OBJECTIVES: Subarachnoid hemorrhage (SAH) is a serious cerebrovascular disease. Early brain injury (EBI) and cerebral vasospasm are the main reasons for poor prognosis of SAH patients. The specific inhibitor of histone deacetylase 6 (HDAC6), tubastatin A (TubA), has been proved to have a definite neuroprotective effect on a variety of animal models of acute and chronic central nervous system diseases. However, the neuroprotective effect of TubA on SAH remains unclear. This study aims to investigate the expression and localization of HDAC6 in the early stage of SAH, and to evaluate the protective effects of TubA on EBI and cerebral vasospasm after SAH and the underlying mechanisms. METHODS: Adult male SD rats were treated with modified internal carotid artery puncture to establish SAH model. In the first part of the experiment, rats were randomly divided into 6 groups: a sham group, a SAH-3 h group, a SAH-6 h group, a SAH-12 h group, a SAH-24 h group, and a SAH-48 h group. At 3, 6, 12, and 24 h after SAH modeling, the injured cerebral cortex of rats in each group was taken for Western blotting to detect the expression of HDAC6. In addition, the distribution of HDAC6 in the cerebral cortex of the injured side was measured by immunofluorescence double staining in SAH-24 h group rats. In the second part, rats were randomly divided into 4 groups: a sham group, a SAH group, a SAH+TubA_L group (giving 25 mg/kg TubA), and a SAH+TubA_H group (giving 40 mg/kg TubA). At 24 h after modeling, the injured cerebral cortex tissue was taken for Western blotting to detect the expression levels of HDAC6, endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS), terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining to detect apoptosis, and hematoxylin and eosin (HE) staining to detect the diameter of middle cerebral artery. RESULTS: The protein expression of HDAC6 began to increase at 6 h after SAH (P<0.05), peaked at 24 h (P<0.001), and decreased at 48 h, but there was still a difference compared with the sham group (P<0.05). HDAC6 is mainly expressed in the cytoplasm of the neurons. Compared with the sham group, the neurological score was decreased significantly and brain water content was increased significantly in the SAH group (both P<0.01). Compared with the SAH group, the neurological score was increased significantly and brain water content was decreased significantly in the SAH+TubA_H group (both P<0.05), while the improvement of the above indexes was not significant in the SAH+TubA_L group (both P>0.05). Compared with the sham group, the expression of eNOS was significantly decreased (P<0.01) and the expressions of iNOS and HDAC6 were significantly increased (P<0.05 and P<0.01, respectively) in the SAH group. Compared with the SAH group, the expression of eNOS was significantly increased, and iNOS and HDAC6 were significantly decreased in the SAH+TubA group (all P<0.05). Compared with the SAH group, the number of TUNEL positive cells was significantly decreased and the diameter of middle cerebral artery was significantly increased in the SAH+TubA group (both P<0.05) . CONCLUSIONS HDAC6 is mainly expressed in neurons and is up-regulated in the cerebral cortex at the early stage of SAH. TubA has protective effects on EBI and cerebral vasospasm in SAH rats by reducing brain edema and cell apoptosis in the early stage of SAH. In addition, its effect of reducing cerebral vasospasm may be related to regulating the expression of eNOS and iNOS.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage/drug therapy* ; Vasospasm, Intracranial/metabolism* ; Histone Deacetylase Inhibitors/therapeutic use* ; Neuroprotective Agents/therapeutic use* ; Histone Deacetylase 6/pharmacology* ; Apoptosis ; Brain Injuries/drug therapy*

Brain Ischemia ; Cerebral Infarction ; Humans ; Subarachnoid Hemorrhage ; Vasospasm, Intracranial/etiology*

A 50-year-old woman reported to the emergency department with thunderclap headache and vomiting. Non-enhanced brain computed tomography (CT) showed a subarachnoid hemorrhage of Hunt-Hess Grade II and Fisher Grade III. Brain angiography CT and transfemoral cerebral angiography (TFCA) revealed an aneurysm of the anterior communicating artery. A direct neck clipping was performed using the pterional approach. The post-operation CT was uneventful. Six days postoperatively, the patient became lethargic. The mean velocity (cm/s) of the middle cerebral artery peaked at 173 cm/s on the right side and 167 cm/s on the left. A TFCA revealed decreased perfusion in both recurrent arteries of Heubner (RAH), but no occlusion in either. Intra-arterial nimodipine injection was administered. On the 7th postoperative day, CT demonstrated a newly developed low-density lesion in the RAH territory bilaterally. The cause of the infarction was attributed to decreased perfusion caused by cerebral vasospasm. The patient was discharged with no definite neurologic deficit except for mild cognitive disorder.
Aneurysm ; Angiography ; Arteries* ; Brain ; Cerebral Angiography ; Emergency Service, Hospital ; Female ; Headache Disorders, Primary ; Humans ; Infarction* ; Infarction, Anterior Cerebral Artery ; Intracranial Aneurysm* ; Middle Aged ; Middle Cerebral Artery ; Neck ; Neurologic Manifestations ; Nimodipine ; Perfusion ; Subarachnoid Hemorrhage ; Vasospasm, Intracranial ; Vomiting

OBJECTIVE: The purpose of this retrospective study is to determine the accuracy of maximum intensity projection (MIP) images of computed tomographic angiography (CTA) for diagnosis of cerebral vasospasm (CV) following subarachnoid hemorrhage (SAH) compared with that of digital subtraction angiography (DSA). MATERIALS AND METHODS: For patients admitted to our hospital for SAH, MIP images of CTA and DSA were checked at admission, and images were taken again 1 week later. This protocol was used in 39 cases. MIP images of CTA and DSA examinations were reviewed by two independent readers. RESULTS: Accuracy of MIP images of CTA in various arterial segments, using DSA as the gold standard: the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for different segments varied from 84 to 97, 33–100, 84–100%, 25–85, and 79–97%, respectively, for readers. Accuracy of CTA in various vasospasm severity, using DSA as the gold standard: the sensitivity, specificity, PPV, NPV, and accuracy for different vasospasm severity varied from 44 to 100, 69–100, 36–100%, 61–100, and 88–100%, respectively, for readers. Accuracy of CTA in central segments versus peripheral segments, using DSA as the gold standard: the sensitivity, specificity, PPV, NPV, and accuracy for central segments and peripheral segments varied from 90 to 94, 68–83, 93–97%, 56–69, and 87–93%, respectively, for readers. CONCLUSION: MIP imaging of CTA is a useful modality when diagnosing CV after SAH.
Angiography* ; Angiography, Digital Subtraction* ; Diagnosis* ; Humans ; Retrospective Studies ; Sensitivity and Specificity ; Subarachnoid Hemorrhage* ; Vasospasm, Intracranial*

A 72-year-old man underwent spinal anesthesia for artificial urinary sphincter placement for urinary incontinence. After the block level was confirmed below T6, 1 g of cefotetan, which had not shown any reaction on skin test, was administered as a prophylactic antibiotic. The patient began complaining of chest discomfort and dyspnea shortly after injection. ST elevation appeared on the electrocardiogram and the patient's pulse could not be palpated. Accordingly, cardiopulmonary resuscitation was performed for 5 minutes; the patient recovered spontaneous circulation. The patient was diagnosed as experienced coronary artery spasm by coronary angiography with spasm test. Because coronary artery spasm can also develop in patients with no history of coronary artery disease and under spinal anesthesia, careful observation, suspicion of coronary artery spasm and prompt response to hemodynamic and electrocardiogram changes are necessary.
Aged ; Anesthesia, Conduction ; Anesthesia, Spinal* ; Cardiopulmonary Resuscitation ; Cefotetan ; Coronary Angiography ; Coronary Artery Disease ; Coronary Vasospasm ; Coronary Vessels* ; Dyspnea ; Electrocardiography ; Heart Arrest* ; Hemodynamics ; Humans ; Skin Tests ; Spasm* ; Thorax ; Urinary Incontinence ; Urinary Sphincter, Artificial

Coronary spasm generally occurs in patients with minimal atherosclerotic plaque lesion, and it has a rather favorable prognosis. However, in some cases, coronary spasm may induce myocardial infarction and even sudden cardiac death (SCD). Here, we report a case in which multi-vessel intractable coronary vasospasm suddenly occurred in a diffuse atherosclerotic lesion after percutaneous coronary intervention (PCI) in a patient with aborted SCD. We identified the characteristics of the spasm portion in intravascular ultrasound (IVUS) images and conducted percutaneous cardiopulmonary bypass support-PCI with stenting as treatment. Intima and media thickening and a large attenuated plaque burden with rupture were identified in IVUS images at the obstructive spasm portion.
Cardiopulmonary Bypass ; Coronary Vasospasm ; Death, Sudden, Cardiac ; Humans ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Plaque, Atherosclerotic ; Prognosis ; Rupture ; Spasm ; Stents ; Ultrasonography

Coronary artery vasospasm (CVS) is an important mechanism of myocardial ischemia and produces any of the manifestations of coronary artery disease from silent myocardial ischemia, to effort-induced angina and variant angina, to acute coronary syndrome including myocardial infarction or sudden cardiac death. The pathogenesis, characteristic clinical features, diagnosis, and treatment of CVS are summarized. Emphasis is placed on correct diagnosis of CVS using pharmacological spasm provocation test, either during coronary angiography or with echocardiographic monitoring of ventricular wall motion. Current underutilization of pharmacologic provocative test at the time of coronary angiography cannot be justified, as there is no evidence supporting that the incidence of CVS is declining. Physicians' vigilance for objective documentation of CVS is necessary for appropriate management of patients with various clinical presentations of ischemic heart disease.
Acute Coronary Syndrome ; Coronary Angiography ; Coronary Artery Disease ; Coronary Vasospasm ; Coronary Vessels ; Death, Sudden, Cardiac ; Diagnosis ; Echocardiography ; Humans ; Incidence ; Myocardial Infarction ; Myocardial Ischemia ; Spasm

Adult ; Anti-Inflammatory Agents ; therapeutic use ; Coronary Vasospasm ; complications ; physiopathology ; Coronary Vessels ; diagnostic imaging ; Electrocardiography ; Gas Gangrene ; complications ; therapy ; Humans ; Inflammation ; Magnetic Resonance Imaging ; Male ; Pericarditis ; complications ; physiopathology

Fluoxetine, an anti-depressant drug, has recently been shown to provide neuroprotection in central nervous system injury, but its roles in subarachnoid hemorrhage (SAH) remain unclear. In this study, we aimed to evaluate whether fluoxetine attenuates early brain injury (EBI) after SAH. We demonstrated that intraperitoneal injection of fluoxetine (10 mg/kg per day) significantly attenuated brain edema and blood-brain barrier (BBB) disruption, microglial activation, and neuronal apoptosis in EBI after experimental SAH, as evidenced by the reduction of brain water content and Evans blue dye extravasation, prevention of disruption of the tight junction proteins zonula occludens-1, claudin-5, and occludin, a decrease of cells staining positive for Iba-1, ED-1, and TUNEL and a decline in IL-1β, IL-6, TNF-α, MDA, 3-nitrotyrosine, and 8-OHDG levels. Moreover, fluoxetine significantly improved the neurological deficits of EBI and long-term sensorimotor behavioral deficits following SAH in a rat model. These results indicated that fluoxetine has a neuroprotective effect after experimental SAH.
Animals ; Apoptosis ; drug effects ; Blood-Brain Barrier ; drug effects ; Brain Edema ; drug therapy ; etiology ; Cytokines ; genetics ; metabolism ; Disease Models, Animal ; Fluoxetine ; pharmacology ; therapeutic use ; In Situ Nick-End Labeling ; Male ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Pain Measurement ; Psychomotor Performance ; drug effects ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; Subarachnoid Hemorrhage ; complications ; drug therapy ; pathology ; Time Factors ; Vasospasm, Intracranial ; drug therapy ; etiology

BACKGROUND AND OBJECTIVES: Ergonovine stress echocardiography (ErgECHO) has been proposed as a noninvasive tool for the diagnosis of coronary vasospasm. However, concern over the safety of ErgECHO remains. This study was undertaken to investigate the safety and prognostic value of ErgECHO in a large population. METHODS: We studied 3,094 consecutive patients from a single-center registry who underwent ErgECHO from November 2002 to June 2009. Medical records, echocardiographic data, and laboratory findings obtained from follow-up periods were analyzed. RESULTS: The overall positive rate of ErgECHO was 8.6%. No procedure-related mortality or myocardial infarction (MI) occurred. Nineteen patients (0.6%) had transient symptomatic complications during ErgECHO including one who was successfully resuscitated. Cumulative major adverse cardiac events (MACEs) occurred in 14.0% and 5.1% of the patients with positive and negative ErgECHO results, respectively (p < 0.001) at a median follow-up of 10.5 years. Cox regression survival analyses revealed that male sex, age, presence of diabetes, total cholesterol level of >220 mg/dL, and positive ErgECHO result itself were independent factors associated with MACEs. CONCLUSIONS: ErgECHO can be performed safely by experienced physicians and its positive result may be an independent risk factor for long-term adverse outcomes. It may also be an alternative tool to invasive ergonovine-provoked coronary angiography for the diagnosis of vasospastic angina.
Cholesterol ; Coronary Angiography ; Coronary Vasospasm ; Diagnosis ; Echocardiography ; Echocardiography, Stress ; Ergonovine ; Follow-Up Studies ; Humans ; Male ; Medical Records ; Mortality ; Myocardial Infarction ; Prognosis ; Risk Factors