Reproducibility of left atrial ablation with high-intensity focused ultrasound energy in a calf model

ObjectiveAchieving transmural tissue ablation might be necessary for successful treatment of atrial fibrillation. The purpose of this study was to evaluate the reproducibility of transmural left atrial ablation using a high-intensity focused ultrasound energy system in a calf model.MethodsNine heparinized bovines underwent a beating-heart left atrial ablation with a single application of the high-intensity focused ultrasound device. All animals were acutely killed, and the left atrium was fixed in formalin. Protocolized histological sections (5 μm) were obtained throughout each lesion and prepared with Masson trichrome and hematoxylin and eosin staining. Measurements were performed on a total of 359 slides from the 9 lesions. In addition, fresh left atrial tissues from 18 unused human donor hearts that did not meet the criteria for cardiac transplantation were measured at the site where the high-intensity focused ultrasound device is normally applied.ResultsCalf left atrial thickness ranged between 2.5 and 20.1 mm, with a mean of 9.10 mm. High-intensity focused ultrasound ablation consistently produced a 100% transmural lesion in left atrial thickness up to 6 mm. In addition, a transmural lesion was observed in 91% of tissues that were up to 10 mm thick and in 85% that were up to 15 mm thick. Human left atrial thickness ranged between 1.2 to 6 mm, with a mean of 3.7 mm.ConclusionsCalf left atrial thickness in this study was greater than human left atrial thickness. Human left atrial thickness is generally less than 6 mm, and in this range high-intensity focused ultrasound ablation achieved 100% transmurality. These histological results might correlate with a high success rate of atrial fibrillation ablation by using the high-intensity focused ultrasound system

Modified ultrafiltration improves cerebral metabolic recovery after circulatory arrest

AbstractModified ultrafiltration uses hemofiltration of the patient and bypass circuit after separation from cardiopulmonary bypass to reverse hemodilution and edema. This study investigated the effect of modified ultrafiltration on cerebral metabolic recovery after deep hypothermic circulatory arrest. Twenty-six 1-week-old piglets (2 to 3 kg) were supported by cardiopulmonary bypass (37° C) at 100 ml · kg-1 · min-1 and cooled to 18° C. Animals underwent 90 minutes of circulatory arrest followed by rewarming to 37° C. After being weaned from cardiopulmonary bypass, animals were divided into three groups: controls ( n = 10); modified ultrafiltration for 20 minutes ( n = 9); transfusion of hemoconcentrated blood for 20 minutes ( n = 7). Global cerebral blood flow was measured by xenon 133 clearance methods: stage I--before cardiopulmonary bypass; stage II—5 minutes after cardiopulmonary bypass; and stage III—25 minutes after cardiopulmonary bypass. Cerebral metabolic rate of oxygen consumption, cerebral oxygen delivery, and hematocrit value were calculated for each time point. At point III, the hematocrit value (percent) was elevated above baseline in the ultrafiltration and transfusion groups (44 ± 1.8, 42 ± 1.8 versus 28 ± 1.7, 30 ± 0.7, respectively, p < 0.05). Cerebral oxygen delivery (ml · 100 gm-1 · min-1 ) increased significantly above baseline at point III after ultrafiltration (4.98 ± 0.32 versus 3.85 ± 0.16, p < 0.05) or transfusion (4.59 ± 0.17 versus 3.89 ± 0.06, p < 0.05) and decreased below baseline in the control group (2.77 ± 0.19 versus 3.81 ± 0.16, p < 0.05). Ninety minutes of deep hypothermic circulatory arrest resulted in impaired cerebral metabolic oxygen consumption (ml · 100 gm-1 · min-1 ) at point III in the control group (1.95 ± 0.15 versus 2.47 ± 0.07, p < 0.05) and transfusion group (1.72 ± 0.10 versus 2.39 ± 0.15, p < 0.05). After modified ultrafiltration, however, cerebral metabolic oxygen consumption at point III had increased significantly from baseline (3.12 ± 0.24 versus 2.48 ± 0.13, p < 0.05), indicating that the decrease in cerebral metabolism immediately after deep hypothermic circulatory arrest is reversible and may not represent permanent cerebral injury. Use of modified ultrafiltration after cardiopulmonary bypass may reduce brain injury associated with deep hypothermic circulatory arrest. (J THORAC CARDIOVASC SURG 1995;109:744-52

T Cell Repertoire Maturation Induced by Persistent and Latent Viral Infection Is Insufficient to Induce Costimulation Blockade Resistant Organ Allograft Rejection in Mice

CD28:CD80/86 pathway costimulation blockade (CoB) with the CD80/86-specific fusion protein CTLA4-Ig prevents T cell-mediated allograft rejection in mice. However, in humans, transplantation with CoB has been hampered by CoB-resistant rejection (CoBRR). CoBRR has been attributed in part to pathogen-driven T cell repertoire maturation and resultant heterologous alloreactive memory. This has been demonstrated experimentally in mice. However, prior murine models have used viral pathogens, CoB regimens, graft types, and/or antigen systems atypically encountered clinically. We therefore sought to explore whether CoBRR would emerge in a model of virus-induced memory differentiation designed to more closely mimic clinical conditions. Specifically, we examined mouse homologs of clinically prevalent viruses including murine polyomavirus, cytomegalovirus, and gammaherpesvirus 68 in the presence of clinically relevant maintenance CoB regimens using a fully MHC-mismatched, vascularized allograft model. Infected mice developed a significant, sustained increase in effector memory T cells consistent with that seen in humans, but neither developed heterologous alloreactivity nor rejected primarily vascularized heterotopic heart transplants at an increased rate compared with uninfected mice. These results indicate that memory acquisition alone is insufficient to provoke CoBRR and suggest that knowledge of prior latent or persistent viral infection may have limited utility in anticipating heterologous CoB-resistant alloimmunity

Elevated Cardiac Troponin I in Preservation Solution Is Associated With Primary Graft Dysfunction

Although primary graft dysfunction (PGD) is a leading cause of mortality and morbidity early post-heart transplant, relatively little is known regarding mechanisms involved in PGD development. We examined the relationship between cardiac troponin I (cTnI) concentrations in the preservation solution from 43 heart transplant procedures and the development of PGD. Donor hearts were flushed with cold preservation solution (University of Wisconsin [UW] or Custodiol) and stored in the same solution. cTnI concentrations were measured utilizing the i-STAT System and normalized to left ventricular mass. Recipient medical records were reviewed to determine PGD according to the 2014 ISHLT consensus conference. Nineteen patients developed PGD following cardiac transplantation. For both UW and Custodiol, normalized cTnI levels were significantly increased (P = .031 and .034, respectively) for those cases that developed PGD versus no PGD. cTnI levels correlated with duration of ischemic time in the UW group, but not for the Custodiol group. Donor age and donor cTnI (obtained prior to organ procurement) did not correlate with preservation cTnI levels in either UW or Custodiol. Increased preservation solution cTnI is associated with the development of PGD suggesting preservation injury may be a dominant mechanism for the development of PGD