Outcomes of patients with moderate-to-severe Ischemia excluded from the ischemia trial

Author(s):  
Mouaz H. Al-Mallah ◽  
Ahmed Ibrahim Ahmed ◽  
Faisal Nabi ◽  
Su Min Chang ◽  
Neal S. Kleiman ◽  
...  
Keyword(s):  
Author(s):  
Yun-Hee Kim ◽  
Sung-Uk Choi ◽  
Jung-Min Youn ◽  
Seung-Ha Cha ◽  
Hyeon-Ju Shin ◽  
...  

BACKGROUND: The prevention of rheologic alterations in erythrocytes may be important for reducing sepsis-associated morbidity and mortality. Remote ischemic preconditioning (RIPC) has been shown to prevent tissue damage caused by severe ischemia and mortality resulting from sepsis. However, the effect of RIPC on erythrocytes in sepsis is yet to be determined. OBJECTIVE: To investigate the effect of RIPC on rheologic alterations in erythrocytes in sepsis. METHODS: Thirty male Sprague-Dawley rats were used in this study. An endotoxin-induced sepsis model was established by intraperitoneally injecting 20 mg/kg LPS (LPS group). RIPC was induced in the right hind limb using a tourniquet, with three 10-minute of ischemia and 10 min of reperfusion cycles immediately before the injection of LPS (RIPC/LPS group) or phosphate-buffered saline (RIPC group). The aggregation index (AI), time to half-maximal aggregation (T1/2), and maximal elongation index (EImax) of the erythrocytes were measured 8 h after injection. RESULTS: The AI, T1/2, and EImax values in the LPS and RIPC/LPS groups differed significantly from those in the RIPC group, but there were no differences between the values in the LPS and RIPC/LPS groups. CONCLUSIONS: RIPC did not prevent rheologic alterations in erythrocytes in the rat model of LPS-induced endotoxemia.


2005 ◽  
Vol 201 (3) ◽  
pp. S89
Author(s):  
Sean C. Glasgow ◽  
Jianluo Jia ◽  
Krista Csontos ◽  
Sabarinathan Ramachandran ◽  
Thalachallour Mohanakumar ◽  
...  

2009 ◽  
Vol 296 (2) ◽  
pp. H237-H246 ◽  
Author(s):  
Arlin B. Blood ◽  
Mauro Tiso ◽  
Shilpa T. Verma ◽  
Jennifer Lo ◽  
Mahesh S. Joshi ◽  
...  

Growing evidence indicates that nitrite, NO2−, serves as a circulating reservoir of nitric oxide (NO) bioactivity that is activated during physiological and pathological hypoxia. One of the intravascular mechanisms for nitrite conversion to NO is a chemical nitrite reductase activity of deoxyhemoglobin. The rate of NO production from this reaction is increased when hemoglobin is in the R conformation. Because the mammalian fetus exists in a low-oxygen environment compared with the adult and is exposed to episodes of severe ischemia during the normal birthing process, and because fetal hemoglobin assumes the R conformation more readily than adult hemoglobin, we hypothesized that nitrite reduction to NO may be enhanced in the fetal circulation. We found that the reaction was faster for fetal than maternal hemoglobin or blood and that the reactions were fastest at 50–80% oxygen saturation, consistent with an R-state catalysis that is predominant for fetal hemoglobin. Nitrite concentrations were similar in blood taken from chronically instrumented normoxic ewes and their fetuses but were elevated in response to chronic hypoxia. The findings suggest an augmented nitrite reductase activity of fetal hemoglobin and that the production of nitrite may participate in the regulation of vascular NO homeostasis in the fetus.


Vascular ◽  
2004 ◽  
Vol 12 (3) ◽  
pp. 192-197 ◽  
Author(s):  
A. Kürşat Bozkurt ◽  
Kazim Beşirli ◽  
Cengiz Köksal ◽  
Gökce Şirin ◽  
Lale Yüceyar ◽  
...  

We aimed to evaluate the characteristics of 198 new patients with Buerger's disease treated surgically in the last decade. We also compared these results with our former series reported in 1993. The records of patients with Buerger's disease who were enrolled in an ongoing investigational protocol between 1991 and 2001 were reviewed. Sympathectomy was carried out in 161 patients and revascularization in 19 patients. The cumulative secondary patency rate was 57.9% for bypass grafts at a mean follow-up of 5.4 years. Clinical outcome following sympathectomy was considered improved in 52.3% of patients, stable in 27.8%, and worse in 19.8%. Seven major and 36 minor amputations were performed, with a limb salvage rate of 95.6%. The aggressiveness of the disease has increased compared with previous series, parallel to the expansion of cigarette consumption. Bypass surgery should be considered for patients with severe ischemia who have target vessels. Sympathectomy still has a role to improve distal flow.


2015 ◽  
Vol 308 (4) ◽  
pp. F298-F308 ◽  
Author(s):  
Jinu Kim ◽  
Kishor Devalaraja-Narashimha ◽  
Babu J. Padanilam

Tp53-induced glycolysis and apoptosis regulator (TIGAR) activation blocks glycolytic ATP synthesis by inhibiting phosphofructokinase-1 activity. Our data indicate that TIGAR is selectively induced and activated in renal outermedullary proximal straight tubules (PSTs) after ischemia-reperfusion injury in a p53-dependent manner. Under severe ischemic conditions, TIGAR expression persisted through 48 h postinjury and induced loss of renal function and histological damage. Furthermore, TIGAR upregulation inhibited phosphofructokinase-1 activity, glucose 6-phosphate dehydrogenase (G6PD) activity, and induced ATP depletion, oxidative stress, autophagy, and apoptosis. Small interfering RNA-mediated TIGAR inhibition prevented the aforementioned malevolent effects and protected the kidneys from functional and histological damage. After mild ischemia, but not severe ischemia, G6PD activity and NADPH levels were restored, suggesting that TIGAR activation may redirect the glycolytic pathway into gluconeogenesis or the pentose phosphate pathway to produce NADPH. The increased level of NADPH maintained the level of GSH to scavenge ROS, resulting in a lower sensitivity of PST cells to injury. Under severe ischemia, G6PD activity and NADPH levels were reduced during reperfusion; however, blockade of TIGAR enhanced their levels and reduced oxidative stress and apoptosis. Collectively, these results demonstrate that inhibition of TIGAR may protect PST cells from energy depletion and apoptotic cell death in the setting of severe ischemia-reperfusion injury. However, under low ischemic burden, TIGAR activation induces the pentose phosphate pathway and autophagy as a protective mechanism.


2005 ◽  
Vol 67 (3) ◽  
pp. 1142-1151 ◽  
Author(s):  
Natalie Serkova ◽  
T. Florian Fuller ◽  
Jost Klawitter ◽  
Chris E. Freise ◽  
Claus U. Niemann

2014 ◽  
Vol 41 (3) ◽  
pp. 316-318
Author(s):  
Stacey L. Schott ◽  
Fernanda Porto Carreiro ◽  
James R. Harkness ◽  
Mahmoud B. Malas ◽  
Stephen M. Sozio ◽  
...  

Advanced atherosclerosis of the aorta can cause severe ischemia in the kidneys, refractory hypertension, and claudication. However, no previous reports have clearly associated infrarenal aortic stenosis with shortness of breath. A 77-year-old woman with hypertension and hyperlipidemia presented with exertional dyspnea. Despite extensive testing and observation, no apparent cause for this patient's dyspnea was found. Images revealed severe infrarenal aortic stenosis. After the patient underwent stenting of the aortic occlusion, she had immediate symptomatic improvement and complete resolution of her dyspnea within one month. Twelve months after vascular intervention, the patient remained asymptomatic. In view of the distinct and lasting elimination of dyspnea after angioplasty and stenting of a nearly occluded infrarenal aortic lesion, we hypothesize that infrarenal aortic stenosis might be a treatable cause of exertional dyspnea. Clinicians should consider infrarenal aortic stenosis as a possible cause of dyspnea. Treatment of the stenosis might relieve symptoms.


2003 ◽  
Vol 284 (3) ◽  
pp. H758-H771 ◽  
Author(s):  
Niraj Varma ◽  
James P. Morgan ◽  
Carl S. Apstein

Increased diastolic chamber stiffness (↑DCS) during ischemia may result from increased diastolic calcium, rigor, or reduced velocity of relaxation. We tested these potential mechanisms during severe ischemia in isolated red blood cell-perfused isovolumic rabbit hearts. Ischemia (coronary flow reduced 83%) reduced left ventricular (LV) contractility by 70%, which then remained stable. DCS progressively increased. When LV end-diastolic pressure had increased 5 mmHg, myofilament calcium responsiveness was altered with 50 mmol/l NH4Cl or 10 mmol/l butanedione monoxime. These affected contractility (i.e., a calcium-mediated force) but not ↑DCS. Second, quick length changes reversed ↑DCS, supporting a rigor mechanism. Third, ischemia increased the time constant of isovolumic pressure decline from 47 ± 3 to 58 ± 3 ms ( P < 0.02) but concomitantly abbreviated the contraction-relaxation cycle, i.e., pressure dissipation occurred earlier without diastolic tetanization. Finally, to assess any link between rate of relaxation and ↑DCS, hearts were exposed to 10 mmol/l calcium. Calcium doubled contractility and accelerated relaxation velocity, but without affecting ↑DCS. Thus ↑DCS developed during ischemia despite severely reduced contractility via a rigor (and not calcium mediated) mechanism. Calcium resequestration capacity was preserved, and reduced relaxation velocity was not linked to ↑DCS.


Author(s):  
D.A. Yakhontov ◽  
◽  
Yu.O. Ostanina ◽  

Introduction. Approaches to the stable coronary heart disease (CHD) treatment have been the subject to debate a long time. One of the fi rst and fundamental studies in the treatment of stable coronary heart disease patients is the COURAGE trial, which showed the advantage of rational drug therapy in comparison with percutaneous intervention in such patients. However, the CHD high prevalence with medical and social signifi cance necessitate the future consideration of the relationship between medical, that is conservative, and invasive approaches in treatment of this disease. It was particularly the focus of the recently completed multicentre ISCHEMIA trial. Another urgent problem of modern cardiology is myocardial ischemia in non-obstructive (<50% luminal occlusion) coronary arteries (INOCA) identifi ed in approximately 70% of patients who underwent coronary angiography. Aim of the research. Analysis of the available data on the management of stable CHD patients based on the ISCHEMIA trial data and review of publications on the INOCA problem. Results. In the ISCHEMIA trial, the occurrence rate of the primary outcome (cardiovascular death, myocardial infarction (MI), resuscitated cardiac arrest, hospitalization for chronic heart failure) was 13.3% in the routine invasive strategy group and 15.5% in the conservative strategy group (p = 0.34). The occurrence rate of the main secondary outcomes also did not differ between the groups signifi cantly. Quality of life in the invasive group was higher only in patients who had angina at baseline. The study subanalysis demonstrated that borderline left coronary artery stenosis is associated with a poor prognosis, and an invasive strategy relieves the angina symptoms. Women who participated in the ISCHEMIA trial had a higher incidence of angina attacks, despite less extensive coronary arteries (CA) lesions and less severe ischemia manifestations than men. Among patients with stable CHD accompanied with moderate to severe ischemia and severe chronic kidney disease patients, no evidence for the benefi t of the initial invasive strategy in reducing the risk of death or nonfatal myocardial infarction compared to the conservative strategy was found. As for ischemia in non-obstructive coronary arteries (INOCA), it is diagnosed in at least one in five patients who have undergone coronary angiography. This requires the search for new diagnostic methods, verifi cation of risk factors, causes, and optimal treatment approaches. Conclusion. The ISCHEMIA trial data demonstrated the necessity for a more careful selection of patients with stable CHD for invasive treatment, taking into account the angina pectoris severity and modern antianginal therapy possibilities. Management of patients with myocardial ischemia accompanied by non-obstructive CA lesions should be carried out on the basis of the EAPCI Expert Consensus Document on Ischaemia with INOCA (2020) which discusses the genesis of angina, as well as the diagnosis and treatment of this condition.


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