lee, J H

2016-04-01

The role of peripheral sigma-1 receptors (Sig-1Rs) in normal nociception and in pathologically induced pain conditions has not been thoroughly investigated. Since there is mounting evidence that Sig-1Rs modulate ischaemia-induced pathological conditions, we investigated the role of Sig-1Rs in ischaemia-induced mechanical allodynia (MA) and addressed their possible interaction with acid-sensing ion channels (ASICs) and P2X receptors at the ischaemic site. We used a rodent model of hindlimb thrombus-induced ischaemic pain (TIIP) to investigate their role. Western blot was performed to observe changes in Sig-1R expression in peripheral nervous tissues. MA was measured after intraplantar (i.pl.) injections of antagonists for the Sig-1, ASIC and P2X receptors in TIIP rats or agonists of each receptor in naïve rats. Sig-1R expression significantly increased in skin, sciatic nerve and dorsal root ganglia at 3 days post-TIIP surgery. I.pl. injections of the Sig-1R antagonist, BD-1047 on post-operative days 0-3 significantly attenuated the development of MA during the induction phase, but had no effect on MA when given during the maintenance phase (days 3-6 post-surgery). BD-1047 synergistically increased amiloride (an ASICs blocker)- and TNP-ATP (a P2X antagonist)-induced analgesic effects in TIIP rats. In naïve rats, i.pl. injection of Sig-1R agonist PRE-084 alone did not produce MA; but it did induce MA when co-administered with either an acidic pH solution or a sub-effective dose of αβmeATP. Peripheral Sig-1Rs contribute to the induction of ischaemia-induced MA via facilitation of ASICs and P2X receptors. Thus, peripheral Sig-1Rs represent a novel therapeutic target for the treatment of ischaemic pain. © 2015 European Pain Federation - EFIC®

Effects of salicylic acid on post-ischaemic ventricular function and purine efflux in isolated mouse hearts.

PubMed

Farthing, Don; Gehr, Lynne; Karnes, H Thomas; Sica, Domenic; Gehr, Todd; Larus, Terri; Farthing, Christine; Xi, Lei

2007-01-01

Acetyl salicylic acid (aspirin) is one of the most widely used drugs in the world. Various plasma concentrations of aspirin and its predominant metabolite, salicylic acid, are required for its antiarthritic (1.5-2.5 mM), anti-inflammatory (0.5-5.0 mM) or antiplatelet (0.18-0.36 mM) actions. A recent study demonstrated the inhibitory effects of both aspirin and salicylic acid on oxidative phosphorylation and ATP synthesis in isolated rat cardiac mitochondria in a dose-dependent manner (0-10 mM concentration range). In this context, the present study was conducted to determine the effects of salicylic acid on inosine efflux (a potential biomarker of acute cardiac ischaemia) as well as cardiac contractile function in the isolated mouse heart following 20 min of zero-flow global ischaemia. Inosine efflux was found at significantly higher concentrations in ischaemic hearts perfused with Krebs buffer fortified with 1.0 mM salicylic acid compared with those without salicylic acid (12575+/-3319 vs. 1437+/-348 ng ml(-1) min(-1), mean+/-SEM, n=6 per group, p<0.01). These results indicate that 1.0 mM salicylic acid potentiates 8.8-fold ATP nucleotide purine catabolism into its metabolites (e.g. inosine, hypoxanthine). Salicylic acid (0.1 or 1.0 mM) did not appreciably inhibit purine nucleoside phosphorylase (the enzyme converts inosine to hypoxanthine) suggesting the augmented inosine efflux was due to the salicylic acid effect on upstream elements of cellular respiration. Whereas post-ischaemic cardiac function was further depressed by 1.0 mM salicylic acid, perfusion with 0.1 mM salicylic acid led to a remarkable functional improvement despite moderately increased inosine efflux (2.7-fold). We conclude that inosine is a sensitive biomarker for detecting cardiac ischaemia and salicylic acid-induced effects on cellular respiration. However, the inosine efflux level appears to be a poor predictor of the individual post-ischaemic cardiac functional recovery in this ex vivo model.

Evidence that the adenosine A3 receptor may mediate the protection afforded by preconditioning in the isolated rabbit heart.

PubMed

Liu, G S; Richards, S C; Olsson, R A; Mullane, K; Walsh, R S; Downey, J M

1994-07-01

Agonists selective for the A1 adenosine receptor mimic the protective effect of ischaemic preconditioning against infarction in the rabbit heart. Unselective adenosine antagonists block this protection but, paradoxically, the A1 adenosine receptor selective antagonist 8-cyclopentyl- 1,3-dipropylxanthine (DPCPX) does not. The aim of this study was to test the hypothesis that the newly described A3 adenosine receptor, which has an agonist profile similar to the A1 receptor but is insensitive to DPCPX, might mediate preconditioning. Isolated rabbit hearts perfused with Krebs buffer experienced 30 min of regional ischaemia followed by 120 min of reperfusion. Infarct size was measured by tetrazolium staining. In control hearts infarction was 32.2(SEM 1.5)% of the risk zone. Preconditioning by 5 min ischaemia and 10 min reperfusion reduced infarct size to 8.8(2.3)%. Replacing the regional ischaemia with 5 min perfusion with 10 microM adenosine or 65 nM N6-[2-(4-aminophenyl)ethyl]adenosine (APNEA), an adenosine A3 receptor agonist, was equally protective. The unselective antagonist 8-p-sulphophenyl theophylline at 100 microM abolished protection by preconditioning, adenosine, and APNEA, but 200 nM DPCPX did not block protection by any of the interventions. Likewise the potent but unselective A3 receptor antagonist 8-(4-carboxyethenylphenyl)-1,3-dipropylxanthine (BW A1433) completely blocked protection from ischaemic preconditioning. Because protection against infarction afforded by ischaemic preconditioning, adenosine, or the A3 receptor agonist APNEA could not be blocked by DPCPX and because the potent A3 receptor antagonist BW A1433 blocked protection from ischaemic preconditioning, these data indicate that the protection of preconditioning is not exclusively mediated by the adenosine A1 receptor in rabbit heart and could involve the A3 receptor.

Depletion of kidney CD11c+ F4/80+ cells impairs the recovery process in ischaemia/reperfusion-induced acute kidney injury.

PubMed

Kim, Myung-Gyu; Boo, Chang Su; Ko, Yoon Sook; Lee, Hee Young; Cho, Won Yong; Kim, Hyoung Kyu; Jo, Sang-Kyung

2010-09-01

Recent studies provided evidence of the potential role of CD11c(+) F4/80(+) dendritic subset in mediating injury and repair. The purpose of this study was to examine the role of kidney CD11c(+) F4/80(+) dendritic subset in the recovery phase of ischaemia/reperfusion injury (IRI). Following ischaemia/reperfusion (I/R), liposome clodronate or phosphate buffered saline (PBS) was administered, and on day 7 biochemical and histologic kidney damage was assessed. Activation and depletion of CD11c(+) F4/80(+) dendritic subset were confirmed by flow cytometry. Isolation of kidney CD11c(+) cells on days 1 and 7 with in vitro culture for measuring cytokines was performed to define functional characteristics of these cells, and adoptive transfer of CD11c(+) cells was also done. Following kidney IRI, the percentage of CD11c(+) F4/80(+) kidney dendritic cell subset that co-expresses maturation marker increased. Liposome clodronate injection after I/R resulted in preferential depletion of CD11c(+) F4/80(+) kidney dendritic subset, and depletion of these cells was associated with persistent kidney injury, more apoptosis, inflammation and impaired tubular cell proliferation. CD11c(+) F4/80(+) cell depletion was also associated with higher tissue levels of pro-inflammatory cytokines and lower level of IL-10, indicating the persistence of inflammatory milieu. Isolated kidney CD11c(+) cells on day 7 showed different phenotype with increased production of IL-10 compared with those on day 1. Adoptive transfer of CD11c(+) cells partially reversed impaired tissue recovery. Our results suggest that kidney CD11c(+) F4/80(+) dendritic subset might contribute to the recovery process by dynamic phenotypic change from pro-inflammatory to anti-inflammatory with modulation of immune response.

The impact of global warming on Mount Everest.

PubMed

Moore, G W K; Semple, John L

2009-01-01

Global warming impacts a wide range of human activities and ecosystems. One unanticipated consequence of the warming is an increase in barometric pressure throughout the troposphere. Mount Everest's extreme height and resulting low barometric pressure places humans near its summit in an extreme state of hypoxia. Here we quantify the degree with which this warming is increasing the barometric pressure near Everest's summit and argue that it is of such a magnitude as to make the mountain, over time, easier to climb.

Global assessment of experimental climate warming on tundra vegetation: heterogeneity over space and time

Treesearch

Sarah C. Elmendorf; Gregory H.R. Henry; Robert D. Hollister; Robert G. Björk; Anne D. Bjorkman; Terry V. Callaghan; [and others] NO-VALUE; William Gould; Joel Mercado

2012-01-01

Understanding the sensitivity of tundra vegetation to climate warming is critical to forecasting future biodiversity and vegetation feedbacks to climate. In situ warming experiments accelerate climate change on a small scale to forecast responses of local plant communities. Limitations of this approach include the apparent site-specificity of results and uncertainty...

From Static Stretching to Dynamic Exercises: Changing the Warm-Up Paradigm

ERIC Educational Resources Information Center

Young, Shawna

2010-01-01

In the United States, pre-exercise static stretching seems to have become common practice and routine. However, research suggests that it is time for a paradigm shift--that pre-exercise static stretching be replaced with dynamic warm-up exercises. Research indicates that a dynamic warm-up elevates body temperature, decreases muscle and joint…

Experiment, monitoring, and gradient methods used to infer climate change effects on plant communities yield consistent patterns.

PubMed

Elmendorf, Sarah C; Henry, Gregory H R; Hollister, Robert D; Fosaa, Anna Maria; Gould, William A; Hermanutz, Luise; Hofgaard, Annika; Jónsdóttir, Ingibjörg S; Jónsdóttir, Ingibjörg I; Jorgenson, Janet C; Lévesque, Esther; Magnusson, Borgþór; Molau, Ulf; Myers-Smith, Isla H; Oberbauer, Steven F; Rixen, Christian; Tweedie, Craig E; Walker, Marilyn D; Walker, Marilyn

2015-01-13

Inference about future climate change impacts typically relies on one of three approaches: manipulative experiments, historical comparisons (broadly defined to include monitoring the response to ambient climate fluctuations using repeat sampling of plots, dendroecology, and paleoecology techniques), and space-for-time substitutions derived from sampling along environmental gradients. Potential limitations of all three approaches are recognized. Here we address the congruence among these three main approaches by comparing the degree to which tundra plant community composition changes (i) in response to in situ experimental warming, (ii) with interannual variability in summer temperature within sites, and (iii) over spatial gradients in summer temperature. We analyzed changes in plant community composition from repeat sampling (85 plant communities in 28 regions) and experimental warming studies (28 experiments in 14 regions) throughout arctic and alpine North America and Europe. Increases in the relative abundance of species with a warmer thermal niche were observed in response to warmer summer temperatures using all three methods; however, effect sizes were greater over broad-scale spatial gradients relative to either temporal variability in summer temperature within a site or summer temperature increases induced by experimental warming. The effect sizes for change over time within a site and with experimental warming were nearly identical. These results support the view that inferences based on space-for-time substitution overestimate the magnitude of responses to contemporary climate warming, because spatial gradients reflect long-term processes. In contrast, in situ experimental warming and monitoring approaches yield consistent estimates of the magnitude of response of plant communities to climate warming.

Warming experiments underpredict plant phenological responses to climate change

USGS Publications Warehouse

Wolkovich, Elizabeth M.; Cook, Benjamin I.; Allen, Jenica M.; Crimmins, Theresa M.; Betancourt, Julio L.; Travers, Steven E.; Pau, Stephanie; Regetz, James; Davies, T. Jonathan; Kraft, Nathan J.B.; Ault, Toby R.; Bolmgren, Kjell; Mazer, Susan J.; McCabe, Gregory J.; McGill, Brian J.; Parmesan, Camille; Salamin, Nicolas; Schwartz, Mark D.; Cleland, Elsa E.

2012-01-01

Warming experiments are increasingly relied on to estimate plant responses to global climate change. For experiments to provide meaningful predictions of future responses, they should reflect the empirical record of responses to temperature variability and recent warming, including advances in the timing of flowering and leafing. We compared phenology (the timing of recurring life history events) in observational studies and warming experiments spanning four continents and 1,634 plant species using a common measure of temperature sensitivity (change in days per degree Celsius). We show that warming experiments underpredict advances in the timing of flowering and leafing by 8.5-fold and 4.0-fold, respectively, compared with long-term observations. For species that were common to both study types, the experimental results did not match the observational data in sign or magnitude. The observational data also showed that species that flower earliest in the spring have the highest temperature sensitivities, but this trend was not reflected in the experimental data. These significant mismatches seem to be unrelated to the study length or to the degree of manipulated warming in experiments. The discrepancy between experiments and observations, however, could arise from complex interactions among multiple drivers in the observational data, or it could arise from remediable artefacts in the experiments that result in lower irradiance and drier soils, thus dampening the phenological responses to manipulated warming. Our results introduce uncertainty into ecosystem models that are informed solely by experiments and suggest that responses to climate change that are predicted using such models should be re-evaluated.

Warming Experiments Underpredict Plant Phenological Responses to Climate Change

NASA Technical Reports Server (NTRS)

Wolkovich, E. M.; Cook, B. I.; Allen, J. M.; Crimmins, T. M.; Betancourt, J. L.; Travers, S. E.; Pau, S.; Regetz, J.; Davies, T. J.; Kraft, N. J. B.;

A nested mechanistic sub-study into the effect of tranexamic acid versus placebo on intracranial haemorrhage and cerebral ischaemia in isolated traumatic brain injury: study protocol for a randomised controlled trial (CRASH-3 Trial Intracranial Bleeding Mechanistic Sub-Study [CRASH-3 IBMS]).

PubMed

Mahmood, Abda; Roberts, Ian; Shakur, Haleema

2017-07-17

Tranexamic acid prevents blood clots from breaking down and reduces bleeding. However, it is uncertain whether tranexamic acid is effective in traumatic brain injury. The CRASH-3 trial is a randomised controlled trial that will examine the effect of tranexamic acid (versus placebo) on death and disability in 13,000 patients with traumatic brain injury. The CRASH-3 trial hypothesizes that tranexamic acid will reduce intracranial haemorrhage, which will reduce the risk of death. Although it is possible that tranexamic acid will reduce intracranial bleeding, there is also a potential for harm. In particular, tranexamic acid may increase the risk of cerebral thrombosis and ischaemia. The protocol detailed here is for a mechanistic sub-study nested within the CRASH-3 trial. This mechanistic sub-study aims to examine the effect of tranexamic acid (versus placebo) on intracranial bleeding and cerebral ischaemia. The CRASH-3 Intracranial Bleeding Mechanistic Sub-Study (CRASH-3 IBMS) is nested within a prospective, double-blind, multi-centre, parallel-arm randomised trial called the CRASH-3 trial. The CRASH-3 IBMS will be conducted in a cohort of approximately 1000 isolated traumatic brain injury patients enrolled in the CRASH-3 trial. In the CRASH-3 IBMS, brain scans acquired before and after randomisation are examined, using validated methods, for evidence of intracranial bleeding and cerebral ischaemia. The primary outcome is the total volume of intracranial bleeding measured on computed tomography after randomisation, adjusting for baseline bleeding volume. Secondary outcomes include progression of intracranial haemorrhage (from pre- to post-randomisation scans), new intracranial haemorrhage (seen on post- but not pre-randomisation scans), intracranial haemorrhage following neurosurgery, and new focal ischaemic lesions (seen on post-but not pre-randomisation scans). A linear regression model will examine whether receipt of the trial treatment can predict haemorrhage volume. Bleeding volumes and new ischaemic lesions will be compared across treatment groups using relative risks and 95% confidence intervals. The CRASH-3 IBMS will provide an insight into the mechanism of action of tranexamic acid in traumatic brain injury, as well as information about the risks and benefits. Evidence from this trial could inform the management of patients with traumatic brain injury. The CRASH-3 trial was prospectively registered and the CRASH-3 IBMS is an addition to the original protocol registered at the International Standard Randomised Controlled Trials registry ( ISRCTN15088122 ) 19 July 2011, and ClinicalTrials.gov on 25 July 2011 (NCT01402882).

Scaling Potential Evapotranspiration with Greenhouse Warming (Invited)

NASA Astrophysics Data System (ADS)

Scheff, J.; Frierson, D. M.

2013-12-01

Potential evapotranspiration (PET) is a supply-independent measure of the evaporative demand of a terrestrial climate, of basic importance in climatology, hydrology, and agriculture. Future increases in PET from greenhouse warming are often cited as key drivers of global trends toward drought and aridity. The present work computes recent and business-as-usual-future Penman-Monteith (i.e. physically-based) PET fields at 3-hourly resolution in 14 modern global climate models. The %-change in local annual-mean PET over the upcoming century is almost always positive, modally low double-digit in magnitude, usually increasing with latitude, yet quite divergent between models. These patterns are understood as follows. In every model, the global field of PET %-change is found to be dominated by the direct, positive effects of constant-relative-humidity warming (via increasing vapor pressure deficit and increasing Clausius-Clapeyron slope.) This direct-warming term very accurately scales as the PET-weighted (warm-season daytime) local warming, times 5-6% per degree (related to the Clausius-Clapeyron equation), times an analytic factor ranging from about 0.25 in warm climates to 0.75 in cold climates, plus a small correction. With warming of several degrees, this product is of low double-digit magnitude, and the strong temperature dependence gives the latitude dependence. Similarly, the inter-model spread in the amount of warming gives most of the spread in this term. Additional spread in the total change comes from strong disagreement on radiation, relative-humidity, and windspeed changes, which make smaller yet substantial contributions to the full PET %-change fields.

Considering time in LCA: dynamic LCA and its application to global warming impact assessments.

PubMed

Levasseur, Annie; Lesage, Pascal; Margni, Manuele; Deschênes, Louise; Samson, Réjean

2010-04-15

The lack of temporal information is an important limitation of life cycle assessment (LCA). A dynamic LCA approach is proposed to improve the accuracy of LCA by addressing the inconsistency of temporal assessment. This approach consists of first computing a dynamic life cycle inventory (LCI), considering the temporal profile of emissions. Then, time-dependent characterization factors are calculated to assess the dynamic LCI in real-time impact scores for any given time horizon. Although generally applicable to any impact category, this approach is developed here for global warming, based on the radiative forcing concept. This case study demonstrates that the use of global warming potentials for a given time horizon to characterize greenhouse gas emissions leads to an inconsistency between the time frame chosen for the analysis and the time period covered by the LCA results. Dynamic LCA is applied to the US EPA LCA on renewable fuels, which compares the life cycle greenhouse gas emissions of different biofuels with fossil fuels including land-use change emissions. The comparison of the results obtained with both traditional and dynamic LCA approaches shows that the difference can be important enough to change the conclusions on whether or not a biofuel meets some given global warming reduction targets.

Time-dependent climate sensitivity and the legacy of anthropogenic greenhouse gas emissions

PubMed Central

Zeebe, Richard E.

2013-01-01

Climate sensitivity measures the response of Earth’s surface temperature to changes in forcing. The response depends on various climate processes that feed back on the initial forcing on different timescales. Understanding climate sensitivity is fundamental to reconstructing Earth’s climatic history as well as predicting future climate change. On timescales shorter than centuries, only fast climate feedbacks including water vapor, lapse rate, clouds, and snow/sea ice albedo are usually considered. However, on timescales longer than millennia, the generally higher Earth system sensitivity becomes relevant, including changes in ice sheets, vegetation, ocean circulation, biogeochemical cycling, etc. Here, I introduce the time-dependent climate sensitivity, which unifies fast-feedback and Earth system sensitivity. I show that warming projections, which include a time-dependent climate sensitivity, exhibit an enhanced feedback between surface warming and ocean CO2 solubility, which in turn leads to higher atmospheric CO2 levels and further warming. Compared with earlier studies, my results predict a much longer lifetime of human-induced future warming (23,000–165,000 y), which increases the likelihood of large ice sheet melting and major sea level rise. The main point regarding the legacy of anthropogenic greenhouse gas emissions is that, even if the fast-feedback sensitivity is no more than 3 K per CO2 doubling, there will likely be additional long-term warming from slow climate feedbacks. Time-dependent climate sensitivity also helps explaining intense and prolonged warming in response to massive carbon release as documented for past events such as the Paleocene–Eocene Thermal Maximum. PMID:23918402

Time-dependent climate sensitivity and the legacy of anthropogenic greenhouse gas emissions.

PubMed

Zeebe, Richard E

2013-08-20

Climate sensitivity measures the response of Earth's surface temperature to changes in forcing. The response depends on various climate processes that feed back on the initial forcing on different timescales. Understanding climate sensitivity is fundamental to reconstructing Earth's climatic history as well as predicting future climate change. On timescales shorter than centuries, only fast climate feedbacks including water vapor, lapse rate, clouds, and snow/sea ice albedo are usually considered. However, on timescales longer than millennia, the generally higher Earth system sensitivity becomes relevant, including changes in ice sheets, vegetation, ocean circulation, biogeochemical cycling, etc. Here, I introduce the time-dependent climate sensitivity, which unifies fast-feedback and Earth system sensitivity. I show that warming projections, which include a time-dependent climate sensitivity, exhibit an enhanced feedback between surface warming and ocean CO2 solubility, which in turn leads to higher atmospheric CO2 levels and further warming. Compared with earlier studies, my results predict a much longer lifetime of human-induced future warming (23,000-165,000 y), which increases the likelihood of large ice sheet melting and major sea level rise. The main point regarding the legacy of anthropogenic greenhouse gas emissions is that, even if the fast-feedback sensitivity is no more than 3 K per CO2 doubling, there will likely be additional long-term warming from slow climate feedbacks. Time-dependent climate sensitivity also helps explaining intense and prolonged warming in response to massive carbon release as documented for past events such as the Paleocene-Eocene Thermal Maximum.

Warm-up for Sprint Swimming: Race-Pace or Aerobic Stimulation? A Randomized Study.

PubMed

Neiva, Henrique P; Marques, Mário C; Barbosa, Tiago M; Izquierdo, Mikel; Viana, João L; Teixeira, Ana M; Marinho, Daniel A

2017-09-01

Neiva, HP, Marques, MC, Barbosa, TM, Izquierdo, M, Viana, JL, Teixeira, AM, and Marinho, DA. Warm-up for sprint swimming: race-pace or aerobic stimulation? A randomized study. J Strength Cond Res 31(9): 2423-2431, 2017-The aim of this study was to compare the effects of 2 different warm-up intensities on 100-m swimming performance in a randomized controlled trial. Thirteen competitive swimmers performed two 100-m freestyle time-trials on separate days after either control or experimental warm-up in a randomized design. The control warm-up included a typical race-pace set (4 × 25 m), whereas the experimental warm-up included an aerobic set (8 × 50 m at 98-102% of critical velocity). Cortisol, testosterone, blood lactate ([La]), oxygen uptake (V[Combining Dot Above]O2), heart rate, core (Tcore and Tcorenet) and tympanic temperatures, and rating of perceived exertion (RPE) were monitored. Stroke length (SL), stroke frequency (SF), stroke index (SI), and propelling efficiency (ηp) were assessed for each 50-m lap. We found that V[Combining Dot Above]O2, heart rate, and Tcorenet were higher after experimental warm-up (d > 0.73), but only the positive effect for Tcorenet was maintained until the trial. Performance was not different between conditions (d = 0.07). Experimental warm-up was found to slow SF (mean change ±90% CL = 2.06 ± 1.48%) and increase SL (1.65 ± 1.40%) and ηp (1.87 ± 1.33%) in the first lap. After the time-trials, this warm-up had a positive effect on Tcorenet (d = 0.69) and a negative effect on [La] (d = 0.56). Although the warm-ups had similar outcomes in the 100-m freestyle, performance was achieved through different biomechanical strategies. Stroke length and efficiency were higher in the first lap after the experimental warm-up, whereas SF was higher after control warm-up. Physiological adaptations were observed mainly through an increased Tcore after experimental warm-up. In this condition, the lower [La] after the trial suggests lower dependency on anaerobic metabolism.

Little effects on soil organic matter chemistry of density fractions after seven years of forest soil warming.

PubMed

Schnecker, Jörg; Borken, Werner; Schindlbacher, Andreas; Wanek, Wolfgang

2016-12-01

Rising temperatures enhance microbial decomposition of soil organic matter (SOM) and thereby increase the soil CO 2 efflux. Elevated decomposition rates might differently affect distinct SOM pools, depending on their stability and accessibility. Soil fractions derived from density fractionation have been suggested to represent SOM pools with different turnover times and stability against microbial decomposition. To investigate the effect of soil warming on functionally different soil organic matter pools, we here investigated the chemical and isotopic composition of bulk soil and three density fractions (free particulate organic matter, fPOM; occluded particulate organic matter, oPOM; and mineral associated organic matter, MaOM) of a C-rich soil from a long-term warming experiment in a spruce forest in the Austrian Alps. At the time of sampling, the soil in this experiment had been warmed during the snow-free period for seven consecutive years. During that time no thermal adaptation of the microbial community could be identified and CO 2 release from the soil continued to be elevated by the warming treatment. Our results, which included organic carbon content, total nitrogen content, δ 13 C, Δ 14 C, δ 15 N and the chemical composition, identified by pyrolysis-GC/MS, showed no significant differences in bulk soil between warming treatment and control. Surprisingly, the differences in the three density fractions were mostly small and the direction of warming induced change was variable with fraction and soil depth. Warming led to reduced N content in topsoil oPOM and subsoil fPOM and to reduced relative abundance of N-bearing compounds in subsoil MaOM. Further, warming increased the δ 13 C of MaOM at both sampling depths, reduced the relative abundance of carbohydrates while it increased the relative abundance of lignins in subsoil oPOM. As the size of the functionally different SOM pools did not significantly change, we assume that the few and small modifications in SOM chemistry result from an interplay of enhanced microbial decomposition of SOM and increased root litter input in the warmed plots. Overall, stable functional SOM pool sizes indicate that soil warming had similarly affected easily decomposable and stabilized SOM of this C-rich forest soil.

Warm Rain Processes Over the Tropical Oceans and Implications on Climate Change: Results from TRMM and GOES GCM

NASA Technical Reports Server (NTRS)

Lau, William K. M.; Wu, H. T.

2004-01-01

In this talk, we will first show results from TRMM data regarding the characteristics of warm rains over the tropical oceans, and the dependence of rate of warm rain production on sea surface temperature. Results lead to the hypothesis that warm rain production efficiency, i.e., autoconversion, may be increased in a warm climate. We use the GEOS-II GCM to test this hypothesis. Our modeling results show that in a climate with increased rate of autoconversion, the total rain amount is increased, with warm rain contributing to a larger portion of the increase. The abundant rainout of warm precipitation causes a reduction of low and middle cloud amount due to rainout, and reduced high clouds due to less water vapor available for ice-phase convection. However, clod radiation feedback caused by the increased rainfall efficiency, leads to differential vertical heating/cooling producing a more unstable atmosphere, allowing, more intense, but isolated penetrative convection, with contracted anvils to develop. Results also show that increased autoconversion reduces the convective adjustment time scale, resulting in faster recycling of atmospheric water. Most interestingly, the increased low level heating associated with warm rain leads to more energetic Madden and Julian oscillations in the tropics, with well-defined eastward propagation. While reducing the autoconversion leads to an abundant mix of westward and eastward tropical disturbances on daily to weekly time scales. The crucial link of precipitation microphysical processes to climate change including the effects of aerosols will be discussed.

Warm Rain Processes over the Tropical Oceans and Implications on Climate Change: Results from TRMM and GEOS GCM

NASA Technical Reports Server (NTRS)

Lau, William K. M.; Wu, H. T.

2004-01-01

In this talk, we will first show results from TRMM data regarding the characteristics of warm rains over the tropical oceans, and the dependence of rate of warm rain production on sea surface temperature. Results lead to the hypothesis that warm rain production efficiency, i.e., autoconversion, may be increased in a warm climate. We use the GEOS-II GCM to test this hypothesis. Our modeling results show that in a climate with increased rate of autoconversion, the total rain amount is increased, with warm rain contributing to larger portion of the increase. The abundant rainout of warm precipitation causes a reduction of low and middle cloud amount due to rainout, and reduced high clouds due to less water vapor available for ice-phase convection. However, clod radiation feedback caused by the increased rainfall efficiency, leads to differential vertical heating/cooling producing a more unstable atmosphere, allowing, more intense, but isolated penetrative convection, with contracted anvils to develop. Results also show that increased autoconversion reduces the convective adjustment time scale, resulting in faster recycling of atmospheric water. Most interestingly, the increased low level heating associated with warm rain leads to more energetic Madden and Julian oscillations in the tropics, with well-defined eastward propagation. While reducing the autoconversion leads to an abundant mix of westward and eastward tropical disturbances on daily to weekly time scales. The crucial link of precipitation microphysical processes to climate change including the effects of aerosols will be discussed.

[Warming up with endotrainer prior to laparoscopic cholecystectomy].

PubMed

Troncoso-Bacelis, Alicia; Soto-Amaro, Jaime; Ramírez-Velázquez, Carlos

Laparoscopic cholecystectomy is a safe and effective treatment and remains the gold standard in patients with benign disease. However it presents difficulties such as: the limited movement range of the instruments, the loss of depth perception, haptic feedback and the fulcrum effect. Previous training can optimize surgical performance in patients to master basic skills. Assess the effectiveness of surgeons warming up with an endotrainer before performing laparoscopic cholecystectomy. Single-blind controlled clinical trial with 16 surgeons who performed 2 laparoscopic cholecystectomies, the first according to standard practice and the second with warm-up comprising 5 MISTELS system exercises. Patient and surgeon demographics were recorded, in addition to findings and complications during and after surgery for each procedured. We found a decrease in surgical time of 76.88 (±18.87) minutes in the group that did not warm up to prior to surgery compared with 72.81 (±35.5) minutes in the group with warm-up (p=0.0196). In addition, increased bleeding occurred in the procedures performed with warm-up 31.25 (±30.85) ml compared with the group that had no warm-up 23.94 (±15.9) (p=0.0146). Performing warm up on a MISTELS system endotrainer before performing laparoscopic cholecystectomy reduces the operating time of surgery for all surgeons. Surgery bleeding increases in operations performed by surgeons with less experience in laparoscopic surgery. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

Effect of prior warm-up duration on the time limit at peak speed in untrained men.

PubMed

da Cruz, Victor H; Peserico, Cecília S; Machado, Fabiana A

2017-10-01

The peak speed (Vpeak) and its time limit (tlim) are variables used to prescribe training loads and the intervals durations during interval training, respectively. The aim of this study was to test different warm-up durations (5, 10 and 15 minutes), adapted from the protocol proposed by Billat et al.,1 to determine tlim in untrained men. Fifteen untrained men were submitted to the following laboratory evaluations: 1) an incremental running exercise test on a treadmill starting with a speed of 8 km/h, after a warm-up of walking at 6 km/h for three minutes, and increased by 1 km/h between each successive 3-minute stage until volitional exhaustion to determine Vpeak; 2) three rectangular tests, performed in randomized order, with warm-up durations of 5, 10, and 15 minutes at 60% of Vpeak to determine the tlim5, tlim10, and tlim15; after the warm-up the tests were performed at the speed of the individual Vpeak until volitional exhaustion. It was demonstrated that the duration of the warm-up affected the test duration (tlim). Significant differences were observed between tlim5 and tlim15, and between tlim10 and tlim15. However, tlim15 and tlim10 did not differ. Additionally, duration of the warm-up did not influence other variables (HRmax, RPEmax and post lactate concentrations). Therefore, it was concluded that the duration of the warm-up in tlim tests modifies the test duration in untrained men.

Coarsening of AA6013-T6 Precipitates During Sheet Warm Forming Applications

NASA Astrophysics Data System (ADS)

Di Ciano, M.; DiCecco, S.; Esmaeili, S.; Wells, M. A.; Worswick, M. J.

2018-03-01

The use of warm forming for AA6xxx-T6 sheet is of interest to improve its formability; however, the effect warm forming may have on the coarsening of precipitates and the mechanical strength of these sheets has not been well studied. In this research, the coarsening behavior of AA6013-T6 precipitates has been explored, in the temperature range of 200-300 °C, and time of 30 s up to 50 h. Additionally, the effect of warm deformation on coarsening behavior was explored using: (1) simulated warm forming tests in a Gleeble thermo-mechanical simulator and (2) bi-axial warm deformation tests. Using a strong obstacle model to describe the yield strength (YS) evolution of the AA6013-T6 material, and a Lifshitz, Slyozov, and Wagner (LSW) particle coarsening law to describe the change in precipitate size with time, the coarsening kinetics were modeled for this alloy. The coarsening kinetics in the range of 220-300 °C followed a trend similar to that previously found for AA6111 for the 180-220 °C range. There was strong evidence that coarsening kinetics were not altered due to warm deformation above 220 °C. For warm forming between 200 and 220 °C, the YS of the AA6013-T6 material increased slightly, which could be attributed to strain hardening during warm deformation. Finally, a non-isothermal coarsening model was used to assess the potential reduction in the YS of AA6013-T6 for practical processing conditions related to auto-body manufacturing. The model calculations showed that 90% of the original AA6013-T6 YS could be maintained, for warm forming temperatures up to 280 °C, if the heating schedule used to get the part to the warm forming temperature was limited to 1 min.

Communicating the Science of Global Warming — the Role of Astronomers

NASA Astrophysics Data System (ADS)

Bennett, Jeffrey

2018-06-01

Global Warming is one of the most important and issues of our times, yet it is widely misunderstood among the general public (and politicians!). The American Astronomical Society has already joined many other scientific organizations in advocating for action on global warming (by supporting the AGU statement on global warming), but we as astronomers can do much more. The high public profile of astronomy gives us a unique platform — and credibility as scientists — for doing our part to educate the public about the underlying science of global warming. And while astronomers are not climate scientists, we use the same basic physics, and many aspects of global warming science come directly from astronomy, including the ways in which we measure the heat-absorbing potential of carbon dioxide and the hard evidence of greenhouse warming provided by studies of Venus. In this session, I will briefly introduce a few methods for communicating about global warming that I believe you will find effective in your own education efforts.

Ocean acidification ameliorates harmful effects of warming in primary consumer.

PubMed

Pedersen, Sindre Andre; Hanssen, Anja Elise

2018-01-01

Climate change-induced warming and ocean acidification are considered two imminent threats to marine biodiversity and current ecosystem structures. Here, we have for the first time examined an animal's response to a complete life cycle of exposure to co-occurring warming (+3°C) and ocean acidification (+1,600 μatm CO 2 ), using the key subarctic planktonic copepod, Calanus finmarchicus , as a model species. The animals were generally negatively affected by warming, which significantly reduced the females' energy status and reproductive parameters (respectively, 95% and 69%-87% vs. control). Unexpectedly, simultaneous acidification partially offset the negative effect of warming in an antagonistic manner, significantly improving reproductive parameters and hatching success (233%-340% improvement vs. single warming exposure). The results provide proof of concept that ocean acidification may partially offset negative effects caused by warming in some species. Possible explanations and ecological implications for the observed antagonistic effect are discussed.

Impact of upper body precooling during warm-up on subsequent time trial paced cycling in the heat.

PubMed

Katica, Charles P; Wingo, Jonathan E; Herron, Robert L; Ryan, Greg A; Bishop, Stacy H; Richardson, Mark

2018-06-01

The purpose of this study was to test the hypothesis that cooling the upper body during a warm-up enhances performance during a subsequent 16.1-km simulated cycling time trial in a hot environment. Counterbalanced, repeated measures design. Eight trained, male cyclists (peak oxygen uptake=57.8±5.0mLkg -1 min -1 ) completed two simulated 16.1-km time trials in a hot environment (35.0±0.5°C, 43.8±2.0% relative humidity) each separated by 72h. Treatments were counterbalanced; participants warmed up for 20min while either wearing head and neck ice wraps and an ice vest (COOLING) or no cooling apparatus (CONTROL). Following the warm-up mean skin temperature (T¯ sk ), mean body temperature (T¯ b ) and rating of thermal comfort were significantly lower than baseline following the COOLING trial (all P<0.05); however, rectal temperature was unaffected (P=0.35). Because the effects of precooling on T¯ sk and T¯ b were not sustained during exercise, values for COOLING and CONTROL were not different throughout the time trial (P=0.38). Nonetheless, time to completion was significantly faster following the COOLING intervention when compared to the CONTROL (29.3±3.6min, vs. 30.3±3.1min; P=0.04). These data suggest that in short distance time trials in hot conditions cyclists may benefit from utilizing a cooling modality during the warm-up. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Robot-assisted partial nephrectomy: Superiority over laparoscopic partial nephrectomy.

PubMed

Shiroki, Ryoichi; Fukami, Naohiko; Fukaya, Kosuke; Kusaka, Mamoru; Natsume, Takahiro; Ichihara, Takashi; Toyama, Hiroshi

2016-02-01

Nephron-sparing surgery has been proven to positively impact the postoperative quality of life for the treatment of small renal tumors, possibly leading to functional improvements. Laparoscopic partial nephrectomy is still one of the most demanding procedures in urological surgery. Laparoscopic partial nephrectomy sometimes results in extended warm ischemic time and severe complications, such as open conversion, postoperative hemorrhage and urine leakage. Robot-assisted partial nephrectomy exploits the advantages offered by the da Vinci Surgical System to laparoscopic partial nephrectomy, equipped with 3-D vision and a better degree in the freedom of surgical instruments. The introduction of the da Vinci Surgical System made nephron-sparing surgery, specifically robot-assisted partial nephrectomy, safe with promising results, leading to the shortening of warm ischemic time and a reduction in perioperative complications. Even for complex and challenging tumors, robotic assistance is expected to provide the benefit of minimally-invasive surgery with safe and satisfactory renal function. Warm ischemic time is the modifiable factor during robot-assisted partial nephrectomy to affect postoperative kidney function. We analyzed the predictive factors for extended warm ischemic time from our robot-assisted partial nephrectomy series. The surface area of the tumor attached to the kidney parenchyma was shown to significantly affect the extended warm ischemic time during robot-assisted partial nephrectomy. In cases with tumor-attached surface area more than 15 cm(2) , we should consider switching robot-assisted partial nephrectomy to open partial nephrectomy under cold ischemia if it is imperative. In Japan, a nationwide prospective study has been carried out to show the superiority of robot-assisted partial nephrectomy to laparoscopic partial nephrectomy in improving warm ischemic time and complications. By facilitating robotic technology, robot-assisted partial nephrectomy will be more frequently carried out as a safe, effective and minimally-invasive nephron-sparing surgery procedure. © 2015 The Japanese Urological Association.

Projected changes in diverse ecosystems from climate warming and biophysical drivers in northwest Alaska

Treesearch

Mark Torre Jorgenson; Bruce G. Marcot; David K. Swanson; Janet C. Jorgenson; Anthony R. DeGange

2015-01-01

Climate warming affects arctic and boreal ecosystems by interacting with numerous biophysical factors across heterogeneous landscapes. To assess potential effects of warming on diverse local-scale ecosystems (ecotypes) across northwest Alaska, we compiled data on historical areal changes over the last 25–50 years. Based on historical rates of change relative to time...

A Feasibility Randomized Controlled Crossover Trial of Home-Based Warm Footbath to Improve Sleep in the Chronic Phase of Traumatic Brain Injury.

PubMed

Chiu, Hsiao-Yean; Lin, En-Yuan; Chiu, Hsiao-Ting; Chen, Pin-Yuan

2017-12-01

Sleep disturbance is a common complaint after traumatic brain injury (TBI). The aim of this study was to examine the effects of a home-based warm footbath intervention on sleep in patients with TBI. This was a randomized controlled crossover study, and 23 adults with TBI were recruited and randomized to receive first a 30-minute, 41°C warm footbath and then a usual care, or vice versa, with each lasting 3 days and separated by a 3-day washout. Sleep efficiency, sleep onset latency (SOL), total sleep time, and wake after sleep onset (WASO) were assessed by actigraphy. We found that home-based warm footbath significantly had a reduced SOL (difference, -5.11 minutes) and a suppressed WASO (difference, -2.57 minutes) compared with those of usual care, but not in sleep efficiency and total sleep time. No adverse effect was reported. This study suggested that home-based warm footbath is practical and effective in relieving post-TBI sleep disturbances, particular in SOL and WASO. Nurses can use home-based warm footbath as an effective intervention for management of sleep disturbances after TBI.

Maximum warming occurs about one decade after a carbon dioxide emission

NASA Astrophysics Data System (ADS)

Ricke, Katharine L.; Caldeira, Ken

2014-12-01

It is known that carbon dioxide emissions cause the Earth to warm, but no previous study has focused on examining how long it takes to reach maximum warming following a particular CO2 emission. Using conjoined results of carbon-cycle and physical-climate model intercomparison projects (Taylor et al 2012, Joos et al 2013), we find the median time between an emission and maximum warming is 10.1 years, with a 90% probability range of 6.6-30.7 years. We evaluate uncertainties in timing and amount of warming, partitioning them into three contributing factors: carbon cycle, climate sensitivity and ocean thermal inertia. If uncertainty in any one factor is reduced to zero without reducing uncertainty in the other factors, the majority of overall uncertainty remains. Thus, narrowing uncertainty in century-scale warming depends on narrowing uncertainty in all contributing factors. Our results indicate that benefit from avoided climate damage from avoided CO2 emissions will be manifested within the lifetimes of people who acted to avoid that emission. While such avoidance could be expected to benefit future generations, there is potential for emissions avoidance to provide substantial benefit to current generations.

Internal combustion engine controls for reduced exhausts contaminants

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matthews, D.R. Jr.

1974-06-04

An electrochemical control system for achieving optimum efficiency in the catalytic conversion of hydrocarbon and carbon monoxide emissions from internal combustion engines is described. The system automatically maintains catalyst temperature at a point for maximum pollutant conversion by adjusting ignition timing and fuel/air ratio during warm-up and subsequent operation. Ignition timing is retarded during engine warm-up to bring the catalytic converter to an efficient operating temperature within a minimum period of time. After the converter reaches a predetermined minimum temperature, the spark is advanced to within its normal operating range. A needle-valve adjustment during warm-up is employed to enrich themore » fuel/air mixture by approximately 10 percent. Following warm-up and attainment of a predetermined catalyst temperature, the needle valve is moved automatically to its normal position (e.g., a fuel/air ratio of 16:1). Although the normal lean mixture causes increased amounts of nitrogen oxide emissions, present NO/sub x/ converters appear capable of handling the increased emissions under normal operating conditions.« less

Consistent leaf respiratory response to experimental warming of three North American deciduous trees: a comparison across seasons, years, habitats and sites.

PubMed

Wei, Xiaorong; Sendall, Kerrie M; Stefanski, Artur; Zhao, Changming; Hou, Jihua; Rich, Roy L; Montgomery, Rebecca A; Reich, Peter B

2017-03-01

Most vascular plants acclimate respiration to changes in ambient temperature, but explicit tests of these responses in field settings are rare, and how acclimation responses vary in space and time is relatively unstudied, hindering our ability to predict respiratory release of carbon under future climatic conditions. We measured temperature response curves of leaf respiration for three deciduous tree species from 2009 to 2012 in a field warming experiment (+3.4 °C above ambient) in both open and understory conditions at two sites in the southern boreal forest in Minnesota, USA. We analyzed the effects of warming on leaf respiration, and how the effects varied among species, times of season (early, middle and late parts of the growing season), sites, habitats (understory, open) and years. We hypothesized that the respiration exponent (Q10) of the short-term temperature response curve and the degree of acclimation would be smaller under conditions where plants were more likely to be substrate limited, such as in the understory or the margins of the growing season. However, in contrast to these predictions, stable Q10 and strong respiratory acclimation were consistently observed. For each species, the Q10 did not vary with experimental warming, nor was its response to warming influenced by time of season, year, site or habitat. Strong leaf respiratory acclimation to warming occurred in each species and was consistent across most sources of variation. Most of the leaf traits studied were not affected by warming, while the Q10-leaf nitrogen and R25-soluble carbohydrate relationships were observed, and shifted with warming, implying that acclimation may be associated with the adjustment in respiratory capacity and its relation to leaf nitrogen and soluble carbohydrate content. Consistent Q10 and acclimation across habitats, sites, times of season and years suggest that modeling of temperature acclimation may be possible with relatively simple functions. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Worldwide Emerging Environmental Issues Affecting the U.S. Military. December 2005 Report

DTIC Science & Technology

2005-12-01

6 7.1 Climate Change……………..………………………………………………………..6 7.1.1 Melting Permafrost Releases Methane Twenty Times More Dangerous for Global Warming than...Dangerous for Global Warming than CO2 Permafrost covers much of Russia, Canada, and Alaska. As it melts, trapped methane gas is released, which is...period of time; however, the phenomenon has not been properly factored into global warming forecasts. With less snow and ice, solar radiation that used

The Role of Frozen Soil in Groundwater Discharge Predictions for Warming Alpine Watersheds

NASA Astrophysics Data System (ADS)

Evans, Sarah G.; Ge, Shemin; Voss, Clifford I.; Molotch, Noah P.

2018-03-01

Climate warming may alter the quantity and timing of groundwater discharge to streams in high alpine watersheds due to changes in the timing of the duration of seasonal freezing in the subsurface and snowmelt recharge. It is imperative to understand the effects of seasonal freezing and recharge on groundwater discharge to streams in warming alpine watersheds as streamflow originating from these watersheds is a critical water resource for downstream users. This study evaluates how climate warming may alter groundwater discharge due to changes in seasonally frozen ground and snowmelt using a 2-D coupled flow and heat transport model with freeze and thaw capabilities for variably saturated media. The model is applied to a representative snowmelt-dominated watershed in the Rocky Mountains of central Colorado, USA, with snowmelt time series reconstructed from a 12 year data set of hydrometeorological records and satellite-derived snow covered area. Model analyses indicate that the duration of seasonal freezing in the subsurface controls groundwater discharge to streams, while snowmelt timing controls groundwater discharge to hillslope faces. Climate warming causes changes to subsurface ice content and duration, rerouting groundwater flow paths but not altering the total magnitude of future groundwater discharge outside of the bounds of hydrologic parameter uncertainties. These findings suggest that frozen soil routines play an important role for predicting the future location of groundwater discharge in watersheds underlain by seasonally frozen ground.

The role of frozen soil in groundwater discharge predictions for warming alpine watersheds

USGS Publications Warehouse

Evans, Sarah G.; Ge, Shemin; Voss, Clifford I.; Molotch, Noah P.

2018-01-01

Climate warming may alter the quantity and timing of groundwater discharge to streams in high alpine watersheds due to changes in the timing of the duration of seasonal freezing in the subsurface and snowmelt recharge. It is imperative to understand the effects of seasonal freezing and recharge on groundwater discharge to streams in warming alpine watersheds as streamflow originating from these watersheds is a critical water resource for downstream users. This study evaluates how climate warming may alter groundwater discharge due to changes in seasonally frozen ground and snowmelt using a 2‐D coupled flow and heat transport model with freeze and thaw capabilities for variably saturated media. The model is applied to a representative snowmelt‐dominated watershed in the Rocky Mountains of central Colorado, USA, with snowmelt time series reconstructed from a 12 year data set of hydrometeorological records and satellite‐derived snow covered area. Model analyses indicate that the duration of seasonal freezing in the subsurface controls groundwater discharge to streams, while snowmelt timing controls groundwater discharge to hillslope faces. Climate warming causes changes to subsurface ice content and duration, rerouting groundwater flow paths but not altering the total magnitude of future groundwater discharge outside of the bounds of hydrologic parameter uncertainties. These findings suggest that frozen soil routines play an important role for predicting the future location of groundwater discharge in watersheds underlain by seasonally frozen ground.

Alternative "global warming" metrics in life cycle assessment: a case study with existing transportation data.

PubMed

Peters, Glen P; Aamaas, Borgar; T Lund, Marianne; Solli, Christian; Fuglestvedt, Jan S

2011-10-15

The Life Cycle Assessment (LCA) impact category "global warming" compares emissions of long-lived greenhouse gases (LLGHGs) using Global Warming Potential (GWP) with a 100-year time-horizon as specified in the Kyoto Protocol. Two weaknesses of this approach are (1) the exclusion of short-lived climate forcers (SLCFs) and biophysical factors despite their established importance, and (2) the use of a particular emission metric (GWP) with a choice of specific time-horizons (20, 100, and 500 years). The GWP and the three time-horizons were based on an illustrative example with value judgments and vague interpretations. Here we illustrate, using LCA data of the transportation sector, the importance of SLCFs relative to LLGHGs, different emission metrics, and different treatments of time. We find that both the inclusion of SLCFs and the choice of emission metric can alter results and thereby change mitigation priorities. The explicit inclusion of time, both for emissions and impacts, can remove value-laden assumptions and provide additional information for impact assessments. We believe that our results show that a debate is needed in the LCA community on the impact category "global warming" covering which emissions to include, the emission metric(s) to use, and the treatment of time.

Root and Shoot Phenology May Respond Differently to Warming

NASA Astrophysics Data System (ADS)

Radville, L.; Eissenstat, D. M.; Post, E.

2015-12-01

Climate change is increasing temperatures and extending the growing season for many organisms. Shifts in phenology have been widely reported in response to global warming and have strong effects on ecosystem processes and greenhouse gas emissions. It is well understood that warming generally advances aboveground plant phenology, but the influence of temperature on root phenology is unclear. Most terrestrial biosphere models assume that root and shoot growth occur at the same time and are influenced by warming in the same way, but recent studies suggest that this may not be the case. Testing this assumption is particularly important in the Arctic where over 70% of plant biomass can be belowground and warming is happening faster than in other ecosystems. In 2013 and 2014 we examined the timing of root growth in the Arctic in plots that had been warmed or unwarmed for 10 years. We found that peak root growth occurred about one month before leaf growth, suggesting that spring root phenology is not controlled by carbon produced during spring photosynthesis. If root phenology is not controlled by photosynthate early in the season, earlier spring leaf growth may not cause earlier spring root growth. In support of this, we found that warming advanced spring leaf cover but did not significantly affect root phenology. Root growth was not significantly correlated with soil temperature and did not appear to be limited by near-freezing temperatures above the permafrost. These results suggest that although shoots are influenced by temperature, roots in this system may be more influenced by photosynthesis and carbon storage. Aboveground phenology, one of the most widely measured aspects of climate change, may not represent whole-plant phenology and may be a poor indicator of the timing of whole-plant carbon fluxes. Additionally, climate model assumptions that roots and shoots grow at the same time may need to be revised.

Proper accounting for time increases crop-based biofuels' greenhouse gas deficit versus petroleum

NASA Astrophysics Data System (ADS)

O'Hare, M.; Plevin, R. J.; Martin, J. I.; Jones, A. D.; Kendall, A.; Hopson, E.

2009-04-01

The global warming intensities of crop-based biofuels and fossil fuels differ not only in amount but also in their discharge patterns over time. Early discharges, for example, from market-mediated land use change, will have created more global warming by any time in the future than later discharges, owing to the slow decay of atmospheric CO2. A spreadsheet model of this process, BTIME, captures this important time pattern effect using the Bern CO2 decay model to allow fuels to be compared for policy decisions on the basis of their real warming effects with a variety of user-supplied parameter values. The model also allows economic discounting of climate effects extended far into the future. Compared to approaches that simply sum greenhouse gas emissions over time, recognizing the physics of atmospheric CO2 decay significantly increases the deficit relative to fossil fuel of any biofuel causing land use change.

[Effects of sowing times on the spike differentiation of different wheat varieties under the climate of warm winter].

PubMed

Gao, Qinglu; Xue, Xiang; Wu, Yu; Ru, Zhengang

2003-10-01

Spike differentiation processes and freezing damage of three wheat varieties were studied by sowing in different stages. The results showed that under the condition of weather changing warm, the time of entering each stage of spike differentiation of wheat of strong spring variety was earlier than that of wheat of spring variety and semi-winter variety. Sowing times had more effects on durative time of the elongation stage, single-prism stage and two-prism stage of the spike differentiation. Under sowing early, the stronger the springness of wheat was, the quicker it developed, the higher spike differentiation phases it reached before winter, and the more serious freezing damage it suffered in wintering. According to this, the semi-winter varieties of wheat should be adopted first and arranged in pairs with spring varieties in wheat production, and the sowing times should not be too early as the weather becoming warm.

Simulation of future global warming scenarios in rice paddies with an open-field warming facility

PubMed Central

2011-01-01

To simulate expected future global warming, hexagonal arrays of infrared heaters have previously been used to warm open-field canopies of upland crops such as wheat. Through the use of concrete-anchored posts, improved software, overhead wires, extensive grounding, and monitoring with a thermal camera, the technology was safely and reliably extended to paddy rice fields. The system maintained canopy temperature increases within 0.5°C of daytime and nighttime set-point differences of 1.3 and 2.7°C 67% of the time. PMID:22145582

Effects of Baseline Levels of Flexibility and Vertical Jump Ability on Performance Following Different Volumes of Static Stretching and Potentiating Exercises in Elite Gymnasts

PubMed Central

Donti, Olyvia; Tsolakis, Charilaos; Bogdanis, Gregory C.

2014-01-01

This study examined the effects of baseline flexibility and vertical jump ability on straight leg raise range of motion (ROM) and counter-movement jump performance (CMJ) following different volumes of stretching and potentiating exercises. ROM and CMJ were measured after two different warm-up protocols involving static stretching and potentiating exercises. Three groups of elite athletes (10 male, 14 female artistic gymnasts and 10 female rhythmic gymnasts) varying greatly in ROM and CMJ, performed two warm-up routines. One warm-up included short (15 s) static stretching followed by 5 tuck jumps, while the other included long static stretching (30 s) followed by 3x5 tuck jumps. ROM and CMJ were measured before, during and for 12 min after the two warm-up routines. Three-way ANOVA showed large differences between the three groups in baseline ROM and CMJ performance. A type of warm-up x time interaction was found for both ROM (p = 0.031) and CMJ (p = 0.016). However, all athletes, irrespective of group, responded in a similar fashion to the different warm-up protocols for both ROM and CMJ, as indicated from the lack of significant interactions for group (condition x group, time x group or condition x time x group). In the short warm-up protocol, ROM was not affected by stretching, while in the long warm-up protocol ROM increased by 5.9% ± 0.7% (p = 0.001) after stretching. Similarly, CMJ remained unchanged after the short warm-up protocol, but increased by 4.6 ± 0.9% (p = 0.012) 4 min after the long warm- up protocol, despite the increased ROM. It is concluded that the initial levels of flexibility and CMJ performance do not alter the responses of elite gymnasts to warm-up protocols differing in stretching and potentiating exercise volumes. Furthermore, 3 sets of 5 tuck jumps result in a relatively large increase in CMJ performance despite an increase in flexibility in these highly-trained athletes. Key Points The initial levels of flexibility and vertical jump ability have no effect on straight leg raise range of motion (ROM) and counter-movement jump performance (CMJ) of elite gymnasts following warm-up protocols differing in stretching and potentiating exercise volumes Stretching of the main leg muscle groups for only 15 s has no effect on ROM of elite gymnasts In these highly-trained athletes, one set of 5 tuck jumps during warm-up is not adequate to increase CMJ performance, while 3 sets of 5 tuck jumps result in a relatively large increase in CMJ performance (by 4.6% above baseline), despite a 5.9% increase in flexibility due to the 30 s stretching exercises PMID:24570613

Complex regional pain syndrome: evidence for warm and cold subtypes in a large prospective clinical sample.

PubMed

Bruehl, Stephen; Maihöfner, Christian; Stanton-Hicks, Michael; Perez, Roberto S G M; Vatine, Jean-Jacques; Brunner, Florian; Birklein, Frank; Schlereth, Tanja; Mackey, Sean; Mailis-Gagnon, Angela; Livshitz, Anatoly; Harden, R Norman

2016-08-01

Limited research suggests that there may be Warm complex regional pain syndrome (CRPS) and Cold CRPS subtypes, with inflammatory mechanisms contributing most strongly to the former. This study for the first time used an unbiased statistical pattern recognition technique to evaluate whether distinct Warm vs Cold CRPS subtypes can be discerned in the clinical population. An international, multisite study was conducted using standardized procedures to evaluate signs and symptoms in 152 patients with clinical CRPS at baseline, with 3-month follow-up evaluations in 112 of these patients. Two-step cluster analysis using automated cluster selection identified a 2-cluster solution as optimal. Results revealed a Warm CRPS patient cluster characterized by a warm, red, edematous, and sweaty extremity and a Cold CRPS patient cluster characterized by a cold, blue, and less edematous extremity. Median pain duration was significantly (P < 0.001) shorter in the Warm CRPS (4.7 months) than in the Cold CRPS subtype (20 months), with pain intensity comparable. A derived total inflammatory score was significantly (P < 0.001) elevated in the Warm CRPS group (compared with Cold CRPS) at baseline but diminished significantly (P < 0.001) over the follow-up period, whereas this score did not diminish in the Cold CRPS group (time × subtype interaction: P < 0.001). Results support the existence of a Warm CRPS subtype common in patients with acute (<6 months) CRPS and a relatively distinct Cold CRPS subtype most common in chronic CRPS. The pattern of clinical features suggests that inflammatory mechanisms contribute most prominently to the Warm CRPS subtype but that these mechanisms diminish substantially during the first year postinjury.

Warming of the Global Ocean: Spatial Structure and Water-Mass Trends

NASA Technical Reports Server (NTRS)

Hakkinen, Sirpa; Rhines, Peter B.; Worthen, Denise L.

2016-01-01

This study investigates the multidecadal warming and interannual-to-decadal heat content changes in the upper ocean (0-700 m), focusing on vertical and horizontal patterns of variability. These results support a nearly monotonic warming over much of the World Ocean, with a shift toward Southern Hemisphere warming during the well-observed past decade. This is based on objectively analyzed gridded observational datasets and on a modeled state estimate. Besides the surface warming, a warming climate also has a subsurface effect manifesting as a strong deepening of the midthermocline isopycnals, which can be diagnosed directly from hydrographic data. This deepening appears to be a result of heat entering via subduction and spreading laterally from the high-latitude ventilation regions of subtropical mode waters. The basin-average multidecadal warming mainly expands the subtropical mode water volume, with weak changes in the temperature-salinity (u-S) relationship (known as ''spice'' variability). However, the spice contribution to the heat content can be locally large, for example in Southern Hemisphere. Multidecadal isopycnal sinking has been strongest over the southern basins and weaker elsewhere with the exception of the Gulf Stream/North Atlantic Current/subtropical recirculation gyre. At interannual to decadal time scales, wind-driven sinking and shoaling of density surfaces still dominate ocean heat content changes, while the contribution from temperature changes along density surfaces tends to decrease as time scales shorten.

Radiocarbon age-offsets in an arctic lake reveal the long-term response of permafrost carbon to climate change

USGS Publications Warehouse

Gaglioti, Benjamin V.; Mann, Daniel H.; Jones, Benjamin M.; Pohlman, John W.; Kunz, Michael L.; Wooller, Matthew J.

2014-01-01

Continued warming of the Arctic may cause permafrost to thaw and speed the decomposition of large stores of soil organic carbon (OC), thereby accentuating global warming. However, it is unclear if recent warming has raised the current rates of permafrost OC release to anomalous levels or to what extent soil carbon release is sensitive to climate forcing. Here we use a time series of radiocarbon age-offsets (14C) between the bulk lake sediment and plant macrofossils deposited in an arctic lake as an archive for soil and permafrost OC release over the last 14,500 years. The lake traps and archives OC imported from the watershed and allows us to test whether prior warming events stimulated old carbon release and heightened age-offsets. Today, the age-offset (2 ka; thousand of calibrated years before A.D. 1950) and the depositional rate of ancient OC from the watershed into the lake are relatively low and similar to those during the Younger Dryas cold interval (occurring 12.9–11.7 ka). In contrast, age-offsets were higher (3.0–5.0 ka) when summer air temperatures were warmer than present during the Holocene Thermal Maximum (11.7–9.0 ka) and Bølling-Allerød periods (14.5–12.9 ka). During these warm times, permafrost thaw contributed to ancient OC depositional rates that were ~10 times greater than today. Although permafrost OC was vulnerable to climate warming in the past, we suggest surface soil organic horizons and peat are presently limiting summer thaw and carbon release. As a result, the temperature threshold to trigger widespread permafrost OC release is higher than during previous warming events.

Optimal Detection of Global Warming using Temperature Profiles

NASA Technical Reports Server (NTRS)

Leroy, Stephen S.

1997-01-01

Optimal fingerprinting is applied to estimate the amount of time it would take to detect warming by increased concentrations of carbon dioxide in monthly averages of temperature profiles over the Indian Ocean.

Consequences of Global Warming of 1.5 °C and 2 °C for Regional Temperature and Precipitation Changes in the Contiguous United States

PubMed Central

Bradley, Raymond S.

2017-01-01

The differential warming of land and ocean leads to many continental regions in the Northern Hemisphere warming at rates higher than the global mean temperature. Adaptation and conservation efforts will, therefore, benefit from understanding regional consequences of limiting the global mean temperature increase to well below 2°C above pre-industrial levels, a limit agreed upon at the United Nations Climate Summit in Paris in December 2015. Here, we analyze climate model simulations from the Coupled Model Intercomparison Project Phase 5 (CMIP5) to determine the timing and magnitude of regional temperature and precipitation changes across the contiguous United States (US) for global warming of 1.5 and 2°C and highlight consensus and uncertainties in model projections and their implications for making decisions. The regional warming rates differ considerably across the contiguous US, but all regions are projected to reach 2°C about 10-20 years before the global mean temperature. Although there is uncertainty in the timing of exactly when the 1.5 and 2°C thresholds will be crossed regionally, over 80% of the models project at least 2°C warming by 2050 for all regions for the high emissions scenario. This threshold-based approach also highlights regional variations in the rate of warming across the US. The fastest warming region in the contiguous US is the Northeast, which is projected to warm by 3°C when global warming reaches 2°C. The signal-to-noise ratio calculations indicate that the regional warming estimates remain outside the envelope of uncertainty throughout the twenty-first century, making them potentially useful to planners. The regional precipitation projections for global warming of 1.5°C and 2°C are uncertain, but the eastern US is projected to experience wetter winters and the Great Plains and the Northwest US are projected to experience drier summers in the future. The impact of different scenarios on regional precipitation projections is negligible throughout the twenty-first century compared to uncertainties associated with internal variability and model diversity. PMID:28076360

Consequences of Global Warming of 1.5 °C and 2 °C for Regional Temperature and Precipitation Changes in the Contiguous United States.

PubMed

Karmalkar, Ambarish V; Bradley, Raymond S

2017-01-01

The differential warming of land and ocean leads to many continental regions in the Northern Hemisphere warming at rates higher than the global mean temperature. Adaptation and conservation efforts will, therefore, benefit from understanding regional consequences of limiting the global mean temperature increase to well below 2°C above pre-industrial levels, a limit agreed upon at the United Nations Climate Summit in Paris in December 2015. Here, we analyze climate model simulations from the Coupled Model Intercomparison Project Phase 5 (CMIP5) to determine the timing and magnitude of regional temperature and precipitation changes across the contiguous United States (US) for global warming of 1.5 and 2°C and highlight consensus and uncertainties in model projections and their implications for making decisions. The regional warming rates differ considerably across the contiguous US, but all regions are projected to reach 2°C about 10-20 years before the global mean temperature. Although there is uncertainty in the timing of exactly when the 1.5 and 2°C thresholds will be crossed regionally, over 80% of the models project at least 2°C warming by 2050 for all regions for the high emissions scenario. This threshold-based approach also highlights regional variations in the rate of warming across the US. The fastest warming region in the contiguous US is the Northeast, which is projected to warm by 3°C when global warming reaches 2°C. The signal-to-noise ratio calculations indicate that the regional warming estimates remain outside the envelope of uncertainty throughout the twenty-first century, making them potentially useful to planners. The regional precipitation projections for global warming of 1.5°C and 2°C are uncertain, but the eastern US is projected to experience wetter winters and the Great Plains and the Northwest US are projected to experience drier summers in the future. The impact of different scenarios on regional precipitation projections is negligible throughout the twenty-first century compared to uncertainties associated with internal variability and model diversity.

Earlier snowmelt and warming lead to earlier but not necessarily more plant growth.

PubMed

Livensperger, Carolyn; Steltzer, Heidi; Darrouzet-Nardi, Anthony; Sullivan, Patrick F; Wallenstein, Matthew; Weintraub, Michael N

2016-01-01

Climate change over the past ∼50 years has resulted in earlier occurrence of plant life-cycle events for many species. Across temperate, boreal and polar latitudes, earlier seasonal warming is considered the key mechanism leading to earlier leaf expansion and growth. Yet, in seasonally snow-covered ecosystems, the timing of spring plant growth may also be cued by snowmelt, which may occur earlier in a warmer climate. Multiple environmental cues protect plants from growing too early, but to understand how climate change will alter the timing and magnitude of plant growth, experiments need to independently manipulate temperature and snowmelt. Here, we demonstrate that altered seasonality through experimental warming and earlier snowmelt led to earlier plant growth, but the aboveground production response varied among plant functional groups. Earlier snowmelt without warming led to early leaf emergence, but often slowed the rate of leaf expansion and had limited effects on aboveground production. Experimental warming alone had small and inconsistent effects on aboveground phenology, while the effect of the combined treatment resembled that of early snowmelt alone. Experimental warming led to greater aboveground production among the graminoids, limited changes among deciduous shrubs and decreased production in one of the dominant evergreen shrubs. As a result, we predict that early onset of the growing season may favour early growing plant species, even those that do not shift the timing of leaf expansion. Published by Oxford University Press on behalf of the Annals of Botany Company.

Effects of plyometrics performed during warm-up on 20 and 40 m sprint performance.

PubMed

Creekmur, Ceith C; Haworth, Joshua L; Cox, Ronald H; Walsh, Mark S

2017-05-01

Postactivation potentiation in the form of a plyometric during warm-ups have been shown to improve performance in some speed/power events. This study aimed to determine if a plyometric during warm up can increase sprint performance in a 20 and 40 m sprint. In this study we measured sprint times of 10 male track and field athletes over distances of 20 and 40 m after warm-ups with and without a plyometric exercise. The subjects performed the sprints at the same time on 2 different days, once with the experimental treatment, a plyometric exercise in the form of a plate jump, and once without. Plate jumps were chosen as the plyometric treatment because they do not require special equipment or facilities. The plate used for the plate jumps had a mass of 11.2 kilograms, which was between 12.8-16.6% of each athlete's body mass. Statistical analysis showed a decrease in sprint time when a plyometric was performed during the warm-up for both 20 (t-test P<0.05) and 40 m sprints (t-test P<0.01). The effect sizes of the improvement for both the 20 and 40 m sprints were d=0.459 and d=0.405, respectively, which is considered a small to medium effect. These results indicate that including a plyometric exercise during warm-ups can improve sprint performance in collegiate aged male sprinters during short sprints.

Authropogenic Warming in North Alaska?.

NASA Astrophysics Data System (ADS)

Michaels, Patrick J.; Sappington, David E.; Stooksbury, David E.

1988-09-01

Using permafrost boreholes, Lachenbruch and Marshall recently reported evidence for a 2°-4°C warming in North Alaska occurring at some undetermined time during the last century. Popular accounts suggest their findings are evidence for anthropogenic warming caused by trace gases. Analyses of North Alaskan 1000-500 mb thickness onwards back to 1948 indicate that the warming was prior to that date. Relatively sparse thermometric data for the early twentieth century from Jones et al. are too noisy to support any trend since the data record begins in 1910, or to apply to any subperiod of climatic significance. Any warming detected from the permafrost record therefore occurred before the major emissions of thermally active trace gases.

Application of wavelet analysis in determining the periodicity of global warming

NASA Astrophysics Data System (ADS)

Feng, Xiao

2018-04-01

In the last two decades of the last century, the global average temperature has risen by 0.48 ° C over 100 years ago. Since then, global warming has become a hot topic. Global warming will have complex and potential impacts on humans and the Earth. However, the negative impacts far outweigh the positive impacts. The most obvious external manifestation of global warming is temperature. Therefore, this study uses wavelet analysis study the characteristics of temperature time series, solve the periodicity of the sequence, find out the trend of temperature change and predict the extent of global warming in the future, so as to take the necessary precautionary measures.

Reconciling controversies about the ‘global warming hiatus’

NASA Astrophysics Data System (ADS)

Medhaug, Iselin; Stolpe, Martin B.; Fischer, Erich M.; Knutti, Reto

2017-05-01

Between about 1998 and 2012, a time that coincided with political negotiations for preventing climate change, the surface of Earth seemed hardly to warm. This phenomenon, often termed the ‘global warming hiatus’, caused doubt in the public mind about how well anthropogenic climate change and natural variability are understood. Here we show that apparently contradictory conclusions stem from different definitions of ‘hiatus’ and from different datasets. A combination of changes in forcing, uptake of heat by the oceans, natural variability and incomplete observational coverage reconciles models and data. Combined with stronger recent warming trends in newer datasets, we are now more confident than ever that human influence is dominant in long-term warming.

Reconciling controversies about the 'global warming hiatus'.

PubMed

Medhaug, Iselin; Stolpe, Martin B; Fischer, Erich M; Knutti, Reto

2017-05-03

Between about 1998 and 2012, a time that coincided with political negotiations for preventing climate change, the surface of Earth seemed hardly to warm. This phenomenon, often termed the 'global warming hiatus', caused doubt in the public mind about how well anthropogenic climate change and natural variability are understood. Here we show that apparently contradictory conclusions stem from different definitions of 'hiatus' and from different datasets. A combination of changes in forcing, uptake of heat by the oceans, natural variability and incomplete observational coverage reconciles models and data. Combined with stronger recent warming trends in newer datasets, we are now more confident than ever that human influence is dominant in long-term warming.

Warm-up and performance in competitive swimming.

PubMed

Neiva, Henrique P; Marques, Mário C; Barbosa, Tiago M; Izquierdo, Mikel; Marinho, Daniel A

2014-03-01

Warm-up before physical activity is commonly accepted to be fundamental, and any priming practices are usually thought to optimize performance. However, specifically in swimming, studies on the effects of warm-up are scarce, which may be due to the swimming pool environment, which has a high temperature and humidity, and to the complexity of warm-up procedures. The purpose of this study is to review and summarize the different studies on how warming up affects swimming performance, and to develop recommendations for improving the efficiency of warm-up before competition. Most of the main proposed effects of warm-up, such as elevated core and muscular temperatures, increased blood flow and oxygen delivery to muscle cells and higher efficiency of muscle contractions, support the hypothesis that warm-up enhances performance. However, while many researchers have reported improvements in performance after warm-up, others have found no benefits to warm-up. This lack of consensus emphasizes the need to evaluate the real effects of warm-up and optimize its design. Little is known about the effectiveness of warm-up in competitive swimming, and the variety of warm-up methods and swimming events studied makes it difficult to compare the published conclusions about the role of warm-up in swimming. Recent findings have shown that warm-up has a positive effect on the swimmer's performance, especially for distances greater than 200 m. We recommend that swimmers warm-up for a relatively moderate distance (between 1,000 and 1,500 m) with a proper intensity (a brief approach to race pace velocity) and recovery time sufficient to prevent the early onset of fatigue and to allow the restoration of energy reserves (8-20 min).

Evaluation of ischaemia in obese patients: feasibility and accuracy of a low-dose protocol with a cadmium-zinc telluride camera.

PubMed

Gimelli, Alessia; Bottai, Matteo; Giorgetti, Assuero; Genovesi, Dario; Filidei, Elena; Marzullo, Paolo

2012-08-01

Obesity is a significant and independent risk factor for cardiovascular disease, and assessing ischaemia in obese patients is clinically important but sometimes difficult because of imaging artefacts. The aim of this study was to evaluate the feasibility and diagnostic accuracy of stress/rest imaging with a cadmium-zinc telluride (CZT) camera using a low-dose protocol in a series of consecutive obese patients referred for the evaluation of coronary artery disease. We considered 148 consecutive obese patients (mean BMI 39 ± 7 kg/m(2)) with known or suspected coronary artery disease referred to our laboratory for stress/rest myocardial perfusion imaging. A subgroup of 103 of the 148 patients underwent invasive coronary angiography for clinical reasons. All patients underwent a single-day stress/rest low-dose ultrafast protocol. Patients were injected with (99m)Tc-tetrofosmin at a dose in the range 185-222 MBq during bicycle exercise or dipyridamole stress, and underwent the first scan with an acquisition time of 7 min starting 15 min after the end of the stress. The rest scan with an acquisition time of 6 min was started from 30 to 45 min after (99m)Tc-tetrofosmin injection at a dose in the range 370-444 MBq. Images were visually inspected, and the summed stress score (SSS) and summed rest score (SRS) were obtained. Image quality was graded very good or excellent in all patients. Of the 103 patients who underwent coronary angiography, 12 (12 %), 26 (25 %) and 56 (54 %) showed one-, two- and three-vessel disease, and 9 showed normal coronary vessels. In the 103 patients submitted to coronary angiography, the mean SSS and SRS were 7 ± 6 and 2 ± 3, respectively. Semiquantitative regional and global SSS was a good discriminant of coronary artery disease and the area under the overall ROC curve was 0.848 (95 % CI 0.723-0.975). In obese patients, a single-day stress/rest low-dose ultrafast protocol with a CZT camera is clinically feasible and provides high image quality.

Relationship between the Arctic oscillation and surface air temperature in multi-decadal time-scale

NASA Astrophysics Data System (ADS)

Tanaka, Hiroshi L.; Tamura, Mina

2016-09-01

In this study, a simple energy balance model (EBM) was integrated in time, considering a hypothetical long-term variability in ice-albedo feedback mimicking the observed multi-decadal temperature variability. A natural variability was superimposed on a linear warming trend due to the increasing radiative forcing of CO2. The result demonstrates that the superposition of the natural variability and the background linear trend can offset with each other to show the warming hiatus for some period. It is also stressed that the rapid warming during 1970-2000 can be explained by the superposition of the natural variability and the background linear trend at least within the simple model. The key process of the fluctuating planetary albedo in multi-decadal time scale is investigated using the JRA-55 reanalysis data. It is found that the planetary albedo increased for 1958-1970, decreased for 1970-2000, and increased for 2000-2012, as expected by the simple EBM experiments. The multi-decadal variability in the planetary albedo is compared with the time series of the AO mode and Barents Sea mode of surface air temperature. It is shown that the recent AO negative pattern showing warm Arctic and cold mid-latitudes is in good agreement with planetary albedo change indicating negative anomaly in high latitudes and positive anomaly in mid-latitudes. Moreover, the Barents Sea mode with the warm Barents Sea and cold mid-latitudes shows long-term variability similar to planetary albedo change. Although further studies are needed, the natural variabilities of both the AO mode and Barents Sea mode indicate some possible link to the planetary albedo as suggested by the simple EBM to cause the warming hiatus in recent years.

Perioperative warming with a thermal gown prevents maternal temperature loss during elective cesarean section. A randomized clinical trial.

PubMed

de Bernardis, Ricardo Caio Gracco; Siaulys, Monica Maria; Vieira, Joaquim Edson; Mathias, Lígia Andrade Silva Telles

2016-01-01

Decrease in body temperature is common during general and regional anesthesia. Forced-air warming intraoperative during cesarean section under spinal anesthesia seems not able to prevent it. The hypothesis considers that active warming before the intraoperative period avoids temperature loss during cesarean. Forty healthy pregnant patients undergoing elective cesarean section with spinal anesthesia received active warming from a thermal gown in the preoperative care unit 30min before spinal anesthesia and during surgery (Go, n=20), or no active warming at any time (Ct, n=20). After induction of spinal anesthesia, the thermal gown was replaced over the chest and upper limbs and maintained throughout study. Room temperature, hemoglobin saturation, heart rate, arterial pressure, and tympanic body temperature were registered 30min before (baseline) spinal anesthesia, right after it (time zero) and every 15min thereafter. There was no difference for temperature at baseline, but they were significant throughout the study (p<0.0001; repeated measure ANCOVA). Tympanic temperature baseline was 36.6±0.3°C, measured 36.5±0.3°C at time zero and reached 36.1±0.2°C for gown group, while control group had baseline temperature of 36.4±0.4°C, measured 36.3±0.3°C at time zero and reached 35.4±0.4°C (F=32.53; 95% CI 0.45-0.86; p<0.001). Hemodynamics did not differ throughout the study for both groups of patients. Active warming 30min before spinal anesthesia and during surgery prevented a fall in body temperature in full-term pregnant women during elective cesarean delivery. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

[Perioperative warming with a thermal gown prevents maternal temperature loss during elective cesarean section. A randomized clinical trial].

PubMed

Bernardis, Ricardo Caio Gracco de; Siaulys, Monica Maria; Vieira, Joaquim Edson; Mathias, Lígia Andrade Silva Telles

2016-01-01

Decrease in body temperature is common during general and regional anesthesia. Forced-air warming intraoperative during cesarean section under spinal anesthesia seems not able to prevent it. The hypothesis considers that active warming before the intraoperative period avoids temperature loss during cesarean. Forty healthy pregnant patients undergoing elective cesarean section with spinal anesthesia received active warming from a thermal gown in the preoperative care unit 30min before spinal anesthesia and during surgery (Go, n=20), or no active warming at any time (Ct, n=20). After induction of spinal anesthesia, the thermal gown was replaced over the chest and upper limbs and maintained throughout study. Room temperature, hemoglobin saturation, heart rate, arterial pressure, and tympanic body temperature were registered 30min before (baseline) spinal anesthesia, right after it (time zero) and every 15min thereafter. There was no difference for temperature at baseline, but they were significant throughout the study (p<0.0001; repeated measure ANCOVA). Tympanic temperature baseline was 36.6±0.3°C, measured 36.5±0.3°C at time zero and reached 36.1±0.2°C for gown group, while control group had baseline temperature of 36.4±0.4°C, measured 36.3±0.3°C at time zero and reached 35.4±0.4°C (F=32.53; 95% CI 0.45-0.86; p<0.001). Hemodynamics did not differ throughout the study for both groups of patients. Active warming 30min before spinal anesthesia and during surgery prevented a fall in body temperature in full-term pregnant women during elective cesarean delivery. Copyright © 2015 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Climate Change, Instability and a Full Spectrum Approach to Conflict Prevention in Africa

DTIC Science & Technology

2009-10-23

commander to follow. 15. SUBJECT TERMS Climate Change, Global Warming , Security Cooperation, Stability, Instability, Stabilization, Security...note that global warming could also create similar impacts on resources.19 In modern times disputes over natural resources have erupted into conflict...16. Center for Naval Analysis, National Security and the Threat of Climate Change, 18. 17. Michael T. Klare, ― Global Warming Battlefields: How

Global Warming, Africa and National Security

DTIC Science & Technology

2008-01-15

African populations. This includes awareness from a global perspective in line with The Army Strategy for the Environment, the UN’s Intergovernmental...2 attention. At the time, computer models did not indicate a significant issue with global warming suggesting only a modest increase of 2°C9...projected climate changes. Current Science The science surrounding climate change and global warming was, until recently, a point of

Elevated CO2 and warming effects on grassland plant mortality are determined by the timing of rainfall.

PubMed

Hovenden, Mark J; Newton, Paul C D; Porter, Meagan

2017-05-01

Global warming is expected to increase the mortality rate of established plants in water-limited systems because of its effect on evapotranspiration. The rising CO 2 concentration ([CO 2 ]), however, should have the opposite effect because it reduces plant transpiration, delaying the onset of drought. This potential for elevated [CO 2 ] (eCO 2 ) to modify the warming effect on mortality should be related to prevailing moisture conditions. This study aimed to determine the impacts of warming by 2 °C and eCO 2 (550 μmol mol -1 ) on plant mortality in an Australian temperate grassland over a 6-year period and to test how interannual variation in rainfall influenced treatment effects. Analyses were based on results from a field experiment, TasFACE, in which grassland plots were exposed to a combination of eCO 2 by free air CO 2 enrichment (FACE) and warming by infrared heaters. Using an annual census of established plants and detailed estimates of recruitment, annual mortality of all established plants was calculated. The influence of rainfall amount and timing on the relative impact of treatments on mortality in each year was analysed using multiple regression techniques. Warming and eCO 2 effects had an interactive influence on mortality which varied strongly from year to year and this variation was determined by temporal rainfall patterns. Warming tended to increase density-adjusted mortality and eCO 2 moderated that effect, but to a greater extent in years with fewer dry periods. These results show that eCO 2 reduced the negative effect of warming but this influence varied strongly with rainfall timing. Importantly, indices involving the amount of rainfall were not required to explain interannual variation in mortality or treatment effects on mortality. Therefore, predictions of global warming effects on plant mortality will be reliant not only on other climate change factors, but also on the temporal distribution of rainfall. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Virtual reality robotic surgery warm-up improves task performance in a dry laboratory environment: a prospective randomized controlled study.

PubMed

Lendvay, Thomas S; Brand, Timothy C; White, Lee; Kowalewski, Timothy; Jonnadula, Saikiran; Mercer, Laina D; Khorsand, Derek; Andros, Justin; Hannaford, Blake; Satava, Richard M

2013-06-01

Preoperative simulation warm-up has been shown to improve performance and reduce errors in novice and experienced surgeons, yet existing studies have only investigated conventional laparoscopy. We hypothesized that a brief virtual reality (VR) robotic warm-up would enhance robotic task performance and reduce errors. In a 2-center randomized trial, 51 residents and experienced minimally invasive surgery faculty in General Surgery, Urology, and Gynecology underwent a validated robotic surgery proficiency curriculum on a VR robotic simulator and on the da Vinci surgical robot (Intuitive Surgical Inc). Once they successfully achieved performance benchmarks, surgeons were randomized to either receive a 3- to 5-minute VR simulator warm-up or read a leisure book for 10 minutes before performing similar and dissimilar (intracorporeal suturing) robotic surgery tasks. The primary outcomes compared were task time, tool path length, economy of motion, technical, and cognitive errors. Task time (-29.29 seconds, p = 0.001; 95% CI, -47.03 to -11.56), path length (-79.87 mm; p = 0.014; 95% CI, -144.48 to -15.25), and cognitive errors were reduced in the warm-up group compared with the control group for similar tasks. Global technical errors in intracorporeal suturing (0.32; p = 0.020; 95% CI, 0.06-0.59) were reduced after the dissimilar VR task. When surgeons were stratified by earlier robotic and laparoscopic clinical experience, the more experienced surgeons (n = 17) demonstrated significant improvements from warm-up in task time (-53.5 seconds; p = 0.001; 95% CI, -83.9 to -23.0) and economy of motion (0.63 mm/s; p = 0.007; 95% CI, 0.18-1.09), and improvement in these metrics was not statistically significantly appreciated in the less-experienced cohort (n = 34). We observed significant performance improvement and error reduction rates among surgeons of varying experience after VR warm-up for basic robotic surgery tasks. In addition, the VR warm-up reduced errors on a more complex task (robotic suturing), suggesting the generalizability of the warm-up. Copyright © 2013 American College of Surgeons. All rights reserved.

Virtual Reality Robotic Surgery Warm-Up Improves Task Performance in a Dry Lab Environment: A Prospective Randomized Controlled Study

PubMed Central

Lendvay, Thomas S.; Brand, Timothy C.; White, Lee; Kowalewski, Timothy; Jonnadula, Saikiran; Mercer, Laina; Khorsand, Derek; Andros, Justin; Hannaford, Blake; Satava, Richard M.

2014-01-01

Background Pre-operative simulation “warm-up” has been shown to improve performance and reduce errors in novice and experienced surgeons, yet existing studies have only investigated conventional laparoscopy. We hypothesized a brief virtual reality (VR) robotic warm-up would enhance robotic task performance and reduce errors. Study Design In a two-center randomized trial, fifty-one residents and experienced minimally invasive surgery faculty in General Surgery, Urology, and Gynecology underwent a validated robotic surgery proficiency curriculum on a VR robotic simulator and on the da Vinci surgical robot. Once successfully achieving performance benchmarks, surgeons were randomized to either receive a 3-5 minute VR simulator warm-up or read a leisure book for 10 minutes prior to performing similar and dissimilar (intracorporeal suturing) robotic surgery tasks. The primary outcomes compared were task time, tool path length, economy of motion, technical and cognitive errors. Results Task time (-29.29sec, p=0.001, 95%CI-47.03,-11.56), path length (-79.87mm, p=0.014, 95%CI -144.48,-15.25), and cognitive errors were reduced in the warm-up group compared to the control group for similar tasks. Global technical errors in intracorporeal suturing (0.32, p=0.020, 95%CI 0.06,0.59) were reduced after the dissimilar VR task. When surgeons were stratified by prior robotic and laparoscopic clinical experience, the more experienced surgeons(n=17) demonstrated significant improvements from warm-up in task time (-53.5sec, p=0.001, 95%CI -83.9,-23.0) and economy of motion (0.63mm/sec, p=0.007, 95%CI 0.18,1.09), whereas improvement in these metrics was not statistically significantly appreciated in the less experienced cohort(n=34). Conclusions We observed a significant performance improvement and error reduction rate among surgeons of varying experience after VR warm-up for basic robotic surgery tasks. In addition, the VR warm-up reduced errors on a more complex task (robotic suturing) suggesting the generalizability of the warm-up. PMID:23583618

Elevated CO2 and warming effects on grassland plant mortality are determined by the timing of rainfall

PubMed Central

Newton, Paul C. D.; Porter, Meagan

2017-01-01

Abstract Background and aims Global warming is expected to increase the mortality rate of established plants in water-limited systems because of its effect on evapotranspiration. The rising CO2 concentration ([CO2]), however, should have the opposite effect because it reduces plant transpiration, delaying the onset of drought. This potential for elevated [CO2] (eCO2) to modify the warming effect on mortality should be related to prevailing moisture conditions. This study aimed to determine the impacts of warming by 2 °C and eCO2 (550 μmol mol−1) on plant mortality in an Australian temperate grassland over a 6-year period and to test how interannual variation in rainfall influenced treatment effects. Methods Analyses were based on results from a field experiment, TasFACE, in which grassland plots were exposed to a combination of eCO2 by free air CO2 enrichment (FACE) and warming by infrared heaters. Using an annual census of established plants and detailed estimates of recruitment, annual mortality of all established plants was calculated. The influence of rainfall amount and timing on the relative impact of treatments on mortality in each year was analysed using multiple regression techniques. Key Results Warming and eCO2 effects had an interactive influence on mortality which varied strongly from year to year and this variation was determined by temporal rainfall patterns. Warming tended to increase density-adjusted mortality and eCO2 moderated that effect, but to a greater extent in years with fewer dry periods. Conclusions These results show that eCO2 reduced the negative effect of warming but this influence varied strongly with rainfall timing. Importantly, indices involving the amount of rainfall were not required to explain interannual variation in mortality or treatment effects on mortality. Therefore, predictions of global warming effects on plant mortality will be reliant not only on other climate change factors, but also on the temporal distribution of rainfall. PMID:28334161

Dual hypothermic oxygenated machine perfusion in liver transplants donated after circulatory death.

PubMed

van Rijn, R; Karimian, N; Matton, A P M; Burlage, L C; Westerkamp, A C; van den Berg, A P; de Kleine, R H J; de Boer, M T; Lisman, T; Porte, R J

2017-06-01

Experimental studies have suggested that end-ischaemic dual hypothermic oxygenated machine perfusion (DHOPE) may restore hepatocellular energy status and reduce reperfusion injury in donation after circulatory death (DCD) liver grafts. The aim of this prospective case-control study was to assess the safety and feasibility of DHOPE in DCD liver transplantation. In consecutive DCD liver transplantations, liver grafts were treated with end-ischaemic DHOPE. Outcome was compared with that in a control group of DCD liver transplantations without DHOPE, matched for donor age, donor warm ischaemia time, and recipient Model for End-stage Liver Disease (MELD) score. All patients were followed for 1 year. Ten transplantations involving liver grafts treated with DHOPE were compared with 20 control procedures. There were no technical problems. All 6-month and 1-year graft and patient survival rates were 100 per cent in the DHOPE group. Six-month graft survival and 1-year graft and patient survival rates in the control group were 80, 67 and 85 per cent respectively. During DHOPE, median (i.q.r.) hepatic adenosine 5'-triphosphate (ATP) content increased 11-fold, from 6 (3-10) to 66 (42-87) µmol per g protein (P = 0·005). All DHOPE-preserved livers showed excellent early function. At 1 week after transplantation peak serum alanine aminotransferase (ALT) and bilirubin levels were twofold lower in the DHOPE group than in the control group (ALT: median 966 versus 1858 units/l respectively, P = 0·006; bilirubin: median 1·0 (i.q.r. 0·7-1·4) versus 2·6 (0·9-5·1) mg/dl, P = 0·044). None of the ten DHOPE-preserved livers required retransplantation for non-anastomotic biliary stricture, compared with five of 20 in the control group (P = 0·140). This clinical study of end-ischaemic DHOPE in DCD liver transplantation suggests that the technique restores hepatic ATP, reduces reperfusion injury, and is safe and feasible. RCTs with larger numbers of patients are warranted to assess the efficacy in reducing post-transplant biliary complications. © 2017 The Authors. BJS published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.

Rayleigh lidar observations of enhanced stratopause temperature over Gadanki (13.5° N, 79.2° E) during major stratospheric warming in 2006

NASA Astrophysics Data System (ADS)

Sridharan, S.; Sathishkumar, S.; Raghunath, K.

2009-01-01

Rayleigh lidar observations of temperature structure and gravity wave activity were carried out at Gadanki (13.5° N, 79.2° E) during January-February 2006. A major stratospheric warming event occurred at high latitude during the end of January and early February. There was a sudden enhancement in the stratopause temperature over Gadanki coinciding with the date of onset of the major stratospheric warming event which occurred at high latitudes. The temperature enhancement persisted even after the end of the high latitude major warming event. During the same time, the UKMO (United Kingdom Meteorological Office) zonal mean temperature showed a similar warming episode at 10° N and cooling episode at 60° N around the region of stratopause. This could be due to ascending (descending) motions at high (low) latitudes above the critical level of planetary waves, where there was no planetary wave flux. The time variation of the gravity wave potential energy computed from the temperature perturbations over Gadanki shows variabilities at planetary wave periods, suggesting a non-linear interaction between gravity waves and planetary waves. The space-time analysis of UKMO temperature data at high and low latitudes shows the presence of similar periodicities of planetary wave of zonal wavenumber 1.

The Change in Oceanic O2 Inventory Associated with Recent Global Warming

NASA Technical Reports Server (NTRS)

Keeling, Ralph; Garcia, Hernan

2002-01-01

Oceans general circulation models predict that global warming may cause a decrease in the oceanic O2 inventory and an associated O2 outgassing. An independent argument is presented here in support of this prediction based on observational evidence of the ocean's biogeochemical response to natural warming. On time scales from seasonal to centennial, natural O2 flux/heat flux ratios are shown to occur in a range of 2 to 10 nmol O2 per Joule of warming, with larger ratios typically occurring at higher latitudes and over longer time scales. The ratios are several times larger than would be expected solely from the effect of heating on the O2 solubility, indicating that most of the O2 exchange is biologically mediated through links between heating and stratification. The change in oceanic O2 inventory through the 1990's is estimated to be 0.3 - 0.4 x 10(exp 14) mol O2 per year based on scaling the observed anomalous long-term ocean warming by natural O2 flux/heating ratios and allowing for uncertainty due to decadal variability. Implications are discussed for carbon budgets based on observed changes in atmospheric O2/N2 ratio and based on observed changes in ocean dissolved inorganic carbon.

Go4Life:Flexibility | NIH MedlinePlus the Magazine

MedlinePlus

... Upper Arm How Much, How Often Do each stretching exercise 3 to 5 times at each session. ... lower-back flexibility exercises. Always warm up before stretching exercises. Stretching your muscles before they are warmed ...