NADPH oxidase overexpression and mitochondrial OxPhos impairment are more profound in human hearts donated after circulatory death than brain death.

This study investigated cardiac stress and mitochondrial oxidative phosphorylation (OxPhos) in human donation after circulatory death (DCD) hearts regarding warm ischemic time (WIT) and subsequent cold storage and compared them with that of human brain death donor (DBD) hearts. A total of 24 human hearts were procured for the research study-6 in the DBD group and 18 in the DCD group. DCD group was divided into three groups (n = 6) based on different WITs (20, 40, and 60 min). All hearts received del Nido cardioplegia before being placed in normal saline cold storage for 6 h. Left ventricular biopsies were performed at hours 0, 2, 4, and 6. Cardiac stress [nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits: 47-kDa protein of phagocyte oxidase (p47phox), 91-kDa glycoprotein of phagocyte oxidase (gp91phox)] and mitochondrial oxidative phosphorylation [OxPhos, complex I (NADH dehydrogenase) subunit of ETC (CI)-complex V (ATP synthase) subunit of ETC (CV)] proteins were measured in cardiac tissue and mitochondria respectively. Modulation of cardiac stress and mitochondrial dysfunction were observed in both DCD and DBD hearts. However, DCD hearts suffered more cardiac stress (overexpressed NADPH oxidase subunits) and diminished mitochondrial OxPhos than DBD hearts. The severity of cardiac stress and impaired oxidative phosphorylation in DCD hearts correlated with the longer WIT and subsequent cold storage time. More drastic changes were evident in DCD hearts with a WIT of 60 min or more. Activation of NADPH oxidase via overproduction of p47phox and gp91phox proteins in cardiac tissue may be responsible for cardiac stress leading to diminished mitochondrial oxidative phosphorylation. These protein changes can be used as biomarkers for myocardium damage and might help assess DCD and DBD heart transplant suitability.NEW & NOTEWORTHY First human DCD heart research studied cardiac stress and mitochondrial dysfunction concerning WIT and the efficacy of del Nido cardioplegia as an organ procurement solution and subsequent cold storage. Mild to moderate cardiac stress and mitochondrial dysfunction were noticed in DCD hearts with WIT 20 and 40 min and cold storage for 4 and 2 h, respectively. These changes can serve as biomarkers, allowing interventions to preserve mitochondria and extend WIT in DCD hearts.

Myocardial edema, inflammation, and injury in human heart donated after circulatory death are sensitive to warm ischemia and subsequent cold storage.

BACKGROUND: Single-dose del Nido solution was recently used in human donation after circulatory death (DCD) heart procurement. We compared the effect of del Nido cardioplegia on myocardial edema, inflammatory response, and injury in human DCD hearts and human donation after brain death (DBD) hearts with different warm ischemic times (WIT) and subsequent cold saline storage times (CST). METHODS: A total of 24 human hearts, including 6 in the DBD group and 18 in the DCD group-were procured for the research study. The DCD group was divided into 3 subgroups based on WIT: 20, 40, and ≥60 minutes. All hearts received 1 L of del Nido cardioplegia before being placed in cold saline for 6 hours. Left ventricular biopsies were performed at 0, 2, 4, and 6 hours. Temporal changes in myocardial edema, inflammatory cytokines (TNF-α, IL-6, and IL-1ß), and histopathology injury scores were compared between the DBD and DCD groups. RESULTS: DCD hearts showed more profound changes in myocardial edema, inflammation, and injury than DBD hearts at baseline and subsequent CST. The DCD heart with WIT of 20 and 40 minutes with CST of 4 and 2 hours, respectively, appeared to have limited myocardial edema, inflammation, and injury. DCD hearts with WIT ≥60 minutes showed severe myocardial edema, inflammation, and injury at baseline and subsequent CST. CONCLUSIONS: Single-dose cold del Nido cardioplegia and subsequent cold normal saline storage can preserve both DCD and DBD hearts. DCD hearts have been shown to be able to tolerate a WIT of 20 minutes and subsequent CST of 4 hours without experiencing significant myocardial edema, inflammation, and injury.

Effect of intraoperative support mode on circulating inflammatory biomarkers after lung transplantation surgery.

BACKGROUND: Processes that activate the immune system during lung transplantation can lead to primary graft dysfunction (PGD) or allograft rejection. METHODS: We analyzed cytokine expression profiles after reperfusion and allograft outcomes in a cohort of patients (n = 59) who underwent lung transplantation off-pump (n = 26), with cardiopulmonary bypass (CPB; n = 18), or with extracorporeal membrane oxygenation (ECMO; n = 15). Peripheral blood was collected from patients at baseline and at 6 and 72 h after reperfusion. To adjust for clinical differences between groups, we utilized a linear mixed model with overlap weighting. RESULTS: PGD3 was present at 48 or 72 h after reperfusion in 7.7% (2/26) of off-pump cases, 20.0% (3/15) of ECMO cases, and 38.9% (7/18) of CPB cases (p = 0.04). The ECMO and CPB groups had greater reperfusion-induced increases in MIP-1B, IL-6, IL-8, IL-9, IL1-ra, TNF-alpha, RANTES, eotaxin, IP-10, and MCP-1 levels than the off-pump group. Cytokine expression profiles after reperfusion were not significantly different between ECMO and CPB groups. CONCLUSION: Our data suggest that, compared with an off-pump approach, the intraoperative use of ECMO or CPB during lung transplantation is associated with greater reperfusion-induced cytokine release and graft injury.

Neurological outcomes and cure rates of embolization of brain arteriovenous malformations with n-butyl cyanoacrylate or Onyx: a meta-analysis.

BACKGROUND: In the past decade, preoperative endovascular embolization of cerebral arteriovenous malformations (AVMs) became an essential tool in the treatment of these entities. With the current expansion of technology and wide incorporation of new devices, the indications for the use of endovascular embolization have expanded to include embolization for cure. This has been facilitated by the wide use of the new liquid embolic agents (ethylene-vinyl alcohol co-polymer (EVOH)) in addition to n-butyl cyanoacrylate (NBCA). The aim of this study was to review the current published literature for these two agents and report on permanent neurological injuries and cure rate. METHODS: Published literature citing embolization results for AVMs using liquid embolic agents was reviewed. Papers reporting on permanent complication rates and complete angiographic cure were reviewed. A meta-analysis was performed based on these two variables for the two embolic agents. RESULTS: 103 studies met the selection criteria. Poor neurological outcomes for NBCA and EVOH were 5.2% and 6.8%, respectively (OR 1.4; p=0.56). AVM complete obliteration rate was seen in 13.7% in the NBCA group and in 24% in the EVOH group (OR 1.9). This OR decreased to 1.35 in the subgroup analysis for patients treated after the year 2000. CONCLUSIONS: NBCA continues to have a trend towards lower permanent complication rates, but EVOH had higher angiographic cure rates. The recent literature has demonstrated an increase in the cure rate of AVMs with endovascular embolization techniques yet with a possible increase in permanent neurological deficits and mortality.

Virtual reality cerebral aneurysm clipping simulation with real-time haptic feedback.

BACKGROUND: With the decrease in the number of cerebral aneurysms treated surgically and the increase of complexity of those treated surgically, there is a need for simulation-based tools to teach future neurosurgeons the operative techniques of aneurysm clipping. OBJECTIVE: To develop and evaluate the usefulness of a new haptic-based virtual reality simulator in the training of neurosurgical residents. METHODS: A real-time sensory haptic feedback virtual reality aneurysm clipping simulator was developed using the ImmersiveTouch platform. A prototype middle cerebral artery aneurysm simulation was created from a computed tomographic angiogram. Aneurysm and vessel volume deformation and haptic feedback are provided in a 3-dimensional immersive virtual reality environment. Intraoperative aneurysm rupture was also simulated. Seventeen neurosurgery residents from 3 residency programs tested the simulator and provided feedback on its usefulness and resemblance to real aneurysm clipping surgery. RESULTS: Residents thought that the simulation would be useful in preparing for real-life surgery. About two-thirds of the residents thought that the 3-dimensional immersive anatomic details provided a close resemblance to real operative anatomy and accurate guidance for deciding surgical approaches. They thought the simulation was useful for preoperative surgical rehearsal and neurosurgical training. A third of the residents thought that the technology in its current form provided realistic haptic feedback for aneurysm surgery. CONCLUSION: Neurosurgical residents thought that the novel immersive VR simulator is helpful in their training, especially because they do not get a chance to perform aneurysm clippings until late in their residency programs.