Kuo-Yang Wang

Ginkgo biloba extract 761 reduces doxorubicin-induced apoptotic damage in rat hearts and neonatal cardiomyocytes

AIMS The objective of this study was to investigate whether a cytoprotective herb-derived agent, Ginkgo biloba extract (EGb) 761, could have a beneficial effect on doxorubicin-induced cardiac toxicity in vitro and in vivo. METHODS AND RESULTS Primary cultured neonatal rat cardiomyocytes were treated with the vehicle, doxorubicin (1 microM), EGb761 (25 microg/mL), or EGb761 plus doxorubicin. After 24 h, doxorubicin upregulated p53 mRNA expression, disturbed Bcl-2 family protein balance, disrupted mitochondrial membrane potential, precipitated mitochondrion-dependent apoptotic signalling, induced apoptotic cell death, and reduced viability of cardiomyocytes, whereas EGb761 pretreatment suppressed all the actions of doxorubicin. Similarly, rats treated with doxorubicin [3 mg/kg intraperitoneally (i.p.) three doses every other day] displayed retarded growth of body and heart as well as elevated apoptotic indexes in heart tissue at both 7 and 28 days after exposure, whereas EGb761 pretreatment (5 mg/kg i.p. 1 day before each dose of doxorubicin) effectively neutralized the aforementioned gross and cellular adverse effects of doxorubicin. CONCLUSION Doxorubicin impairs viability of cardiomyocytes at least partially by activating the p53-mediated, mitochondrion-dependent apoptotic signalling. EGb761 can effectively and extensively counteract this action of doxorubicin, and may potentially protect the heart from the severe toxicity of doxorubicin.

Doxycycline suppresses doxorubicin-induced oxidative stress and cellular apoptosis in mouse hearts

Cardiac toxicity remains a serious yet unsolved complication of doxorubicin. This study was designed to examine whether doxycycline, a tetracycline-derived synthetic antibiotic with potential cytoprotective properties, could ameliorate this complication of doxorubicin. Male mice at 4-week of age were administrated with vehicle, doxorubicin (3mg/kg intraperitoneally every other day at 3 doses), doxycycline (2.5mg/kg intraperitoneally every other day for 3 doses), or doxycycline plus doxorubicin (each dose given 1day post doxycycline). After 28days, left ventricular geometric and systolic parameters were measured by transthoracic echocardiography, and hearts were harvested for extensive analyses regarding oxidative stress and cellular apoptosis. At 28days, hearts of doxorubicin-treated mice were characterized by less weight compared with controls, also with remodeling and depressed systolic function of the left ventricle. Biochemical analyses disclosed that content of malondialdehyde was increased and activity of antioxidant enzymes, including superoxide dismutase and glutathione peroxidase, was decreased in these hearts. Both mitochondrion-dependent and endoplasmic reticulum stress-induced apoptotic pathways were also activated in the hearts of doxorubicin-treated mice as reflected by decreased Bcl-2/Bcl-(XL) and elevated Bax/Bad, p53/Apaf-1, endoplasmic reticulum glucose-related protein 78, C/EBP homologous protein, cytochrome c release from mitochondria, caspases-9/-3 cleavage, and cardiomyocyte apoptosis. In contrast, all the above left ventricular remodeling, systolic depressing, oxidative and pro-apoptotic actions of doxorubicin could be significantly alleviated by doxycycline pretreatment. Thus, doxycycline extensively counteracts multiple oxidative and apoptotic actions of doxorubicin in heart, hence may serve as an adjuvant agent to assuage the untoward cardiac effects of doxorubicin in clinical application.

Propofol ameliorates doxorubicin-induced oxidative stress and cellular apoptosis in rat cardiomyocytes

BACKGROUND Propofol is an anesthetic with pluripotent cytoprotective properties against various extrinsic insults. This study was designed to examine whether this agent could also ameliorate the infamous toxicity of doxorubicin, a widely-used chemotherapeutic agent against a variety of cancer diseases, on myocardial cells. METHODS Cultured neonatal rat cardiomyocytes were administrated with vehicle, doxorubicin (1μM), propofol (1μM), or propofol plus doxorubicin (given 1h post propofol). After 24h, cells were harvested and specific analyses regarding oxidative/nitrative stress and cellular apoptosis were conducted. RESULTS Trypan blue exclusion and MTT assays disclosed that viability of cardiomyocytes was significantly reduced by doxorubicin. Contents of reactive oxygen and nitrogen species were increased and antioxidant enzymes SOD1, SOD2, and GPx were decreased in these doxorubicin-treated cells. Mitochondrial dehydrogenase activity and membrane potential were also depressed, along with activation of key effectors downstream of mitochondrion-dependent apoptotic signaling. Besides, abundance of p53 was elevated and cleavage of PKC-δ was induced in these myocardial cells. In contrast, all of the above oxidative, nitrative and pro-apoptotic events could be suppressed by propofol pretreatment. CONCLUSIONS Propofol could extensively counteract oxidative/nitrative and multiple apoptotic effects of doxorubicin in the heart; hence, this anesthetic may serve as an adjuvant agent to assuage the untoward cardiac effects of doxorubicin in clinical application.

Impact of chronic advanced aortic regurgitation on the perioperative outcome of noncardiac surgery.

Background: Whether and how chronic advanced aortic regurgitation (AR) impacts the perioperative outcome of noncardiac surgery remains unclear.

Dosage of statin, cardiovascular comorbidities, and risk of atrial fibrillation: A nationwide population-based cohort study

BACKGROUND Statin has potential protective effects against atrial fibrillation. Clinically, there is a need to predict the atrial fibrillation protective effects in statin-treated patients. The purpose of this study was to investigate if cardiovascular co-morbidities or cumulative defined daily doses (cDDDs) of statin use could predict statin efficacy in atrial fibrillation prevention. METHODS Patients aged ≥ 50 years were identified from the Taiwan National Health Insurance Research Database. Medical records of 171,885 patients were used in this study, and 40,001 (23.3%) of the patients received statin therapy (≥ 28 cDDDs). Risk of new-onset atrial fibrillation in statin users and non-users (<28 cDDDs) was estimated. RESULTS During the 9-year follow-up period, 6049 patients experienced new-onset atrial fibrillation. Overall, statin therapy reduced the risk of atrial fibrillation by 28% (adjusted hazard ratio [HR] 0.72; 95% CI 0.68 to 0.77). There was a dose-response relationship between statin use and the risk of atrial fibrillation. The adjusted HRs for atrial fibrillation were 1.04, 0.85, and 0.50 when cDDDs ranged from 28 to 90, 91 to 365, and more than 365, respectively. Subgroup analysis showed that statin use was more beneficial in patients with higher CHADS2 and CHA2DS2VASc scores than those with a score of 0 (P value for interaction<0.001). The therapy provided no obvious beneficial effect in those with a CHADS2 score of 0, a CHA2DS2VASc score of 0, or cDDDs less than 91. CONCLUSIONS Statin therapy reduces the risk of new-onset atrial fibrillation in a dose-dependent manner, and is beneficial in patients with cardiovascular co-morbidities.

Statin therapy reduces the risk of ventricular arrhythmias, sudden cardiac death, and mortality in heart failure patients: a nationwide population-based cohort study.

the drug. Therefore, one should always have in mind that during treatment of systemic inflammatory, neoplastic or hematological diseases with monoclonal antibodies the production of anti-drug antibodies is a reality. These antibodies can cause hypersensitivity reactions, worsen overt or incipient heart failure [11] and induce myocardial infarction manifesting as Kounis syndrome [3]. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology.

True Lumen Stenting for a Spontaneously Dissected Superior Mesenteric Artery May Compromise Major Intestinal Branches and Aggravate Bowel Ischemia

Optimal endovascular therapy for isolated superior mesenteric artery (SMA) dissection remains undetermined. Here, we report a 56-year-old male with ischemic bowel syndrome caused by such a serious vascular disease. He was treated with endovascular true lumen stenting yet got aggravated in bowel ischemia from unexpected jail of major intestinal branches perfused by the false lumen, requiring subsequent complex rewiring and dilatation procedures to resolve at the cost of excessive fluoroscopic and contrast medium exposure. Thus, when treating patients with isolated SMA dissection with a functioning false lumen, true lumen stenting may inadvertently compromise crucial intestinal branches and should not be indiscriminately considered as the prime therapeutic option.

Resistant Hypertension, Patient Characteristics, and Risk of Stroke

Background Little is known about the prognosis of resistant hypertension (RH) in Asian population. This study aimed to evaluate the impacts of RH in Taiwanese patients with hypertension, and to ascertain whether patient characteristics influence the association of RH with adverse outcomes. Methods and Results Patients aged ≥45 years with hypertension were identified from the National Health Insurance Research Database. Medical records of 111,986 patients were reviewed in this study, and 16,402 (14.6%) patients were recognized as having RH (continuously concomitant use of ≥3 anti-hypertensive medications, including a diuretic, for ≥2 years). Risk of major adverse cardiovascular events (MACE, a composite of all-cause mortality, acute coronary syndrome, and stroke [included both fatal and nonfatal events]) in patients with RH and non-RH was analyzed. A total of 11,856 patients experienced MACE in the follow-up period (average 7.1±3.0 years). There was a higher proportion of females in the RH group, they were older than the non-RH (63.1 vs. 60.5 years) patients, and had a higher prevalence of cardiovascular co-morbidities. Overall, patients with RH had higher risks of MACE (adjusted HR 1.17; 95%CI 1.09–1.26; p<0.001). Significantly elevated risks of stroke (10,211 events; adjusted HR 1.17; 95%CI 1.08–1.27; p<0.001), especially ischemic stroke (6,235 events; adjusted HR 1.34; 95%CI 1.20–1.48; p<0.001), but not all-cause mortality (4,594 events; adjusted HR 1.06; 95%CI 0.95–1.19; p = 0.312) or acute coronary syndrome (2,145 events; adjusted HR 1.17; 95%CI 0.99–1.39; p = 0.070) were noted in patients with RH compared to those with non-RH. Subgroup analysis showed that RH increased the risks of stroke in female and elderly patients. However, no significant influence was noted in young or male patients. Conclusions Patients with RH were associated with higher risks of MACE and stroke, especially ischemic stroke. The risks were greater in female and elderly patients than in male or young patients.

Axillofemoral Bypass Relieves Visceral Malperfusion in Type B Aortic Dissection

A 58-year-old man with acute type B aortic dissection presented with right lower limb cyanosis, mesenteric ischemia, and acute renal failure. He was treated with extraanatomic right axillofemoral bypass surgery alone, recovered completely from renal, mesenteric, and lower extremity malperfusion shortly thereafter, and lived free of symptoms for the following year. Follow-up computed tomography angiograms documented adequate expansion of the true aortic lumen and good perfusion of visceral organs. Thus, managing such patients with coexisting visceral and extremity malperfusion may be accomplished with axillofemoral bypass exclusively, which can relieve ischemia of upstream abdominal organs and downstream lower extremities effectively and durably.

Coronary severity score and C-reactive protein predict major adverse cardiovascular events in patients with stable coronary artery disease (from the Taichung CAD study)

BACKGROUND Whether angiographic coronary severity really predicts future major adverse cardiovascular events (MACEs) in patients with coronary artery disease (CAD) is uncertain. Few studies have compared the efficacy of SYNTAX, Gensini and Jeopardy scores in predicting MACE in stable CAD. METHODS We collected data of MACE, including all-cause mortality, all strokes, new myocardial infarction and unplanned repeat revascularization, in subjects with stable CAD from our catheterization databank. Coronary severity was graded with SYNTAX, Gensini and Jeopardy scoring systems. RESULTS During a median follow-up period of 42months, 39 out of the 181 subjects developed at least 1 MACE. Those with MACE had a significantly higher baseline high sensitivity C-reactive protein (hs-CRP) (p=0.025). Multivariate analysis showed that coronary severity score, hs-CRP and diabetes mellitus were significant predictors for MACE. Kaplan-Meier estimates showed a significant difference in MACE-free rates between SYNTAX binary scores (≥15 vs. <15, p=0.043), Gensini binary scores (≥36 vs. <36, p=0.048) and Jeopardy binary scores (≥4 vs. <4, p=0.001). CONCLUSION Coronary severity score, hs-CRP and diabetes mellitus independently predicted MACE in patients with stable CAD. The Jeopardy score is simple to calculate and as effective for predicting MACE in stable CAD as the complex SYNTAX score.