Low-dose intravenous recombinant tissue plasminogen activator in acute ischemic stroke without large vessel occlusion screened by 3T MRI.

OBJECTIVE: Globally, there are more than six million deaths due to cerebrovascular disease, which is the second leading cause of death. Although the imaging findings of magnetic resonance imaging (MRI) are more accurate than computed tomography for acute ischemic stroke (AIS), it is uncommon in recombinant tissue plasminogen activator (rTPA) treatment. Alteplase is not only strongly recommended treatment for acute ischemic stroke within 4.5 hours, but also decreases the disability and mortality rate. Besides, low-dose rTPA was associated with significant reductions in symptomatic intracerebral hemorrhage (sICH), compared with standard one. However, the benefits of low-dose rTPA for the treatment of AIS without large vessel occlusion (LVO) have not been fully demonstrated. We evaluated whether the low-dose rTPA in AIS without LVO could improve prognosis in patients three months post-treatment. PATIENTS AND METHODS: This was a cross-sectional study on patients with AIS treated within 4.5 hours of symptom onset admitted to Can Tho S.I.S General Hospital between February 2019 and July 2021. The eligibility criteria were patients aged > 18 years treated with low-dose rTPA (0.6 mg/kg) and screened by 3T MRI. Patients with a pre-hospital modified Rankin score (mRS) ≥ 2 points, intracranial hemorrhage, LVO, or ≥ 3 microbleeds on brain MRI were excluded. The primary outcomes were the favorable outcome rate at three months and safety, which were evaluated by the rates of intracranial hemorrhage and mortality at three months. RESULTS: This study enrolled 92 eligible patients between February 2019 and July 2021. Their National Institute of Health Stroke Scale (NIHSS) scores were 7.5 ± 3.7 at admission, 3.3 ± 3.5 at discharge or seven days after discharge, and 2.2 ± 2.8 at three months. Their mRS were 2.9 ± 0.8 at admission, 1.4 ± 1.3 at discharge or seven days after discharge, and 1.1 ± 1.1 at three months. Elevated cardiac enzymes, age ≥ 75 years, and body mass index ≥ 25 were associated with increased poor outcomes at three months. While AIS was more common in men than women, a similar number of men (33.3%) and women had poor mRS. Three patients had complications associated with low-dose rTPA treatment: one (1.1%) had intracranial hemorrhage, one (1.1%) had new infarcts, and one (1.1%) had gastrointestinal bleeding. No deaths occurred within three months. CONCLUSIONS: Our study indicates the efficacy and safety of low-dose rTPA treatment for AIS without LVO within 4.5 hours. Patient selection for rTPA by 3T MRI decreased complications and mortality.

Rescue intracranial stenting in acute ischemic stroke: a preliminary Vietnamese study.

OBJECTIVE: In cases of acute ischemic stroke (AIS) caused by intracranial large vessel occlusion, rescue intracranial stenting (RIS) has recently emerged as a treatment option for achieving recanalization when mechanical thrombectomy (MT) fails. However, few studies to date have reported on the beneficial outcomes of RIS. Our goal was to analyze whether RIS use can improve prognosis in patients 3 months post-treatment. PATIENTS AND METHODS: A retrospective analysis was performed on a prospective cohort of patients with AIS treated with RIS at Can Tho S.I.S General Hospital. The study inclusion criteria were evidence of intracranial large vessel occlusion, absence of intracranial hemorrhage (ICH), and severe stenosis or reocclusion after MT. Patients with tandem occlusions, failure to follow up after discharge, or severe or fatal illness concomitant with AIS were excluded from the study. The primary outcome was the "non-poor" prognosis status rate at 3 months after RIS and post-procedural symptomatic ICH (sICH). RESULTS: The post-treatment outcomes of 85 eligible patients who received RIS between August 2019 and May 2021 were assessed. Of the 85 included patients, 82 (96.5%) achieved successful recanalization, and 4 (4.7%) experienced sICH. At 3-months post-treatment, 47 (55.3%) patients had "non-poor" outcomes, whereas 35 (41.2%) had good outcomes. The use of dual antiplatelet therapy was associated with new infarcts (relative risk [RR]: 0.1; 95% confidence interval [CI]: 0.01-0.7) and sICH occurrence (RR: 0.1; 95% CI: 0.01-0.9). CONCLUSIONS: Our study suggests that despite the occurrence of post-procedural sICH in a small proportion of cases, RIS could serve as a useful alternative or additional treatment in the event of MT failure.

Rescue stenting after the failure of intravenous thrombolysis and bridging thrombolysis: an initial Vietnamese report.

OBJECTIVE: Intravenous (IV) recombinant tissue plasminogen activator is the standard of care for patients with acute ischemic stroke (AIS) who present to the hospital within 4.5 hours of symptom onset. However, IV thrombolysis, even bridging thrombolysis (combining intravenous thrombolysis and mechanical thrombectomy) has limited efficacy among patients who had occlusive lesions associated with high-grade arterial stenosis requiring revascularization to improve neurological deficits. We evaluated whether rescue stenting results in good outcomes among patients after the failure of intravenous thrombolysis and bridging thrombolysis. PATIENTS AND METHODS: We retrospectively analyzed patients with AIS who underwent rescue stenting for large vessel occlusion with severe atherosclerotic stenosis between May 2020 and August 2022 at Can Tho S.I.S General Hospital. Primary outcomes included the incidence of hemorrhagic transformation and the rate of good outcomes (modified Rankin Scale < 3) at 3-month follow-up. RESULTS: We identified 13 patients who received rescue stenting after the failure of IV alteplase and bridging thrombolysis, but only 11 patients met the inclusion criteria. All patients experienced successful recanalization, and 1 (9.1%) patient experienced new infarcts. Of these 11 patients, 10 (90.9%) had good outcomes 3 months after rescue stenting. Additionally, a loading dose of dual antiplatelet therapy (DAPT) applied concurrently with IV alteplase improved the recanalization rate for large target arteries but had no significant effect on the incidence of symptomatic intracranial hemorrhage. CONCLUSIONS: Rescue stenting appears to represent an additional therapeutic option in cases that fail to resolve with IV alteplase, which may improve clinical outcomes.

Brief exposure to -2 Gz reduces cerebral blood flow velocity during subsequent +2 Gz acceleration.

In order to determine the implication of the cerebral vasoconstriction occurring under -Gz acceleration in the mechanism of the push-pull effect, four healthy male non-pilots were submitted to a control centrifugation at +2 Gz, and then to an experimental run with identical +2 Gz plateau, but preceded by -2 Gz exposure. Cerebral blood flow velocity (CBFV), pulsatility index, and resistance index (RI) were continually measured with a transcranial Doppler instrument. The decrease in blood pressure and in CBFV was more important during the experimental run, when the change in RI was not different. We concluded that the cerebral vasoconstriction occurring under -2 Gz exposure seems not to be a major contributor in the mechanism of the push-pull effect appearing during subsequent +2 Gz acceleration.

[Effect of upright tilt on venous hemodynamics in rat after three-week tail suspension]. / Effet d'une mise en orthostatisme sur l'hemodynamique veineuse chez le rat apres trois semaines de suspension.

The aim of this work was to know if the venous tone measured in vivo in rat was decreased after 3-week tail suspension, a ground-based model to simulate the effects of microgravity. Arterial and venous pressure measurements during upright tilt did not show any cardiovascular deconditioning. A longer period of tail suspension appears to be necessary to induce changes in venous tone.

Venous tone and repeated +Gz accelerations.

The purpose of the present work was to study in vivo in rat the consequences of repeated exposures to sustained +Gz centrifugations on the venous pressure and on the venous tone, that one evaluated by measuring the equilibrium pressure of all vessels in the circulation when the flow is null or MCFP (mean circulatory filling pressure).

The venous tone is not altered after three-week tail suspension in rats.

Cardiovascular deconditioning observed in humans during spaceflight has been suggested to be related in part to changes in venous compliance, mechanisms including skeletal muscle deconditioning. However, increased venous compliance was observed during very short term simulations (24 to 48 hours), and during an over 28-day simulation the hyperdistensibility tended to decrease whereas the muscular changes were still present (2). In the first case, muscular changes can not explain the venous alterations because of the short delay. In the second case, the relationship between muscular and venous alterations disappeared. Finally, it is suggested that factors other than muscular ones could explain the changes in venous compliance observed during spaceflights. The fact that orthostatic hypotension has never been observed after hindlimb suspension in the rat raises issue with the use of tail-suspended rats as a valid model for the study of the mechanisms involved in cardiovascular deconditioning induced by spaceflight in humans. However, in vitro altered responsiveness of the vena cava to norepinephrine were observed in rat after spaceflight and tail suspension. The purpose of the experiments was to verify if any change occurs in venous tone measured in vivo in rats after three-week tail suspension.

G-induced myocardium functional alterations are not related to structural changes in rat heart.

BACKGROUND: Left ventricular myocardial hypertrophy with a redistribution of the isomyosins is classically observed under chronic pressure overload. HYPOTHESIS: Structural changes will also occur in myocardial cells after repeated exposures to high sustained +Gz acceleration. METHOD: Rats were exposed to three plateaus of 30 s at 10 +Gz, 4 times a week, for 4 weeks. The myocardial mass was evaluated by measuring the ratio between left ventricular weight and body weight, and the myocardial fiber cross-sectional area. Changes in capillary density were evaluated using the myosin ATPase method. The distribution of myosin isoforms was determined by electrophoresis. RESULTS: Contrary to expectations, no myocardial hypertrophy developed, and no transition was observed in myosin isoforms of centrifuged rats. CONCLUSION: The functional mechanical and energetic transformations observed in a previous investigation using an identical experimental protocol probably took place at an early stage of myocardial adaptation to +Gz acceleration. We conclude that our protocol of repeated +Gz exposures is a model of chronic overloading very different from classical models.

Bioenergetic effects of repeated +Gz acceleration on rat heart: a 31P-NMR study on isolated hearts.

This investigation was designed to determine whether repeated exposure to high sustained +Gz acceleration induces persisting changes in the myocardial energetic metabolism. Rats were exposed to three plateaus of 30 s at 10 +Gz, four times a week, for 4 weeks. Myocardial concentrations of high-energy phosphorylated compounds were evaluated by 31P-nuclear magnetic resonance (NMR) spectroscopy on isolated hearts submitted to isovolumic aortic perfusion. Heart performances were recorded using the intraventricular balloon method. Compared to the hearts of control rats (n = 5), the hearts of centrifuged rats (n = 5) had higher concentrations of inorganic phosphate (Pi:1.40 +/- 0.33 nM vs. 0.36 +/- 0.07 mM; p < 0.01), decreased phosphocreatine concentrations (PC:15 +/- 0.39 mM vs. 15.69 +/- 0.19 mM; p < 0.01), and a lower left ventricular developed pressure (LVDP) (21 +/- 1 mmHg vs. 34 +/- 2 mmHg; p < 0.01). The workload was increased by sequential augmentation of calcium in the perfusion medium. The relationship between LVDP and the Pi/PC ratio showed that the cost of the cardiac work was greater for the centrifuged rats.

Effect of upright tilt on ventricular/vascular coupling in chronically instrumented primates.

Studies of the hydraulic loading conditions on the heart in humans, especially pulsatile load, have primarily been limited to the supine state. Therefore, we have chosen a nonhuman primate model, the baboon, to assess left ventricular/vascular coupling in both supine and upright positions. Primate subjects were studied by catheterization under sedation and then after surgical implantation of transducers. This allowed the evaluation of postural stress in the chronically instrumented conscious baboon and then after light dissociative doses of ketamine. Basic hemodynamic variables were evaluated for baboons in supine and upright positions. Fourier analysis was applied to aortic pressure and flow to obtain input and characteristic impedance and the ratio of pulsatile (Wp) to total (Wt) left ventricular power (Wp/Wt). The aortic reflected, or backward, pressure was also calculated. Peripheral resistance increased (P = 0.01) and reflected pressure decreased (17.74 +/- 1.50 vs. 15.21 +/- 2 mmHg; P < 0.01) in upright subjects. Characteristic impedance and Wp/Wt were unchanged. Postoperatively, peripheral resistance increased (2,651 +/- 311 vs. 3,667 +/- 276; P < 0.05) and mean power and Wt decreased (P < 0.01) without changes in reflected pressure. All variables were unchanged after light dissociative doses of ketamine. Thus there is no significant change in efficiency of left ventricular/vascular coupling formulated in terms of Wp/Wt or input impedance with postural stress.

Preactivated merocyanine 540 inactivates HIV-1 and SIV: potential therapeutic and blood banking applications.

A novel photodynamic procedure employing "preactivated" merocyanine 540 (P-MC 540) was assessed for its effectiveness in inactivating human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV). Merocyanine 540 was preactivated by exposure to laser light at 514 nm prior to addition to viruses or infected cells. Treatment of cell-free HIV-1 and SIV with P-MC 540 significantly reduced their ability to infect and kill MT-4 cells in vitro. Preactivated MC 540 treatment of in vitro HIV-1-infected human peripheral blood mononuclear cells also decreased viral infection as assessed by a reduction in the amounts of HIV-1 p24 antigen produced and in the number of HIV-1 antigen-positive cells. Indirect immunofluorescence assays of target cell binding showed that treatment of cell-free HIV-1 and SIV with P-MC 540 interfered with their ability to bind to CD4+ target cells. Immunoprecipitation with a monoclonal anti-CD4 antibody of P-MC 540-treated and radiolabeled HIV-1 incubated with soluble recombinant CD4 (srCD4) resulted in coprecipitation of HIV-1 viral p17 and p24 core antigens with the envelope gp120/CD4 complex, suggesting cross-linking of viral components. However, no significant decrease in the binding of treated HIV-1 to srCD4 was observed. Because of the antitumor and antiviral properties of P-MC 540, this photopreactivation procedure may represent a promising therapeutic means for controlling systemic malignancies and viral infections, and for eliminating viral contaminants in biological fluids. Unlike conventional phototherapy, this procedure does not require the delivery of light energy at the target sites following binding of the photosensitizing compounds.