Tissue plasminogen activator(tPA) is a fibrin-specific fibrinolytic agent that has recently been shown to be effective in accelerating the clearance of hyphema. Intravitreal injection of tPA can promote rapid lysis of experimental intravitreal fibrin clots. The purpose of this study was to investigate the efficacy of intravitreal tPA injection for the treatment of vitreous hemorrhage in normal phakic non-vitrectomized rabbit eyes. Vitreous hemorrhages were produced by intravitreal injections of 0.05 ml of autologous whole blood in 25 rabbit eyes with intact vitreous. The injection of 25 or 100 micrograms of tPA in 15 eyes resulted in the clearance of vitreous hemorrhage in 99 +/- 19 or 34 +/- 6.5 days, respectively. This was significantly faster than in the control eyes in which the clearance was not seen until 131 +/- 17 days later. No tractional retinal detachment was observed.
Animals ; Rabbits ; Retina/drug effects ; Tissue Plasminogen Activator/*therapeutic use ; Vitreous Body/drug effects ; Vitreous Hemorrhage/*drug therapy

Thrombolysis with intravenous tissue plasminogen activator (t-PA) is currently an approved therapy for patients with acute ischemic stroke. Acute myocardial infarction (AMI) immediately following t-PA treatment for stroke is a rare but serious complication. A case of acute myocardial infarction (MI) following IV t-PA infusion for acute stroke was observed. This is a 52-year-old male with a known history of hypertension and chest pain, who subsequently developed MI four hours after IV t-PA was administered for acute ischemic stroke. The disruption of intra-cardiac thrombus and subsequent embolization to the coronary arteries may be an important mechanism. In addition, spontaneous recanalization of infarct-related arteries may be associated with greater myocardial salvage and better prognosis.
Humans ; Male ; Middle Aged ; Myocardial Infarction ; diagnosis ; etiology ; Stroke ; complications ; drug therapy ; Tissue Plasminogen Activator ; therapeutic use

OBJECTIVEIn this randomized, open-label, multicenter, angiographic trial, we compared the efficacy and safety of tenecteplase (TNK-tPA) with alteplase (rt-PA) in Chinese patients with acute myocardial infarction.

METHODPatients with acute ST-elevation myocardial infarction and pain to hospital time within 6 hours from October 2002, to March 2004 were randomly assigned a body weight-adjusted bolus of TNK-tPA (0.53 mg/kg over more than 10 s, n = 58) or front loaded rt-PA (< or = 100 mg, n = 52). Coronary angiography was performed at 90 min after initiating study drugs. All patients received aspirin and heparin (target activated partial thromboplastin time: 50-70 s). The primary end point of the trial was the rate of TIMI grade 3 flow at 90 minutes. Other end points included the rate of TIMI grade 2/3 flow at 90 minutes, all cause mortality at 30 days, the moderate/severe hemorrhage without intracranial hemorrhage (ICH) and ICH within 30 days.

RESULTSTIMI grade 3 flow at 90 minutes (68.4% vs. 66.7%, P = 1.00), TIMI grade 2 or 3 at 90 minutes (89.5% vs. 80.4%, P = 0.278), total mortality at 30 days (13.8% vs. 9.6%, P = 0.565), the rate of moderate/severe hemorrhage (8.6% vs. 5.8%, P = 0.72) and incidence of ICH (3.5% vs. 1.9%, P = 1.00) were all similar in TNK-tPA treated patients compared to rt-PA treated patients.

CONCLUSIONThe efficacy of single-bolus, weight-adjusted TNK-tPA fibrinolytic regimen is equivalent to front-loaded alteplase in terms of the rates of TIMI grade 3 flow, TIMI 2 or 3 flow. Incidences of moderate/severe hemorrhage, ICH and 30-days mortality were similar in TNK-tPA and rt-PA treated patients.

Aged ; Humans ; Middle Aged ; Myocardial Infarction ; drug therapy ; Thrombolytic Therapy ; Tissue Plasminogen Activator ; adverse effects ; therapeutic use ; Treatment Outcome

Ischemic stroke caused by intracranial vascular occlusion has become increasingly prevalent with considerable mortality and disability, which gravely burdens the global economy. Current relatively effective clinical treatments are limited to intravenous alteplase and thrombectomy. Even so, patients still benefit little due to the short therapeutic window and the risk of ischemia/reperfusion injury. It is therefore urgent to figure out the neuronal death mechanisms following ischemic stroke in order to develop new neuroprotective strategies. Regarding the pathogenesis, multiple pathological events trigger the activation of cell death pathways. Particular attention should be devoted to excitotoxicity, oxidative stress, and inflammatory responses. Thus, in this article, we first review the principal mechanisms underlying neuronal death mediated by these significant events, such as intrinsic and extrinsic apoptosis, ferroptosis, parthanatos, pyroptosis, necroptosis, and autophagic cell death. Then, we further discuss the possibility of interventions targeting these pathological events and summarize the present pharmacological achievements.
Brain Ischemia/pathology* ; Cell Death ; Humans ; Ischemic Stroke ; Reperfusion Injury/pathology* ; Stroke/pathology* ; Tissue Plasminogen Activator/therapeutic use*

OBJECTIVETo compare the efficacy of low dose recombinant tissue-type plasminogen activator (rt-PA) thrombolysis with primary coronary stenting after acute myocardial infarction.

METHODSOf 261 patients with first acute myocardial infarction, 131 were given low dose rt-PA intravenous thrombolysis, and 130 primary coronary stenting.

RESULTSThe age, time from onset of chest pain to hospital presentation and infarct location between these two groups were comparable. The patency rate of the infarct-related artery (IRA) in patients in the thrombolysis group was significantly lower than that of patients in the primary stenting group (P < 0.001). Recurrent myocardial infarction, and selective coronary stenting of patients with thrombolytic therapy were higher than that of patients in the primary stenting group (7.6% vs 1.5%, P < 0.05; 20.6% vs 0, P < 0.001, respectively). Left ventricular ejection fraction (LVEF) in patients in the thrombolysis group was lower than that of the stent group (55.6% +/- 13.4% vs 65.8% +/- 9.2%, P < 0.001). Total hospitalization time of the thrombolysis group was longer than that of the stent group (16 +/- 7 d vs 11 +/- 4 d, P < 0.001). Mortality in the thrombolysis group was higher than that of the stent group, but this difference was not significant (6.1% vs 3.1%, P > 0.05).

CONCLUSIONComparing with low dose rt-PA thrombolytic therapy after acute myocardial infarction, primary coronary stenting has a higher patency rate of the IRA, better cardiac function and shorter hospitalization time.

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; therapy ; Recombinant Proteins ; therapeutic use ; Stents ; Thrombolytic Therapy ; Tissue Plasminogen Activator ; therapeutic use

OBJECTIVETo explore the effect of puerarin in improving the insulin resistance (IR) and its closely related abnormal lipid and fibrinolytic activity in patients with coronary heart disease (CHD).

METHODSSeventy-six patients with CHD were randomly divided into two groups, 40 in the puerarin group and 36 in the routine treated group. Puerarin 500 mg was given to the former in addition to routine therapy by adding to 250 ml of normal saline for intravenous dripping once a day with a therapeutic course of 3 weeks. The changes of fasting blood glucose (FBG), fasting plasma insulin (FINS), plasma total cholesterol (TC), triglyceride (TG), low and high density lipoprotein cholesterol (LDL-C & HDL-C) and plasminogen activator inhibitor-1 (PAI-1) activity were measured before and after treatment, and the insulin sensitivity index (ISI) calculated. At the same time, tissue plasminogen activator (tPA) activity before and during venous occlusion test (VOT) was tested. Besides, 30 healthy subjects were taken as control.

RESULTSIn CHD patients, FINS, TC, TG, LDL-C and PAI-1 levels were higher and ISI, HDL-C and tPA before and during VOT were lower than those in the healthy controls. FINS and ISI correlated well with lipids and fibrinolytic abnormality. After puerarin treatment, FINS level lowered and ISI increased significantly (P < 0.01), while comparing with the routine group, TC, TG, LDL-C and PAI-1 were lower but HDL-C and tPA activity before and during VOT were higher in the puerarin group (P < 0.05, P < 0.01). Correlation analysis showed that FINS was positively correlated with TC, TG, LDL-C and PAI-1 and negatively correlated with HDL-C, tPA before and during VOT; ISI was negatively correlated with TC, TG, LDL-C and PAI-1 and positively correlated with HDL-C and tPA before and during VOT in the puerarin group.

CONCLUSIONPuerarin could improve the IR, IR related lipid and fibrinolytic activity abnormality in CHD patients.

Aged ; Cholesterol ; blood ; Coronary Disease ; blood ; drug therapy ; Female ; Humans ; Insulin ; blood ; Insulin Resistance ; Isoflavones ; therapeutic use ; Male ; Middle Aged ; Tissue Plasminogen Activator ; blood ; Vasodilator Agents ; therapeutic use

Ischemic stroke is a major health crisis causing high mortality and morbidity. The key treatment relies on the rapid intervention to dissolve thrombus, to reduce bleeding side effect and re-canalize clotted blood vessels using clot lysis drugs. Tissue plasminogen activator (tPA) is the only FDA-approved drug for ischemic stroke, but it has many limitations in clinical use. In recent years, the development of thrombolytic drugs and treatment strategies based on tPA has been progressed rapidly. Here we review the recent progress in this field, including the contributions from us and others, to promote the future development of novel thrombolytic drugs.
Brain Ischemia/drug therapy* ; Fibrinolytic Agents/therapeutic use* ; Humans ; Research/trends* ; Stroke/drug therapy* ; Thrombolytic Therapy/trends* ; Tissue Plasminogen Activator/therapeutic use*

OBJECTIVE: To establish a machine learning model to predict the risk of early neurological deterioration (END) based on the clinical and laboratory data of patients with acute ischemic stroke (AIS) before intravenous thrombolysis. METHODS: The clinical data of AIS patients who received intravenous thrombolytic with recombinant tissue plasminogen activator (rt-PA) at the Stroke Center of the First Hospital of Qinhuangdao City from January 2019 to July 2022 were retrospectively analyzed. Patients were divided into END group and non-END group according to whether END appeared after intravenous thrombolytic. Clinical data of patients at admission were collected, including demographic characteristics, clinical evaluation, comorbidification, drug use history, laboratory tests, etc. Univariate and multivariate Logistic regression analysis were performed to screen out the independent predictors of the END of AIS patients after intravenous thrombolytic. The study subjects were randomly divided into a training set and a test set in a 7 : 3 ratio. Four machine learning prediction models, including Logistic regression (LR), K-nearest neighbor (KNN), support vector machine (SVM) and random forest (RF), were established based on independent predictors. The receiver operator characteristic curve (ROC curve) was used to evaluate the predictive ability of each model in END. RESULTS: A total of 704 patients were enrolled, of whom 99 were identified as END and 605 as non-END. Univariate and multivariate Logistic regression analysis was used to screen out the National Institutes of Health stroke scale [NIHSS, odds ratio (OR) = 1.049, 95% confidence interval (95%CI) was 1.015-1.082, P = 0.004], systolic blood pressure (OR = 1.013, 95%CI was 1.004-1.022, P = 0.004), lymphocyte percentage (LYM%, OR = 0.903, 95%CI was 0.853-0.953, P < 0.001), platelet to lymphocyte ratio (PLR, OR = 1.007, 95%CI was 1.002-1.014, P = 0.013) were the independent predictors of END in AIS patients after intravenous thrombolysis. The area under the curve (AUC) of LR, KNN, SVM, and RF machine learning models in the test dataset were 0.789 (95%CI was 0.675-0.902), 0.797 (95%CI was 0.685-0.910), 0.851 (95%CI was 0.751-0.952) and 0.809 (95%CI was 0.699-0.919), respectively. The RF model had the highest sensitivity (95.7%). The accuracy (0.736), specificity (72.0%) and AUC of SVM model were the highest, and its overall prediction ability was better than the other three models. CONCLUSIONS Machine learning models have a potential role in early predicting the risk of END after intravenous thrombolysis in AIS patients, and can provide help in clinical decision-making for intravenous thrombolysis.
Humans ; Tissue Plasminogen Activator/therapeutic use* ; Ischemic Stroke/drug therapy* ; Brain Ischemia ; Retrospective Studies ; Thrombolytic Therapy ; Stroke ; Fibrinolytic Agents/therapeutic use*

OBJECTIVEThis study investigated the thrombolitic effect of Tianma Xinnao capsule and its preliminary mechanism, as well as the effect on coagulation system.

METHODCharlton's and Tomihisa's methods were modified to investigate the thrombolytic effect of Tianma Xinnao capsule. The activities of type 1 plasminogen activator inhibitor (PAI-1) and tissue-type plasminogen activator (tPA) in rabbit plasma were assayed by use of ELISA. The effects of Tianma Xinnao capsule were also evaluated on euglobulin lysis time (ELT), prothrombin time (PT), kaolin partial thromboplastin time (KPTT), thrombin time (TT), fibrinogen (Fib) and hemorheology.

RESULTThe results showed that Tianma Xinnao capsule had a dose-dependent thrombolytic effect in rats. Tianma Xinnao capsule at 0.6 and 1.2 g x kg(-1) produced 40% and 50% of reperfusion rate, while obtained 50% and 40% of reocclusion rate; 0.3 g x kg(-1) of Tianma Xinnao capsule, however, had no effect on the reperfusion or reocclusion rate. Tianma Xinnao capsule significantly inhibited PAI-1 activity, while elevated tPA activity in rabbit plasma. Tianma Xinnao capsule markedly prolonged ELT, PT, and KPTT, and decreased Fib level. Tianma Xinnao capsule showed no significant influence on TT or high, medium, or low sheering viscosity.

CONCLUSIONIt is indicated that Tianma Xinnao capsule inhibited PAI-1 activity and increased tPA activity, and this property of Tianma Xinnao capsule is assigned to be responsible for the thrombolytic effect.

Animals ; Blood Coagulation ; drug effects ; Blood Viscosity ; drug effects ; Capsules ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Male ; Plasminogen Activator Inhibitor 1 ; metabolism ; Rabbits ; Rats ; Thrombosis ; blood ; drug therapy ; metabolism ; Tissue Plasminogen Activator ; metabolism

OBJECTIVETo investigate the effects of propyl gallate (PrG) on the thrombus formation time and the coagulation/fibrinolysis system in an experimental carotid artery thrombosis model in rats.

METHODSFifty SD rats were randomly divided into 5 groups (10 animals/group): the normal group (normal saline 2 mL/kg), the model group (normal saline, 2 mL/kg), the heparin control group (1,250 IU/kg), the low dose PrG group (30 mg/kg), and the high dose PrG group (60 mg/kg). Thirty minutes after intravenous injection of saline or the corresponding drugs, a carotid artery thrombus was induced by continuous electric stimulation in all rats except for those in the normal group. The duration from the initiation of the electric stimulation to the sudden drop in carotid temperature was recorded as the thrombus formation time. Levels of plasma tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) were determined by ELISA.

RESULTSPrG (30 and 60 mg/kg) can prolong the thrombus formation time, but the effect was obviously weaker than that of heparin (P<0.05, P<0.01). Compared with the model group, PrG (30 and 60 mg/kg) elevated the plasma activity of t-PA (both P<0.05) and showed an increasing tendency in elevating the ratio of t-PA/PAI-1 (P>0.05), while it had no significant effect on the level of PAI-1.

CONCLUSIONPrG has a certain antithrombotic effect and can slightly regulate the imbalance of the t-PA /PAI-1 ratio.

Animals ; Blood Coagulation ; drug effects ; Carotid Artery Thrombosis ; drug therapy ; Female ; Fibrinolysis ; drug effects ; Male ; Plasminogen Activator Inhibitor 1 ; blood ; Propyl Gallate ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Tissue Plasminogen Activator ; blood