The Physiological Function of Cardiac Shunting in Crocodilians: An Experimental Approach

鳄鱼心脏分流的生理功能：实验方法

• 批准号: 0445680
• 负责人: James Hicks
• 金额: $ 60.09万
• 依托单位: University of California-Irvine
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0445680&HistoricalAwards=false
• 关键词: Physiological; Function; Cardiac; Shunting; Crocodilians

The primary function of the cardiovascular system is to provide adequate oxygen and nutrients to the tissues, while ensuring the removal of carbon dioxide and other metabolic waste products. In vertebrates this goal is achieved through circulatory and cardiac designs that are often represented as an evolutionary progression from the two-chambered heart of fish to the completely divided four-chambered heart of birds and mammals. The completely divided four-chambered heart has evolved at least twice in vertebrates, once in the lineage that gave rise to mammals and once in ancestral archosaurs, the ancient group of reptiles that gave rise to modern birds and crocodiles. In crocodilians, the heart is four-chambered, just like birds and mammals, but retains two aortae (vessels that transport blood to the body). The left aorta arises from the right ventricle, alongside the pulmonary artery and consequently this anatomical arrangement results in the potential for oxygen poor blood to bypass the lungs and recirculate to the body. This type of blood flow is termed a right-to-left (R-L) cardiac shunt. This unique circulatory feature of crocodilians has been known for over 170 years and is often assumed to provide important physiological benefits. However few, if any, of these benefits have been experimentally verified. Here the PI will investigate the functional consequences of R-L cardiac shunting in the American alligator, Alligator mississippiensis, and in the broad-nose caiman, Caiman latirostris. The physiological functions of R-L cardiac shunting will be determined following surgical modification of the heart. The surgical procedure removes the left aorta and permanently eliminates the capacity for R-L cardiac shunt. In one set of experiments the hearts of hatchling alligators will be surgically modified and raised under controlled environmental conditions in the vivarium facilities at UC Irvine. In a second set of experiments, the hearts of hatchling caimans will be modified and the animals raised in semi-natural outdoor facilities in Rio Claro, Brazil. Animals will be measured periodically and at the end of a 12-18 month growth period a variety of physiological functions will be assessed. A third series of experiments will determine the physiological functions of R-L cardiac shunting in older animals. In these experiments, both alligators and caimans will be collected from the field, the hearts surgically modified and the effects of eliminating R-L cardiac shunt on a variety of physiological functions will be determined. The proposed research will form an integrated picture of the interactive functioning of the cardiovascular system and more importantly will addresses a notable and unanswered question in comparative biology vertebrate-what is the physiological function of R-L cardiac shunting in crocodilians? In addition to the specific scientific goals, the proposed research will directly contribute to the training of individuals in how to investigate and integrate complex biological systems. The project will provide undergraduates, graduates and postdoctoral fellows, a framework within which to think in terms of biological diversity, evaluate and consider environmental influences, and place research results within developmental and/or evolutionary trajectories. The integrative nature of the proposed research and the resulting training of students and postgraduate researchers will, in general, make a positive and lasting contribution to the health and strength of physiological sciences- a health and strength that is required to insure significant advances in the physiological sciences during the 21st century.

心血管系统的主要功能是为组织提供足够的氧气和营养，同时确保二氧化碳和其他代谢废物的清除。在脊椎动物中，这一目标是通过循环和心脏设计实现的，这些设计通常被表示为从鱼类的两室心脏到鸟类和哺乳动物的完全分离的四室心脏的进化过程。完全分裂的四腔心脏在脊椎动物中至少进化了两次，一次是在起源哺乳动物的谱系中，另一次是在始祖龙身上，始祖龙是一种古老的爬行动物群体，产生了现代鸟类和鳄鱼。鳄鱼的心脏是四腔的，就像鸟类和哺乳动物一样，但保留了两根主动脉(将血液输送到身体的血管)。左主动脉起自右心室，与肺动脉并排，因此这种解剖排列导致缺氧血液有可能绕过肺，再循环到身体。这种类型的血流称为从右向左(R-L)心脏分流。鳄鱼的这种独特的循环功能已经被人们知道了170多年，通常被认为提供了重要的生理益处。然而，这些益处中很少有(如果有的话)得到实验验证的。在这里，PI将研究R-L心脏分流在美洲扬子鳄和宽鼻凯曼的心脏分流中的功能后果。R-L心脏分流术的生理功能将在心脏手术后确定。手术切除左主动脉，永久消除R-L心脏分流能力。在一组实验中，幼年扬子鳄的心脏将被手术改造，并在加州大学欧文分校的间隔室设施中受控的环境条件下饲养。在第二组实验中，幼崽凯门鳄的心脏将被改造，并在巴西里奥克拉罗的半自然户外设施中饲养。动物将被定期测量，在12-18个月的生长期结束时，将评估各种生理功能。第三系列实验将确定R-L心脏分流术在老年动物中的生理功能。在这些实验中，将从野外采集扬子鳄和凯门鳄，对心脏进行手术修饰，并测定消除R-L心脏分流对各种生理功能的影响。这项拟议的研究将形成心血管系统相互作用功能的综合图景，更重要的是将解决脊椎动物比较生物学中一个值得注意和尚未回答的问题-R-L心脏分流在鳄鱼中的生理功能是什么？除了具体的科学目标外，拟议的研究还将直接有助于培训个人如何调查和整合复杂的生物系统。该项目将为本科生、毕业生和博士后研究员提供一个框架，在这个框架内思考生物多样性，评估和考虑环境影响，并将研究成果置于发展和/或进化轨迹中。总的来说，拟议研究的综合性以及由此对学生和研究生研究人员的培训将对生理科学的健康和力量做出积极和持久的贡献--这种健康和力量是确保21世纪生理科学取得重大进展所必需的。