A well-developed heart is essential for embryonic survival. There are constant interactions between cardiac tissue motion and blood flow, which determine the heart shape itself. Hemodynamic forces are a powerful stimulus for cardiac growth and differentiation. Therefore, it is particularly interesting to investigate how the blood flows through the heart and how hemodynamics is linked to a particular species and its development, including human. The appropriate patterns and magnitude of hemodynamic stresses are necessary for the proper formation of cardiac structures, and hemodynamic perturbations have been found to cause malformations via identifiable mechanobiological molecular pathways. There are significant differences in cardiac hemodynamics among vertebrate species, which go hand in hand with the presence of specific anatomical structures. However, strong similarities during development suggest a common pattern for cardiac hemodynamics in human adults. In the human fetal heart, hemodynamic abnormalities during gestation are known to progress to congenital heart malformations by birth. In this chapter, we discuss the current state of the knowledge of the prenatal cardiac hemodynamics, as discovered through small and large animal models, as well as from clinical investigations, with parallels gathered from the poikilotherm vertebrates that emulate some hemodynamically significant human congenital heart diseases.

• Keywords
• Axolotl, Chick embryo, DORV, Developing myocardium, ET1, Embryogenesis, Endothelin 1, Fetal heart, Guinea pig, HLHS, Hemodynamics, Hyperplasia, Hypertrophy, Hypoplastic left heart syndrome, KLF2, Krüppel-like factor 2, Lamb, Mouse, NOS3, Nitric oxide synthase 3, Pressure overload, Rat, Reptile, VSD, Volume overload, Zebrafish,
• MeSH
• Hemodynamics * physiology   MeSH
• Humans MeSH
• Heart * growth & development   physiology   MeSH
• Heart Defects, Congenital physiopathology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Valvular heart disease leads to ventricular pressure and/or volume overload. Pressure overload leads to fibrosis, which might regress with its resolution, but the limits and details of this reverse remodeling are not known. To gain more insight into the extent and nature of cardiac fibrosis in valve disease, we analyzed needle biopsies taken from the interventricular septum of patients undergoing surgery for valve replacement focusing on the expression and distribution of major extracellular matrix protein involved in this process. Proteomic analysis performed using mass spectrometry revealed an excellent correlation between the expression of collagen type I and III, but there was little correlation with the immunohistochemical staining performed on sister sections, which included antibodies against collagen I, III, fibronectin, sarcomeric actin, and histochemistry for wheat germ agglutinin. Surprisingly, the immunofluorescence intensity did not correlate significantly with the gold standard for fibrosis quantification, which was performed using Picrosirius Red (PSR) staining, unless multiplexed on the same tissue section. There was also little correlation between the immunohistochemical markers and pressure gradient severity. It appears that at least in humans, the immunohistochemical pattern of fibrosis is not clearly correlated with standard Picrosirius Red staining on sister sections or quantitative proteomic data, possibly due to tissue heterogeneity at microscale, comorbidities, or other patient-specific factors. For precise correlation of different types of staining, multiplexing on the same section is the best approach.

• Keywords
• Collagen, Fibronectin, Fibrosis, Pressure overload, Valvular heart disease,
• MeSH
• Aortic Valve Insufficiency metabolism   pathology   surgery   MeSH
• Aortic Valve Stenosis * metabolism   pathology   surgery   MeSH
• Extracellular Matrix Proteins * metabolism   analysis   MeSH
• Fibrosis * metabolism   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Ventricular Septum pathology   metabolism   MeSH
• Aged MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Extracellular Matrix Proteins * MeSH

BACKGROUND: Hypoplastic left heart syndrome (HLHS) is a rare but deadly form of human congenital heart disease, most likely of diverse etiologies. Hemodynamic alterations such as those resulting from premature foramen ovale closure or aortic stenosis are among the possible pathways. METHODS: The information gained from studies performed in the chick model of HLHS is reviewed. Altered hemodynamics leads to a decrease in myocyte proliferation causing hypoplasia of the left heart structures and their functional changes. CONCLUSIONS: Although the chick phenocopy of HLHS caused by left atrial ligation is certainly not representative of all the possible etiologies, it provides many useful hints regarding the plasticity of the genetically normal developing myocardium under altered hemodynamic loading leading to the HLHS phenotype, and even suggestions on some potential strategies for prenatal repair.

• Keywords
• embryonic myocardium, hemodynamic alteration, left atrial ligation, left ventricular hypoplasia, myocyte proliferation,
• Publication type
• Journal Article MeSH
• Review MeSH