h_kaishi
Online edition:ISSN 2758-089X

Turtle spongious ventricles exhibit more compliant diastolic property and possess larger elastic regions of connectin in comparison to rat compact left ventricles

There is growing evidence that ventricular diastolic dysfunction is a major pathological factor in heart failure. Although many basic and clinical studies have been reported, there is little information available about the comparative and evolutionary aspects of the diastolic properties of vertebrate ventricles. Cardiac tissues in extant vertebrates are roughly divided into two types; compact myocardium in mammals and aves, and spongious myocardium in amphibians and some of reptilians. Here we compared the mechanical properties of both whole ventricles and the biochemical properties of isolated cardiomyocytes (including intracelluar Ca2+ ([Ca2+]i) handling, and the lengths of elastic regions of connectin, a protein that determines elasticity of cardiomyocytes) between spongious ventricles of turtles (Trachemys scripta elegans) and compact ventricles of Wister rats. Ventricular diastolic function is composed of active relaxation and passive compliance. We investigated ventricular compliance by analyzing normalized end-diastolic pressure-volume relationship (EDPVR) of diastolic-arrested ventricles to compare different-sized hearts and ventricular relaxation by determining logistic time constants of pressure decay. We measured [Ca2+]i handling using isolated cardiomyocytes. Stiffness constants obtained from exponential curve fitting were significantly larger in rat left ventricles (LVs) compared with turtle ventricles (99.0 ± 7.3 and 2.07 ± 0.62, respectively) showing that rat LVs were much stiffer than turtle ventricles. Normalization of EDPVRs revealed that the turtle ventricle and rat LV exhibit species-specific characteristics in ventricular compliance. At the cellular level, the initial normalized stiffness of rat cardiomyocytes (8.03 ± 1.33 kPa) was 2.8 times higher than in those of the turtle (2.82 ± 0.38 kPa), showing that turtle cardiomyocytes were much more compliant than those of rats. With respect to relaxation, the time constant of isovolumic relaxation in the rat LV pressuretime curve was significantly smaller than that in turtle ventricles (10.7 ± 0.96 and 67.4 ± 3.55 ms, respectively), resulting in early-phase-dominant ventricular filling patterns in rats. The time to peak [Ca2+]i and the decay time after peak [Ca2+]i in turtle cardiomyocytes were significantly longer than in rat. The numbers of amino acids of the PEVK domain of connectin, which is enriched in proline, glutamic acid, valine and lysine and encodes a random coil shown to be an important region in the passive elasticity of connectin were 821 and 204 in turtle and rat ventricles, respectively. These results suggest that vertebrate hearts have been becoming less compliant at the ventricle, cardiomyocyte, and molecular levels during the course of evolution. One possible physiological meaning of restricted compliance in rat ventricles could be related to a well-developed coronary circulation, because the less compliant mechanical properties of the ventricle are largely advantageous to preserve diastolic-dominant coronary arterial flow by preventing excessive ventricular expansion. Future research aimed at understanding the regulatory mechanisms of cardiac connectin among vertebrates may contribute to the investigation of the therapeutic potential of diastolic heart failure. doi:10.11482/KMJ-E44(1)1 (Accepted on February 14, 2018)

著者名
Honda T, et al
44
1
1-17
DOI
10.11482/KMJ-E44(1)1
掲載日
2018.5.10

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