Cardiac Manifestations with Chemotherapeutic Agents: 5 Fluorouracil-Induced Coronary Artery Vasospasm

5-fluorouracil (5-FU) is a fluorinated, pyrimidine analog, antineoplastic agent that is used in the treatment of several solid organ cancers. Cardiotoxicity is uncommon but life-threatening manifestations such as myocardial infarction may manifest owing to 5-FU-induced coronary artery spasm. Administering smaller doses of the drug, more frequently than not, decreases the risk of cardiotoxicity compared to large doses or with continuous infusions. We present a case of ST-segment elevation in a patient without known coronary artery disease who had presented following continuous 5-FU infusion. Coronary angiogram confirmed absence of coronary artery disease and intravenous calcium channel blockers administration was commensurate with the patient’s improvement in symptoms. We discuss the literature on 5-FU and its association with coronary artery spasm, and also briefly review chemotherapy-induced cardiotoxicities to help better prepare internists and other primary health care providers to face similar challenges, particularly of the uncommon but potentially life-threatening manifestations.

Diffuse coronary artery vasospasm in a patient with subarachnoid hemorrhage: A case report

BACKGROUND Coronary artery vasospasm(CAV)is a reversible,transient form of vasoconstriction with clinical manifestations ranging from stable angina to acute coronary syndromes(ACS).Vasospasm of epicardial coronary arteries or associated micro-vasculature can lead to total or subtotal occlusion and has been demonstrated in nearly 50%of patients undergoing angiography for suspected ACS.The mechanism for CAV has been described in literature,but in a subgroup of patients presenting with intracranial hemorrhage,it appears to be multifactorial.These patients tend to have electrocardiographic changes,elevation of cardiac biomarkers of injury and neurogenic stress cardiomyopathy.CASE SUMMARY A 44-year-old woman presented with severe headaches and tonic-clonic seizures.She was found to have diffuse subarachnoid hemorrhage(SAH)requiring ventricular drain placement,coil embolization and induced hypertension.She subsequently developed chest pain with ST elevations in anterior precordial leads,elevated cardiac enzymes and apical ballooning with left ventricular ejection fraction of 35%on transthoracic echocardiogram.Coronary angiogram revealed severe diffuse triple vessel stenoses secondary to CAV seen distally.Subsequent cardiac MRI notable for apical non-viability and scar formation.CONCLUSION This case highlights a unique etiology of acute myocardial infarction in a patient with SAH leading to ST elevations,diffuse triple vessel CAV and apical scar.

Current advances in the understanding of coronary vasospasm

Recent years have witnessed progress in our understanding of coronary vasospasm(CVS).It is evident that this is not only an East Asian but also a global disease associated with significant symptoms and possible lethal sequelae for afflicted individuals.A correct diagnosis depends on the understanding of pathogenesis and symptomatology of CVS.With the correct diagnosis,we can manage CVS patients effectively and promptly,providing optimal patient safety.Advances in our understanding of interactions between inflammation,endothelium,and smooth muscle cells have led to substantial progress in understanding the pathogenesis of symptoms in CVS and have provided some insights into the basic etiology of this disorder in some patient subpopulations.We look forward to a time when therapy will address pathophysiology and perhaps,even the primary etiology.

Revisiting normal perfusion pressure breakthrough in light of hemorrhage-induced vasospasm

Cerebral arteriovenous malformations(AVMs) have abnormally enlarged arteries and veins prone to spontaneous hemorrhage.Immediately following surgical excision of a cerebral AVM,even normal brain tissue surrounding the lesion is subject to hemorrhage,a phenomenon termed normal perfusion pressure breakthrough(NPPB) syndrome.According to this theory,arteries supplying cerebral AVMs become dilated and lose their capacity to dilate or constrict to autoregulate pressure.Acutely after removal of a cerebral AVM,excessive blood pressure in these arterial feeders can cause normal brain tissue to bleed.However,this theory remains controversial.We present a patient with a cerebral AVM that demonstrated cerebrovascular reactivity and argues against an assumption underlying the theory of NPPB syndrome.

Inhibitory effects of lidocaine on cerebral vasospasm in a rabbit model of subarachnoid hemorrhage

Following subarachnoid hemorrhage, vasoconstrictor substances, cellular apoptosis, blood coagulation, and vascular cell proliferation affect the onset of cerebral vasospasm. Previous studies from our laboratory have revealed that injection of lidocaine （2 mg） into the cisterna magna reduces cerebral vasospasm and nerve functional impairment in an animal model of subarachnoid hemorrhage. The present study determined the optimal lidocaine dose for vasospasm and brain injury by injecting different doses of lidocaine into the cisterna magna in a rabbit model of subarachnoid hemorrhage. Results showed that endothelin, tumor necrosis factor-a, and interleukin-6 levels significantly increased in plasma, and calcitonin gene-related peptide levels significantly decreased in plasma （P 〈 0.05）. The number of neurons was decreased, the number of cells expressing c-Fos increased in the hippocampus, and cross-sections and diameters of basilar arteries were reduced （P 〈 0.05）. These changes significantly improved following injection of lidocaine （1,2, 4, and 6 mg） into the cisterna magna. A dose of 6 mg lidocaine into the cisterna magna resulted in optimal effects on cerebral vasospasm and brain injury following subarachnoid hemorrhage.

Hypertensive-Nimodipine Therapy for Middle Cerebral Artery Vasospasm after Resection of Glioblastoma Multiforme: A Case Report and Literature Review

Delayed cerebral ischemia (DCI) due to post-brain tumor resection vasospasm is an often unrecognized yet debilitating complication. We present a patient with DCI after the resection of glioblastoma multiforme (GBM). To our knowledge, this is the first report on DCI after GBM resection. A 52-year-old female patient with headache for one month underwent subtotal resection of a left temporal GBM encasing the proximal middle cerebral artery (MCA). She was well during the immediate postoperative period but developed right upper limb dense monoparesis on postoperative day four with computed tomographic angiography confirming left MCA vasospasm. Symptoms were significantly alleviated with weeklong hypertensive therapy and nimodipine administration;however they recurred soon after cessation of treatment. A high index of clinical suspicion is needed for the diagnosis of post-tumor resection DCI. Any new postoperative neurological deficit that cannot be explained by hemorrhage, seizures or infection should be expeditiously investigated by angiography or transcranial Doppler sonography. Prompt initiation of hypertensive and nimodipine therapy can possibly reverse neurological deficit. Treatment should be guided by Doppler, angiographic or perfusion imaging studies and not by clinical improvement alone.

Coronary vasospasm:A narrative review

Coronary artery vasospasm(CAVS)plays an important role in acute chest pain syndrome caused by transient and partial or complete occlusion of the coronary arteries.Pathophysiology of the disease remains incompletely understood,with autonomic and endothelial dysfunction thought to play an important role.Due to the dynamic nature of the disease,its exact prevalence is not entirely clear but is found to be more prevalent in East Asian and female population.Cigarette smoking remains a prominent risk factor,although CAVS does not follow traditional coronary artery disease risk factors.Many triggers continue to be identified,with recent findings identifying chemotherapeutics,allergens,and inflammatory mediators as playing some role in the exacerbation of CAVS.Provocative testing with direct visualization is currently the gold-standard for diagnosis,but non-invasive tests,including the use of biomarkers,are being increasingly studied to aid in the diagnosis.Treatment of the CAVS is an area of active research.Apart from risk factor modification,calcium channel blockers are currently the first line treatment,with nitrates playing an important adjunct role.High-risk patients with life-threatening complications should be considered for implantable cardioverter defibrillator(ICD),although timing criteria for escalated therapy require further investigation.The role of pharmaceuticals targeting oxidative stress remains incompletely understood.

Prospective Evaluation of Post-Traumatic Vasospasm and Post-Injury Functional Outcome Assessment: Is Cerebral Ischemia Going Unrecognized in Patients with Traumatic Brain Injury?

Background: Secondary injury processes such as posttraumatic vasospasm (PTV) play a critical role in the development of cerebral ischemia/infarction after traumatic brain injury (TBI). The objectives of this study were to evaluate the incidence of cerebral vasospasm in patients with moderate to severe TBI and to assess post-injury functional outcome. Study Design: A prospective observational study was conducted in patients with moderate and severe blunt TBI. Transcranial Doppler (TCD) ultrasound was performed within the first 72 hours and then daily for up to 7 days. Patient characteristics and outcome data including functional outcome as assessed by the Extended Glasgow Outcome Scale (GOS-E) were collected and compared between patients with and without PTV. Results: Twenty-three patients met our inclusion criteria. While there was a 47.8% incidence of vasospasm as detected by TCD, there was no significant difference in hospital LOS or mortality between patients with and without PTV. Of the two patients with PTV who died, both had a cerebral infarct or cerebral ischemia. In evaluating overall GOS-E among patients with a cerebral focal injury, patients with PTV had a significantly higher GOS-E score when compared to patients without PTV (8.0 vs. 6.8, p = 0.01). Conclusions: The high incidence of PTV and the role of clinically significant vasospasm after TBI remain unclear. While functional outcome was better in patients with a focal injury and vasospasm, patients who died had cerebral ischemia or infarction. We hypothesize that there is an interaction between impaired cerebral autoregulation, PTV and poor outcomes in patients with TBI.

Penehyclidine hydrochloride attenuates cerebral vasospasm after subarachnoid hemorrhage

A new cholinergic antagonist, penehyclidine hydrochloride （PHC）, was developed independently by Chinese scientists. Administration of PHC into muscle and the cisterna magna could relieve basilar artery vasospasm following subarachnoJd hemorrhage in animals. In addition, injecting PHC into the cisterna magna had better therapeutic effect. Moreover, PHC had the capability of reducing the expression of neuron specific enolase and S-1OOI3 protein in cerebrospinal fluid. There was no effect on the number of surviving neurons in the hippocampal CA1 region, or on the levels of superoxide dismutase and malondialdehyde.

Effect of HX0507,a water-soluble propofol pro-drug,on subarachnoid hemorrhage-induced cerebral vasospasm in rabbits

BACKGROUND： Propofol has been shown to attenuate neuronal injury in a number of experimental conditions. However, its effect in models of cerebral ischemia after subarachnoid hemorrhage （SAH） remains controversial. OBJECTIVE： To explore the effects of intracisternal injection of HX0507, a water-soluble propofol prodrug, on basilar artery vasospasm and brain tissue injury in a rabbit model of SAH. DESIGN, TIME AND SETTING： A randomized, controlled, in vivo animal experiment based on behavior and morphology. The study was performed at the Laboratory of Anesthesiology and Critical Care Medicine, West China Hospital, Sichuan University from April to December 2007. MATERIALS： HX0507 was provided by the Laboratory of Anesthesiology and Critical Care Medicine, West China Hospital of Sichuan University. METHODS： A total of 30 healthy, male, New Zealand rabbits were randomly assigned to sham-operation, SAH-control, and SAH-HX0507 groups, with 10 animals in each group. The single-hemorrhage SAH model was established by injecting autologous arterial blood （1.0 mL/kg） into the cisterna magna in the SAH-control and SAH-HX0507 groups, while the sham-operation group was injected with normal saline （1.0 mL/kg）. Thirty minutes after injection, the sham-operation and SAH-control groups were injected with normal saline （0.1 mL/kg） into the cisterna magna, while the SAH-HX0507 group received an injection of HX0507 （4.8 mg/kg）. MAIN OUTCOME MEASURES： The cross-sectional area and corrugation coefficients of basilar arteries and hippocampal CA1 neuronal densities were measured 48 hours after SAH （peak stage of vasospasm） using the Computer-Assisted Stereological Toolbox system. The ultrastructural structure of the basilar artery wall was examined by transmission electron microscopy. In addition, neurological behavioral impairment was evaluated by appetite score at pre-SAH, and 1 and 2 days after SAH. RESULTS： The cross-sectional area of basilar arteries and hippocampal CA1 neuronal densities, as well as ultrastructural structure scores of the SAH-control group were significantly less than the other groups （P 〈 0.01 or P 〈 0.05）, while the corrugation coefficients of basilar arteries and appetite score 2 days after SAH were significantly greater than the other groups （P 〈 0.01 or P 〈 0.05）. The appetite score 1 day after modeling was remarkably greater than the SAH-control group （P 〈 0.05）. However, no significant difference was determined between the sham-operation and SAH-HX0507 groups （P 〉 0.05）. CONCLUSION： Intracisternal administration of HX0507 attenuated basilar artery vasospasm and hippocampal ischemic injury in a rabbit model of SAH.

Studies of the antagonistic effect of BQ-123 on cerebral vasospasm induced by intracisternal injection of endothelin-1 and subarachnoid hemorrhage

To clarify whether the endothelin A (ETA)-receptor antagonist BQ-123 can prevent the development of cerebral vasospasm (CVS) induced by endothelin (ET-1) and subarachnoid hemorrhage (SAH), which has been controversia11y reported by various authors. We have performed investigations in anesthetized Sprague-Dawley rats- Intracisternal injection (i. c. ) of ET-l (10-11, 10-10, 10-9 mol/kg) could induce acute dose-dependent CVS, furthermore, the highest dose of ET-l (lO-’ mo1/kg) had a biphasic response in CVS of a 24-hour duration. However, the CVS by ET-1 (10-9 mol/kg) could be prevented effectively by previous i. c. of BQ-123 in a dose-dependent manner (10-9, 10-8, 10-7 mol/kg), of which the i. c- of BQ-123 (10-7mol/kg) could abolish the CVS completely. i. c. of BQ-123 (10-7 mol/kg) before SAH induced by a single i. c, of 150 pl autologous fresh blood directly to the Willis circle cou1d prevent the following CVS largely, which was a biphasic response and long-lasting (duration of 72 h). We conclude that subarachnoid application of ETA-receptor antagonist can effecti vely prevent CVS induced by ET-1 and SAH, and ET-1 may be the major mediator responsible for the CVS following SAH.

Role of endothelin in the pathogenesis of cerebral vasospasm following subarachnoid hemorrhage

A model of cerebral vasospasm (CVS) associated with subarachnoid hemorrhage (SAH) was prepared on male Sprague-Dawley rats by a single intracisternal injection (i. c.) of 150 μl autologous fresh blood directly to Willis circle.The process of CVS was monit

INFLUENCE OF GINKGO BILOBA EXTRACT ON NITRIC OXIDE AND ENDOTHELIN-1 DURING CEREBRAL VASOSPASM IN RATS

Objective.To investigate the effects of Ginkgo biloba extracton cer ebral vasospasmafter subarachnoid hemorrhageand its influence on n itric oxideand endothelin-l .Methods.Noncraniotomy models of SAH in Wistar rats were used and animals were divided into sham-operated group ,SAH group,saline-treated group and EGb-treated group.Diameter of basilar a rtery was measured.Regional cerebral blood flow,NO and ET-1levels in blood,and calcium content in brain tissue within24hours after SAH were dete cted.Pathological examination of hippocampus CA1sub-field was also performed .Results.Sham operation did not alter the above parameters.Induction of SAH l ed to a marked spasm of basilar artery.rCBF decreased obviously and consecutive ly within24hours after SAH.Meanwhile NO level in serum decreased,ET-1level in plasma and calcium content in brain tissue significantly in-creased.Pyra midal cells in hippocampus CA1subfield were severely damaged.EGb significantly antago-nized the pathological alterations of the above parameters.Conclusion .Alterations of NO,and ET-1play an important role in the development of CV S after SAH.EGb exerts its protective effects on CVS by inhibitng the above pat hological alterations.

Vasospasm as a Complication after Aneurysmal Rupture and Its Relation with Surgical Clipping and Endovascular Coiling among a Georgian Sample

Background: Potentially lethal, aneurysmal subarachnoid hemorrhage has a bad prognosis for many individuals. Over the past few decades, endovascular and surgical interventions have been developed, including surgical clipping, and endovascular coiling. Patients who have aSAH are also susceptible to delayed cerebral ischemia and cerebral vasospasm. The aim of this study is to compare the outcome of endovascular coiling with surgical clipping in patients with SAH, specifically in relation to prevalence of vasospasm, in the country of Georgia. Method: In this study, we present a retrospective review of the outcomes of 217 patients with acute subarachnoid hemorrhage who underwent endovascular coiling or surgical clipping. The data were gathered from patients who are admitted to New Vision University Hospital and Caucasus Medical Center in Tbilisi, Georgia, between 2017 and 2022. Results: Vasospasm was prevalent in 217 of the patients who had aneurysmal rupture when they first appeared. Endovascular coiling or surgical clipping was used to treat aneurysmal rupture. In our sample, 24.81 percent of patients who underwent coiling experienced vasospasm after 14 days, compared to 31.25 percent of patients who underwent clipping. After endovascular coiling and surgical clipping, the severity of vasospasm was only slightly different, according to Lindegaard ratios. Finally, 32 patients (23.35 percent) died after coiling whereas 55 patients (68.75 percent) died within three decades of clipping. Conclusion: After 5 years of data collection, this study has demonstrated the most favorable option for treatment is endovascular coiling. However, the treatment choice takes multiple factors into account, and clipping is not ideal for some ruptured aneurysms. Despite the fact that endovascular coiling is usually successful and minimally invasive, complications can occur and additional monitoring and potential surgical intervention are indicated.

Mechanically-induced vasospasm-revaluation of spasmolytic efficacy of 10 pharmaceutical agents using LSCI

Vasospasm is a thorny problem often encountered in microvascular surgery.This investigation is dedicated to establishing a model of vasospasm and to evaluating the antispasmodic efficacy of 10 pharmacologic agents under direct monitoring of laser speckle contrast imaging(LSCI).80 SD rats were used.A pair of microsurgical forceps were used to trigger vasospasm of the femoral vessels by blunt dissection.Five minutes later,10 pharmacological agents were dripped to the femoral vessels,after which LSCI was used to collect perfusion images,acquiring the perfusion intensity and the inner caliber of the femoral vessels at multiple time points.

Research on the pathogenesis of cerebral vasospasm following subarachnoid hemorrhage

目的 :进一步研究脑血管痉挛的发生机理 ,为临床治疗服务。方法 :采用 1 4只成年家犬 ,实验组 9只 ,对照组 5只 ,通过 2次枕大池注血法建立蛛网膜下腔出血 (SAH)模型。观察痉挛血管的自由基变化、血管活性、血管造影像、超微结构变化。另外 2 0只犬用来观察血管扩张剂的作用。结果 :实验组较对照组自由基含量高 ,血管活性降低 ,血管狭窄 ,管壁损害重。结论 :尼莫地平对急性痉挛有效 ,对慢性痉挛无效 ;慢性血管痉挛是以管壁结构性狭窄为特点。

Post-Aneurysmal Subarachnoid Hemorrhage Vasospasm, Clinical Correlation between the Aneurysm Site and Clinical Vasospasm

Background: Intracranial vasospasm is a common complication following subarachnoid hemorrhage (SAH). The radiographic vasospasm can reach up to 90% of aneurysmal SAH. Materials and Methods: 139 consecutive patients admitted to Cairo University Hospitals from June 2013 to September 2014 with SAH who had been enrolled in a retrospective controlled study were analyzed retrospectively for the occurrence of vasospasm. The data collected from the charts of Cairo University Hospitals were the patient’s demographics, clinical presentation, aneurysm location, treatment modality, and Glasgow Outcome Scale (GOS) scores. We excluded 24 patients with nonaneurysmal SAH, 3 internal carotid artery (ICA) aneurysms, 7 with multiple aneurysms and 4 patients died before treatment. Results: 72 males and 29 females were included in the study, mean age 53.5 ± 11.5 years. Twelve patients had aneurysms located in the vertebral artery group, 24 had middle cerebral artery aneurysms, 11 had pericallosal aneurysms, and 54 patients had anterior communicating artery (ACoA) complex aneurysms. Radiographic vasospasm occurred in 62.4% with the highest incidence (75.9%) at the ACoA complex group. Symptomatic vasospasm occurred in 48.5% with the highest incidence (63%) at the anterior communicating artery complex aneurysm location. The mean GOS at 6 months follow-up was 4.2. The worse GOS was found in the vertebral artery (VA) aneurysm group with a mean of 3.75. Conclusion: Aneurysms of the anterior communicating artery complex group have a greater risk of both radiographic and clinical vasospasm. Also, the worse 6 months follow-up GOS when an aneurysm was located in the VA group.

Mitigation effect of atorvastatin on cerebral vasospasm after subarachnoid hemorrhage in rats and its effect on expression of Mitofusin-2 and BDNF

Objective:To investigate the mitigation effect of atorvastatin on cerebral vasospasm (CVS) after subarachnoid hemorrhage (SAH) in rats and its effect on mitochondrial fusion protein 2 (Mitofusin-2) and brain-derived neurotrophic factor (BDNF), which provides an experimental basis and a new method for the prevention and treatment of CVS after SAH.Methods:30 male SD rats were randomly divided into the sham operation group, the model group and the treatment group, with 10 rats in each group. In the model group and the treatment group, the subarachnoid hemorrhage model was made by the double injection of blood in the occipital cistern, and the sham operation group was injected with physiological saline in the same manner. The treatment group was given atorvastatin 20 mg/kg, which was dissolved in 2 mL of distilled water. The sham operation group and the model group were given 2 mL of distilled water. The body weight, mortality, neurological deficit, basilar artery inner diameter, wall thickness and smooth muscle cell apoptosis were observed in the rats 5 d after intervention. The expression levels of Mitofusin-2 and BDNF in each group were observed.Results:The body weight of the three groups was from low to high in the sham operation group, the treatment group and the model group, and the difference was statistically significant. One rat died in the sham operation group and the treatment group, respectively, 2 rats died in the model group and there was no significant difference in mortality between the three groups. The scores of the three groups of neurological function were from low to high among the model group, treatment group and sham operation group, and the difference was statistically significant. The diameter of the three groups of blood vessels was from small to large among the model group, treatment group and sham operation group, and the difference was statistically significant. The apoptotic rate of the three groups of vascular endothelial cells was from small to large among the model group, treatment group and sham operation group, and the difference was statistically significant. The expression levels of Mitofusin-2 were from low to high among the sham operation group, model group and treatment group, respectively.Conclusion:Atorvastatin can alleviate the occurrence of CVS after SAH and alleviate brain tissue damage, and its mechanism may be related to up-regulation of Mitofusin-2 expression.

Clinical Efficacy of Shenmai Injection in the Treatment of Cerebral Vasospasm after Ruptured Aneurysm Surgery

Objective: To investigate the therapeutic effect of Shenmai Injection on postoperative cerebral vasospasm in patients with ruptured aneurysms. Methods: Seventy patients undergoing craniotomy for ruptured aneurysms in our hospital were selected as study subjects and randomly divided into control (n = 33) and research (n = 37) groups, they were treated with nimodipine and nimodipine combined with Shenmai injection after operation. The blood flow velocity in the middle cerebral artery (MCA) before and at 1, 3, 7, 11 and 14 days after surgery and the incidence of cerebral vasospasm during these days were compared, and the GCS scores at 14 days postoperatively and GOS scores at 6 months postoperatively were compared between the two groups. Results: There were no statistically significant differences in the occurrence of cerebral vasospasm, GCS or GOS scores between the two groups (P > 0.05), but the period of postoperative cerebral vasospasm in the study group was significantly shorter than that in the control group. Conclusion: Shenmai injection has the effect of shortening the cycle of occurrence of cerebral vasospasm after the operation of ruptured aneurysms, promoting patients to recover as early as possible and reducing their physical and mental burden.

New Developments in Drug Therapy and Research of Cerebral Vasospasm

In this manuscript a comprehensive coverage of recent developments in the drug therapy of vasospasm while providing the background information that neuroscientists need to understand its rationale. The range of new agents available for treatment of cerebral vasospasm is expanding rapidly along with rapid advances in pharmacology and physiology that are uncovering the mechanisms of this disease. Although there are many publications for treatment of cerebral vaso-spasm, most are focusing on different aspects of vasospasm treatment and many have limited value due to insufficient quality. Moreover, the complexity of this, in many cases deleterious condition, is enormous and the information needed to understand drug effects is accordingly often not readily available in a single source. A number of pharmacological and medical therapies are currently in use or being investigated in an attempt to reverse cerebral vasospasm, but only a few have proven to be useful. Current research efforts promise the eventual production of new medical therapies. At last, recommendations for the use of different treatment stages based on currently available clinical data are provided.