Relationship between myocardial amiodarone concentration and antiarrhythmic effect in dogs with myocardial infarction and electrically induced ventricular arrhythmias

1991 ◽  
Vol 69 (6) ◽  
pp. 812-817 ◽  
Author(s):  
Hoshiar Abdollah ◽  
F. James Brennan ◽  
Sandra Jimmo ◽  
James F. Brien

The relationship between the antiarrhythmic effect of amiodarone and its myocardial concentration was studied in dogs with 1-week-old myocardial infarction and reproducibly inducible sustained ventricular tachycardia or ventricular fibrillation. Three groups of animals (n = 10/group) received amiodarone, 40 mg∙kg−1∙day−1 (low-dose amiodarone), amiodarone 60 mg∙kg−1∙day−1 (high-dose amiodarone), or no amiodarone (control group). After 1 week of treatment, programmed electrical stimulation was repeated, and plasma and myocardial amiodarone and desethylamiodarone concentrations were measured. In the control group, sustained ventricular tachycardia or ventricular fibrillation was induced in six dogs (p = NS) when compared with baseline data. In the low-dose amiodarone group, sustained ventricular tachycardia or ventricular fibrillation was induced only in two dogs after 1 week of treatment (p < 0.01 vs. baseline data). Sustained ventricular tachycardia or ventricular fibrillation was induced in seven dogs after treatment with high-dose amiodarone (p = NS vs. baseline data). Plasma amiodarone concentration in the low-dose amiodarone group (2.54 ± 1.9 μg/mL) was significantly less (p < 0.01) than that in the high-dose amiodarone group (4.64 ± 1.66 μg/mL). Similarly, the plasma desethylamiodarone in the low-dose amiodarone group (0.32 ± 0.16 μg/mL) was significantly less (p < 0.001) than that in the high-amiodarone dose group (0.56 ± 0.23 μg/mL). The myocardial amiodarone concentration in the low-dose amiodarone group (49.7 ± 23.1 μg/g) was significantly lower (p < 0.001) than that in the high-dose group (98.4 ± 32.1 μg/g). There was no significant difference in the myocardial desethylamiodarone concentrations between the two treatment groups (25.1 ± 12.2 μg/g in the low-dose amiodarione group vs. 37.4 ± 16.4 μg/g in the high-dose amiodarone group). These data show that the high-dose amiodarone regimen, which produced high myocardial amiodarone concentration, didn't suppress sustained ventricular arrhythmias.Key words: amiodarone, ventricular arrhythmias, plasma and myocardial drug concentrations.

2020 ◽  
Vol 22 (1) ◽  
pp. 176
Author(s):  
Toshiaki Iba ◽  
Jerrold H. Levy ◽  
Koichiro Aihara ◽  
Katsuhiko Kadota ◽  
Hiroshi Tanaka ◽  
...  

(1) Background: The endothelial glycocalyx is a primary target during the early phase of sepsis. We previously reported a newly developed recombinant non-fucosylated antithrombin has protective effects in vitro. We further evaluated the effects of this recombinant antithrombin on the glycocalyx damage in an animal model of sepsis. (2) Methods: Following endotoxin injection, in Wistar rats, circulating levels of hyaluronan, syndecan-1 and other biomarkers were evaluated in low-dose or high-dose recombinant antithrombin-treated animals and a control group (n = 7 per group). Leukocyte adhesion and blood flow were evaluated with intravital microscopy. The glycocalyx was also examined using side-stream dark-field imaging. (3) Results: The activation of coagulation was inhibited by recombinant antithrombin, leukocyte adhesion was significantly decreased, and flow was better maintained in the high-dose group (both p < 0.05). Circulating levels of syndecan-1 (p < 0.01, high-dose group) and hyaluronan (p < 0.05, low-dose group; p < 0.01, high-dose group) were significantly reduced by recombinant antithrombin treatment. Increases in lactate and decreases in albumin levels were significantly attenuated in the high-dose group (p < 0.05, respectively). The glycocalyx thickness was reduced over time in control animals, but the derangement was attenuated and microvascular perfusion was better maintained in the high-dose group recombinant antithrombin group (p < 0.05). (4) Conclusions: Recombinant antithrombin maintained vascular integrity and the microcirculation by preserving the glycocalyx in this sepsis model, effects that were more prominent with high-dose therapy.


2017 ◽  
Vol 7 (1) ◽  
pp. 171
Author(s):  
Hamid Reza Adeli Bhroz ◽  
Kazem Parivar ◽  
Iraj Amiri ◽  
Nasim Hayati Roodbari

Background and Aim: Thyroid is one of the endocrine glands, (T3 and T4) play a significant role in the development of prenatal brain and the following stages. The study aimed to evaluate the effect of hypothyroidism on the amount of expression of NT4, NT3, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in brain of one-day rat neonates with hypothyroidism.Materials and Methods: In total, 25 mature mice of Albino NMRI race were selected after mating, divided into three group, control, as well as low-dose and high-dose intervention groups. Samples of the control group received pure water during pregnancy, whereas subjects of the intervention group with low and high doses of the medication were administered with 20 mg and 100 mg methimazole powder (dissolved in 100 cc water), respectively. After child delivery, blood samples were obtained from mother mice to determine the level of T3 and T4 in blood serum. Following that, the brain of one-day mice were removed by surgery and assessed to determine the amount of expression of NT4, NT3, NGF and BDNF using the complete kit of RT-PCR.Results: Levels of T4 and T3 in the control group were 28 ug/dl and 1.59 ug/dl, respectively. In the low-dose intervention group, the amounts of the mentioned hormones were 8 ug/dl and 0.85 ug/dl, significantly, indicating a significant reduction in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group. Moreover, T4 and T3 were 6 ug/dl and 0.79 ug/dl in the high-dose group, respectively, conveying a significant decrease in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group (P<0.05).


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Tao Hong ◽  
Long-Xue Li ◽  
Xiao-ping Han ◽  
Jing-liang Shi ◽  
Cai-yun Dan ◽  
...  

In this study, the effects of Astragalus membranaceus oral solution on lifespan and learning and memory abilities of honey bees were evaluated. Two groups of bees were fed with sucrose syrup (50%) containing low dose (1.33%) and high dose (13.3%) of A. membranaceus oral solution, respectively. The proboscis extension response (PER) analysis was applied to examine the learning and memory capabilities of bees. Two genes related to memory formation in honey bees were determined by real-time PCR. High dose (13.3%) of A. membranaceus significantly decreased the mean lifespan of bees compared to the bees fed with low dose (1.33%) and control bees. No significant differences in lifespan of bees were found between low-dose-fed bees and control bees. The results of PER experiments showed apparent improvement in the memorizing ability of the high-dose group (in comparison with the control group). Moreover, the relative expression levels of Nmdar1 in the low-dose group and control group were significantly lower than those in the high-dose group. It is preliminarily concluded that A. membranaceus has an adverse effect on the mean lifespan of honey bees but might be helpful in strengthening memories.


2021 ◽  
Vol 70 (2) ◽  
pp. 235-243
Author(s):  
TONG TONG ◽  
XIAOHUI NIU ◽  
QIAN LI ◽  
YUXI LING ◽  
ZUMING LI ◽  
...  

Lactobacillus plantarum BW2013 was isolated from the fermented Chinese cabbage. This study aimed to test the effect of this strain on the gut microbiota in BALB/c mice by 16S rRNA amplicon sequencing. The mice were randomly allocated to the control group and three treatment groups of L. plantarum BW2013 (a low-dose group of 108 CFU/ml, a medium-dose group of 109 CFU/ml, and a high-dose group of 1010 CFU/ml). The weight of mice was recorded once a week, and the fecal samples were collected for 16S rRNA amplicon sequencing after 28 days of continuous treatment. Compared with the control group, the body weight gain in the treatment groups was not significant. The 16S rRNA amplicon sequencing analysis showed that both the Chao1 and ACE indexes increased slightly in the medium-dose group compared to the control group, but the difference was not significant. Based on PCoA results, there was no significant difference in β diversity between the treatment groups. Compared to the control group, the abundance of Bacteroidetes increased in the low-dose group. The abundance of Firmicutes increased in the medium-dose group. At the genus level, the abundance of Alloprevotella increased in the low-dose group compared to the control group. The increased abundance of Ruminococcaceae and decreased abundance of Candidatus_Saccharimonas was observed in the medium-dose group. Additionally, the abundance of Bacteroides increased, and Alistipes and Candidatus_Saccharimonas decreased in the high-dose group. These results indicated that L. plantarum BW2013 could ameliorate gut microbiota composition, but its effects vary with the dose.


Author(s):  
Agnieszka Smoczyńska ◽  
Vera Loen ◽  
David J. Sprenkeler ◽  
Anton E. Tuinenburg ◽  
Henk J. Ritsema van Eck ◽  
...  

Background Short‐term variability of the QT interval (STV QT ) has been proposed as a novel electrophysiological marker for the prediction of imminent ventricular arrhythmias in animal models. Our aim is to study whether STV QT can predict imminent ventricular arrhythmias in patients. Methods and Results In 2331 patients with primary prophylactic implantable cardioverter defibrillators, 24‐hour ECG Holter recordings were obtained as part of the EU‐CERT‐ICD (European Comparative Effectiveness Research to Assess the Use of Primary Prophylactic Implantable Cardioverter Defibrillators) study. ECG Holter recordings showing ventricular arrhythmias of >4 consecutive complexes were selected for the arrhythmic groups (n=170), whereas a control group was randomly selected from the remaining Holter recordings (n=37). STV QT was determined from 31 beats with fiducial segment averaging and calculated as , where D n represents the QT interval. STV QT was determined before the ventricular arrhythmia or 8:00  am in the control group and between 1:30 and 4:30  am as baseline. STV QT at baseline was 0.84±0.47 ms and increased to 1.18±0.74 ms ( P <0.05) before the ventricular arrhythmia, whereas the STV QT in the control group remained unchanged. The arrhythmic patients were divided into three groups based on the severity of the arrhythmia: (1) nonsustained ventricular arrhythmia (n=32), (2) nonsustained ventricular tachycardia (n=134), (3) sustained ventricular tachycardia (n=4). STV QT increased before nonsustained ventricular arrhythmia, nonsustained ventricular tachycardia, and sustained ventricular tachycardia from 0.80±0.43 ms to 1.18±0.78 ms ( P <0.05), from 0.90±0.49 ms to 1.14±0.70 ms ( P <0.05), and from 1.05±0.22 ms to 2.33±1.25 ms ( P <0.05). This rise in STV QT was significantly higher in sustained ventricular tachycardia compared with nonsustained ventricular arrhythmia (+1.28±1.05 ms versus +0.24±0.57 ms [ P <0.05]) and compared with nonsustained ventricular arrhythmia (+0.34±0.87 ms [ P <0.05]). Conclusions STV QT increases before imminent ventricular arrhythmias in patients, and the extent of the increase is associated with the severity of the ventricular arrhythmia.


2020 ◽  
Author(s):  
Randi Ugleholdt ◽  
Åse Krogh Rasmussen ◽  
Pernille Agnete Heldager Haderslev ◽  
Bjarne Kromann-Andersen ◽  
Claus Larsen Feltoft

Abstract Background. Alpha-receptor blockade is the mainstay in preoperative treatment of patients with pheochromocytoma and paraganglioma (PPGL). However, evidence regarding optimal dosage regimen is lacking. This study compares the per- and postoperative hemodynamics in patients pre-treated with a high or low dose of phenoxybenzamine. Methods. 30 consecutive patients with PPGL undergoing laparoscopic adrenalectomy were identified retrospectively. All were pretreated with phenoxybenzamine but at two separate endocrine departments aiming at different blood pressure target. End-dosage of phenoxybenzamine differed significantly between departments with 14 patients receiving a high dose regimen and 16 a low dose regimen. As a control group, we included 42 patients undergoing laparoscopic adrenalectomy for other reasons. Primary purpose was to compare per- and postoperative hemodynamics in the high and low dose groups. Secondly, to compare these endpoints to the control group. Results. Baseline characteristics did not differ between the phenoxybenzamine treated groups. The high dose group had less intra-operative systolic and diastolic blood pressure fluctuation (p = 0.03) and less periods with heart rate above 100 bpm (p = 0.04) as compared to the low dose group. Use of intravenous fluids were similar between the two groups. However, postoperatively, more intravenous fluids were administered in the high dose group. Overall, the control group was more hemodynamic stable as compared to either group treated for PPGL. Conclusions. High dose phenoxybenzamine improves per-operative hemodynamic stability but causes a higher postoperative requirement for intravenous fluids. Overall, PPGL surgery is related to greater hemodynamic instability compared to adrenalectomy for other reasons.


2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Jun Won Park ◽  
Jeffrey R. Curtis ◽  
Min Jung Kim ◽  
Hajeong Lee ◽  
Yeong Wook Song ◽  
...  

Abstract Objectives To investigate the incidence of pneumocystis pneumonia (PCP) and its risk factors in patients with rheumatic disease receiving non-high-dose steroid treatment, along with the risks and benefits of PCP prophylaxis. Methods This study included 28,292 treatment episodes with prolonged (≥ 4 weeks), non-high-dose steroids (low dose [< 15 mg/day, n = 27,227] and medium dose [≥ 15 to < 30 mg/day, n = 1065], based on prednisone) over a 14-year period. Risk factors for PCP and prophylactic effect of trimethoprim–sulfamethoxazole (TMP-SMX) were investigated if the 1-year incidence rate (IR) of PCP in each dose group was > 0.1/100 person-years. Cox regression with LASSO was used for analysis. Results One-year PCP IR in the low-dose group was 0.01 (95% CI 0.001–0.03)/100 person-years, and only the medium-dose group showed eligible PCP IR for further analysis. In the medium-dose group, prophylactic TMP-SMX was administered in 45 treatment episodes while other episodes involved no prophylaxis (prophylaxis group vs. control group). In 1018.0 person-years, 5 PCP cases occurred exclusively in the control group, yielding an IR of 0.5 (0.2–1.2)/100 person-years. Concomitant steroid-pulse treatment and baseline lymphopenia were the most significant risk factors for PCP. Treatment episodes with at least one of these factors (n = 173, high-risk subgroup) showed higher 1-year PCP IR (3.4 (1.1–8.0)/100 person-years), while no PCP occurred in other treatment episodes. TMP-SMX numerically reduced the risk (adjusted HR = 0.2 (0.001–2.3)) in the high-risk subgroup. The IR of adverse drug reactions (ADRs) related to TMP-SMX was 41.5 (22.3–71.6)/100 person-years, including one serious ADR. The number needed to treat with TMP-SMX to prevent one PCP in the high-risk subgroup (31 (17–226)) was lower than the number needed to harm by serious ADR (45 (15–∞)). Conclusion Incidence of PCP in patients with rheumatic diseases receiving prolonged, medium-dose steroids depends on the presence of risk factors. Prophylactic TMP-SMX may have greater benefit than potential risk in the high-risk subgroup.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jae Hyung Cho ◽  
Ali Namazi ◽  
Richard Shelton ◽  
Archana Ramireddy ◽  
Ashkan Ehdaie ◽  
...  

Introduction: Arrhythmias have been reported frequent in COVID-19 patients, but the incidence and nature have not been well characterized. Hypothesis: Atrial and ventricular arrhythmias are common complications of patients with COVID-19. Methods: Patients admitted with COVID-19 and monitored by telemetry were prospectively enrolled in the study. Baseline characteristics, hospital course, treatment and complications were collected from the patients’ medical records. Telemetry was monitored to detect the incidence of cardiac arrhythmias. The incidence and types of cardiac arrhythmias were analyzed and compared between survivors and non-survivors. Results: Among 143 patients admitted with telemetry monitoring, overall in-hospital mortality was 23.1% (33/143 patients) during the period of observation (mean follow up 19.9 ± 13.7 days). Survivors were younger (68.1 ± 17.2 vs. 77.6 ± 15.9 years old, p=0.006), had higher body mass index (28.1 ± 8.3 vs. 24.3 ± 6.2, p=0.019), were less tachycardic on initial presentation (heart rate 90.6 ± 19.4 vs. 99.8 ± 23.7 bpm, p=0.026) and had lower troponin (peak troponin 0.03 vs. 0.14 ng/ml. p=0.006) and interleukin-6 levels (peak interleukin-6 32 vs. 264 pg/ml, p=0.001). Sinus tachycardia, the most common arrhythmia (occurring in 39.9% [57/143] of patients), occurred more frequently in non-survivors (57.6% vs. 34.5% in survivors, p=0.018). Premature ventricular complexes occurred in 28.7% (41/143), and non-sustained ventricular tachycardia in 15.4% (22/143) of patients, with no difference between survivors and non-survivors. Sustained ventricular tachycardia and ventricular fibrillation were rare (seen only in 1.4% and 0.7% of patients, respectively). Conclusions: In this prospective observational study of hospitalized and monitored patients with COVID-19, sinus tachycardia was the most common rhythm disorder, and its presence was associated with higher mortality. Sustained ventricular tachycardia or ventricular fibrillation were infrequent, contradicting previous reports that malignant ventricular arrhythmias are commonly seen in patients hospitalized with COVID-19.


2020 ◽  
Vol 6 (1) ◽  
pp. 44-50
Author(s):  
IO Osonuga ◽  
AS Faponle ◽  
EN Ezima ◽  
TK Adenowo ◽  
AA Adelegan

Background: The leaves of Telfairia occidentalis (locally known as Ugu) are widely consumed as part of a staple in the southern region of Nigeria. Its nutritional benefits include its rich mineral contents and antioxidant properties. It has been suggested that the leaf extracts may affect blood parameters. Objectives: To investigate the effects of aqueous extracts of T. occidentalis leaves on haematological indices and liver enzymes in rats. Methods: Twenty-four male Wistar rats weighing between 150g and 200g were used for the study. They were categorized into four groups of six rats each viz: high-dose, medium-dose, low-dose, and control groups. The leaf extract was administered in doses of 300mg/kg, 200mg/kg, and 100 mg/kg, respectively, while the control group received distilled water rather than leaf extracts.  Results: There was a dose-dependent decrease in the concentrations of liver enzymes and an increase in blood parameters. There was a significant difference (p = 0.000) in the mean red blood cells countof the control group (7.5±0.2×1012/L) compared to the low-dose group (9.1±0.1×1012/L), the medium-dose group (11.7±0.2×1012/L) and the high-dose group (13.3±0.2×1012/L).For the liver enzymes, there was a significant decrease in the mean AST levels in the high-dose group (42.8±3.5 IU/L), the medium-dose group (53.7±5.7IU/L) and the low-dose group (68.5±3.5IU/L) were compared to the value for the control group (88.6 ±2.5× 1012/L). Conclusions: Using an animal model, Telfairia occidentalis may have hepatoprotective and haemopoietic properties.


2019 ◽  
Vol 8 (2) ◽  
pp. 1570-1576
Author(s):  
Kebe E. Obeten ◽  
Victor A. Fischer ◽  
Ugwuja O. Jennifer ◽  
Akim Bonaventure

The study was aimed at determining the effect of aqueous extract of Theobroma cacao on the histology of the ovary of female albino wistar rat. Twenty-four (24) adult wistar female rats weighting about 100- 160g were used for this research work and were divided into three (3) groups of eight (8) animals each. Group A; control, Group B; low dose and Group C; high dose with eight (8) animals in each group. Control group received vital feed; the low dose group was administered 240mgkg body weight of Theobroma cacao extract and the high dose group was administered 500mgkg body weight of the test substance. Extract was given daily by oral gavage method for twenty-one (21) days. Twenty-four hours after the last administration, all animals in each group were sacrificed under chloroform anesthesia. The ovaries were harvested, weighed and fixed in 10% buffered formalin for histological studies. Results showed that following administration of extract of Theoboma cacao at these doses, an insignificant decrease in organ weight was observed. Histological observation showed few follicles as well as loss of the substance of granulose cell this could possibly suggest decrease in production of sex steroids in the ovary.Keywords: Theobroma Cacao, Ovary, Histology


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