**6.5 XVIVO nonischemic heart preservation device**

Rather than perfusing the donor heart beating, with warm solutions using OCS, a Nonischemic Heart Preservation Device (NIHP) is a portable device that perfuses the heart continuously with hypothermic, oxygenated cardioplegia containing blood mixed with a nutrient-hormone solution. XVIVO (**Figure 3**) serves as a mini-cardiopulmonary bypass circuit consists of an oxygenator, roller pump, heat exchanger, filter and reservoir. The XVIVO consists of the XVIVO Sterile Heart Disposable kit, the XVIVO heart box and the XVIVO supplemented solution. The heart box controls the solution's temperature set at 8° C. The mixed O2/CO2 gas flow is supplied to the solution and perfused by the coronary arteries with the control of pressure and flow limits. The sterile disposable kit consists of the tubing, the gas connectors, the pump, pressure and temperature sensors. Machine priming for XVIVO heart preservation system (XVIVO Inc., Gothenburg, Sweden) consists of 2.5 L of supplemented XVIVO heart solution mixed with 500 ml of washed, irradiated leucocyte-depleted red blood cells to achieve a hematocrit of 15%. Heart solution additives consist of sodium bicarbonate, insulin, unfractionated heparin, potassium and imipenem or equivalent broad-spectrum antibiotics. The ascending aorta is cannulated, and connected to the disposable kit then the heart is submerged into a reservoir. The donor heart receives continuous hypothermic oxygenated blood to maintain aortic root pressure at 20 mmHg with 150–250 ml/min of coronary flow in a static, non-beating state [38, 39].

Animal studies have demonstrated the safety of using XVIVO to preserve a porcine heart for 24 hours with at least 8 hours of preserved contractile function and endothelial integrity of the coronary arteries [40–42]. Myocardial contractility and endothelium have been shown to be preserved up to 24 hours with a nonischemic heart preservation device [40].

A nonrandomized phase 2 trial compared six donor hearts perfused with XVIVO and 25 donor hearts perfused with standard cold storage with a median organ preservation time of 223 min in XVIVO and 194 min in the standard cold storage group. The study demonstrated excellent outcomes in XVIVO group with 100% major event-free

#### **Figure 3.**

*The XVIVO heart preservation system, the heart is submerged in the cold oxygenated perfusion solution in a protective reservoir. Pressure-controlled pump is used to control the perfusion pressure during perfusion of the heart. The system has integrated sensors that monitor real-time flows, pressures, and temperatures. The picture has been adapted by permission of XVIVO perfusion, Inc.*

survival at 6 months (including primary graft dysfunction within 24 hours, need for ECMO within 7 days or acute rejection >2R) compared to 72% major event-free survival in the standard cold storage cohort [38].

XVIVO was used for organ preservation in the first successful pig-to-human transplant by a team at the University of Maryland School of Medicine on January 7, 2022 [43, 44]. Further studies of the XVIVO should be evaluated and compared among the OCS and static cold storage to demonstrate itself as a feasible alternative preservation method. Moreover, this device should be evaluated on extended criteria donors [39].
