The effect of pulsatile versus non-pulsatile flow during cardiopulmonary bypass on cerebral oxygenation: A randomized trial

Background The present study aims to compare regional oxygen supply determined by Near-Infrared Spectroscopy in the course of pulsatile perfusion with non-pulsatile perfusion during cardiopulmonary bypass in patients undergoing valvular heart surgery. Methods In this prospective randomized single-blinded trial, we enrolled adult subjects aged 18–65 years scheduled for elective valvular heart repair/replacement surgery with non-stenotic carotid arteries, employing a consecutive sampling method. Eligible patients were then randomly assigned in a 1:1 ratio to pulsatile or non-pulsatile perfusion during aortic cross-clamp. The primary outcome was regional cerebral oxygenation monitored by Near-Infrared Spectroscopy in each group. Results Seventy patients were randomly assigned, and each group comprised 35 patients. Mean age was 46.8 and 46.5 years in pulsatile and non-pulsatile groups, respectively. There were no significant between-group differences in regional cerebral oxygen saturation at different time points of cardiopulmonary bypass ( p-value for analysis of variance repeated measures: 0.923 and 0.223 for left and right hemispheres, respectively). Moreover, no significant differences in regional cerebral oxygen saturation levels from baseline between pulsatile and non-pulsatile groups at all desired time points for the left ( p = 0.51) and right ( p = 0.22) hemispheres of the brain were detected. Conclusion Pulsatile perfusion during cardiopulmonary bypass does not offer superior regional cerebral oxygenation measured by Near-Infrared Spectroscopy than non-pulsatile perfusion during cardiopulmonary bypass. Nonetheless, the efficacy of pulsatile flow in the subgroup of patients in whom cerebral blood flow is impaired due to carotid artery stenosis needs to be explored and evaluated by this method in future studies.

Engineering Functional Vasculature in Decellularized Lungs Depends on Comprehensive Endothelial Cell Tropism

Tissue engineering using decellularized whole lungs as matrix scaffolds began as a promise for creating autologous transplantable lungs for patients with end-stage lung disease and can also be used to study strategies for lung regeneration. Vascularization remains a critical component for all solid organ bioengineering, yet there has been limited success in generating functional re-endothelialization of most pulmonary vascular segments. We evaluated recellularization of the blood vessel conduits of acellular mouse scaffolds with highly proliferating, rat pulmonary microvascular endothelial progenitor cells (RMEPCs), pulmonary arterial endothelial cells (PAECs) or microvascular endothelial cells (MVECs). After 8 days of pulsatile perfusion, histological analysis showed that PAECs and MVECs possessed selective tropism for larger vessels or microvasculature, respectively. In contrast, RMEPCs lacked site preference and repopulated all vascular segments. RMEPC-derived endothelium exhibited thrombomodulin activity, expression of junctional genes, ability to synthesize endothelial signaling molecules, and formation of a restrictive barrier. The RMEPC phenotype described here could be useful for identifying endothelial progenitors suitable for efficient vascular organ and tissue engineering, regeneration and repair.

Preimplantation Histological Score Associates with 6-Month GFR in Recipients of Perfused, Older Kidney Grafts: Results from a Pilot Study

<b><i>Background:</i></b> Biopsy-guided selection of older kidneys safely expands the organ pool, and pretransplant perfusion improves the preservation of these fragile organs. Herein, we studied morphofunctional variables associated with graft outcomes in perfused, histologically evaluated older kidneys. <b><i>Methods:</i></b> This single-center prospective cohort pilot study evaluated the relationships between preimplantation histologic scores and renal perfusion parameters during hypothermic, pulsatile, machine perfusion (MP) and assessed whether these morphofunctional parameters associated with GFR (iohexol plasma clearance) at 6 months after transplantation in 20 consecutive consenting recipients of a biopsy-guided single or dual kidney transplant from &#x3e;60-year-old deceased donors. <b><i>Results:</i></b> The donor and recipient age was 70.4 ± 6.5 and 63.6 ± 7.9 years (<i>p</i> = 0.005), respectively. The kidney donor profile index (KDPI) was 93.3 ± 8.4% (&#x3e;80% in 19 cases), histologic score 4.4 ± 1.4, and median (IQR) cold ischemia time 19.8 (17.8–22.8 h; &#x3e;24 h in 5 cases). The 6-month GFR was 41.2 (34.9–55.7) mL/min. Vascular resistances positively correlated with global histologic score (<i>p</i> = 0.018) at MP start and then decreased from 0.88 ± 0.43 to 0.36 ± 0.13 mm Hg/mL/min (<i>p</i> &#x3c; 0.001) in parallel with a three-fold renal flow increase from 24.0 ± 14.7 to 74.7 ± 31.8 mL/min (<i>p</i> &#x3c; 0.001). Consistently, vascular resistance reductions positively correlated with global histologic score (<i>p</i> = 0.009, <i>r</i> = −0.429). Unlike KDPI or vascular resistances, histologic score was independently associated with 6-month GFR (beta standardized coefficient: −0.894, <i>p</i> = 0.005). <b><i>Conclusions:</i></b> MP safely improves graft perfusion, particularly in kidneys with severe histologic changes that would not be considered for transplantation because of high KDPI. The preimplantation histologic score associates with the functional recovery of older kidneys even in the context of a standardized program of pulsatile perfusion.

Evaluating the translational value of postmortem brain reperfusion technology

A novel pulsatile-perfusion technology, dubbed BrainEx, has been shown to restore microcirculation and cellular functions in the pig brain, 4 h postmortem. This technology has generated enthusiasm for its translational value for human neuroresuscitation. I offer a critical analysis of the study and its methodology, providing several reasons for skepticism. This includes: all phenomena were observed at different degrees of hypothermia; the physiological and biochemical milieu of the experimental preparation is radically different than the clinical setting of hypoxic-ischemic brain injury; and the study is confounded by uncontrolled traumatic brain injury and lifelong stress in all the animals.