Experimentally modified Fontan circulation in an adolescent pig model without the use of cardiopulmonary bypass

Background

During the past 4 decades, the Fontan operation has been performed for the surgical treatment of children with congenital heart disease in which repair into a 2-ventricle system was impossible [1].

The Fontan operation can be performed by a number of variants. Currently, the most acceptable methods are the extracardiac conduit and the lateral tunnel total cavopulmonary connection techniques, both being accepted for their hemodynamic supremacy [2–4].

The ideal age at which a patient should undergo a Fontan operation remains controversial; however, the best post-surgical results were achieved when the operation was performed from the age of 7 months, where the increased cyanosis and the deterioration of the hemodynamic parameters rendered the operation absolutely necessary [5].

Today, over 40 years since the first use of the Fontan operation [1], the perioperative mortality has decreased significantly, and is stabilized at around 5% [6]. Factors contributing to the improvement of survival from the surgical procedure include the more energy efficient circulation obtained after the application of total cavopulmonary connection techniques [2]. Moreover, the limited duration of cross-clamping of the aortic root, and the decrease in the use of extracorporeal circulation, have both contributed to the better surgical outcome. Mair et al. reported an increase in survival over the “surgical era”, with the most recent patient cohort having improved survival and decreased perioperative mortality compared to those patients in the 2 prior decades. The survival rates 5, 10 and 15 years after surgery have increased, and are 86%, 81% and 73%, respectively [7]. An important finding, from the socioeconomic aspect, is that many of those patients with a Fontan operation had, and continue to enjoy, a long and high quality of life [4,8].

The establishment of the Fontan circulation in an adolescent pig experimental model is extremely difficult, a fact ultimately supported by the very few experimental studies reported in the English literature [9–16]. The present study tested the feasibility of performing the Fontan operation on an animal model, using a modified technique of an extracardiac total cavopulmonary connection (TCPC), without the support of cardiopulmonary bypass or other means of temporary bypass during the performance of the anastomoses. Furthermore, we evaluated acute hemodynamic changes for a period of 1 hour after the completion of the surgical procedure, and its effects on the cardiovascular system when the pulmonary blood flow is switched from normal circulation to Fontan circulation.

Material and Methods

STATISTICAL ANALYSIS:

All hemodynamic data were processed by SPSS 10 (IBM Co, U.S.A.) and expressed as mean ±SD. Results were evaluated using a paired Student t test, and differences of all recorded data before and after the Fontan circulation were considered to be significant at the level of p<0.05.

Results

CARDIAC OUTPUT AND HEART RATE CORRELATION BEFORE AND AFTER THE ESTABLISHMENT OF FONTAN CIRCULATION:

Although heart rate sustained at sinus rhythm, it dropped significantly after the completion of Fontan circulation. In addition, cardiac output decreased significantly after the establishment of Fontan circulation. The above results were expressed on an orthogonal coordinate system in order to determine if there was a linear relation between the decrease of heart rate and cardiac output. No linear relation was found between these parameters (Figure 3).

Pulmonary vascular resistance was calculated as: PVR = (PAP-LAP)/CO. It was increased significantly from 3.56±0.25 Wood’s units at the control stage to 6.22±0.70 Wood’s units when Fontan circulation was established (p<0.05).

Systemic vascular resistance was calculated as: SVR = (MAP – RAP)/CO, where RAP is the right atrial pressure. In the Fontan circulation, RAP was substituted by pulmonary arterial pressure. No significant changes were noticed in the SVR between the baseline and after the Fontan circulation (11.62±0.86 Wood’s units vs. 16.56±1.68 Wood’s units, respectively).

Discussion

The experimental establishment of a total cavopulmonary connection, modified by the interposition of an artificial graft between the 2 vena cavae (end-to-end anastomosis) and the pulmonary artery (end-to-side anastomosis), on a beating heart without the use of extracorporeal circulation, has never before been described in the literature. Experimental data from the present study prove that although this procedure is demanding for an experienced cardiovascular surgeon, it is, however, feasible.

Haller et al. first described an experimental right heart bypass [9]. Years later, other investigators attempted to perform experimental Fontan circulation in animal models [10,11]. After the establishment of total cavopulmonary connection with the use of an extracardiac conduit (2), new experimental studies were conducted using modifications of this method [12,13]. Several investigators have successfully established the Fontan circulation without the use of extracorporeal circulation [13–16].

Nawa et al. constructed a Y-shaped artificial conduit, with the end-to-side anastomosis of 2 separate conduits. They inserted and advanced the upper and lower ends of the conduit to the superior and inferior caval veins, respectively, performing only 1 end-to-side anastomosis of the other upper end of the conduit to the pulmonary trunk [13]. Kaku et al. performed end-to-side anastomosis of the graft to the caval veins using Satinsky vascular clamps [14]. Haneda et al. interimposed an artificial conduit between the right atrium and the main pulmonary artery. Under temporary clamping of the caval veins, they placed a purse-string suture around the tricuspid annulus, which was driven out through the right atrium via a tourniquet. With this technique it was possible to alter volume flow characteristics of the Fontan circulation repeatedly by changing the degree of tricuspid valve stenosis every time [15]. Szabo et al. managed to introduce 2 polyethylene cannulas into the superior and inferior caval veins, and a third one into the distal main pulmonary artery [16].

In the present experimental study, the cavopulmonary bypass was achieved based on the experience gained from the extensive use of the extracardiac conduit techniques, mainly in the Fontan operation [2]. This technique takes into consideration the rheometry of blood in this particular anatomic area. The diameters of the conduits were similar to those of the superior and the inferior vena cavae [18]. Furthermore, with this technique anastomoses were performed by suturing the graft to the caval veins, rather than inserting the graft intraluminally [13,16]. Although a number of difficulties arose with this technique, its ability to maintain a higher volume of blood flowing from the caval veins to the pulmonary artery is a clear advantage. The size of the anastomotic area between the pulmonary artery and the graft was large enough not to interfere with blood volume flow.

The success of this surgical procedure entirely depends on the experience of the surgeon, with the most critical part of the experiment being the anastomosis of the graft to the inferior vena cava. During that period of time, the animals presented with severe hemodynamic instability. Some degree of hemodynamic compromise developed, also, during the anastomosis of the graft to the superior vena cava. To support the animals during these parts of the procedure, crystalloid and colloid fluids were infused, and 3 animals needed inotropic support. Once the anastomoses were completed and the right ventricle was decompressed, the animals were considered to be hemodynamically stable. From our pilot studies we concluded that decompression was imperative for the animals to survive.

The hemodynamic changes after the completion of the surgical procedure were significant. With the establishment of Fontan circulation, and through the 1-hour observation period, significant decreases in mean arterial pressure, mean pulmonary pressure, cardiac output, and heart rate were observed. In addition, a significant increase was noticed in pulmonary resistance and in inferior caval pressure, with only borderline changes in left atrial pressure and systemic vascular resistance.

The recorded hemodynamic parameters confirmed the Fontan paradox; thus, the existence of venous hypertension coexists with hypotension in the pulmonary artery [4]. It must be emphasized that the experimental model described by the aforementioned parameters was hemodynamically stable and free from inotropic support. Furthermore, although the heart rate in the Fontan state decreased significantly, it remained in sinus rhythm.

The pressure in the inferior vena cava was considerably increased, which is in accordance with findings by Nawa et al. [13]. The surgical protocol applied by Haneda et al. [15] allowed pressure measurement in the right atrium, which correlated well with the central venous pressure. Left atrial pressure, in the present study, showed a mild, non-significant decrease, in agreement with the experimental results of Haneda et al. [15]. Nawa et al. and de Leval showed that left atrial pressure originally had a tendency to increase, then decrease, and finally return to a normal level [4,13,16,19]. Cardiac output, as was found in previous studies, displayed a significant decrease in all cases [12,13,15,16].

Systemic arterial resistance in our study demonstrated a relative increase, which was nearly statistically significant. Szabo et al. and Mace et al. found an increase in systemic arterial pressure, as well as in total vascular resistance [12,16], in contrast to data from Haneda et al., where the systemic vascular resistance presented a non-significant decrease [15]. An important finding in our study was the increased pulmonary resistance, which is in accordance with the results of Haneda et al. and Szabo et al. [15,16].

Hypoperfusion in the pulmonary capillary vasculature is responsible for the pulmonary hypertension, and consequently for the increased pulmonary vascular resistance, according to Haneda et al. De Leval considers these findings impressive, and questions whether patients having undergone a Fontan operation should be treated with medication to control pulmonary resistance [16]. In addition, the creation of a fenestration (a technique allowing systemic venous blood to shunt to the left atrium) seems to improve the preload, and indirectly assist with the above problem.

Due to the complex requirement for single-ventricle cardiac anatomy, a chronic animal model of unsupported Fontan physiology has never been produced. Myers et al. managed to achieve 24-hour stability by maintaining pulmonary perfusion and low systemic venous pressure by the use of a device in an animal model [20]. We believe that a modification in the cardiac anatomy of a swine model may permit the creation of a chronic Fontan circulation pattern. Moreover, the fenestration technique may be applied and hemodynamic, and other biochemical parameters could be continuously measured in order to study the experimental Fontan circulation more extensively. Furthermore, coronary blood flow patterns may be studied based on other animal model protocols [21].

In the design of this experimental protocol there are a few limitations that should be considered. It is important to report that all animals used in the present study were healthy and free from any congenital heart diseases such as tricuspid atresia or univentricular heart condition. All experiments were acute, with a short survival period, and performed on animals with an open thoracic cavity, which might modify some hemodynamic parameters such as the venous blood return [4].

Conclusions

This study demonstrates the feasibility of a total cavopulmonary connection on a beating heart, without the use of circulatory support or bypass. This was achieved by the modified use of an appropriate size Y-shaped conduit connecting and draining the superior and inferior caval veins (end-to-end anastomosis) to the pulmonary trunk (end-to-side anastomosis). The obtained hemodynamic data confirmed the known Fontan paradox. The surgical procedure is challenging for a vascular or cardiac surgeon and requires extensive experience. Chronic survival experiments are needed to understand the physiology of the Fontan circulation and the plethora of hemodynamic questions arising from it.