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【medical-news】澳大利亚研究人员解密心脏猝死的“门控”

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Scientists Unlock the 'Gates' on Sudden Cardiac Death
ScienceDaily (Jan. 27, 2011) — Australian researchers have come one step closer to understanding how the rhythm of the heartbeat is controlled and why many common drugs, including some antibiotics, antihistamines and anti-psychotics, can cause a potentially fatal abnormal heart rhythm.
It is estimated around 40-50% of all drugs in development will block one of the main 'channels' that carries electricity in the heart and, as a result, can cause heart rhythm problems called cardiac arrhythmias. Most sudden cardiac deaths are caused by cardiac arrhythmias.
Since 1996, nine drugs have been withdrawn from the market or had their use severely restricted due to this serious side effect.
In a paper published in this month's edition of the journal Nature Structural and Molecular Biology, Victor Chang Institute in Sydney have discovered a key clue as to why this happens, by understanding how the 'gates,' which effectively 'open' and 'close' the channel, operate.
"Just like a set of metal wires that carry electricity to light up our streets, our body has a series of channels that carry tiny charged particles called ions, into and out of cells, to trigger a heartbeat," said Professor Jamie Vandenberg, Head of the Cardiac Electrophysiology Laboratory at the Victor Chang Institute.
"Depending on the position of these gates, many common drugs bind, or attach themselves to these channels, blocking the ions from passing through. This causes what we call Long QT syndrome, where the length of the heart beat is longer than usual, which greatly increases the risk of arrhythmia."
The group of drugs most commonly associated with this side effect are anti-psychotic drugs, taken by patients with schizophrenia and other psychiatric disorders. Patients taking these drugs are up to three times more likely to die of sudden cardiac death due to an abnormal heart rhythm.
The team of researchers, led by Professor Vandenberg, studied the hERG potassium channel, an ion channel that determines how long each heart beat lasts and the channel which is most susceptible to being 'blocked' by drugs.
"The hERG channel is a particularly 'sticky' channel, in that most drugs will bind to it when the outer gate is closed. What we've done is to discover how these outer gates operate, in the hope that we can then design drugs more effectively to minimise the unwanted side effects," said Professor Vandenberg.
"The gates to this channel operate in a much more complex way than was previously thought -- much like a Japanese puzzle box, they require a series of complicated, interrelated movements to open them. It is not simply a matter of lifting and shutting a lid as was commonly believed," says Professor Vandenberg.
The team suspects this 'gate mechanism' will also apply to other channels that are important in the heart's electrical system, as well as those that control electrical communication in the brain.
"The biggest benefit of this research is that it should allow the better design of drugs so they no longer block these important electrical channels in the heart," added Professor Vandenberg. "In time, this should allow patients the freedom and peace of mind to take their medication without the fear of their heart suddenly stopping."
http://www.sciencedaily.com/releases/2011/01/110128095049.htm

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2011-01-31 11:45 浏览 : 1258 回复 : 7

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2011-02-02 23:34

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Scientists Unlock the 'Gates' on Sudden Cardiac Death
科学家解开心脏猝死“门控”
ScienceDaily (Jan. 27, 2011) — Australian researchers have come one step closer to understanding how the rhythm of the heartbeat is controlled and why many common drugs, including some antibiotics, antihistamines and anti-psychotics, can cause a potentially fatal abnormal heart rhythm.
科学日报（2011年1月27日）-----澳大利亚研究人员已经更进一步的了解到心跳的节率是如何控制的？以及为什么很多常用药物，包括一些抗生素，抗组胺药及抗精神病药能导致潜在致死性心律失常。
It is estimated around 40-50% of all drugs in development will block one of the main 'channels' that carries electricity in the heart and, as a result, can cause heart rhythm problems called cardiac arrhythmias. Most sudden cardiac deaths are caused by cardiac arrhythmias.
Since 1996, nine drugs have been withdrawn from the market or had their use severely restricted due to this serious side effect.
根据评估，这些药物中约40-50%可发展为心脏中一种主要的“通道”（其可携带心脏的电信号）的阻滞剂，可以导致心脏节律的出现问题，称为心律失常。多数心脏猝死的患者均为心律失常引发。自1996年以来，有9种药物因其可导致这类严重的副作用退市或严格限制其使用。
In a paper published in this month's edition of the journal Nature Structural and Molecular Biology, Victor Chang Institute in Sydney have discovered a key clue as to why this happens, by understanding how the 'gates,' which effectively 'open' and 'close' the channel, operate.
本月刊登在《自然结构和分子生物学》杂志上的一篇论文中，悉尼的已经发现了通过了解此“门”有效的“开放”和“关闭”该通道的运转机制，揭示了此现象的关键线索。
"Just like a set of metal wires that carry electricity to light up our streets, our body has a series of channels that carry tiny charged particles called ions, into and out of cells, to trigger a heartbeat," said Professor Jamie Vandenberg, Head of the Cardiac Electrophysiology Laboratory at the Victor Chang Institute.
“正如一组金属线，其可运输电流来点亮我们的街道，我们的身体有一系列的通道，岂可携带小的带电分子称为离子，进出细胞内外，触发我们的心跳。”Jamie Vandenberg教授（Victor Chang协会心脏电生理实验室的主管），
"Depending on the position of these gates, many common drugs bind, or attach themselves to these channels, blocking the ions from passing through. This causes what we call Long QT syndrome, where the length of the heart beat is longer than usual, which greatly increases the risk of arrhythmia."
“依靠这些门的位置，很多常用的凝结或粘附在这些通道内，阻滞离子的通过。这可导致所谓的长Q-T综合症。此时心律的长度较正常时延长，可大大增加心律失常的风险。”
The group of drugs most commonly associated with this side effect are anti-psychotic drugs, taken by patients with schizophrenia and other psychiatric disorders. Patients taking these drugs are up to three times more likely to die of sudden cardiac death due to an abnormal heart rhythm.
这组药物多数常伴有该副作用的是抗精神病药物，用于精神分裂及其他精神疾病。服用这类药物的患者发生心律失常所导致的心脏性猝死的几率高出三倍。
The team of researchers, led by Professor Vandenberg, studied the hERG potassium channel, an ion channel that determines how long each heart beat lasts and the channel which is most susceptible to being 'blocked' by drugs.
Vandenberg所领导的研究小组，研究了hERG钾通道，此通道决定每次心跳的持续时间，其最易于受到这些药物的“阻滞”。
"The hERG channel is a particularly 'sticky' channel, in that most drugs will bind to it when the outer gate is closed. What we've done is to discover how these outer gates operate, in the hope that we can then design drugs more effectively to minimise the unwanted side effects," said Professor Vandenberg.
“hERG通道时是格外“粘滞”的通道，当输出门关闭的时候，这类药物多会粘滞其中，我们所做的就是发现这些输出门是如何运转的，因而有望研究出更有效的减低这些不良副作用的药物” Vandenberg教授说.
"The gates to this channel operate in a much more complex way than was previously thought -- much like a Japanese puzzle box, they require a series of complicated, interrelated movements to open them. It is not simply a matter of lifting and shutting a lid as was commonly believed," says Professor Vandenberg.
“该通道门的运转方式比我们预想的复杂的多-----更像个日本迷箱，需要一系列复杂的，相互关联的活动来打开它们，并不是我们通常所想的只是提起来和关闭一个盖子那么简单。” Vandenberg教授说.
The team suspects this 'gate mechanism' will also apply to other channels that are important in the heart's electrical system, as well as those that control electrical communication in the brain.
"The biggest benefit of this research is that it should allow the better design of drugs so they no longer block these important electrical channels in the heart," added Professor Vandenberg. "In time, this should allow patients the freedom and peace of mind to take their medication without the fear of their heart suddenly stopping."
这个小组怀疑此门的运转机制也将适用于对心脏电系统有重要作用的的其他通道。也包括脑组织中电传递的控制。“此研究最大的收益是：将使设计出更好的不再阻滞这些心脏重要的电通道的药物成为可能。” Vandenberg教授补充道“同时，也会使服用这些药物的患者自由、安心的服用，而不必担心它们的心脏会突然停跳”

2011-02-04 21:45

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科学家解开心脏猝死“门控”科学日报（2011年1月27日）-----澳大利亚研究人员已经更进一步的了解到心跳的节率是如何控制的？以及为什么很多常用药物，包括一些抗生素，抗组胺药及抗精神病药能导致潜在致死性心律失常。根据评估，这些药物中约40-50%可发展为心脏中一种主要的“通道”（其可携带心脏的电信号）的阻滞剂，可以导致心脏节律的出现问题，称为心律失常。多数心脏猝死的患者均为心律失常引发。自1996年以来，有9种药物因其可导致这类严重的副作用退市或严格限制其使用。本月刊登在《自然结构和分子生物学》杂志上的一篇论文中，悉尼的已经发现了通过了解此“门”有效的“开放”和“关闭”该通道的运转机制，揭示了此现象的关键线索。
“正如一组金属线，其可运输电流来点亮我们的街道，我们的身体有一系列的通道，岂可携带小的带电分子称为离子，进出细胞内外，触发我们的心跳。”Jamie Vandenberg教授（Victor Chang协会心脏电生理实验室的主管），
“依靠这些门的位置，很多常用的凝结或粘附在这些通道内，阻滞离子的通过。这可导致所谓的长Q-T综合症。此时心律的长度较正常时延长，可大大增加心律失常的风险。”这组药物多数常伴有该副作用的是抗精神病药物，用于精神分裂及其他精神疾病。服用这类药物的患者发生心律失常所导致的心脏性猝死的几率高出三倍。
Vandenberg所领导的研究小组，研究了hERG钾通道，此通道决定每次心跳的持续时间，其最易于受到这些药物的“阻滞”。
“hERG通道时是格外“粘滞”的通道，当输出门关闭的时候，这类药物多会粘滞其中，我们所做的就是发现这些输出门是如何运转的，因而有望研究出更有效的减低这些不良副作用的药物” Vandenberg教授说.
“该通道门的运转方式比我们预想的复杂的多-----更像个日本迷箱，需要一系列复杂的，相互关联的活动来打开它们，并不是我们通常所想的只是提起来和关闭一个盖子那么简单。” Vandenberg教授说.
这个小组怀疑此门的运转机制也将适用于对心脏电系统有重要作用的的其他通道。也包括脑组织中电传递的控制。“此研究最大的收益是：将使设计出更好的不再阻滞这些心脏重要的电通道的药物成为可能。” Vandenberg教授补充道“同时，也会使服用这些药物的患者自由、安心的服用，而不必担心它们的心脏会突然停跳”

2011-02-04 21:47

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