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Trade-Off Between Early Reperfusion and First-Pass Effect With Tenecteplase Versus Alteplase Before Stroke Thrombectomy.

BACKGROUND: Early reperfusion and first-pass effect are key procedural end points in large-vessel occlusion stroke thrombectomy. Because of greater fibrin specificity, tenecteplase may achieve higher early reperfusion rates compared with alteplase, yet impact of thrombolytic agents on first-pass effect remains unclear. METHODS: Consecutive patients with anterior circulation large-vessel occlusion stroke receiving intravenous thrombolysis before endovascular treatment at 2 US stroke centers were reviewed. Early reperfusion was defined as extended Thrombolysis in Cerebral Infarction ≥2b50 on initial angiography. First-pass effect was defined as extended Thrombolysis in Cerebral Infarction 2c-3 after a single pass. Multivariable logistic regression identified predictors of early reperfusion and first-pass effect. Ordinal logistic regression assessed associations of thrombolytic agent, early reperfusion, and first-pass effect with 90-day modified Rankin Scale shift. RESULTS: Among 299 patients (tenecteplase 201, alteplase 98), early reperfusion occurred in 60 (20.1%) and was more frequent with tenecteplase compared with alteplase (24.4% versus 11.2%; adjusted odds ratio [OR], 2.31 [95% CI, 1.07-4.98]). Patients without early reperfusion were evaluated for first-pass effect. Of 237 patients, first-pass effect was less frequent with tenecteplase compared with alteplase (30.3% versus 40.2%; adjusted OR, 0.42 [95% CI, 0.23-0.79]). Early reperfusion and first-pass effect each independently predicted better functional outcome, but functional outcomes were similar between tenecteplase and alteplase overall. CONCLUSIONS: We observed higher early reperfusion rates with tenecteplase, but greater first-pass effect with alteplase, while functional outcomes were comparable. This may suggest that the early reperfusion advantage of tenecteplase could be offset by downstream procedural variables such as first-pass effect, highlighting the importance of jointly evaluating both reperfusion and procedural efficiency when comparing thrombolytic strategies.

Humans

Early Reperfusion in Basilar Artery Occlusion Stroke Managed With Tenecteplase Versus Alteplase Before Endovascular Treatment.

BACKGROUND: Timely reperfusion is a critical determinant of favorable outcomes in basilar artery occlusion (BAO) stroke. We aimed to examine whether the choice of thrombolytic agent predicts early reperfusion (ER) in BAO stroke managed with tenecteplase versus alteplase before endovascular treatment. METHODS: This was a retrospective, multicenter US cohort of consecutive patients with BAO from 14 stroke centers treated with tenecteplase or alteplase within 4.5 hours of last known well before endovascular treatment. The primary end point was ER, defined as angiographic ER (expanded Thrombolysis in Cerebral Infarction grade 2b to 3 on the first diagnostic angiogram), or clinical ER, defined as substantial neurological improvement precluding endovascular treatment and a good functional outcome (modified Rankin Scale score 0-3). RESULTS: Among 163 patients with BAO and a median last known well-to-needle time of 135 minutes (interquartile range, 100-193) and last known well-to-puncture time of 228 minutes (interquartile range, 166-307), ER was observed in 27 (16.6%) patients. Rates of ER were comparable between tenecteplase (14/75, 18.7%) and alteplase (13/88, 14.8%; adjusted odds ratio, 1.082 [95% CI, 0.444-2.631]; P=0.862). In addition, rates of angiographic ER and clinical ER subgroups did not differ between thrombolytic agents. Higher Basilar Artery on Computed Tomography Angiography scores and a nonatherothrombotic cause independently predicted ER. In multivariable analysis, a good functional outcome was associated with younger age, lower stroke burden, and shorter last known well-to-puncture time. CONCLUSIONS: In BAO treated within 4.5 hours of last known well, tenecteplase and alteplase produced comparable early reperfusion rates. Achieving ER did not modify the association between thrombolytic agent and good functional outcome, consistent with rapid thrombectomy in patients with no ER.

basilar artery

Microcirculatory changes following early reperfusion in experimental myocardial infarction.

69 rats underwent temporary or permanent ligation of the left coronary artery and were studied by the injection of colloidal carbon following fixation-perfusion. 10 rats were using the same protocol and served as controls. Localized myocardial ischemia was accompanied by microvascular changes which produced capillary obstruction when blood flow was reestablished. This phenomenon of "no-reflow" was characterized by the presence of large non perfused areas seen after brief periods of ischemia (15 min). These areas were increased when the period of ischemia was lengthened. After 30 to 60 min of interruption of blood flow the non perfused area extended over the major portion of the ischemic area. During reperfusion the "no-reflow" phenomenon displayed during the first hour showing a transitory improvement in capillary perfusion which was soon followed by a progressive reexpansion of the non injected zones. After 24 hours of reperfusion, the latter zones were identical in their extent to those cases showing tissue necrosis following permanent ischemia. This "no-reflow" phenomenon appears to play a role in the evolution of the reperfused ischemic area by excluding certain areas from the benefits of reperfusion. The most probable factors involved in this process are: increased blood viscosity, endothelial changes peri-capillary edema and the contractile state of the myocardium. The incidence of these microvascular changes, using various methods of myocardial preservation during open heart surgery operations, as well as the present attempts directed towards metabolic therapy of myocardial anoxia, are under investigation.

Animals

The effect of coronary artery reperfusion on the extent of myocardial infarction.

The effect of the reperfusion on myocardial infarction has been studied in the rat in order to assess the possible reversibility of myocardial damage. The present study deals with reperfusion of experimental myocardial infarction in the rat. Two groups of animals were compared: one was subjected to permanent ischemia and the other was subjected to ischemia of variable duration 1) hour to 24 hours). The differences between infarction caused by permanent ischemia and the evolution of infarction following reperfusion were studied by means of histologic (121 specimens) histoenzymatic (56 specimens), ECG (100 specimens), techniques and study of the mcirocirculation (70 specimens). The size of the infarctions caused by temporary ischemia was found to be significantly smaller in 60% of the cases as compared to the infarctions caused by permanent ischemia. Histoenzymatic study (phosphorylase activity and succinodehydrogenase activity) confirmed the existance of a marginal zone extending over one third of the surface of the ischemic myocardium: reperfusion permitted the salvage of this zone and thereby diminished the extent of necrosis. The latter findings were further confirmed by the ECG study showing earlier regression of ischemic ST changes following early reperfusion. Microcirculatory changes secondary to anoxia may account for the fact that, in a certain percentage of the cases, early reperfusion does not prevent extension of infarction.

Animals

Disparate electrophysiological alterations accompanying dysrhythmia due to coronary occlusion and reperfusion in the cat.

The electrophysiologic changes associated with dysrhythmias induced by coronary occlusion and by subsequent reperfusion were characterized with six complimentary approaches in chloralose-anesthetized cats (n = 57) with proximal occlusion of the left anterior descending (LAD) coronary artery. Occlusion led to reproducible ventricular dysrhythmia which abated in 35 minutes. The electrophysiologic effects of reperfusion initiated at this time could be studied. Simultaneous bipolar electrograms (epi-, myo- and endocardial) from ischemic and normal zones were analyzed by computer. Before the onset of the dysrhythmia induced by occlusion, conduction was markedly slowed, with dV/dt decreasing to 34% +/- 6% of control and conduction time (endo- to epicardial activation) prolonged to 328 +/- 77% of control. However, these values returned toward normal with reperfusion, even though it also consistently induced dysrhythmia. The idioventricular escape rate (determined by intense vagal stimulation) was 62 +/- 6 beats/min during the dysrhythmia induced by occlusion (equal to control), but increased during the reperfusion dysrhythmia to 188 +/- 12 beats/min. The occlusion dysrhythmia was exacerbated, but the reperfusion dysrhythmia was suppressed by rapid atrial pacing. The refractory period progressively shortened after occlusion and remained decreased during early reperfusion. Thus, increased conduction time through myocardial and epicardial regions, asynchronous depolarization and shortening of the refractory period accompanied dysrhythmia induced by occlusion. In contrast, the dysrhythmia induced by reperfusion was characterized by normal conduction time, through myocardial regions with continued significant epicardial delay, overdrive suppression, synchronous depolarization and a high idioventricular rate.

Animals

Consequences of myocardial reperfusion following temporary coronary occlusion in pigs; effects on morphologic, biochemical and haemodynamic findings.

The effects of myocardial reperfusion have been examined following a 1 h coronary occlusion and compared to a permanent coronary ligation in pigs. Haemodynamic investigations were carried out throughout the surgical intervention and repeated after 7 days. Cellular injury was estimated by serial serum enzyme determinations (creatin phosphokinase, alpha-hydroxybutyric dehydrogenase, aspartate aminotransferase, lactic dehydrogenase) during the first 5 postoperative days; infarct size was assessed morphometrically by a histochemical staining procedure 1 week after the temporary or permanent coronary occlusion. A linear correlation was found between the logarithmically plotted peak serum activity of AST, HBDH, CPK and the morphometrically determined infarct size. Based upon enzyme and morphometrical studies no significant difference could be detected between the two experimental groups. In the animals subjected to transient coronary occlusion, however, the development of a ventricular aneurysm had been prevented to early and sustained reperfusion. Early re-establishment of coronary circulation appears to accelerate the proliferation of a more resistant granulation tissue into the infarcted area. Cardiac performance was not improved by myocardial reperfusion.

Animals

Human biopsy-defined ischemia-reperfusion injury-selective reperfusion signature prioritizes reperfusion-timed mitogen-activated protein kinase kinase inhibition after donation after circulatory death liver transplantation.

Early post-liver transplant ischemia-reperfusion injury (IRI) in donation after circulatory death grafts lacks therapies targeted to the immediate postreperfusion window, in part because generic reperfusion transcription obscures IRI-selective amplification. We analyzed paired prereperfusion/postreperfusion liver biopsies from 2 cohorts (GSE151648 and GSE87487) using a difference-in-differences interaction estimand (&#x394;&#x394; = [Post-Pre]IRI+ - [Post-Pre]IRI-) to define an IRI-selective early reperfusion program. Genome-wide &#x394;&#x394; effects were summarized using pathway-responsive genes, and pathway concordance was tested using permutation (B = 5000). The reproducible &#x394;&#x394; footprint highlighted epidermal growth factor receptor-mitogen-activated protein kinase signaling (Spearman &#x3c1; = 0.811; P = .001). Directional &#x394;&#x394; gene sets (interaction P < .05) were submitted to the L1000 characteristic direction signature search engine2; cross-cohort overlap identified 8 shared perturbagens, including 3 mitogen-activated protein kinase kinase (MEK)1/2 inhibitors. In a hepatic ischemia/reperfusion time course (GSE117915), epidermal growth factor receptor and mitogen-activated protein kinase activities increased within 0.5 hours of reperfusion, and transplant single-cell RNA sequencing (GSE189539) localized MEK/extracellular signal-regulated kinase pathway engagement predominantly to parenchymal cells. A representative MEK inhibitor, PD-0325901, reduced hepatocyte oxygen-glucose deprivation/reoxygenation injury and, when administered at reperfusion in a rat donation after circulatory death liver transplantation model (5-20 mg/kg), attenuated histologic and biochemical injury, apoptosis, and redox-inflammatory readouts and improved 7-day survival. Collectively, this biopsy-anchored &#x394;&#x394; interaction-phenotype framework, with cross-cohort concordance as a prespecified robustness gate, nominates reperfusion-timed MEK inhibition as a mechanism- and window-aligned strategy to blunt early post-liver transplant IRI.

difference-in-differences (time &#xd7; IRI interac

Regional redistribution of myocardial blood flow after coronary occlusion and reperfusion in the conscious dog.

Early and late changes in regional myocardial blood flow distribution within the left circumflex coronary arterial bed after occlusion and after occlusion and reperfusion were compared with the extent of myocardial tissue necrosis. Radiolabeled microspheres, 15 micrometer, were used to study regional myocardial blood flow in conscious dogs at 5 minutes, 2 and 6 hours and 1 month after coronary occlusion. Blood flow was measured in conscious dogs whose hearts were reperfused for 72 hours after 2,6 and 24 hours of occlusion. Blood flow was measured in four distinct transmural myocardial zones delineated by dye injections and gross infarct features of the occluded left circumflex coronary bed. After occlusion, myocardial flow was redistributed from deep layers to outer layers, and within 6 hours after occlusion collateral flow was increased to the outer zones in excess of redistributed flow. After reperfusion, blood flow greately increased to regions containing predominantly normal tissue, and flow was redistributed away from the necrotic zones. The indigenous collateral circulation was a major determinant of infarct size in the occluded and reperfused myocardium. The concept of a migrating and narrowing marginal zone is discussed.

Animals

Detection of serum cardiac myosin light chains in acute experimental myocardial infarction: radioimmunoassay of cardiac myosin light chains.

To develop a more specific plasma test for myocardial infarction, antibodies specific for cardiac myosin light chains (CM-LC) were elicited that showed less than 3% cross-reactivity with skeletal muscle light chains. These antibodies were used to develop a radioimmunoassay for CM-LC that had a sensitivity of 20 ng (+/- 4 SD; P less than 0.001). Normal dog plasma showed no measurable concentrations of CM-LC (n = 6). Plasma samples from 10 dogs with experimental myocardial infarction produced by persistent left anterior descending coronary artery (LAD) occlusion were obtained at 0, 2, 4, 6, 24, 48 and 72 hours. CM-LC were first detectable in all 10 animals 6 hours after occlusion (97.98 +/- 14 ng/ml [mean +/- SEM]; P less than 0.001). Maximal CM-LC levels were usually obtained between 24 and 48 hours. Sham-operated open chest dogs (0--48 hours, n = 3) showed no measurable CM-LC in the plasma samples. Another group of 10 dogs were subjected to 5 hours of LAD occlusion, followed by reperfusion. In four dogs, CM-LC were detectable as early as 1 hour after reperfusion (81.88 +/- 37.75 ng/ml serum). Sera from all 10 dogs showed elevated levels of CM-LC (199.75 +/- 24.0 ng/ml) by 24 hours. Peak CM-LC concentrations were obtained in five dogs at 24 hours (247.0 +/- 35.28 ng/ml) and in another dog at 120 hours (245 ng/ml). Histochemical infarct size was determined to be 0.5--10% of the left ventricular mass at seven days by triphenyltetrazolium chloride staining. The specificity and sensitivity of this radioimmunoassay for detection of CM-LC, unique proteins to the heart, may be valuable in the diagnosis of myocardial infarction.

Acute Disease

[Behavior of some serum enzymes and proteins in experimental revascularization of acute myocardial infarct].

Effect of reoxygenation of the serum enzymatic activities and protein fractions in dog with acute myocardial infarction. The enzymatic activitites creatin phosphokinase (CPK; E.C. 2.7.3.2), glutamate oxalacetate transaminase (GOT; E.C. 2.6.1.1.), diamine oxidase (DAO; E.C. 1.4.3.6.), monoamine oxidase (MAO; E.C. 1.4.3.4.), catalase (E.C. 1.2.1.6.), peroxidase (E.C. 1.2.1.6.) and the protein fractions levels are measured in the dog serum during experimental myocardial infarction, followed by 2 hours of reoxygenation. The alpha, and alpha2 globuline serum proteins increase during anoxic period; after reperfusion alpha1 globuline content further increase again, while alpha2 globuline fraction decrease to control values. The enzymatic activities, particulary CPK, DAO and MAO, significantly enhance during coronary occlusion. After riperfusion the DAO, GOT and peroxidase activities decrease, while the CPK, atalase and MAO activities further increase, particulary at the early stage of the reperfusion. These results are discussed interms of cellular mechanism, induced by oxygen readmission.

Acute Disease

Teaching Acute Coronary Syndrome High-Risk ECG Interpretation and Clinical Decision-Making Through FOAMed Videos and Podcast Versus Print-Based Materials Among Emergency Care Providers: Randomized Controlled Mixed Methods Trial.

BACKGROUND: Accurate interpretation of high-risk acute coronary syndrome (ACS) electrocardiograms (ECGs) is essential for early diagnosis and timely reperfusion, yet substantial deficits persist across health care professions. Digital self-learning formats such as FOAMed (Free Open Access Medical Education) are widely used, but their effectiveness has rarely been evaluated for complex, high-risk ACS ECG patterns. Existing ECG education studies often focus on students or single professional groups and established ST-segment elevation myocardial infarction (STEMI) criteria, leaving newer guideline-recognized STEMI equivalents, selected emerging occlusion myocardial infarction (OMI)-related patterns, and interprofessional emergency care underrepresented. OBJECTIVE: This study aimed to compare the effectiveness of FOAMed podcast and videos versus traditional print-based materials for teaching high-risk ACS ECG patterns and related clinical decision-making in emergency providers. METHODS: We conducted a prospective, interprofessional, controlled mixed methods trial across 5 training sites in Germany. Paramedics, prehospital emergency physicians, and emergency department clinicians received either a FOAMed multimedia module or print-based materials through concealed allocation; deviations from the intended 1:1 ratio resulted from participant no-shows. The intervention consisted of a 30-minute supervised self-learning session. In total, 103 participants were allocated to FOAMed (n=45) or print-based materials (n=58). Two coprimary outcomes were assessed: ECG interpretation accuracy and text-based ACS clinical decision-making. Secondary outcomes included subjective confidence, learning experience, and exploratory qualitative free-text responses. Outcome assessment was automated and blinded; mixed ANOVA was the primary analysis. The study was not prospectively registered because it assessed educational outcomes in health care professionals rather than patient health outcomes. RESULTS: All 103 participants completed the study. Both groups improved, with greater gains in the FOAMed group: ECG interpretation increased from 55% to 65.5% and text-based ACS clinical decision-making from 45% to 68%, versus 57% to 60% and from 47% to 63%, respectively, in the print-based group. Effect sizes were &#x3b7;&#xb2;=0.055 for ECG interpretation and &#x3b7;&#xb2;=0.044 for clinical decision-making. Exploratory subgroup analyses provided no evidence of differential effects across age, gender, or professional background and were likely underpowered. Qualitative responses (46 and 37 entries) provided contextual insights into perceived clarity, engagement, and practical relevance supporting the quantitative findings. CONCLUSIONS: This study is innovative in directly comparing a curated FOAMed multimedia module with selected print-based materials in an interprofessional emergency care population. It differs from existing research by focusing on subtle, emerging ischemic patterns and evaluating realistic, time-limited self-learning formats. The findings provide evidence that curated FOAMed resources can produce greater short-term improvements in ECG interpretation and text-based ACS clinical decision-making than traditional print-based materials in this setting. Although implications for clinical performance remain hypothetical, concise, high-quality digital modules may represent a practical supplement to structured continuing education in emergency care.

Humans

Demonstration of early capillary lesions in the brain by means of artificial reperfusion.

Nine patients are reported in whom functional brain death was determined as exactly as possible by neurological (in part also electroencephalographic and/or angiographic) examination in combination with analysis of the clinical history. During the first hour, at 2-4 hr, and later than 4 hr after the occurrence of functional brain death, the mean systemic pressure was raised to 30% above normal by infusion of Arterenol. The infusions lasted 15-30 min; in spite of the raised blood pressure, the patients died of cardiovascular attention to vascular damage; none was found whenever the reperfusion was completed within the first hour after determination of circulatory arrest. In all three cases in which reperfusion was performed, after more than 4 hr the neuropathological findings were similar. In one case the EEG showed a burst-type pattern during reperfusion within the first hour after determination of brain death.

Blood Pressure

Clinical characteristics and outcomes of post-stroke seizures following reperfusion therapy: a retrospective single-center study.

BACKGROUND: Post-stroke seizures (PSS) are a recognized complication of ischemic stroke and may adversely affect functional outcomes and survival; however, their characteristics in patients receiving contemporary reperfusion therapy remain incompletely defined. We aimed to describe the clinical characteristics, treatment patterns, and outcomes of patients who developed PSS following reperfusion therapy and to compare early- and late-onset seizure subgroups. METHODS: This single-center retrospective study included adult patients with acute ischemic stroke treated with intravenous thrombolysis (IV-tPA), mechanical thrombectomy (MT), or combined therapy between January 2020 and September 2025. Early seizures were defined as occurring within 7&#xa0;days of stroke onset. Clinical, radiological, and treatment-related variables were analyzed, and functional outcome was assessed using the modified Rankin Scale at 3&#xa0;months. RESULTS: Of 1242 patients who received reperfusion therapy, 53 (4.27&#xa0;%; 95&#xa0;% CI 3.28-5.54) developed PSS. Observed seizure rates were 3.39&#xa0;% in the MT group, 4.06&#xa0;% in the IV-tPA group, and 7.02&#xa0;% in the combined therapy group; these observed rates did not differ significantly across treatment modalities. Early seizures occurred in 23 patients and late seizures in 30. No significant differences were found between early- and late-onset seizure subgroups in demographic characteristics, vascular risk factors, stroke severity, reperfusion success, or clinical outcomes, with the exception of an isolated, exploratory difference in stroke laterality. Three-month mortality among patients with PSS was 45.28&#xa0;% (95&#xa0;% CI 32.66-58.55), and in-hospital mortality was 20.75&#xa0;%. CONCLUSIONS: In this single-center cohort, the incidence of PSS after reperfusion therapy was comparable to previously reported rates, with no marked differences across treatment modalities. The high mortality among patients with PSS likely reflects underlying stroke severity rather than a treatment-specific risk.

Humans

Sequential unipolar strength-interval curves and conduction times during myocardial ischemia and reperfusion in the dog.

Computerized techniques were employed to generate alternating anodal and cathodal or sequential anodal strength-interval curves during and following 15-minute coronary artery ligations in 14 anesthetized dogs. The right atrium was paced at 2.5 Hz, and unipolar ventricular strength-interval curves with simultaneous conduction times were recorded every 45-120 seconds during ischemia and reperfusion. Within 1--2 minutes of ligation, anodal midcurve and late diastolic thresholds fell sharply, and cathodal thresholds fell slightly or changed little. After 5 minutes of ischemia, anodal thresholds remained low, cathodal thresholds rose, and conduction times increased. At 10--15 minutes of ligation, if the ischemic zone was small, anodal thresholds were low, often approaching cathodal values, and conduction returned toward control values. When the ischemic zone was large, unipolar thresholds and conduction times increased late during the ligation period. Throughout the course of ischemia, the falling limb of the strength-interval curve shifted progressively to the left indicating shorter refractory periods. Following abrupt reperfusion, anodal phase 3 dips promptly reappeared; refractory periods returned toward control, and supernormal conduction was noted. By 3--5 minutes of reperfusion, the falling limb of the strength-interval curve had shifted to the right of control and conduction times increased. Thus, vulnerability to arrhythmias during early ischemia (i.e., 5 minutes) is characterized by low anodal midcurves and late diastolic thresholds, short refractory periods, and slow conduction. During the first minute of reperfusion, anodal excitability is increased during the early dip and conduction times are supernormal. Increases in anodal excitability correlate better with the peak incidence of early ligation and reperfusion arrhythmias than do changes in cathodal excitability.

Animals

Inotropic agents and functional recovery from ischemic cardiac arrest.

Short periods of ischemic arrest may cause myocardial cell damage so that reperfusion does not result in an immediate return to normal metabolic and contractile activity. Studies have been carried out using a rat heart model of cardiopulmonary bypass and ischemic cardiac arrest in order to determine whether the use of inotropic agents (isoprenaline and dobutamine) to augment contractile activity during the early phase of post-ischemic reperfusion extends pre-existing damage and results in ultimate impairment of contractile activity. The results indicated the existance of a substantial metabolic reserve, capable of providing sufficient energy for a marked increase in dP/dt and heart rate, without inducing tissue damage. However, in this isolated rat heart preparation the use of these agents had relatively little effect upon cardiac output and could be shown to induce a dose-dependent reduction in stroke volume.

Animals

Experimental occlusion of two small coronary arteries in the same heart. A new validation method for infarct size manipulation.

A method for the evaluation of interventions aimed at manipulation of infarct size is described. This method has 2 advantages over other methods: 1. Two small-to-medium sized coronary branches of the same heart are occluded and reperfused in sequence. Thereby a "control-infarct" can be compared with a "test-infarct", both within the same heart. 2. The amount of infarcted tissue in both areas is quantitated by using the p-NBT method. A condition of the method is that the areas of perfusion of both arteries are equal. Infarct size is always expressed as a percentage of the perfusion area of the occluded artery. Validation experiments with simultaneous occlusion and reperfusion of both arteries resulted in infarcts of equal size. Validation experiments with regard to the p-NBT method showed that reperfusion accelerates the washout of dehydrogenases from infarcted tissue which allows early and precise diagnosis of infarcts after relatively short occlusion- and reperfusion periods.

Animals