Artery Reopening Research Articles

AN EXPLANATION FOR UNDERESTIMATION OF SYSTOLIC PRESSURE IN CUFF-BASED MEASUREMENT

Objective: Auscultatory blood pressure measurement is the gold standard used to calibrate other measurement devices. However, auscultatory tests systematically underestimate systolic blood pressure (SBP) and overestimate diastolic blood pressure (DBP). While there is some literature explaining overestimation, there is no physical understanding of the underestimated SBP. Our objective is to understand why auscultatory measurement results in the underestimation of SBP. The SBP is recorded when the artery first begins to reopen, during cuff deflation. Prior to this, the cuff cuts off the blood supply and the pressure in the distal part of the artery drops to the venous pressure. We propose this low pressure as a cause of underestimation and investigate this through a controlled variation of the downstream pressure in an experimental rig. Design and method: Figure 1 shows a schematic of the rig. The tube representing the artery is compressed under an inflatable cuff. The downstream pressure is varied between tests. The upstream pressure is fixed with a header tank for simplicity. Therefore, the ‘blood pressure’ measured in the rig is constant rather than oscillatory, resulting in only a single opening of the artery as the cuff is deflated, rather than repeated opening and closing. This single opening is equivalent to the first opening of the artery in the body and so represents the systolic measurement. Figure 2 depicts an example test run. The cuff around the artery is gradually deflated, and the reopening of the artery is indicated by the rise of the downstream pressure (point a). The cuff pressure at this timestamp is recorded (point b), representing the measured SBP. Results: Figure 3 shows that the recorded cuff pressure is a function of downstream pressure, with the cuff reading giving greater underestimation of SBP when the downstream pressure is lowered. Conclusions: The delay in artery reopening which results from lowering the downstream pressure provides an explanation for the systematic underestimation of SBP. This information may lead to recommendations for new measurement protocol which avoid a drop in the pressure distal to the cuff, and the resulting underestimation of SBP.

Erratum to: Artery reopening is required for the neurorestorative effects of angiotensin modulation after experimental stroke

[This corrects the article DOI: 10.1186/s13231-016-0018-x.].

Artery reopening is required for the neurorestorative effects of angiotensin modulation after experimental stroke.

BackgroundBlood flow restoration with fibrinolysis and thrombectomy is recommended to limit injury in stroke patients with proximal artery occlusion. Angiotensin receptor blockers have been shown to be neuroprotective in models of permanent and temporary occlusion, but the benefits on expression of trophic factors have been seen only when the artery is reopened. It is possible that early artery opening with endovascular intervention may increase the likelihood of identifying an effective combination therapy for patients.MethodsNormotensive male Wistar rats were subjected to mechanical middle cerebral artery occlusion (either temporary or permanent), followed by randomization to receive candesartan (0.3 mg/kg IV) or saline. Functional outcome, infarct size, and biochemical changes were assessed 24 h after ischemia induction.ResultsLack of reperfusion blunted candesartan induced neuroprotection (p < 0.05) and reduced the improvement of functional outcome (p < 0.05). With reperfusion, candesartan increased mature BDNF expression in the contralateral hemisphere (p < 0.05) and activated prosurvival (Akt-GSK3-β) signaling (p < 0.05). Without reperfusion, candesartan significantly reduced VEGF expression and MMP activation and increased NOGO A expression, creating an environment hostile to recovery.ConclusionCandesartan induced pro-recovery effects are dependent on the presence of reperfusion.

Carotid Endarterectomy and Carotid Artery Stenting Lead to Improved Cognitive Performance in Patients with Severe Carotid Artery Stenosis.

In patients with severe carotid artery stenosis, the effects of carotid artery reopening, achieved either by carotid endarterectomy (CEA) or carotid artery stenting (CAS), on cognitive functions remain elusive. Herein, we conducted a prospective study to determine whether and to what extent CEA and CAS affected cognitive performance. Patients admitted to the Department of Neurology or Vascular Surgery in Nanjing First Hospital from December 2012 to March 2015 with a diagnosis of severe carotid artery stenosis (>70%) were included in the study. Among them, 77 patients underwent CEA, 81 patients underwent CAS, and 77 patients who refused to receive aforementioned interventions were enrolled in control group. Of note, all patients in this study received basic pharmacological treatment according to the American Heart Association/American Stroke Association guidelines. Cognitive functions were evaluated by a broad spectrum of neuropsychological tests including the Mini-mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA) and event related potential P300 on the day prior to and at 3 months after indicated intervention. When compared with basic pharmacological treatment, both CEA and CAS significantly increased the scores of MMSE and MoCA at 3 months following procedures. Meanwhile, a significant reduction of P300 score was also observed in patients underwent CEA or CAS. In addition, the changes in MMSE, MoCA and P300 scores over time between CEA and CAS groups were not statistically significant. Taken together, our findings suggest an improvement of cognitive functions following carotid artery reopening. Meanwhile, the beneficial effects of CEA and CAS on cognitive performance seem to be equivalent.

No post-conditioning in the human heart with thrombolysis in myocardial infarction flow 2-3 on admission

Proof-of-concept evidence suggests that mechanical ischaemic post-conditioning (PostC) reduces infarct size when applied immediately after culprit coronary artery re-opening in ST-elevation myocardial infarction (STEMI) patients with thrombolysis in myocardial infarction 0-1 (TIMI 0-1) flow grade at admission. Whether PostC might also be protective in patients with a TIMI 2-3 flow grade on admission (corresponding to a delayed application of the post-conditioning algorithm) remains undetermined. In this multi-centre, randomized, single-blinded, controlled study, STEMI patients with a 2-3 TIMI coronary flow grade at admission underwent direct stenting of the culprit lesion, followed (PostC group) or not (control group) by four cycles of (1 min inflation/1 min deflation) of the angioplasty balloon to trigger post-conditioning. Infarct size was assessed both by cardiac magnetic resonance at Day 5 (primary endpoint) and cardiac enzymes release (secondary endpoint). Ninety-nine patients were prospectively enrolled. Baseline characteristics were comparable between control and PostC groups. Despite comparable size of area at risk (AAR) (38 ± 12 vs. 38 ± 13% of the LV circumference, respectively, P = 0.89) and similar time from onset to intervention (249 ± 148 vs. 263 ± 209 min, respectively, P = 0.93) in the two groups, PostC did not significantly reduce cardiac magnetic resonance infarct size (23 ± 17 and 21 ± 18 g in the treated vs. control group, respectively, P = 0.64). Similar results were found when using creatine kinase and troponin I release, even after adjustment for the size of the AAR. This study shows that infarct size reduction by mechanical ischaemic PostC is lost when applied to patients with a TIMI 2-3 flow grade at admission. This indicates that the timing of the protective intervention with respect to the onset of reperfusion is a key factor for preventing lethal reperfusion injury in STEMI patients. NCT01483755.

Ischemic preconditioning attenuates brain injury induced by ischemia/reperfusion during moderate hypothermia low-flow procedures

Objective: We determined the effects of ischemic preconditioning (IP) on apoptosis in a rat model of brain injury induced by cerebral ischemia/reperfusion following a moderate hypothermic low-flow (MHLF) procedure. Methods: A total of 180 rats were randomly divided into three groups. The surgery group was subjected to body temperature reduction and bilateral common carotid artery occlusion for 120 min at 25 ± 0.5°C, followed by artery reopening and rewarming. The sham-surgery group underwent the same procedure, but common carotid arteries were not occluded. The ischemic preconditioning-treated surgery group was pretreated with four cycles of 2 min occlusion of bilateral common carotid arteries and 5 min reperfusion, before 120 min of cerebral ischemia. Regional cerebral blood flow was measured continuously in 10 rats per group using laser Doppler flowmetry. We investigated brain cell apoptosis levels and mitochondrial apoptosis signaling pathway components at various time points following reperfusion. Results: The ischemic preconditioning-treated surgery group displayed decreases in apoptotic cell numbers and apoptotic protein expression levels after the procedure at 6 h, 24 h, 72 h, and 7 d. Ischemic preconditioning inhibited cytochrome c release, caspase-3 activation, and mitochondrial apoptosis signaling pathway activation. Conclusion: The protective effects of ischemic preconditioning were associated with a reduction of DNA fragmentation, and inhibition of mitochondrial cytochrome c release and caspase-3 activation, which alleviated cerebral ischemia/reperfusion injury after moderate hypothermic low flow in rats. These findings highlight the potential of ischemic preconditioning as a neuroprotective therapy for surgery involving MHLF.

Treatment with tPA Predicts Better Outcome Even if MCA Occlusion Persists

Functional improvement after middle cerebral artery ischaemia seems to depend on recanalization of large-vessel occlusion as early as possible. The only approved medical treatment for acute stroke is early IV tissue plasminogen activator administration. However, while some patients do not benefit from quick recanalization, others recover despite persistent middle cerebral artery occlusion. We wondered whether there are different effects of tissue plasminogen activator treatment on large artery and small artery reopening. We enrolled 55 acute stroke patients who showed persisting middle cerebral artery occlusion evidenced by transcranial colour-coded duplex ultrasonography in follow-up examination within 48 h postonset of middle cerebral artery stroke syndromes (mean 30·8 ± 5·4 h after admission). Twenty-two of 55 had been treated with tissue plasminogen activator and 33/55 had been treated without tissue plasminogen activator. We compared neurological (National Institutes of Health Stroke Scale) and functional (modified Rankin Scale) scores at baseline, after seven-days, and then after two-months. Risk factors, previous stroke prophylaxis, as well as clinical baseline characteristics were analysed to exclude significant differences between both groups. Despite later admission to hospital (tissue plasminogen activator patients 1·6 ± 0·66 h vs. non-tissue plasminogen activator patients 7·4 ± 5·84 h; P < 0·001), there was no significant difference between both groups concerning demographic data, severity of symptoms on admission, risk factors, stroke prophylaxis, as well as basic laboratory values (international normalized ratio, leucocyte count, C-reactive protein) blood pressure and body temperature on admission. Irrespective of Doppler findings demonstrating persistent middle cerebral artery occlusion in all 55 patients, there was a significant neurological and functional improvement in tissue plasminogen activator patients compared to non-tissue plasminogen activator patients. Tissue plasminogen activator patients had a mean improvement on National Institutes of Health Stroke Scale within the first seven-days of 2·8 points, while non-tissue plasminogen activator patients deteriorated by 2·2 points (P < 0·001). Concerning modified Rankin Scale tissue plasminogen activator-treated patients showed a mean improvement within the first seven-days of 0·5 points, while non-tissue plasminogen activator patients deteriorated by 0·3 points (P = 0·019). A favourable overall short-term clinical course (i.e. improvement on National Institutes of Health Stroke Scale >3 points and/or modified Rankin Scale >1 point) was found in 36·4% of tissue plasminogen activator patients and in 6·1% of non-tissue plasminogen activator patients (P = 0·0047). At two-months follow-up, patients still showed a median modified Rankin Scale of 4 points after tissue plasminogen activator treatment and 5 points after non-tissue plasminogen activator treatment (P = 0·023). Although the prognosis of patients with persisting middle cerebral artery occlusion after tissue plasminogen activator administration is known to be poor, patients do better if treated with tissue plasminogen activator vs. those who could not be treated - mainly for late presentation. This may be due to sufficient small vascular territory recanalization despite persistence of large artery occlusion after tissue plasminogen activator treatment.

Genetic Suppression of Akt1 Activity Aggravates Cerebral Ischemia/Reperfusion Injury After Deep Hypothermic Low Flow in Transgenic Mice

We investigated the genetic role of the PI3K/Akt signaling pathway in Akt1 (+/-) mice after cerebral ischemia/reperfusion injury following post-surgery deep hypothermic low flow. 3-week-old Akt1 (+/-) and wild-type C57/B6 mice were randomly and equally divided into sham-surgery and surgery groups. Surgery group mice were subjected to gradual body temperature reduction and bilateral common carotid artery occlusion for 120 min at 18.5 ± 0.5 °C, followed by artery reopening and rewarming. Occlusion was not performed in sham-surgery group animals. Regional cerebral blood flow was determined by laser Doppler flowmetry. Using reverse transcriptase-PCR, apoptotic assays, immunohistology, and Western blot analyses, we determined the apoptotic level of cerebral cells and the expression of Akt signaling pathway components. Regional cerebral blood flow was decreased by ≥ 86% during bilateral common carotid artery occlusion. Akt1 (+/-) mice experienced showed mortality after 24 h of cerebral I/R, and displayed increased numbers of apoptotic cerebral cells and apoptotic protein expression levels. Western analysis revealed Akt1 hypoactivity, which led to less efficient apoptotic signaling pathway inhibition. Akt1 suppresses the mitochondrial apoptosis signaling pathway, and Akt1 haplo-insufficiency exacerbates cerebral ischemia/reperfusion after deep hypothermic low flow conditions in mice. Akt may be a potential molecular therapeutic target for brain protection during surgery in congenital heart disease patients.

Monitoring and imaging the clot during systemic thrombolysis in stroke patients

Intravenous thrombolysis is the only approved treatment for acute ischemic stroke when administered within the first 3 h of stroke onset. Response to systemic thrombolysis depends on several factors including the location of arterial occlusion, clot characteristics and, ultimately, the embolic source. In the last few years, tremendous progress has been made, resulting in the widespread implementation of noninvasive neurovascular techniques. These imaging modalities are being increasingly performed in the acute stroke setting, without substantial delay, in a large number of centers worldwide. Transcranial Doppler ultrasound provides a unique opportunity to assess several aspects of clot dissolution by means of continuous monitoring of recanalization during and after tissue plasminogen activator administration. This approach allows for the evaluationof patients at the bedside and in real time due to the commencement, timing, speed and degree of artery reopening in addition to allowing the documentation of reocclusion after successful recanalization. Gradient refocused echo susceptibility vessel sign (GRE SVS) magnetic resonance imaging may be particularly useful for the identification of an intravascular thrombus during the acute phase of ischemic stroke; GRE SVS may represent a surrogate of clot composition and differential response to thrombolysis. The increasing availability of advanced neurovascular techniques may, in the near future, improve the design of stroke trials. The capability of these techniques to assess not only tissue viability but also key aspects regarding susceptibility to thrombolysis such as location, amount, composition, and age of the offending clot may improve the safety and efficacy profile of thrombolytic therapy for acute ischemic stroke.

Hemorrhagic transformation in focal cerebral ischemia: influence of time to artery reopening and tissue plasminogen activator.

We used an adaptation of a well-established rat model of middle cerebral artery occlusion (MCAO) that is both minimally invasive and reproducible to determine the effects of time to reperfusion and administration of tissue plasminogen activator (t-PA) on the development of hemorrhagic transformation (HT) in a rat model of acute stroke. Animals were randomized to receive either t-PA 10 mg/kg (29 rats) or an equal volume of saline (29 rats) over 20 minutes, beginning 5 minutes before reperfusion. Time to artery reopening varied between 1 and 24 hours after MCAO in both groups. At 18-24 hours after ischemia, the animals were sacrificed and their brains were preserved for analysis of HT. Logistic regression was used to determine the influence of time on HT risk and calculate the time at which 50% of animals developed HT (HT50%). At 24 hours, HT was present in 17 of 29 animals in each group and was significantly influenced by the time of artery reopening: 3 (15%) of 20 animals reperfused less than 3 hours after onset of ischemia and 32 (84%) of 38 reperfused 3 or more hours after the onset of ischemia (p<0.001). There was no difference in HT50% between groups. Time to artery reopening is an important determinant of HT risk in this model of cerebral ischemia. This model may have utility in developing strategies to reduce HT formation after thrombolytic therapy in patients with acute stroke.

Early noninvasive detection of successful reperfusion in patients with acute myocardial infarction.

Myoglobin (Mb) is a protein that enters rapidly and is rapidly cleared from plasma after coronary reperfusion. We sought to determine the accuracy with which a rapid rise in plasma [Mb] could predict successful coronary artery reopening in patients undergoing coronary arteriography in conjunction with attempted reperfusion in acute myocardial infarction. In 42 patients, plasma Mb levels were measured before and for at least 4 hours after attempted reperfusion. Thirty-five patients were successfully reperfused. In each, the plasma Mb level rose rapidly with peak [Mb] occurring at 111 +/- 8.1 (+/- SEM) minutes after application of therapy. In contrast, Mb levels rose more slowly in the seven patients who were not reperfused, with peak [Mb] occurring 360 +/- 61.4 minutes after attempted reperfusion. T25-100 (the time required for [Mb] to rise from 25% to 100% of peak value) was shorter in patients successfully reperfused (71 +/- 7.9 minutes) and longer (341 +/- 35.3 minutes) in patients in whom therapy was unsuccessful. A rapid rise in [Mb] after successful reperfusion was also evident by a more than 4.6-fold rise in [Mb] over the first 2 hours after reperfusion in all but five patients; in contrast, [Mb] rose by less than 4.6-fold over this same interval in every patient not successfully reperfused (sensitivity, 85%; specificity, 100%; predictive accuracy, 88%). We conclude that a rapid rise in plasma Mb level over the initial 2 hours after attempted reperfusion in acute myocardial infarction provides a useful index of successful reperfusion.

Patterns of myoglobin release after reperfusion of injured myocardium.

Myoglobin is an intracardiac protein that is released into the blood after myocardial injury and is then cleared rapidly by the kidneys. This study was undertaken to determine whether successful reperfusion of damaged myocardium could be assessed by examination of blood myoglobin concentration-time patterns. After release of a 2 hr occlusion of the mid left anterior descending coronary artery in 11 dogs that had been instrumented over the long term, immunoreactive arterial plasma concentration of myoglobin, [Mb], rose rapidly to a peak within 25 +/- 2(SEM) min (range 20 to 40). Individual peaks were three to 165 times the myoglobin levels immediately before release of the occlusion. Myoglobin was cleared rapidly from plasma, falling to one-half its peak level 38 +/- 3 min after the peak. Similarly well-defined peaks in [Mb] were evident in plasma from the great cardiac vein (GCV), with a mean time to peak of 16 +/- 2 min and a magnitude of two to 177 times prerelease values. In contrast, arterial and GCV creatine kinase activity-time curves showed less defined peaks and they occurred later and with more variability (60 to 330 min after reperfusion). In nine patients with acute infarction, successful coronary artery reopening was also accompanied by a sharp four- to sixteenfold rise in plasma [Mb] within 1 to 2 hr. Elevations in plasma creatine kinase were slower and more prolonged, peaking at 2 to 18 hr.(ABSTRACT TRUNCATED AT 250 WORDS)