Single ventricle: amphibians and human beings

Abstract

Survival to adult life in patients born with "functionally" single ventricle, without any surgical treatment, as natural history, is extremely rarely reported [1][2][3][4][5][6][7]. In general, these group of patients with "functionally" single ventricle are symptomatic from the first weeks of life, and require two to three staged operations to obtain that the single ventricle pumps the oxygenated blood to the systemic circulation, while the less oxygenated blood is deviated by gravity from the superior and inferior vena cava directly to the lungs [1,8,9]. The result of this artificial "Fontan circulation" is high systemic venous pressure, and the chronic elevation of the systemic venous pressure may results in liver failure, renal failure, protein-losing enteropathy, and plastic bronchitis [10][11][12][13][14][15][16][17]. As a consequence, the long-term surgical outcomes of these patients are complicated by the combination of heart failure and cyanosis, substantially reducing their life expectancy and severely compromising their quality of life [10][11][12][13][14][15][16][17][18][19]. Mathematical and computational fluid dynamic models were used to study the blood flow distribution in single ventricle [20,21], and a better design of circulation, altering the traditional surgical options [22]. Research could greatly benefit from studies performed on animals born with single ventricle, even if the only animal models available in nature are amphibians, like axolotl salamander (Ambystoma mexicanum) [7] and frogs (Xenopus laevis) [23,24], and reptiles.These experimental studies on amphibians, performed with echocardiography and cardiac magnetic resonance imaging, revealed that salamanders and frogs have two elements in common in their double inlet form of single ventricle: intact interatrial septum and excessively trabeculated ventricular chamber.

The Functioning of the Frog’s Single Ventricle

“…However, this finding need be validated in a larger sample. Similarities between the anatomical and physiological findings in frogs and other amphibians and the few reported cases with single ventricle who survived until adult age without surgery have already been proposed [12][13][14][15][16][17]40,41,54]. The presence of intact interatrial septum, preventing any blood mixing at atrial level, may explain why, in the absence of complete mixing in the single ventricular chamber, the amphibians can live unrestrictive long life.…”

“…A large spectrum of ventricular architectural organization exists in nature, suitable for the lives of various animals, with different cardiac working requirements and performance [40]. Some animal's characteristics include to run quite fast while having have large bodies (vertebrates, mammals), while others are mostly sedentary with small bodies (like salamanders) or only intermittently jump (like frogs).…”

“…Experimental research studies on animals born with single ventricle would be potentially useful, but the only animal models with single ventricle available in nature are amphibians like frogs (Xenopus Laevis) and salamanders and reptiles [37][38][39][40][41][42][43][44][45][46][47][48]. Xenopus Laevis (African clawed frog) have a single ventricular chamber providing the systemic and pulmonary circulation, receiving the oxygenated blood returning from the lungs via the left atrium and the less saturated blood returning from the body via the right atrium.…”

Narrative review of single ventricle: where are we after 40 years?

“…Traditionally, potential new surgical approaches were first experimented on animals, despite the difficulties of modeling single ventricle circulation and the various surgical stages in animals born with two ventricles and separate pulmonary and systemic circulations (287)(288)(289)(290)(291). As a result, many comparative studies focused on animals born with single ventricle physiology, such as amphibians, like axolotl salamanders (Ambystoma mexicanum) (292), frogs (Xenopus laevis) (293)(294)(295), and reptiles, who live unrestricted lifestyle for many years. In frogs and salamanders, the two circulations fuse at the level of single ventricle, splitting at the pulmonary and systemic arterial branches, and the amount of blood flow distributed between pulmonary and systemic circulations is determined by the ratio of the peripheral resistances in the two territories.…”

“…Genetic studies of animal hearts with single ventricle is become increasingly important in understanding the relationship between morphology and cardiac function ( 295 ). Moreover, the underlying molecular signals responsible for the adaptive tissue responses seen in other species may be useful in our understanding of post-operative complications and the discovery of novel strategies to prevent them.…”