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

心血管系统的主要功能是为组织提供充足的氧气和营养，同时确保清除二氧化碳和其他代谢废物。 在脊椎动物中，这一目标是通过循环和心脏设计来实现的，这些设计通常表现为从鱼类的两室心脏到鸟类和哺乳动物的完全分开的四室心脏的进化过程。 完全分开的四室心脏在脊椎动物中至少进化了两次，一次是在产生哺乳动物的谱系中，一次是在祖先祖龙中，这是一种古老的爬行动物，产生了现代鸟类和鳄鱼。 鳄鱼的心脏与鸟类和哺乳动物一样，有四个腔室，但保留了两个血管（将血液输送到身体的血管）。 左主动脉从右心室产生，与肺动脉并排，因此这种解剖学布置导致贫氧血液绕过肺并再循环到身体的可能性。 这种类型的血流被称为右向左（R-L）心脏分流。 鳄鱼的这种独特的循环功能已经被发现超过170年，并且通常被认为提供重要的生理益处。 然而，这些好处很少（如果有的话）得到实验验证。 在这里，PI将调查美国短吻鳄，密西西比短吻鳄，和宽鼻凯门鳄，宽吻凯门鳄的R-L心脏分流的功能后果。 R-L心脏分流的生理功能将在心脏手术修改后确定。 外科手术切除了左主动脉，永久性地消除了R-L心脏分流的能力。 在一组实验中，刚孵化的短吻鳄的心脏将被手术改造，并在加州大学欧文分校的动物园设施中在受控的环境条件下饲养。 在第二组实验中，凯门鳄的心脏将被改造，这些动物将在巴西里奥克拉罗的半天然户外设施中饲养。 将定期测量动物，并在12-18个月生长期结束时评估各种生理功能。 第三系列实验将确定老年动物R-L心脏分流的生理功能。 在这些实验中，鳄鱼和凯门鳄都将从现场收集，心脏手术修改和消除R-L心脏分流对各种生理功能的影响将被确定。拟议的研究将形成心血管系统的互动功能的综合图片，更重要的是将解决一个显着的和未回答的问题，在比较生物学脊椎动物-什么是鳄鱼的R-L心脏分流的生理功能？ 除了具体的科学目标，拟议的研究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，研究生和博士后研究员提供一个框架，在此框架内思考生物多样性，评估和考虑环境影响，并将研究结果置于发展和/或进化轨迹中。总体而言，拟议研究的综合性质以及由此产生的学生和研究生研究人员的培训将为生理科学的健康和力量做出积极和持久的贡献-这是确保21世纪世纪生理科学重大进步所必需的健康和力量。

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.