Marinakis, Sotirios; Ferrari, Enrico; Delay, Dominique; Tozzi, Piergiorgio; Berdajs, Denis; Niclauss, Lars; Rolf, Tanina; von Segesser, Ludwig Karl
From the Cardiovascular Surgery, CHUV, Lausanne, Switzerland.
Submitted for consideration November 2013; accepted for publication in revised form February 2014.
Disclosures: The authors have no conflicts of interest to report.
Reprint Requests: Sotirios Marinakis, MD, Rue Bugnon 21, CHUV, CH-1011 Lausanne, Switzerland. Email: email@example.com.
In extreme situations, such as hyperacute rejection of heart transplant or major heart trauma, heart preservation may not be possible. Our experimental team works on a project of peripheral extracorporeal membrane oxygenation (ECMO) support in acardia as a bridge to heart transplantation or artificial heart implantation. An ECMO support was established in five calves (58.6 ± 6.9 kg) by the transjugular insertion to the caval axis of a self-expanded cannula, with carotid artery return. After baseline measurements, ventricular fibrillation was induced, great arteries were clamped, heart was excised, and right and left atria remnants, containing pulmonary veins, were sutured together leaving an atrial septal defect over the caval axis cannula. Measurements of pump flow and arterial pressure were taken with the pulmonary artery clamped and anastomosed with the caval axis for a total of 6 hours. Pulmonary artery anastomosis to the caval axis provided an acceptable 6 hour hemodynamic stability, permitting a peripheral access ECMO support in extreme scenarios indicating a heart explantation.
Extracorporeal membrane oxygenation (ECMO) support has already proved its efficacy in cardiorespiratory support in acute cardiac failure.1,2 Moreover, ECMO has been used for perioperative cardiac allograft failure because of primary graft failure with an important mortality.3 In the present experimental study, we explored the feasibility of an ECMO support in acardia (after heart explantation) as a bridge to cardiac transplantation or implantation of an artificial heart. The practical application of such a decision would be situations where heart preservation is deleterious for survival (hyperacute rejection of heart transplant) or if salvage of the heart is impossible (major heart trauma, uncontrollable perioperative bleeding).4,5
Materials and Methods
Five bovine experiments (58.6 ± 6.9 kg) were performed under general anesthetic. For premedication, we used an intramuscular injection of 0.15 mg/kg of xylazine and 1 mg of atropine. We opted for a volatile general anesthetic using isoflurane 2–4% for induction and 1–2% for maintenance. Analgesia was assured by an intramuscular injection of meloxicam 0.2 mg/kg. Heart rhythm was recorded by continuous electrocardiographic monitoring until heart explantation. The left carotid artery and jugular vein were catheterized for continuous monitoring of arterial and central venous pressure (CVP). Right neck vessels were prepared for arteriovenous cannulation. Middle sternotomy was performed, and the great vessels were prepared for clamping. An ECMO support was established and baseline measurements on full flow, on beating heart, were registered, as follows: heart rate, maximal pump flow, mean arterial pressure (MAP), and CVP. Ventricular fibrillation was induced by an external fibrillator, and after 10 minutes, the above-mentioned measurements were registered. Afterward, we proceeded with the explantation of the heart, preserving the atria. Atria remnants, containing the pulmonary veins, were sutured together over the venous cannula in the caval axis. Air aspiration was avoided during the anastomosis by suspending the wall of atria remnants and by decreasing the pump flow to have the cannula in the caval axis covered with blood. The aorta was closed with a double running suture. Measurements were taken with the pulmonary artery (PA) clamped and anastomosed with the caval axis for a total of 6 hours (Figures 1 and 2). We performed the anastomosis of the PA to the caval axis with a partial clamping of the left auricle. De-airing was achieved by decreasing the pump flow before knotting. During both anastomoses, we used a single roller pump aspiration line connected in a semipermeable bag to reintroduce blood loss in the venous line.
Initial pump flow was 4.1 ± 0.8 L/min and MAP was 71.8 ± 19.7 mm Hg, dropping to 2.6 ± 0.9 L/min (p =0.014) and 32.6 ± 4.7 mm Hg (p = 0.008) 10 minutes after induction of ventricular fibrillation. After cardiectomy, with the PA clamped, pump flow raised not significantly to 3.4 ± 0.9 L/min while MAP augmented significantly to 54.2 ± 16.8 mm Hg (p = 0.046). Pulmonary artery anastomosis to the caval axis was followed by a significant increase in pump flow (3.9 ± 1.1 L/min) and MAP (64.2 ± 12.3 mm Hg). Pump flow and MAP remained stable throughout the 6 hours of hemodynamic support (Figures 3 and 4).
All continuous variables are expressed as mean ± 95% confidence intervals. The analysis of variance test for repeated measures was used to test the null hypothesis (H0) that the mean pump flow and the MAP were equal in the eight groups of perfusion status (Figures 3 and 4). We used a p = 0.05 as the level of significance in the design of our study. The null hypothesis was rejected with a value of significance p < 0.05, so we proceeded in the pairwise comparisons of the difference of the mean pump flow and the MAP in the eight groups using a two-way paired t-test. The pairwise comparison showed no difference in pump flow or in MAP between baseline measurements and measurements done after the anastomosis of the PA to the caval axis until the 6 hours of ECMO support. Statistical analysis was performed using IBM SPSS 20.0 (IBM Corp., Armonk, NY).
There are some rare clinical situations, such as hyperacute rejection of heart transplant, where heart explantation seems to be the only means of survival.4,5 Our experimental team has already shown that the drainage of pulmonary circulation is pivotal in maintaining pump flow in acardia.6 In our initial experiments, this was obtained by direct suction into the PA using an open circuit roller pump cardiopulmonary support. In these experiments, pulmonary circulation drainage was not enough only through pulmonary veins, which were included in our caval axis venous drainage. The pitfall of such a model was that cardiopulmonary support could be assured only with the use of a third cannula in the PA. In our new model, venting of pulmonary circulation was assured by the direct anastomosis of PA to the caval axis (Figure 2). This configuration permits an ECMO support in acardia through a peripheral vascular axis that has the advantage to permit the closure of the chest, which reduces infectious and bleeding complications in attendance of a heart transplant or the implantation of an artificial heart. The animals were kept on ECMO for a total of 6 hours after heart explantation to test the hemodynamic stability of our model.
Pulmonary circulation in an acardia model reflects only the left-to-right shunt of bronchial circulation (approximately 1% of cardiac output).7 When not sufficiently drained (clamped PA), we observed volume loss in pulmonary circulation and decrease in cardiac output during ECMO.6
Our results showed that the anastomosis of the PA to the caval axis ensures an excellent venting of pulmonary circulation, permitting an ECMO support through a peripheral vascular axis without the addition of any extra cannulas. In this model, the venous cannula drains the systemic return and the return of bronchial vessels to pulmonary circulation. The arterial cannula returns the oxygenated blood to the systemic circulation.
Our experimental model shows the feasibility of a peripheral access ECMO support after heart explantation with 6 hour hemodynamic stability. Further investigations should evaluate the long-term hemodynamic stability of this model and the pulmonary function after pulmonary reperfusion.
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7. Baile EM. The anatomy and physiology of the bronchial circulation. J Aerosol Med. 1996;9:1–6
ECMO; acardia; cardiac transplantation; artificial heart