Pathophysiology of acute ischemia: Potential targets for antiarrhythmic drugs

Author(s):  
André G. Kléber
1982 ◽  
Vol 47 (02) ◽  
pp. 150-153 ◽  
Author(s):  
P Han ◽  
C Boatwright ◽  
N G Ardlie

SummaryVarious cardiovascular drugs such as nitrates and propranolol, used in the treatment of coronary artery disease have been shown to have an antiplatelet effect. We have studied the in vitro effects of two antiarrhythmic drugs, verapamil and disopyramide, and have shown their inhibitory effect on platelet function. Verapamil, a calcium channel blocker, inhibited the second phase of platelet aggregation induced by adenosine diphosphate (ADP) and inhibited aggregation induced by collagen. Disopyramide similarly inhibited the second phase of platelet aggregation caused by ADP and aggregation induced by collagen. Either drug in synergism with propranolol inhibited ADP or collagen-induced platelet aggregation. Disopyramide at high concentrations inhibited arachidonic add whereas verapamil was without effect. Verapamil, but not disopyramide, inhibited aggregation induced by the ionophore A23187.


2010 ◽  
Vol 6 (3) ◽  
pp. 60
Author(s):  
Richard Schilling ◽  

Atrial fibrillation (AF) is linked to an increased risk of adverse cardiovascular events. While rhythm control with antiarrhythmic drugs (AADs) is a common strategy for managing patients with AF, catheter ablation may be a more efficacious and safer alternative to AADs for sinus rhythm control. Conventional catheter ablation has been associated with challenges during the arrhythmia mapping and ablation stages; however, the introduction of two remote catheter navigation systems (a robotic and a magnetic navigation system) may potentially overcome these challenges. Initial clinical experience with the robotic navigation system suggests that it offers similar procedural times, efficacy and safety to conventional manual ablation. Furthermore, it has been associated with reduced fluoroscopy exposure to the patient and the operator as well as a shorter fluoroscopy time compared with conventional catheter ablation. In the future, the remote navigation systems may become routinely used for complex catheter ablation procedures.


2011 ◽  
Vol 7 (2) ◽  
pp. 97 ◽  
Author(s):  
Niels Voigt ◽  
Dobromir Dobrev ◽  
◽  

Atrial fibrillation (AF) is the most common arrhythmia and is associated with substantial cardiovascular morbidity and mortality, with stroke being the most critical complication. Present drugs used for the therapy of AF (antiarrhythmics and anticoagulants) have major limitations, including incomplete efficacy, risks of life-threatening proarrhythmic events and bleeding complications. Non-pharmacological ablation procedures are efficient and apparently safe, but the very large size of the patient population allows ablation treatment of only a small number of patients. These limitations largely result from limited knowledge about the underlying mechanisms of AF and there is a hope that a better understanding of the molecular basis of AF may lead to the discovery of safer and more effective therapeutic targets. This article reviews the current knowledge about AF-related ion-channel remodelling and discusses how these alterations might affect the efficacy of antiarrhythmic drugs.


Author(s):  
Shengyuan Wang ◽  
Chuanling Wang ◽  
Lihua Wang ◽  
Zhiyou Cai

Background: Mammalian target of rapamycin (mTOR) has been evidenced as a multimodal therapy in the path-ophysiological process of acute ischemic stroke (AIS). However, the pathway that minocycline targets mTOR signaling is not fully defined in the AIS pathogenesis. This study is to aim at the effects of minocycline on the mTOR signaling in the AIS process and further discover the underlying mechanisms of minocycline involved in the following change of mTOR signaling-autophagy. Methods: Cerebral ischemia/reperfusion (CIR) rat animal models were established with the transient suture occlusion into middle cerebral artery. Minocycline (50mg/kg) was given by intragastric administration. The Morris water maze was used to test the cognitive function of animals. Immunohistochemistry and immunofluorescence were introduced for testing the lev-els of synaptophysin and PSD-95. Western blot was conducted for investigating the levels of mTOR, p-mTOR (Ser2448), p70S6, p-p70S6 (Thr389), eEF2k, p-eEF2k (Ser366), p-eIF4B (Ser406), LC3, p62, synaptophysin and PSD-95. Results: Minocycline prevents cognitive decline of the MCAO stroke rats. Minocycline limits the expression of p-mTOR (Ser2448) and the downstream targets of mTOR [p70S6, p-p70S6 (Thr389), eEF2k, p-eEF2k (Ser366) and p-eIF4B (Ser406)] (P<0.01), while minocycline has no influence on mTOR. LC3-II abundance and the LC3-II/I ratio were upregu-lated in the hippocampus of the MCAO stroke rats by the minocycline therapy (P<0.01). p62 was downregulated in the hippocampus from the MCAO stroke rats administrated with minocycline therapy(P<0.01). The levels of SYP and PSD-95 were up-regulated in the brain of the MCAO stroke rats administrated with minocycline therapy. Conclusion: Minocycline prevents cognitive deficits via inhibiting mTOR signaling and enhancing autophagy process, and promoting the expression of pre-and postsynaptic proteins (synaptophysin and PSD-95) in the brain of the MCAO stroke rats. The potential neuroprotective role of minocycline in the process of cerebral ischemia may be related to mitigating is-chemia-induced synapse injury via inhibiting activation of mTOR signaling.


Author(s):  
Vikram S. ◽  
Saraswathi Devi H.N.

Medical science says that ischemia is a common complication in Diabetes, especially in the lower limb but this is a case presenting ischemic changes in upper limb which is unique and also in such type of acute ischemia amputation is the only choice of treatment to save the life of patient from septicaemia. Such a rare and interesting case was taken at Sri Sri Ayurveda Hospital and handled by proper Ayurvedic line of treatment by which circulation is re-established which saved both limb and life of patient. A patient by name Sundaramma, 62yr Female, visited Sri Sri Ayurveda Hospital on 29/2/2016 with a diagnosis of Right upper limb Ischemia with Diabetes Mellitus and Active TB. The main symptoms were severe pain and burning sensation in Right hand and forearm, discolouration of fingers with ulcers, Bluish black discolouration over right thumb, necrosis, pus dischargeand stiffness, associated with difficulty in movement of right arm, shoulder joint, elbow joint, palm and fingers. Diagnosed as Right Upper Limb Ischemia with Diabetes Mellitus and active TB. Therapeutic interventions like Right upper limb Doppler and CT angiogram were done. Such a complicated case was taken at Sri Sri Ayurveda Hospital, and carefully handled by Ayurvedic methods of management, which was ended up by preventing amputation of the limb and also achieving the re-establishment of arterial circulation.


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