What Is the Purpose of the Embryonic Heart Beat? or How Facts Can Ultimately Prevail over Physiological Dogma

Abstract

Embryonic physiology is often viewed as merely those processes understood for the adult but conducted on a smaller physical scale. Yet striking examples of the inaccuracy of this perspective can be identified in the embryonic cardiovascular system. For example, dogma holds that the embryonic heart begins to beat to pump blood for convective transport, just like that of the adult. This is the major assumption inherent in the hypothesis we have called "convective synchronotropy"; that is, the embryonic heart starts to beat synchronously with the need for convective blood flow. However, there is compelling evidence on many fronts that the convective flow of blood generated by the early embryonic vertebrate heart is simply not required for transport of oxygen, nutrients, metabolic wastes, or hormones, all of which can be achieved entirely by diffusion. In fact, fish, amphibian, and bird embryos lacking a functional heart (either through surgical intervention or mutation) or whose oxygenhemoglobin transport has been chemically eliminated nonetheless continue to function and grow in size for extended periods up to the point at which diffusion alone can no longer serve oxygen transport needs. We advocate the alternative hypothesis of "prosynchronotropy" (i.e., the heart starts to beat well before convective blood flow is needed for bulk transport). So, what is the purpose of the early embryonic heart beat? Evidence is presented herein in support of a morphogenic rationale for prosynchronotropy. Specifically, it appears that the initial rationale for the beat of the vertebrate embryonic heart may be two-fold: to aid in subtle but significant aspects of cardiac growth, shaping, and maturation, and to facilitate cardiac maturation angiogenesis-the formation of new vessels by sprouting from vessel tips. Ultimately, the embryonic cardio-*

Reduced Heart Rate and Cardiac Output Differentially Affect Angiogenesis, Growth, and Development in Early Chicken Embryos (Gallus domesticus)

“…Yet embryonic growth, assessed by wet and dry weight, is significantly reduced. These findings are important in light of the fact that the convective flow of blood is not required for continued oxygen consumption or development at these same developmental stages (Burggren et al 2000;Burggren 2004). This study indicates that convective blood flow is indeed required for absolute growth of the embryo.…”

“…Angiogenesis results from a complex combination of genetically directed morphogenesis and the influence of local environmental factors, both biochemical and mechanical (e.g., Jones et al 2006;Lee et al 2009;Adams and Eichmann 2010;Buschmann et al 2010;Kaunas et al 2011;Knudsen and Kleinstreuer 2011;Heinke et al 2012;Burggren 2013). Chief among the mechanical influences are both blood pressure and flow (Isogai et al 2003;le Noble et al 2008).…”

“…This independence of development and growth from convective blood flow occurs because diffusion provides adequate mass transport during early embryo development. Eventually, a combination of escalating gas exchange and nutrient demands, coupled with increasing diffusion distances of the growing embryo, necessitates the development of an active internal convective blood flow (for review, see Burggren 2004).…”

“…An as yet untested hypothesis is that the initial beating of the heart is not for material transport but rather to provide the pulsatile pressure and flow-and the attendant circumferential stretch and shear stresses-in the peripheral circulation as a necessary stimulant for angiogenesis in the early embryo (Burggren 2004). The hypothesis of prosynchronotropy has recently been refined to that of synangiotropy, namely, that blood pressure and flow appear just in time for the need for angiotropy rather than bulk transport (Burggren 2013). To test this hypothesis, this study used the purely bradycardic drug ZD7288 to induce chronic bradycardia in the chicken embryo from 72 to 120 h of development.…”

Guest Editorial: Special Issue on Fetal Hemodynamics

“…His data suggest that the one function of the early pulsatile embryonic heart is to stimulate angiogenesis by creating cyclic shear/strain on the endothelial linings of sprouting vessels rather than the transport of respiratory gases and nutrients. 4 Johnson et al…”