The impact of temperature in aortic arch surgery patients receiving antegrade cerebral perfusion for >30 minutes: How relevant is it really?

OBJECTIVE: We examined the early outcomes and the long-term survival associated with different degrees of hypothermia in patients who received antegrade cerebral perfusion (ACP) for >30 minutes. METHODS: During a 10-year period, 544 consecutive patients underwent proximal and total aortic arch surgery and received ACP for >30 minutes and 1 of 3 levels of hypothermia: deep (14.1°C-20°C; n = 116 [21.3%]), low-moderate (20.1°C-23.9°C; n = 262 [48.2%]), and high-moderate (24°C-28°C; n = 166 [30.5%]). A variable called "predicted temperature" was used in propensity-score analysis. Multivariate analysis was done to evaluate the effect of actual temperature on outcomes. RESULTS: The operative mortality rate was 12.5% (n = 68) overall and was 15.5%, 11.8%, and 11.5% in the deep, low-moderate, and high-moderate hypothermia patients, respectively (P = .54). The persistent stroke rate was 6.6% overall and 12.2%, 4.6%, and 6.0% in these 3 groups, respectively (P = .024 on univariate analysis). On multivariate analysis, actual temperature was not associated with mortality, but lower temperatures predicted persistent stroke and reoperation for bleeding. In the propensity-matched subgroups, the patients with predicted deep hypothermia had (nonsignificantly) greater rates of persistent stroke (12.2% vs 4.9%; relative risk, 1.08; 95% CI, 0.87-1.15) and reoperation for bleeding (14.6% vs 2.4%; relative risk, 1.14; 95% CI, 0.87-1.15) than the patients with predicted moderate hypothermia. On long-term follow-up (mean duration, 5.12 years), 4- and 8-year survival rates were 62.3% and 55.7% in the deep hypothermia group and 75.4% and 74.2% in the moderate hypothermia group (P = .0015). CONCLUSIONS: In proximal and arch operations involving ACP for >30 minutes, greater actual temperatures were associated with less stroke and reoperation for bleeding. There were no significant differences among the predicted hypothermia levels, although a trend toward a higher rate of adverse events was noticed in the deep hypothermia group. Long-term survival was better in the moderate hypothermia group.

Total aortic arch replacement: A comparative study of zone 0 hybrid arch exclusion versus traditional open repair.

OBJECTIVE: We attempted to identify predictors of adverse outcomes after traditional open and hybrid zone 0 total aortic arch replacement. METHODS: We performed multivariable analysis using 16 variables to identify predictors of adverse outcomes (mortality, permanent neurologic events, and permanent renal failure necessitating hemodialysis) in 319 consecutive patients who underwent total aortic arch replacement in the past 8.5 years and a subgroup analysis in 25 propensity-matched pairs. A total of 274 patients (85.9%) had traditional open repair, and 45 patients (14.1%) had hybrid zone 0 total arch exclusion. RESULTS: Operative mortality was 10.3% (n = 33): 11.1% (n = 5) in the hybrid group and 10.2% (n = 28) in the traditional group (P = .79). A total of 19 patients (5.9%) had permanent stroke (15 traditional [5.5%] vs 4 hybrid [8.9%]; P = .32), and 2 patients (both traditional) had permanent paraplegia (P = 1.00). The hybrid group had more total neurologic events (P = .051) but not more permanent strokes (P = .32). Prior cardiac disease unrelated to the aorta (P = .0033) and congestive heart failure (P = .0053) independently predicted permanent adverse outcome (operative mortality, permanent neurologic event, or permanent renal failure). Concomitant coronary artery bypass grafting independently predicted permanent stroke (P = .032), as did previous cerebrovascular disease (P = .032). In multivariable analysis, procedure type (hybrid or traditional) was not an independent predictor of stroke (P = .09). During a median follow-up of 4.5 years (95% confidence interval, 3.9-4.9), survival was 78.7%, with no intergroup difference (P = .14). CONCLUSIONS: Among contemporary cases, both traditional and hybrid total aortic arch replacement had acceptable results. Comparing these 2 different surgical treatment options is challenging, and an individualized approach offers the best results. Permanent adverse outcome was not significantly different between the 2 groups. Procedure type is not an independent predictor of permanent stroke. Prior cardiac disease, past or current smoking, and congestive heart failure predict adverse outcomes for total aortic arch replacement.

Acute and chronic deficits in the urinary bladder after spinal contusion injury in the adult rat.

Traumatic spinal cord injury (SCI) permanently alters bladder function in humans. Hematuria and cystitis occur in both human SCI as well as in rodent models of SCI. Others have reported early SCI-dependent disruption to bladder uroepithelial integrity that results in increased permeability to urine and urine-borne substances. This can result in cystitis, or inflammation of the bladder, an ongoing pathological condition present throughout the chronic phase of SCI in humans. The goals of our study were twofold: (1) to begin to examine the inflammatory and molecular changes that occur within the bladder uroepithelium using a clinically-relevant spinal contusion model of injury, and (2) to assess whether these alterations continue into the chronic phase of SCI. Rats received either moderate SCI or sham surgery. Urine was collected from SCI and sham subjects over 7 days or at 7 months to assess levels of excreted proteins. Inflammation in the bladder wall was assessed via biochemical and immunohistochemical methods. Bladder tight junction proteins, mediators of uroepithelial integrity, were also measured in both the acute and chronic phases of SCI. Urine protein and hemoglobin levels rapidly increase following SCI. An SCI-dependent elevation in numbers of neutrophils within the bladder wall peaked at 48 h. Bladder tight junction proteins demonstrate a rapid but transient decrease as early as 2 h post-SCI. Surprisingly, elevated levels of urine proteins and significant deficits in bladder tight junction proteins could be detected in chronic SCI, suggesting that early pathological changes to the bladder may continue throughout the chronic phase of injury.

Double homozygous waltzer and Ames waltzer mice provide no evidence of retinal degeneration.

PURPOSE: To determine whether cadherin 23 and protocadherin 15 can substitute for one another in the maintenance of the retina and other tissues in the mouse. Does homozygosity for both v and av mutant alleles (i.e., a double homozygous mouse) cause retinal degeneration or an obvious retinal histopathology? METHODS: We generated mice homozygous for both Cdh23(v-6J) and Pcdh15(av-Jfb) alleles. The retinal phenotypes of double heterozygous and double homozygous mutant mice were determined by light microscopy and electroretinography (ERG). Histology on 32 different tissues, scanning electron microscopy of organ of Corti hair cells as well as serum biochemical and hematological examinations were evaluated. RESULTS: ERG waves of double heterozygous and double homozygous mice showed similar shape, growth of the amplitude with intensity, and implicit time for both rod and cone pathway mediated responses. Mice homozygous for both Cdh23(v-6J) and Pcdh15(av-Jfb) mutations showed no sign of retinitis pigmentosa or photoreceptor degeneration but, as expected, were deaf and had disorganized hair cell sensory bundles. CONCLUSIONS: The simultaneous presence of homozygous mutant alleles of cadherin 23 and protocadherin 15 results only in deafness, not retinal degeneration or any other additional obvious phenotype of the major organ systems. We conclude that in the mouse cadherin 23 or protocadherin 15 appear not to compensate for one another to maintain the retina.

Ames Waltzer deaf mice have reduced electroretinogram amplitudes and complex alternative splicing of Pcdh15 transcripts.

PURPOSE: Mutations of PCDH15, the gene encoding protocadherin 15, cause either nonsyndromic deafness DFNB23 or Usher syndrome type 1F (USH1F) in humans and deafness with balance problems in Ames waltzer (av) mice. Persons with USH1 usually begin to exhibit signs of retinitis pigmentosa (RP) in early adolescence, but av mice are reported to have functional retinas. In this study, the auditory, visual and molecular biological phenotype of Pcdh15av-5J and Pcdh15av-Jfb mice is characterized, and their usefulness as animal models of USH1 is evaluated. METHODS: Hearing thresholds of mice between 6 and 10 weeks of age were measured by auditory brain stem response (ABR). Immunohistochemistry and histology were used to examine the effect of homozygosity of Pcdh15av-5J on stereocilia bundles of inner ear hair cells and on the photoreceptor cells of the retina. Scotopic and photopic Ganzfeld ERGs were recorded from homozygous Pcdh15av-5J and Pcdh15av-Jfb mice at different ages. Heterozygous littermates served as control subjects. Measurements of the width of the outer nuclear layer (ONL) and the length of rod photoreceptor outer segment (ROS) were made. RESULTS: Homozygous Pcdh15av-5J mice have profound hearing loss and disorganized stereocilia bundles of inner ear hair cells. Compared with heterozygous littermates, homozygous Pcdh15av-5J and Pcdh15av-Jfb mutant mice had scotopic ERG amplitudes consistently reduced by approximately 40% at all light intensities. The b-to-a-wave ratio confirmed that the a- and b-waves were reduced proportionally in homozygous mutant mice. Histologic measurements of retinal sections revealed no significant differences in either the ONL width or the ROS length as a function of genotype. The protocadherin 15 labeling pattern with antisera PB303 in the retina of both heterozygous and homozygous Pcdh15av-5J mice was indistinguishable from the wild type. Wild-type Pcdh15 have many alternatively spliced isoforms. A novel isoform was found in the retina of homozygous Pcdh15av-5J mice, which appears to circumvent the effect of the mutant allele (IVS14-2A-->G), which causes skipping of exon 14, a shift in the translation reading frame and a premature stop codon in exon 15. CONCLUSIONS: Pcdh15(av-5J) and Pcdh15(av-Jfb) mice do not faithfully mimic the RP found in USH1 due to mutations of PCDH15, but have significantly attenuated ERG function in the absence of histologic change. The decline in ERG amplitude with a preserved b-to-a-wave ratio suggests a role for Pcdh15 in retinal function and/or generation of the ERG potentials. Understanding the molecular mechanism by which av mice circumvent degeneration of the retina might offer insights into potential therapies for USH1.