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Chronic oral administration of low-dose combination of fenofibrate and rosuvastatin protects the rat heart against experimentally induced acute myocardial infarction

Garg M, Khanna D, Kalra S, Balakumar P

Fundam Clin Pharmacol, 2016 Oct;30(5):394-405.
PMID: 27148865 DOI: 10.1111/fcp.12204

Fenofibrate and rosuvastatin at low doses might have experimental pleiotropic benefits. This study investigated the combined effect of low doses of fenofibrate and rosuvastatin in isoproterenol-induced experimental myocardial infarction. Rats administered isoproterenol (85 mg/kg/day, s.c.) for 2 days (day 29 and day 30) of 30 days experimental protocol developed significant myocardial infarction that was accompanied with high myocardial oxidative stress and lipid peroxidation, elevated serum markers of cardiac injury, lipid abnormalities, and elevated circulatory levels of C-reactive protein. Pretreatment with low doses of fenofibrate (30 mg/kg/day p.o., 30 days) and rosuvastatin (2 mg/kg/day p.o., 30 days) both alone or in combination markedly prevented isoproterenol-induced myocardial infarction and associated abnormalities while the low-dose combination of fenofibrate and rosuvastatin was more effective. Histopathological study in isoproterenol control rat heart showed necrosis with edema and acute inflammation at the margins of necrotic area. The rat heart from low-dose fenofibrate and rosuvastatin pretreated group showed scanty inflammation and no ischemia. In conclusion, fenofibrate and rosuvastatin pretreatment in low doses might have a therapeutic potential to prevent the pathogenesis of myocardial infarction. Moreover, their combined treatment option might offer superior therapeutic benefits via a marked reduction in myocardial infarct size and oxidative stress, suggesting a possibility of their pleiotropic cardioprotective action at low doses.

Matched MeSH terms: Heart/drug effects
Fulltext Tretinoin in pregnancy complicated with acute promyelocytic leukaemia

Leong KW, Teh A, Bosco JJ

Med J Malaysia, 2000 Jun;55(2):277-9.
PMID: 19839162

Acute promyelocytic leukemia (APL) in pregnancy poses serious danger to both the mother and fetus. Cytotoxic chemotherapy may cause teratogenicity to the fetus. APL is unique because it is usually associated with a coagulopathy that markedly increases the risk for the mother and fetus. A 21 year old lady with APL in her third trimester of pregnancy was treated with oral tretinoin. Tretinoin reversed the coagulopathy and normalised her blood counts without causing cytotoxic damage associated with cancer chemotherapy. Fetal distress occurred at 37 weeks of gestation and an emergency caesarean section was performed without complications and no blood transfusion support was needed as her coagulopathy and thrombocytopenia had resolved. A remission was achieved with only tretinoin induction. She subsequently had consolidation and maintenance chemotherapy. The mother and baby remain well at 4 years from completion of chemotherapy. A total of 10 pregnancies associated with APL have been reported in the current literature. Premature delivery and a fetal arrhythmia were the only complications. Although retinoin is considered teratogenic, its use so far in second and third trimester has been safe.

Matched MeSH terms: Heart Rate, Fetal/drug effects
Fulltext Deaths of children during an outbreak of hand, foot, and mouth disease in Sarawak, Malaysia: clinical and pathological characteristics of the disease. For the Outbreak Study Group

Chan LG, Parashar UD, Lye MS, Ong FG, Zaki SR, Alexander JP, et al.

Clin Infect Dis, 2000 Sep;31(3):678-83.
PMID: 11017815

From April through June 1997, 29 previously healthy children aged <6 years (median, 1.5 years) in Sarawak, Malaysia, died of rapidly progressive cardiorespiratory failure during an outbreak of hand, foot, and mouth disease caused primarily by enterovirus 71 (EV71). The case children were hospitalized after a short illness (median duration, 2 days) that usually included fever (in 100% of case children), oral ulcers (66%), and extremity rashes (62%). The illness rapidly progressed to include seizures (28%), flaccid limb weakness (17%), or cardiopulmonary symptoms (of 24 children, 17 had chest radiographs showing pulmonary edema, and 24 had echocardiograms showing left ventricular dysfunction), resulting in cardiopulmonary arrest soon after hospitalization (median time, 9 h). Cardiac tissue from 10 patients showed normal myocardium, but central nervous system tissue from 5 patients showed inflammatory changes. Brain-stem specimens from 2 patients were available, and both specimens showed extensive neuronal degeneration, inflammation, and necrosis, suggesting that a central nervous system infection was responsible for the disease, with the cardiopulmonary dysfunction being neurogenic in origin. EV71 and possibly an adenovirus, other enteroviruses, or unknown cofactors are likely responsible for this rapidly fatal disease.

Matched MeSH terms: Heart Arrest/etiology
Risk factors for early death in acute ischemic stroke and intracerebral hemorrhage: A prospective hospital-based study in Asia. Asian Acute Stroke Advisory Panel

Wong KS

Stroke, 1999 Nov;30(11):2326-30.
PMID: 10548666

BACKGROUND AND PURPOSE: In Asia, there has been no international study to investigate the risk factors for early death in patients with ischemic stroke and intracerebral hemorrhage.
METHODS: We conducted a prospective study of consecutive patients with acute stroke who were admitted to 36 participating hospitals in China, India, Indonesia, Korea, Malaysia, the Philippines, Singapore, Taiwan, Thailand, and Vietnam. With the use of a simple identical data sheet, we recorded the demographics and cardiovascular risk factors of each patient. Early death was defined as death on discharge from the acute hospital.
RESULTS: We enrolled 2403 patients with ischemic stroke and 783 patients with intracerebral hemorrhage. Among patients with ischemic stroke, previous use of antiplatelet drugs (adjusted odds ratio [OR] 0.53; 95% confidence interval [CI] 0. 30 to 0.95) and relatively young age group 56 to 75 years (OR 0.65; 95% CI 0.42 to 1.00) were protective factors; atrial fibrillation (OR 2.23; 95% CI 1.40 to 3.57), ischemic heart disease (OR 2.03; 95% CI 1.37 to 3.05), diabetes (OR 1.52; 95% CI 1.04 to 2.22), and ex-smoker status (OR 2.18; 95% CI 1.18 to 4.05) were risk factors for early death. Among patients with intracerebral hemorrhage, hypertension (OR 0.56; 95% CI 0.38 to 0.82) and young age group 56 to 75 years old (OR 0.55; 95% CI 0.34 to 0.87) were associated with lower death rate, whereas diabetes (OR 1.74; 95% CI 1.01 to 2.98) was a risk factor for early death.
CONCLUSIONS: In Asian patients with stroke, previous use of antiplatelet drugs nearly halved the risk of early death in patients with ischemic stroke, whereas atrial fibrillation, ischemic heart disease, diabetes, and ex-smoker status were risk factors for early death. Among patients with intracerebral hemorrhage, diabetes was associated with early death, whereas young age group and hypertension were associated with lower death rates, though no clear explanation for the hypertension association could be discerned from the data available.

Matched MeSH terms: Heart Diseases/epidemiology
The effect of prophylactic metaraminol on systemic hypotension caused by induction of anaesthesia with propofol in patients over 55 years old

Chiu CL, Tew GP, Wang CY

Anaesthesia, 2001 Sep;56(9):893-7.
PMID: 11531679

We conducted a double-blind, randomised, placebo-controlled study evaluating the efficacy of prophylactic metaraminol for preventing propofol-induced hypotension. Thirty patients aged 55-75 years undergoing general anaesthesia were randomly allocated to receive either metaraminol 0.5 mg or saline before administration of fentanyl 1 microg.kg(-1) and propofol 2 mg.kg(-1). Induction of anaesthesia was associated with a decrease in mean and systolic arterial pressure in both groups (p = 0.0001). However, there was no significant difference between the two groups. These results show that prophylactic use of metaraminol 0.5 mg does not prevent the decrease in blood pressure following fentanyl and propofol induction in older patients.

Matched MeSH terms: Heart Rate/drug effects
Microbiology of cerebral abscess: a four-year study in Malaysia

Pit S, Jamal F, Cheah FK

J Trop Med Hyg, 1993 Jun;96(3):191-6.
PMID: 8505776

A prospective study was carried out to determine the aetiology of cerebral abscess in relation to the primary source of infections. Seventy-five patients with cerebral abscess were included in the study in the period January 1985 to December 1988. More than half of the patients studied had single lesions and the overall most common sites were in the frontal and parietal regions. Chronic suppurative otitis media, cyanotic congenital heart diseases and meningitis were among the important predisposing conditions in these patients. Approximately 25% of the patients with cerebral abscesses had no documented antecedent infections. Pure cultures were found to be predominant (66.7%) and sterile cultures were obtained from 10 (13.3%) patients. Streptococci were isolated from 23 (30.7%) patients, the commonest species being Streptococcus milleri. Proteus sp, Pseudomonas aeruginosa, Pseudomonas putrifaciens and Bacteroides sp were almost exclusively found in cerebral abscesses secondary to chronic suppurative otitis media; these organisms were found in mixed cultures. Streptococcus milleri, Bacteroides sp and Eikenella corrodens were found in pure cultures in patients with cyanotic congenital heart disease. In patients with ventriculoperitoneal shunts in-situ, Staphylococcus aureus, Staphylococcus epidermidis and diphtheroids were common. Anaerobes were found in 15 (20.0%) patients, the majority in mixed cultures. Culture, as well as gas-liquid chromatographic analysis of volatile fatty acids of cerebral pus, was carried out to enhance the detection of the anaerobes. Based on these findings, an antibiotic regimen consisting of penicillin, chloramphenicol and metronidazole is recommended as an initial therapy while awaiting culture and sensitivity results.

Matched MeSH terms: Heart Defects, Congenital/complications
Influence of a kinin antagonist on acute hypotensive responses induced by bradykinin and captopril in spontaneously hypertensive rats

Sharma JN, Stewart JM, Mohsin SS, Katori M, Vavrek R

Agents Actions Suppl., 1992;38 ( Pt 3):258-69.
PMID: 1334354

We have evaluated the effects of a B2 receptor antagonist (B5630) of kinins on BK and captopril-induced acute hypotensive responses in anaesthetized SHR. Intravenous treatment of BK (1.0 microgram) and captopril (0.3 mg/kg) caused significant (p < 0.05) fall in the SBP and DBP. Whereas BK caused greater fall in the SBP (p < 0.05), DBP (p < 0.01) and duration of hypotension (p < 0.05) when administered after captopril (Fig 1 and 2). All the hypotensive effects of BK and captopril were significantly antagonised (p < 0.05) in the presence of B5630 (2.0 mg/kg). Further, the duration of hypotensive responses of BK and captopril were blocked (p < 0.05) by B5630. The agonists and BK-antagonist did not cause significant (p > 0.05) alterations in HR during the entire investigation. These findings provide evidence to support the suggestion that B2 receptor might be involved in the regulation of the hypotensive actions of BK and captopril. Kinins should also have valuable functions in the antihypertensive property of captopril-like drugs.

Matched MeSH terms: Heart Rate/drug effects*
Induced expression of the antimicrobial peptide melittin inhibits experimental infection by Mycoplasma gallisepticum in chickens

Lazarev VN, Stipkovits L, Biro J, Miklodi D, Shkarupeta MM, Titova GA, et al.

Microbes Infect., 2004 May;6(6):536-41.
PMID: 15158186

The in vivo action of the antimicrobial peptide melittin, expressed from a recombinant plasmid vector, on chickens experimentally infected with Mycoplasma gallisepticum was studied. The plasmid vector pBI/mel2/rtTA includes the melittin gene under the control of an inducible tetracycline-dependent human cytomegalovirus promoter and the gene coding for the trans-activation protein rtTA. Aerosol administration of the vector, followed by infecting the chickens with M. gallisepticum 1226, is shown to inhibit development of infection. The inhibitory action was confirmed by a complex of clinical, pathomorphological, histological and serological studies, and also by comparing the M. gallisepticum reisolation frequency from the respiratory tract and internal organs. The data suggest that plasmid vectors expressing genes of antimicrobial peptides can be considered as potential agents for the prevention and treatment of mycoplasma infections in poultry farming.

Matched MeSH terms: Heart/microbiology
Fulltext Ion channels, long QT syndrome and arrhythmogenesis in ageing

Jeevaratnam K, Chadda KR, Salvage SC, Valli H, Ahmad S, Grace AA, et al.

Clin Exp Pharmacol Physiol, 2017 12;44 Suppl 1:38-45.
PMID: 28024120 DOI: 10.1111/1440-1681.12721

Ageing is associated with increased prevalences of both atrial and ventricular arrhythmias, reflecting disruption of the normal sequence of ion channel activation and inactivation generating the propagated cardiac action potential. Experimental models with specific ion channel genetic modifications have helped clarify the interacting functional roles of ion channels and how their dysregulation contributes to arrhythmogenic processes at the cellular and systems level. They have also investigated interactions between these ion channel abnormalities and age-related processes in producing arrhythmic tendency. Previous reviews have explored the relationships between age and loss-of-function Nav 1.5 mutations in producing arrhythmogenicity. The present review now explores complementary relationships arising from gain-of-function Nav 1.5 mutations associated with long QT3 (LQTS3). LQTS3 patients show increased risks of life-threatening ventricular arrhythmias, particularly after 40 years of age, consistent with such interactions between the ion channel abnormailities and ageing. In turn clinical evidence suggests that ageing is accompanied by structural, particularly fibrotic, as well as electrophysiological change. These abnormalities may result from biochemical changes producing low-grade inflammation resulting from increased production of reactive oxygen species and superoxide. Experimental studies offer further insights into the underlying mechanisms underlying these phenotypes. Thus, studies in genetically modified murine models for LQTS implicated action potential recovery processes in arrhythmogenesis resulting from functional ion channel abnormalities. In addition, ageing wild type (WT) murine models demonstrated both ion channel alterations and fibrotic changes with ageing. Murine models then suggested evidence for interactions between ageing and ion channel mutations and provided insights into potential arrhythmic mechanisms inviting future exploration.

Matched MeSH terms: Heart Rate/genetics*
Fulltext The effect of sedation with a combination of butorphanol and midazolam on quantitative contrast-enhanced ultrasonography of duodenum in healthy dogs

Nisa K, Lim SY, Osuga T, Yokoyama N, Tamura M, Nagata N, et al.

J Vet Med Sci, 2018 Mar 24;80(3):453-459.
PMID: 29398670 DOI: 10.1292/jvms.17-0525

Quantitative contrast-enhanced ultrasonography (CEUS) enables non-invasive and objective evaluation of intestinal perfusion by quantifying the intensity of enhancement on the intestine after microbubble contrast administration. During CEUS scanning, sedation is sometimes necessary to maintain animal cooperation. Nevertheless, the effect of sedative administration on the canine intestinal CEUS is unknown. This study aimed to investigate the effect of sedation with a combination of butorphanol and midazolam on the duodenal CEUS-derived perfusion parameters of healthy dogs. For this purpose, duodenum was imaged following contrast administration (Sonazoid®, 0.01 ml/kg) in six healthy beagles before and after intravenous injection of a combination of butorphanol (0.2 mg/kg) and midazolam (0.1 mg/kg). Furthermore, hemodynamic parameters including blood pressure and heart rate were recorded during the procedure. Five CEUS derived perfusion parameters including time-to-peak (TTP), peak intensity (PI), area under the curve (AUC), wash-in and wash-out rates (WiR and WoR, respectively) before and after sedation were statistically compared. The result showed that no significant change was detected in any of perfusion parameters. Systolic and mean arterial pressures significantly reduced after sedative administration, but diastolic arterial pressure and heart rate did not significantly change. Moreover, no significant partial correlation was observed between perfusion parameters and hemodynamic parameters. Thus, we concluded that the combination did not cause significant influence in duodenal CEUS perfusion parameters and could be a good option for sedation prior to duodenal CEUS in debilitated dogs.

Matched MeSH terms: Heart Rate/drug effects
Histopathology of cultured sea bass (Lates calcarifer) (Centropomidae) infected with Cruoricola lates (Trematoda: Sanguinicolidae) from Pulau Ketam, Malaysia

Herbert BW, Shaharom FM, Anderson IG

Int J Parasitol, 1995 Jan;25(1):3-13.
PMID: 7797370

Cruoricola lates are found throughout sea bass (Lates calcarifer), most commonly in the mesenteric blood vessels, kidney, pericardial vessels, and eye. Eggs of C. lates were predominantly found in the gills, ventricle, hepatopancreas, and kidneys, but only develop to miracidia regularly in the gills and heart. Single miracidia escaping appear to cause little damage, but groups induce an inflammatory response and haemorrhage. Endocardial macrophages encapsulate eggs trapped between trabeculae in the heart. The reaction to eggs in the kidneys, hepatopancreas and spleen consists of fibrocytic encapsulation. Infection at the levels observed in this study were insufficient to cause lethal pathological changes, but could result in reduced food conversion ratios or impaired immunological capacity.

Matched MeSH terms: Heart/parasitology
Isolation and genotyping of Toxoplasma gondii from free-range ducks in Malaysia

Puvanesuaran VR, Noordin R, Balakrishnan V

Avian Dis, 2013 Mar;57(1):128-32.
PMID: 23678741

Toxoplasma gondii is a parasitic protozoan that infects nearly one-third of humans. The present study was performed to isolate and genotype T. gondii from free-range ducks in Malaysia. Sera, heads, and hearts from 205 ducks were obtained from four states in Peninsular Malaysia, and 30 (14.63%) sera were found to be seropositive when assayed with the modified agglutination test (MAT > or = 1:6). All the positive samples were inoculated into mice, and T. gondii was successfully isolated from four individual duck samples (1.95%), which were initially found to be strongly seropositive (MAT > or = 1:24). The isolates were subjected to PCR-RFLP analysis, and two T. gondii strains were identified: type I and type II. This is the first reported study on the genetic characterization of T. gondii isolates from free-range farm animals in Southeast Asia.

Matched MeSH terms: Heart/parasitology
Standardized ethanol-water extract of Ficus deltoidea Angustifolia reduces blood pressure in spontaneously hypertensive rats

Kamal MSA, Ismail NH, Satar NA, Azis NA, Radjeni Z, Mohammad Noor HS, et al.

Clin Exp Hypertens, 2019;41(5):444-451.
PMID: 30648895 DOI: 10.1080/10641963.2018.1506467

Ficus deltoidea is used in Malay traditional medicine for the treatment of a number of disorders, including hypertension. There is, however, no scientific evidence on its anti-hypertensive effects. This study, therefore, investigated the effects of a standardized ethanolic-water extract of Ficus deltoidea Angustifolia (FD-A) on blood pressure (BP) in spontaneously hypertensive rats (SHR). Male SHR with systolic BP of >150 were divided into 4 groups (n = 8) and given either FD-A (800 or 1000 mg kg-1 day-1) or losartan (10 mg kg-1 day-1) or 0.5 ml of distilled water (control) daily for 28 days. BP, body weight, food and water intake, serum and urinary electrolytes, endothelin-1 (ET-1), total antioxidant capacity (TAC) and components of the renin-angiotensin-aldosterone system were measured. Data were analyzed using ANOVA with statistical significance set at p heart rate, and heart weight in FD-A and losartan-treated rats were significantly lower than those in the controls. Serum TAC and urinary calcium excretion were significantly higher, whereas serum ET-1 concentration was significantly lower in FD-A treated rats when compared to those in controls. No significant differences were found in the components of the renin-angiotensin-aldosterone system between controls and FD-A treated rats. In conclusion, FD-A when given daily at doses of either 800 or 1000 mg kg-1 day-1 body weight reduces BP in SHR. This effect does not seem to involve the renin-angiotensin-aldosterone-system but might involve some other mechanisms. Abbreviations: FD-A: Ficus deltoidea Angustifolia; ACE: Angiotensin-converting enzyme; SHR: Spontaneously hypertensive rats; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; AUC: Area under curve; RAAS: Renin Angiotensin Aldosterone System.

Matched MeSH terms: Heart Rate/drug effects
Right atrial tuberculoma: a diagnosis too late

Ngow HA, Khairina WM

Cardiol J, 2011;18(5):560-3.
PMID: 21947994

Solitary intra-cardiac cavity tuberculoma is extremely rare and often only diagnosed during a post-mortem. We report a case of right atrial tuberculoma causing right atrial outflow tract obstruction in an immune-compromised man. The diagnosis of cardiac tuberculoma was made through the detection of mycobacterium tuberculosis DNA by tuberculosis-polymerase chain reaction in the pericardial fluid. The patient succumbed five days after admission but an autopsy was refused by his family.

Matched MeSH terms: Heart Atria/microbiology
Fulltext Protective effects of Mucuna pruriens seed extract pretreatment against cardiovascular and respiratory depressant effects of Calloselasma rhodostoma (Malayan pit viper) venom in rats

Fung SY, Tan NH, Sim SM

Trop Biomed, 2010 Dec;27(3):366-72.
PMID: 21399576 MyJurnal

The protective effects of Mucuna pruriens seed extract (MPE) against the cardio-respiratory depressant and neuromuscular paralytic effects induced by injection of Calloselasma rhodostoma (Malayan pit viper) venom in anaesthetized rats were investigated. While MPE pretreatment did not reverse the inhibitory effect of the venom on the gastrocnemius muscle excitability, it significantly attenuated the venom-induced cardio-respiratory depressant effects (p < 0.05). The protection effects may have an immunological mechanism, as indicated by the presence of several proteins in the venom that are immunoreactive against anti-MPE. However, we cannot rule out the possibility that the pretreatment may exert a direct, non-immunological protective action against the venom.

Matched MeSH terms: Heart Failure/prevention & control*
Salbutamol in premature labour--a preliminary report

Ken DK, Ng KH

Med J Malaysia, 1974 Mar;28(3):191-3.
PMID: 4278259
Matched MeSH terms: Heart Rate/drug effects
Fulltext Bile acids and their respective conjugates elicit different responses in neonatal cardiomyocytes: role of Gi protein, muscarinic receptors and TGR5

Ibrahim E, Diakonov I, Arunthavarajah D, Swift T, Goodwin M, McIlvride S, et al.

Sci Rep, 2018 05 08;8(1):7110.
PMID: 29740092 DOI: 10.1038/s41598-018-25569-4

Bile acids are recognised as bioactive signalling molecules. While they are known to influence arrhythmia susceptibility in cholestasis, there is limited knowledge about the underlying mechanisms. To delineate mechanisms underlying fetal heart rhythm disturbances in cholestatic pregnancy, we used FRET microscopy to monitor cAMP release and contraction measurements in isolated rodent neonatal cardiomyocytes. The unconjugated bile acids CDCA, DCA and UDCA and, to a lesser extent, CA were found to be relatively potent agonists for the GPBAR1 (TGR5) receptor and elicit cAMP release, whereas all glyco- and tauro- conjugated bile acids are weak agonists. The bile acid-induced cAMP production does not lead to an increase in contraction rate, and seems to be mediated by the RI isoform of adenylate cyclase, unlike adrenaline-dependent release which is mediated by the RII isoform. In contrast, bile acids elicited slowing of neonatal cardiomyocyte contraction indicating that other signalling pathways are involved. The conjugated bile acids were found to be partial agonists of the muscarinic M2, but not sphingosin-1-phosphate-2, receptors, and act partially through the Gi pathway. Furthermore, the contraction slowing effect of unconjugated bile acids may also relate to cytotoxicity at higher concentrations.

Matched MeSH terms: Heart Rate, Fetal/physiology
Preclinical safety assessments of nano-sized constructs on cardiovascular system toxicity: A case for telemetry

Cheah HY, Kiew LV, Lee HB, Japundžić-Žigon N, Vicent MJ, Hoe SZ, et al.

J Appl Toxicol, 2017 Nov;37(11):1268-1285.
PMID: 28165137 DOI: 10.1002/jat.3437

While nano-sized construct (NSC) use in medicine has grown significantly in recent years, reported unwanted side effects have raised safety concerns. However, the toxicity of NSCs to the cardiovascular system (CVS) and the relative merits of the associated evaluation methods have not been thoroughly studied. This review discusses the toxicological profiles of selected NSCs and provides an overview of the assessment methods, including in silico, in vitro, ex vivo and in vivo models and how they are related to CVS toxicity. We conclude the review by outlining the merits of telemetry coupled with spectral analysis, baroreceptor reflex sensitivity analysis and echocardiography as an appropriate integrated strategy for the assessment of the acute and chronic impact of NSCs on the CVS. Copyright © 2017 John Wiley & Sons, Ltd.

Matched MeSH terms: Heart Rate/drug effects
INR Control of Patients with Mechanical Heart Valve on Long-Term Warfarin Therapy

Tan CSY, Fong AYY, Jong YH, Ong TK

Glob Heart, 2018 12;13(4):241-244.
PMID: 30213574 DOI: 10.1016/j.gheart.2018.08.003

BACKGROUND: Warfarin is an anticoagulant indicated for patients who had undergone mechanical heart valve(s) replacement (MHVR). In these patients, time in therapeutic range (TTR) is important in predicting the bleeding and thrombotic risks.
OBJECTIVE: This study aimed to describe the anticoagulation control of warfarin using TTR in patients with MHVR in a tertiary health care referral Center.
METHODS: Data were collected retrospectively by reviewing clinical notes of outpatients who attended international normalized ratio (INR) clinics in November 2015. Patients who had MHVR and who took warfarin were included. The data collected were demographics, relevant laboratory investigations, and patients' prior medical history. TTR was calculated using Rosendaal and traditional methods.
RESULTS: A total of 103 patients with MHVR were recruited. The mean age was 51.72 ± 13.97 years and 46.6% were male. A total of 54.4% had mitral valve replacement (MVR), whereas 26.2% had aortic valve replacement (AVR). The mean TTR calculated using the Rosendaal method was 57.1%. There was no significant difference among patients with AVR, MVR, and both valves (AMVR) in terms of TTR (AVR vs. MVR vs. AMVR, 62.94 ± 23.08, 54.12 ± 21.62, 57.63 ± 17.47; p = 0.213). The average dose of warfarin for all groups was approximately 3 mg/day. Moreover, MVR, AVR, and AMVR patients who had TTR (Rosendaal method) ≤60% were 58.9%, 37.0%, and 45.0%, respectively. Only 4.8% had minor bleeding, whereas none had stroke in the period of TTR determination.
CONCLUSIONS: Despite a majority of patients having <60% TTR, there were low incidences of bleeding and stroke events in this center. There were no factors found to be associated with INR control in this study.
Study site: INR clinic, Sarawak Heart Centre, Sarawak General Hospital, Malaysia

Matched MeSH terms: Heart Valve Prosthesis/adverse effects*
Cardiovascular autonomic effects of transcutaneous auricular nerve stimulation via the tragus in the rat involve spinal cervical sensory afferent pathways

Mahadi KM, Lall VK, Deuchars SA, Deuchars J

Brain Stimul, 2019 05 06;12(5):1151-1158.
PMID: 31129152 DOI: 10.1016/j.brs.2019.05.002

BACKGROUND: Electrical stimulation on select areas of the external auricular dermatome influences the autonomic nervous system. It has been postulated that activation of the Auricular Branch of the Vagus Nerve (ABVN) mediates such autonomic changes. However, the underlying neural pathways mediating these effects are unknown and, further, our understanding of the anatomical distribution of the ABVN in the auricle has now been questioned.
OBJECTIVE: To investigate the effects of electrical stimulation of the tragus on autonomic outputs in the rat and probe the underlying neural pathways.
METHODS: Central neuronal projections from nerves innervating the external auricle were investigated by injections of the transganglionic tracer cholera toxin B chain (CTB) into the right tragus of Wistar rats. Physiological recordings of heart rate, perfusion pressure, respiratory rate and sympathetic nerve activity were made in an anaesthetic free Working Heart Brainstem Preparation (WHBP) of the rat and changes in response to electrical stimulation of the tragus analysed.
RESULTS: Neuronal tracing from the tragus revealed that the densest CTB labelling was within laminae III-IV of the dorsal horn of the upper cervical spinal cord, ipsilateral to the injection sites. In the medulla oblongata, CTB labelled afferents were observed in the paratrigeminal nucleus, spinal trigeminal tract and cuneate nucleus. Surprisingly, only sparse labelling was observed in the vagal afferent termination site, the nucleus tractus solitarius. Recordings made from rats at night time revealed more robust sympathetic activity in comparison to day time rats, thus subsequent experiments were conducted in rats at night time. Electrical stimulation was delivered across the tragus for 5 min. Direct recording from the sympathetic chain revealed a central sympathoinhibition by up to 36% following tragus stimulation. Sympathoinhibition remained following sectioning of the cervical vagus nerve ipsilateral to the stimulation site, but was attenuated by sectioning of the upper cervical afferent nerve roots.
CONCLUSIONS: Inhibition of the sympathetic nervous system activity upon electrical stimulation of the tragus in the rat is mediated at least in part through sensory afferent projections to the upper cervical spinal cord. This challenges the notion that tragal stimulation is mediated by the auricular branch of the vagus nerve and suggests that alternative mechanisms may be involved.

Matched MeSH terms: Heart Rate/physiology*

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