Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.694257
Title: Thermal remodelling of the ectothermic heart
Author: Keen, Adam
ISNI:       0000 0004 5990 4733
Awarding Body: University of Manchester
Current Institution: University of Manchester
Date of Award: 2016
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Abstract:
Chronic changes in cardiac load can cause the vertebrate heart to remodel. For ectotherms, ambient temperature can directly alter cardiac load. Therefore, long-term ambient temperature change can initiate a dynamic cardiac remodelling response to preserve cardiac function. The aims of my PhD thesis were to study the effects of chronic temperature change on the ectothermic heart and cardiovascular system, using the cold-active rainbow trout and the cold-dormant freshwater turtle. In contrast to the majority of previous studies, my experiments focused on the passive, rather than active, properties of the heart. In results chapters 3, 4, 5 and 6, I studied the effects of thermal remodelling on the rainbow trout heart. Chronic cold caused a global increase in chamber stiffness, both at the whole chamber and micromechanical level, with an associated myocardial fibrosis. In the ventricle and atrium there was an up-regulation of collagen promoting genes. In the ventricle, I found cold-induced hypertrophy of the spongy myocardium with an up-regulation of hypertrophic growth factors, which was associated with an increase in tissue lipid suggesting an increase in fatty acid oxidation (FAO). In the atrium, there was no hypertrophy, but there was an increase in extra-bundular sinus, suggesting chronic dilation. Chronic warming initiated an opposite response, with increased cardiac compliance associated with an up-regulation of collagen degrading genes in the ventricle and atrium. In the outflow tract (OFT) and atrium, this increased activity of matrix metalloproteinase (MMPs) and in the OFT abundance of MMPs was increased. The warmed ventricle showed atrophy of the spongy myocardium with a decrease in lipid and an increase in glycogen suggesting a switch in cellular energetics from FAO to glycolytic pathways. In chapters 7, 8 and 9, I studied the effects of thermal remodelling on the freshwater turtle heart. I found an in vivo decrease in systemic resistance causing an increased right to left cardiac shunt flow, associated with an increased elastin content of the major outflow vessels. Cold acclimation increased cardiac sensitivity to preload as well as whole chamber passive stiffness and micromechanical stiffness of tissue sections, associated ventricular fibrosis and increased collagen coherency. In addition, chronic cold decreased the gelatinase activity of MMPs and increased mRNA expression of a tissue inhibitor of MMPs. Furthermore, chronic cold was associated with a decrease in tissue lipid and phosphates, but an increase in tissue protein, glycogen and lactate. These changes in tissue biochemistry suggest a switch in cellular energetics from FAO to glycolytic pathways, likely due to the decreased oxygen availability associated with winter inactivity. Overall, the chambers of the ectothermic heart show distinct remodelling phenotypes, which likely reflect their in cardiac function. Thermal remodelling of the fish ventricle serves both cardio-protection, from the haemodynamic strain of changes in cardiac preload and afterload, as well as compensation for the direct effects of temperature. In the turtle, changes in compliance and cellular energetics of the ventricle suggest a cardio-protective mechanism preparing the heart for increased haemodynamic stress and hypoxic or anoxic conditions during inactive winter hibernation.
Supervisor: Gardner, Peter ; Shiels, Holly Sponsor: BBSRC
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.694257  DOI: Not available
Keywords: Temperature acclimation ; Collagen ; Elastin ; Compliance ; Fourier transform infrared spectroscopy
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