Stroke while driving: Frequency and association with automobile accidents.

Background Cardiovascular events while driving have occasionally been reported. In contrast, there have been few studies on stroke while driving. Aim The objectives of this study were to (1) report the frequency of stroke while driving and (2) evaluate its association with automobile accidents. Methods Clinical data prospectively acquired between January 2011 and December 2016 on 2145 stroke patients (1301 with ischemic stroke, 585 with intracerebral hemorrhage, and 259 with subarachnoid hemorrhage) were reviewed to identify patients who sustained a stroke while driving. The ratio of driving to performing other activities was evaluated for each stroke type. Furthermore, the drivers' response to stroke was reviewed to understand how automobile accidents occurred. Results Among the 2145 patients, 85 (63 ischemic stroke, 20 intracerebral hemorrhage, and 2 subarachnoid hemorrhage) sustained a stroke while driving. The ratio of driving to performing other activities was significantly higher in ischemic stroke (4.8%) than in intracerebral hemorrhage (3.4%) or subarachnoid hemorrhage (0.8%). A majority of drivers either continued driving or pulled over to the roadside after suffering a stroke. However, 14 (16%) patients were involved in automobile accidents. In most patients, an altered mental status due to severe stroke was the presumed cause of the accident. Conclusion Stroke occurred while driving in 4.0% of all strokes and accidents occurred in 16% of these instances.

Clinical characteristics of stroke occurring in the toilet: Are older adults more vulnerable?

AIM: While autonomic imbalance during defecation/micturition can cause hemodynamic instability, stroke occurring in the toilet has rarely been investigated. The objective of the present study was to clarify the frequency and clinical characteristics of toilet-related stroke. METHODS: Clinical data prospectively acquired between January 2011 and December 2015 on 1939 patients with acute stroke (1224 cerebral infarctions [CI], 505 intracerebral hemorrhages [ICH] and 210 subarachnoid hemorrhages [SAH]) were reviewed to identify patients with a toilet-related stroke. For each stroke type, the ratios of stroke occurring during defecation/micturition to those occurring during other activities were calculated. Subsequently, how patients with toilet-related stroke were brought to medical attention was investigated. Whether older patients (aged >65 years) had an elevated ratio of toilet-related stroke was investigated in each stroke type. RESULTS: A total of 108 patients (41 CI, 37 ICH and 30 subarachnoid hemorrhages) sustained a stroke in the toilet. The ratio of toilet-related stroke was highest in subarachnoid hemorrhages (14.3%), followed by ICH (7.3%). Circadian differences existed among the three stroke types: toilet-related CI were more likely to occur in the night-time than ICH. Patients with toilet-related CI were significantly more likely to sustain cardioembolic stroke. In all three stroke types, <40% of patients could call for help by themselves. Older patients showed a significantly higher proportion of toilet-related stroke in CI, but not in hemorrhagic strokes. CONCLUSIONS: The toilet is a closed space where stroke occurs disproportionately frequently. Effort to reduce the incidence of toilet-related strokes is warranted, as early patient detection is not always feasible. Geriatr Gerontol Int 2018; 18: 250-255.

Acute coronary syndromes occurring while driving: frequency and patient characteristics.

BACKGROUND: Acute coronary syndrome (ACS) may occur during any human activity, including driving. The objectives of this study were to report the frequency of ACS occurring while driving, clarify patient characteristics, and analyze the behavioral patterns of drivers who sustained ACS. METHODS: A single-center, retrospective observational study was conducted using prospectively acquired data. Among 1605 ACS patients admitted between January 2011 and December 2016, 65 (60 men/5 women) patients who sustained ACS while driving were identified. Clinical variables were compared between these 65 patients and 1540 patients who sustained ACS while performing other activities. Furthermore, multivariable regression analysis was performed to identify variables associated with ACS. RESULTS: The frequency of ACS occurring while driving was 4.0% (65/1605). Compared with patients who sustained ACS while performing other activities, those who sustained ACS while driving were significantly younger (66.2 ± 13.0 vs. 57.5 ± 12.2 years, p < 0.001) and more likely to smoke (34.2 vs. 60.0%, p < 0.001). Multivariable regression analysis showed that age (OR 0.961; 95% CI 0.940-0.982) and current smoking (OR 1.978; 95% CI 1.145-3.417) were associated with ACS. While 55 drivers (85%) who remained conscious after ACS could seek medical attention without causing accidents, the other 10 (15%) who sustained cardiac arrest caused accidents. CONCLUSIONS: The association between current smoking and ACS occurring while driving suggests that smoking cessation is advised for smokers who drive from the standpoint of driving safety. We expect that prospective studies be conducted to verify our findings and identify individuals at risk for ACS while driving.

Cardiac arrest in the toilet: clinical characteristics and resuscitation profiles.

OBJECTIVES: The great majority of non-traumatic cardiac arrests (CA) occur at home. The toilet is a closed and private room where CA occurs frequently. However, due to the feelings of privacy that are associated with this room, the circumstances and causes of CA in the toilet have rarely been investigated. METHODS: A retrospective study was conducted to clarify clinical characteristics and resuscitation profiles of patients sustaining CA in the toilet. RESULTS: Among 907 CA patients treated during a 4-year period, 101 (11 %) sustained CA in the toilet. While the collapse was witnessed in only 10 % of these patients, return of spontaneous circulation (ROSC) was achieved in 41 %. However, the long-term survival rate was 1 %. Multivariate regression analysis revealed that a history of cardiac diseases was predictive of CA in the toilet (odds ratio 3.045; 95 % confidence interval 1.756-5.282) but that there was no correlation with advanced age. The frequency of CA in the toilet may be influenced moderately by seasonal/circadian variations. The 101 patients were classified into four subgroups according to mode of discovery of CA. The frequency of ROSC was highest in those who collapsed in the presence of caregivers and lowest in those whose collapse were discovered later by family members being worried that the patient stayed in the toilet "too long." Imaging studies revealed life-threatening extra-cardiac lesions responsible for CA, such as subarachnoid hemorrhage and aortic dissection, in 23 % of the patient cohort. CONCLUSIONS: The rarity of long-term survival among individuals sustaining CA in the toilet is mainly due to the delay in discovering the individual who collapsed. Although a history of cardiac diseases is a risk factor, predicting who may sustain CA in the toilet remains difficult due to etiological heterogeneity.

Subarachnoid hemorrhage complicated with neurogenic pulmonary edema and takotsubo-like cardiomyopathy.

Patients with poor-grade subarachnoid hemorrhage (SAH) are often complicated with acute cardiopulmonary dysfunctions, particularly neurogenic pulmonary edema (NPE) and takotsubo-like cardiomyopathy (TCM). This study retrospectively investigated the incidence, demographics, clinical characteristics, and outcomes of patients with SAH complicated with both NPE and TCM (NPE-TCM). The effects of aneurysm location and other clinical variables on the incidence of NPE-TCM were also investigated. Among 234 SAH patients treated during 5-year period, 16 (7%) presented with NPE, and transthoracic ultrasonography revealed that 14 of these 16 patients (88%) also had TCM. All 14 patients with NPE-TCM had poor-grade SAH (World Federation of Neurosurgical Societies grades IV and V). Ruptured posterior circulation aneurysm was predictive of NPE-TCM, but other clinical variables were not. Eight of the 14 patients with NPE-TCM could undergo treatment for ruptured aneurysm. Long-term outcomes were favorable in 5 of the 8 patients. Grade IV SAH patients had significantly better outcomes than grade V patients. TCM develops frequently in SAH patients presenting with NPE, and transthoracic ultrasonography should be conducted routinely in that population. Patients with ruptured posterior circulation aneurysm may have elevated risk of developing NPE-TCM. Endovascular obliteration of the aneurysm may be preferable to open surgery, but the optimal treatment modality needs to be evaluated further. Considering the limited number of SAH patients complicated with NPE-TCM, a multi-center cooperative study may be required.

Influence of warfarin and low-dose aspirin on the outcomes of geriatric patients with traumatic intracranial hemorrhage resulting from ground-level fall.

AIM: Ground-level fall is the most common cause of traumatic intracranial hemorrhage (TICH) in the elderly, and is a major cause of morbidity and mortality in that population. A retrospective study was carried out to evaluate whether the use of warfarin/low-dose aspirin (LDA) is predictive of unfavorable outcomes in geriatric patients who sustain a fall-induced TICH. METHODS: Charts of 76 geriatric patients (≥ 65 years-of-age) with fall-induced TICH were reviewed. The number of patients taking warfarin and LDA was 12 and 21, respectively, whereas the other 43 took neither medication (non-user group). The frequency of patients with unfavorable outcomes (Glasgow Outcome Scale score of 1-3) at discharge was calculated. Furthermore, variables predictive of unfavorable outcomes were identified by logistic regression analysis. RESULTS: The frequency of patients with unfavorable outcomes was 75% in the warfarin group, 33% in the LDA group and 27% in the non-user group, respectively. The risk of having unfavorable outcomes was significantly higher in the warfarin group compared with the LDA group (P = 0.03) and non-user group (P < 0.01). Logistic regression analysis showed that variables predictive of unfavorable outcomes were: age, initial Glasgow Coma Scale score ≤ 13 and presence of midline shift ≥ 5 mm. CONCLUSION: The use of warfarin, but not of LDA, might be associated with unfavorable outcomes in elderly with fall-induced TICH. The risk of TICH should be communicated properly to elderly taking warfarin. The information might be important not only to trauma surgeons who take care of injured elderly, but also to geriatric physicians who prescribe warfarin/LDA to them.

Subarachnoid hemorrhage causing cardiopulmonary arrest: resuscitation profiles and outcomes.

Aneurysmal subarachnoid hemorrhage (SAH) is a common cause of cardiopulmonary arrest (CPA). The outcomes of SAH patients presenting with CPA are extremely poor, and long-term survivors have occasionally been reported, but the circumstances under which SAH-CPA patients achieve long-term survival are unclear. Neurosurgeons will have to determine whether a SAH-CPA patient is brain-dead or not more often after enactment of the revised Organ Transplantation Act. Prediction of survival length may be important not only to neurosurgeons, but also to the transplantation team. A retrospective study was conducted to elucidate how often brainstem function was recovered in resuscitated SAH-CPA patients and whether the recovery was associated with longer survival. Among 315 patients with non-traumatic SAH admitted to our institution during 6 years, 35 (11%) presented with CPA. Ventricular fibrillation (VF) as initial cardiac rhythm was rare, observed only in 1 patient. The survival length ranged from 1 to 15 days (mean 3.5 ± 0.7 days), and none achieved long-term survival. Return of brainstem function, represented by spontaneous respiration and/or reactive pupils, was observed in 6 patients (17%), but was only partial and transient. Cardiac arrest to return of spontaneous circulation interval tended to be shorter in patients with transient recovery of the brainstem function than in those without recovery. However, the survival length was not significantly different between the two groups. In addition to the 35 SAH-CPA patients, another 44 SAH patients lost both brainstem reflexes and spontaneous respiration within 72 hours of admission. As a result, 79 (25%) of the 315 SAH patients were considered to have sustained fatal, irreversible brain damage. Review of previous experience suggests that SAH-CPA patients may survive only if the cause of cardiac arrest is VF and not brainstem damage/respiratory arrest. Approximately one-third of resuscitated SAH-CPA patients may die within 24 hours of arrival, for whom the declaration of brain death may be difficult.

Loss of gray-white matter discrimination as an early CT sign of brain ischemia/hypoxia in victims of asphyxial cardiac arrest.

Brain CT obtained from cardiac arrest (CA) victims immediately after resuscitation may be useful in predicting their outcomes. Most data have been derived from CA victims of cardiac etiology, however, CT signs of brain ischemia/hypoxia have rarely been studied in victims of asphyxial CA. Loss of gray-white matter discrimination (GWMD) at the basal ganglia seems to be the most reliable early CT sign of brain ischemia/hypoxia; a retrospective study was conducted to clarify its incidence, prognostic significance, and temporal profile in resuscitated victims of CA by food asphyxiation. Brain CT scans of each victim were interpreted by two blinded observers. During a 5-year period, 39 resuscitated victims of CA by food asphyxiation underwent brain CT. Thirty-one (79%) showed loss of GWMD, none of whom survived to discharge. Among the other eight victims with seemingly intact brain CT, five (63%) survived to discharge. Loss of GWMD predicted fatality with sensitivity of 100% and specificity of 63%. The interobserver concordance was 82% with kappa coefficient of 0.56. Loss of GWMD developed almost invariably when the asphyxiation-return of spontaneous circulation (ROSC) interval exceeded 10 min. There were five victims with asphyxiation-ROSC interval ≤ 10 min, all of whom survived to discharge. In contrast, none of the 34 victims with the interval >10 min survived to discharge. Loss of GWMD may develop in a relatively time-dependent manner and may be a reliable radiographic indicator of poor outcome in resuscitated victims of asphyxial CA.

Prognostic significance of acute pain preceding out-of-hospital cardiac arrest.

BACKGROUND: Sudden loss of consciousness (LOC) and chest pain are common manifestations of out-of-hospital cardiac arrest (OHCA). History of acute pain may be helpful in estimating aetiology and prognosis of OHCA victims. The objective of this study was to evaluate the relationship between acute pain at various locations preceding collapse and outcome. METHODS: Clinical data of 250 witnessed, non-traumatic OHCA victims were reviewed, and the incidence of pain based on anatomical distribution was documented. The focus was on identifying the difference between those collapsing with LOC alone and those collapsing with chest pain (CP). Clinical variables predictive of survival were identified using a logistic regression model. RESULTS: Among the 250 victims, 55.2% collapsed with LOC alone. The incidence of acute pain was: 28.0% for CP, 3.2% for headache, 2.8% for abdominal pain and 2.4% for back pain. The overall 6-month survival rate was 7.2%. The LOC group had a significantly higher return of spontaneous circulation (ROSC) rate compared with the CP group (48.6% vs 31.4%, p<0.05). The rate was elevated in the LOC group; however, only when the initial rhythm was non-shockable. There was no significant intergroup difference in the survival rate. Initial shockable rhythm positively and history of cardiovascular diseases negatively predicted survival. None of the victims in the headache, abdominal pain or back pain groups survived. CONCLUSION: The LOC group's seemingly higher ROSC rate may be due to its aetiological heterogeneity. Complaint of a headache, abdominal pain or back pain in OHCA victims carries a poor prognosis.

Cardiac arrest due to food asphyxiation in adults: resuscitation profiles and outcomes.

AIM: Food asphyxiation is uncommon but unignorable cause of sudden death in the elderly. Several autopsy studies, which identified those at particular risk, have been conducted on the subject. Resuscitation profiles and outcomes of food asphyxiation victims presenting with out-of-hospital cardiac arrest (OHCA) to the emergency department, however, have rarely been reported. METHODS: Data on adults (> or = 20 years) presenting with OHCA after witnessed food asphyxiation were retrieved from an institutional database. Clinical variables were evaluated to identify their demographic characteristics. Their outcomes, represented by return of spontaneous circulation (ROSC) and survival rate, were also investigated. RESULTS: Sixty-nine food asphyxiation victims presenting with OHCA were identified during the 4-year period. Food asphyxiation occurred most frequently in the age group of 71-80 years, followed by that of 81-90 years. The majority of victims had medical conditions that adversely affected mastication/swallowing, such as dementia. Bystander cardiopulmonary resuscitation (CPR) was performed only in 26%, although bystanders often attempted to clear the airway without performing CPR. Despite the high ROSC rate of 78%, only 7% survived to discharge. Asphyxiation-ROSC interval might play a crucial role in determining the outcomes: the interval was < or = 10 min in all survivors, while it was longer than 10 min in all non-survivors. CONCLUSION: Because of their advanced age and debilitating general condition, it may be difficult to substantially improve the outcomes of food asphyxiation victims. Effort should be directed to prevent food asphyxiation, and public education to perform standard CPR for food asphyxiation victims including the Heimlich manoeuvre is warranted.

Early CT signs in out-of-hospital cardiac arrest survivors: Temporal profile and prognostic significance.

AIM: Although computed tomography (CT) signs of ischaemia, including loss of boundary (LOB) between grey matter and white matter and cortical sulcal effacement, in cardiac arrest (CA) survivors are known, their temporal profile and prognostic significance remains unclear; their clarification is necessary. METHODS: Brain CT scans were obtained immediately after resuscitation in 75 non-traumatic CA survivors in a prospective fashion. They were divided into two groups according to the CA-return of spontaneous circulation (ROSC) interval: < or =20 min vs. >20 min. The incidence of the CT signs and predictability of these signs for outcome, assessed 6 months after CA, was evaluated and compared. RESULTS: The incidence of the positive LOB sign was 24% in the < or =20-min group and 83% in the >20-min group, and the difference was statistically significant (p<0.001). The interval of 20 min seemed to be the time window for the LOB development. The incidence of the positive sulcal effacement sign was 0% in the < or =20 min group and 34% in the >20-min group, and the difference was statistically significant (p=0.004). A positive LOB sign was predictive of unfavourable outcome with an 81% sensitivity and 92% specificity. A positive sulcal effacement sign was predictive of unfavourable outcome with a 32% sensitivity and 100% specificity. CONCLUSION: A time window may exist for ischaemic CT signs in CA survivors. The LOB sign may develop when the CA-ROSC interval exceeds 20 min, whereas the sulcal effacement sign may develop later. However, their temporal profile and outcome predictability should be verified by multicentre studies.

Influence of age and anti-platelet/anti-coagulant use on the outcome of elderly patients with fall-related traumatic intracranial hemorrhage.

Ground-level fall is the most common cause of traumatic intracranial hemorrhage (TICH) in the elderly. Many studies on geriatric TICH have regarded patients aged ≥65 years as a single group, but substantial heterogeneity is likely to exist within this population. Eighty-two elderly patients with fall-related TICH treated in our institution during a 6-year period were stratified into 3 age groups (65-74, 75-84, and ≥85 years), and intergroup differences in the demographics and outcomes at discharge were evaluated. The influence of the use of anti-platelet/anti-coagulant (AP/AC) agent on outcomes was also investigated. Comparison of demographic variables demonstrated significant differences in the frequency of preinjury alcohol consumption and use of AP/AC agents between the 3 groups, indicating that the causes or triggers of fall might be substantially different between the 65-74 years group and the other two groups combined. The frequency of unfavorable outcomes increased with age, and the increase was statistically significant. The 82 patients were divided into two subgroups depending on the use of AP/AC agents. The outcomes of the ≥85 years group taking AP/AC agents were particularly poor compared with those of the ≥85 years group not using AP/AC agents. Advancing age may be associated with unfavorable outcomes in elderly patients with fall-related TICH, and patients aged ≥85 years taking AP/AC have the greatest risk of unfavorable outcomes. Physicians must consider the risk/benefit analysis before prescribing AP/AC agents to patients aged ≥85 years.

Therapeutic hypothermia for out-of-hospital cardiac arrest: an update for neurosurgeons.

BACKGROUND: Neurosurgeons have been familiar with the idea that hypothermia is protective against various types of brain injuries, including traumatic brain injury (TBI). Recent randomized controlled trials, however, have failed to demonstrate the efficacy of therapeutic hypothermia (TH) in patients with TBI. On the other hand, TH becomes popular in the treatment of out-of-hospital cardiac arrest (OHCA) survivors, after randomized controlled trials have shown that survival rate and functional outcome is improved with the use of TH in selected patients. We believe that knowledge on the recent progress in TH for OHCA is useful for neurosurgeons, because feedback of information obtained in the treatment of OHCA may revitalize the interest in TH for neurosurgical disorders, particularly TBI. METHODS: A review of the literature was conducted with the use of PubMed. RESULTS: Various cooling techniques and devices have been developed and trialed in the treatment of OHCA survivors, including prehospital cooling with bolus ice-cold saline, endovascular cooling catheters, and new generation surface cooling devices, some of which have already been known to neurosurgeons. The efficacy of these new methods and devices has been demonstrated in many preliminary studies, and phase III trials are also expected. CONCLUSIONS: Neurosurgeons and critical care medicine physicians pursue the same goal of rescuing the brain from the secondary injury despite the difference in etiology (focal trauma vs. global ischemia), with the presumption that earlier and faster implementation of TH will result in better outcome. Thoughtful application of knowledge and techniques obtained in OHCA to TBI under a rigorously controlled situation will make a small, but significant difference in the outcome of TBI victims.

Headache, cardiac arrest, and intracranial hemorrhage.

Headache is one of the most common manifestations of non-traumatic intracranial hemorrhage, which is an uncommon, but not rare, cause of cardiac arrest in adults. History of a sudden headache preceding collapse may be a helpful clue to estimate the cause of out-of-hospital cardiac arrest (OHCA). Medical records of witnessed OHCA patients were reviewed to identify those who complained of a sudden headache preceding collapse, and the incidence of intracranial hemorrhage among them as well as their clinical characteristics was investigated retrospectively. During the 12-month period, 124 patients who sustained a witnessed OHCA were treated. Among them, 74 (60%) collapsed without any pain complaint, and only 6 (5%) complained of a sudden headache preceding collapse. All of the six patients were resuscitated: four had a severe subarachnoid hemorrhage (SAH), while the other two had a massive cerebellar hemorrhage. By contrast, 39 of the 74 patients who collapsed without any pain were resuscitated. Among them, another six patients were found to harbor an SAH. Thus, a total of 12 among the 124 witnessed OHCA (10%) sustained a fatal intracranial hemorrhage. While OHCA patients who collapse complaining of a sudden headache are uncommonly seen in the emergency room, they have a high likelihood of harboring a severe intracranial hemorrhage. It should also be reminded that approximately half of patients whose cardiac arrest is due to an intracranial hemorrhage may collapse without complaining of a headache. The prognosis of those with cerebral origin of OHCA is invariably poor, although they may relatively easily be resuscitated temporarily. Focus needs to be directed to avoid sudden death from a potentially treatable cerebral lesion, and public education to promote the awareness for the symptoms of potentially lethal hemorrhagic stroke is warranted.

Subarachnoid haemorrhage as a cause of out-of-hospital cardiac arrest: a prospective computed tomography study.

AIM: Aneurysmal subarachnoid haemorrhage (SAH) is a relatively common cause of out-of-hospital cardiac arrest (OHCA). Early identification of SAH-induced OHCA with the use of brain computed tomography (CT) scan obtained immediately after resuscitation may help emergency physicians make therapeutic decision as quickly as they can. METHODS: During the 4-year observation period, brain CT scan was obtained prospectively in 142 witnessed non-traumatic OHCA survivors who remained haemodynamically stable after resuscitation. Demographics and clinical characteristics of SAH-induced OHCA survivors were compared with those with "negative" CT finding. RESULTS: Brain CT scan was feasible with an average door-to-CT time of 40.0 min. SAH was found in 16.2% of the 142 OHCA survivors. Compared with 116 survivors who were negative for SAH, SAH-induced OHCA survivors were significantly more likely to be female, to have experienced a sudden headache, and trended to have achieved return of spontaneous circulation (ROSC) prior to arrival in the emergency department less frequently. Ventricular fibrillation (VF) was significantly less likely to be seen in SAH-induced than SAH-negative OHCA (OR, 0.06; 95% CI, 0.01-0.46). Similarly, Cardiac Trop-T assay was significantly less likely to be positive in SAH-induced OHCA (OR, 0.08; 95% CI, 0.01-0.61). CONCLUSION: Aneurysmal SAH causes OHCA more frequently than had been believed. Immediate brain CT scan may particularly be useful in excluding SAH-induced OHCA from thrombolytic trial enrollment, for whom the use of thrombolytics is contraindicated. The low VF incidence suggests that VF by itself may not be a common cause of SAH-induced OHCA.

Megacolon in an adult case of hypoganglionosis, a pseudo-Hirschsprung's disease: an autopsy study.

We report an autopsied 20-year-old man case of intestinal necrosis associated with megacolon from hypoganglionosis, a pseudo-Hirschsprung's disease. The patient had suffered from severe constipation since two years of age, and presented abdominal distention from age ten. Autopsy revealed marked dilatation and necrosis of the entire large intestine. Although ganglion cells in the intestinal plexus were found throughout the large intestine, their number was reduced to 12-20% of that in the normal control. In pseudo-Hirschsprung's disease, there are occasional cases where an acute abdomen first presents itself in adulthood after running its course as chronic constipation.

Prostaglandin E2 induces hypertrophic changes and suppresses alpha-skeletal actin gene expression in rat cardiomyocytes.

Prostaglandin E2 (PGE2) is a potent lipid mediator in a diverse range of biological processes. This study examined the hypertrophic effect of PGE2 in primary cultured rat neonatal cardiomyocytes. PGE2 increased total protein synthesis in a dose-dependent manner, as measured by [3H]-phenylalanine uptake. PGE2 increased the cell size and surface area and induced the reorganization of myofilaments. Phosphorylation of the p42/44 and p38 mitogen-activated protein kinases (MAPK) was also induced by PGE2, and U0126 [a mitogen-activated extracellular signal regulated kinase kinase (MEK) 1/2 inhibitor] significantly inhibited the PGE2-induced protein synthesis. Expression of the hypertrophic marker genes, atrial natriuretic peptide and brain natriuretic peptide, was increased by PGE2, but expression of the alpha-skeletal actin gene was significantly attenuated. Transcripts for all 4 PGE2 receptor subtypes (EP1, EP2, EP3, and EP4) were detected in the cardiomyocytes. AE3-208 (an EP4-selective antagonist) significantly inhibited the alpha-skeletal actin gene suppression induced by PGE2, whereas SC51322 (an EP1-selective antagonist) did not. In conclusion, PGE2 induced hypertrophic changes in cardiomyocytes and attenuated alpha-skeletal actin gene expression in part via EP4.