aconitine and Cardiomyopathy--Dilated

Seizures are associated with altered autonomic activity, which has been implicated in the development of cardiac dysfunction and structural damage. This study aimed to investigate the involvement of the autonomic nervous system in seizure-induced cardiomyopathy. Male Sprague-Dawley rats (320-350 g) were implanted with EEG/ECG electrodes to allow simultaneous telemetric recordings during seizures induced by intrahippocampal (2 nmol, 1 μl/min) kainic acid and monitored for 7 days. Seizure activity occurred in conjunction with increased heart rate (20%), blood pressure (25%), and QTc prolongation (15%). This increased sympathetic activity was confirmed by the presence of raised plasma noradrenaline levels at 3 h post-seizure induction. By 48 h post-seizure induction, sympathovagal balance was shifted in favor of sympathetic dominance, as indicated by both heart rate variability (LF/HF ratio of 3.5 ± 1.0) and pharmacological autonomic blockade. Functional cardiac deficits were evident at 7 and 28 days, as demonstrated by echocardiography showing a decreased ejection fraction (14% compared with control, P < 0.05) and dilated cardiomyopathy present at 28 days following seizure induction. Histological changes, including cardiomyocyte vacuolization, cardiac fibrosis, and inflammatory cell infiltration, were evident within 48 h of seizure induction and remained present for up to 28 days. These structural changes most probably contributed to an increased susceptibility to aconitine-induced arrhythmias. This study confirms that prolonged seizure activity results in acute and chronic alterations in cardiovascular control, leading to a deterioration in cardiac structure and function. This study further supports the need for modulation of sympathetic activity as a promising therapeutic approach in seizure-induced cardiomyopathy.

Topics: Aconitine; Animals; Arrhythmias, Cardiac; Autonomic Nervous System; Blood Pressure; Cardiomyopathies; Cardiomyopathy, Dilated; Excitatory Amino Acid Agonists; Fibrosis; Heart Rate; Kainic Acid; Male; Myocardium; Myocytes, Cardiac; Norepinephrine; Rats; Rats, Sprague-Dawley; Status Epilepticus; Stroke Volume; Sympathetic Nervous System; Vacuoles; Voltage-Gated Sodium Channel Agonists

Doxorubicin (Dox) is an anthracycline antibiotic used as anticancer agent. However, its use is limited due to its cardiotoxicity which is mainly attributed to accumulation of reactive oxygen species.. This study was conducted to assess whether the antioxidant, proanthocyanidins (Pro) can ameliorate Dox-induced cardiotoxicity in rats.. Male Sprague-Dawely rats were divided into four groups. Group I was control. Group II received Pro (70 mg/kg, orally) once daily for 10 days. Group III received doxorubicin 15 mg/kg i.p. as a single dose on the 7th day and Group IV animals were treated with Pro once daily for 10 days and Dox on the 7th day. The parameters of study were serum biomarkers, cardiac tissue antioxidant status, ECG, and effect on aconitine-induced cardiotoxicity.. Cardiac toxicity of doxorubicin was manifested as a significant increase in heart rate, elevation of the ST segment, prolongation of the QT interval and an increase in T wave amplitude. In addition, Dox enhanced aconitine-induced cardiotoxicity by a significant decrease in the aconitine dose producing ventricular tachycardia (VT). Administration of Pro significantly suppressed Dox-induced ECG changes and normalized the aconitine dose producing VT. The toxicity of Dox was also confirmed biochemically by significant elevation of serum CK-MB and LDH activities as well as myocardial MDA and GSH contents and decrease in serum catalase and myocardial SOD activities. Administration of Pro significantly suppressed these biochemical changes.. These results suggest that proanthocyanidins might be a potential cardioprotective agent against Dox-induced cardiotoxicity due to its antioxidant properties.

Topics: Aconitine; Animals; Antibiotics, Antineoplastic; Antioxidants; Arrhythmias, Cardiac; Biomarkers; Cardiomyopathy, Dilated; Cardiotonic Agents; Cardiotoxins; Doxorubicin; Drug Resistance; Grape Seed Extract; Heart; Male; Myocardium; Oxidative Stress; Phytotherapy; Proanthocyanidins; Rats; Rats, Sprague-Dawley; Tachycardia; Voltage-Gated Sodium Channel Agonists

The antiarrhythmic effects of allapinine were studied in 57 patients with chronic circulatory failure (CCF) and cardiac arrhythmias by employing 48-hour Holter monitoring. Allapinine was found to suppress premature ventricular contraction, group premature ventricular contraction and 'runs' of ventricular tachycardia by 82.5, 88.6, and 93.1%, respectively. The antiarrhythmic activity of the agent was more pronounced in patients with coronary heart disease, Stages I-IIA CCF and left ventricular ejection fraction greater than 40%. In addition, in Stages I-IIA CCF allapinine increased myocardial contractility and left ventricular ejection fraction, whereas in Stages IIB-III CCF it showed a slight cardiodepressive effect. Thus, when given in the course therapy in patients with CCF, allapinine has a high antiarrhythmic activity and, to a lesser extent, affects central hemodynamics.

Topics: Aconitine; Adult; Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiomyopathy, Dilated; Coronary Disease; Electrocardiography, Ambulatory; Female; Heart Diseases; Heart Valve Diseases; Hemodynamics; Humans; Male; Middle Aged