Optimization of Iodinated Contrast Media Inventory Management: Effect of Inventory Diversification on Waste Reduction.

PURPOSE: Iodinated contrast medium (ICM) is available in single- and multiuse vials of varying sizes, but CT departments often preferentially stock only a single or a limited number of vial sizes. The aims of this study were to assess actual ICM waste at a large safety-net hospital and to compare with estimated waste if single-use vials in a variety of vial sizes or multiuse vials were used. METHODS: ICM administrations were retrospectively reviewed for all CT examinations performed in 2021 in a department that stocked only 100-mL ICM vials. Administered ICM dose, opened ICM volume and number of vials, and wasted ICM were compared with hypothetical models using optimally sized single-use vials and multiuse vials. Contrast use was also compared by patient class. RESULTS: In total, 40,393 ICM administrations over 49,670 CT examinations among 26,028 patients were reviewed, totaling 4,168,335 mL of contrast media. The mean dose was 103 mL, with mode of 100 mL. Exclusive use of 100-mL vials resulted in 1,006,165 mL waste (mean waste, 26 mL/administration). Optimally sized single-use vials resulted in 436,515 mL waste (mean waste, 11 mL/administration). Multiuse vials resulted in 537,074 mL waste (mean waste, 13 mL/administration). The distribution of optimal single-use vial size differed significantly by patient class (P < .001), with inpatient examinations more amenable to the use of smaller single-use vials. CONCLUSIONS: Optimizing ICM inventory can reduce contrast waste by 50% to 59%. Regular monitoring of contrast use may help optimize inventory selection across care settings. This retrospective review supports scrutiny of ICM inventory management to reduce waste, save costs, and mitigate the impacts of supply-chain disruptions.

Production, isolation, and shipment of clinically relevant quantities of astatine-211: A simple and efficient approach to increasing supply.

The alpha emitter astatine-211 (211At) is a promising candidate for cancer treatment based on Targeted Alpha (α) Therapy (TAT). A small number of facilities, distributed across the United States, are capable of accelerating α-particle beams to produce 211At. However, challenges remain regarding strategic methods for shipping 211At in a form adaptable to advanced radiochemistry reactions and other uses of the radioisotope. PURPOSE: Our method allows shipment of 211At in various quantities in a form convenient for further radiochemistry. PROCEDURES: For this study, a 3-octanone impregnated Amberchrom CG300M resin bed in a column cartridge was used to separate 211At from the bismuth matrix on site at the production accelerator (Texas A&M) in preparation for shipping. Aliquots of 6 M HNO3 containing up to ≈2.22 GBq of 211At from the dissolved target were successfully loaded and retained on columns. Exempt packages (<370 MBq) were shipped to a destination radiochemistry facility, University of Texas MD Anderson Cancer Center, in the form of a convenient air-dried column. Type A packages have been shipped overnight to University of Alabama at Birmingham. MAIN FINDINGS: Air-dried column hold times of various lengths did not inhibit simple and efficient recovery of 211At. Solution eluted from the column was sufficiently high in specific activity to successfully radiolabel a model compound, 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (1), with 211At. The method to prepare and ship 211At described in this manuscript has also been used to ship larger quantities of 211At a greater distance to University of Alabama at Birmingham. PRINCIPAL CONCLUSIONS: The successful proof of this method paves the way for the distribution of 211At from Texas A&M University to research institutions and clinical oncology centers in Texas and elsewhere. Use of this simple method at other facilities has the potential increase the overall availability of 211At for preclinical and clinical studies.

Complexation of Astatine(III) with Ketones: Roles of NO3- Counterion and Exploration of Possible Binding Modes.

Ketones have been proven effective in extracting astatine(III) from aqueous solvents. Previous theoretical studies suggested a mechanism where the "sp2" lone pair on the carbonyl oxygen donates electron density into the π system of the AtO+ molecular cation to form a dative-type bond. In this study, co-extraction of NO3- as AtO(NO3)·(O═CR1R2) species into the organic phase appears to be a key factor. Adjusting the electronic properties of the ketone, by having an aryl group instead of an alkyl group in the alpha position of the ketone, increased the electron density on C═O, increased the bond strength between the ketone and AtO+, and in turn increased the extraction of 211At into the organic phase. Extraction with diketones shows dependence on the bridging distance between the two carbonyl moieties, where a C3 or longer bridge results in a 10-fold increase in extraction into the organic phase. DFT calculations show the longer bridge allows for the chelation of AtO(NO3) by either the second carbonyl or the phenyl ring.

Posttraumatic nuchal pseudolipoma in a high school athlete after weight training.

Pseudolipomas are an uncommon clinical manifestation appearing as a non-encapsulated prominence of subcutaneous fat on MRI. Post-traumatic pseudolipomas (PTLs) are thought to arise from neoadipogenesis following acute or chronic trauma. These are most commonly located on the lower extremities, gluteal, and trochanteric regions. Here, we report a case of PTL in a high school athlete, arising in the posterior neck after weight training with performing barbell squats without neck padding. To our knowledge, this case represents a novel association between PTLs and weight training exercises.

Does simulation improve clinical performance in management of postpartum hemorrhage?

BACKGROUND: Although simulation is now widely used to improve teamwork and communication, data demonstrating improvement in clinical outcomes are limited. OBJECTIVE: This study aimed to examine the clinical performance and outcomes associated with postpartum hemorrhage because of uterine atony following the implementation of a multidisciplinary simulation program. STUDY DESIGN: This was a prospective observational study of response to postpartum hemorrhage because of uterine atony in an academic medical center before (epoch 1: July 2017-June 2018) and after (epoch 2: July 2019-June 2020) implementing a multidisciplinary simulation program. A total of 22 postpartum hemorrhage simulations were performed from July 2018 to June 2019 involving more than 300 nursing, obstetrical, and anesthesia providers. The simulation program focused on managing postpartum hemorrhage events and improving teamwork and communication of the multidisciplinary teams. To evaluate the clinical effectiveness of the simulation program, the primary outcome was response to postpartum hemorrhage defined as the time from the administration of uterotonic medications to transfusion of the first unit of blood in the first 12 hours following delivery, comparing epoch 2 to epoch 1 following the implementation of a simulation program. Statistical analysis included the use of the Pearson chi-square test, Wilcoxon rank-sum test, Hodges-Lehmann statistic for differences, and bootstrap methods with a P value of <.05 considered significant. RESULTS: Between July 1, 2017, and June 30, 2018, there were 12,305 patients who delivered, of which 495 patients (4%) required transfusion. Between July 1, 2019, and June 30, 2020, there were 12,414 patients who delivered, of which 480 patients (4%) required transfusion. When isolating cases of postpartum hemorrhage because of uterine atony in both transfused groups, there were 157 women in the presimulation group (epoch 1) and 165 women in the postsimulation group (epoch 2), respectively. There was no difference in age, race, parity, or perinatal outcomes between the 2 epochs. Women in epoch 2 began receiving blood products significantly earlier in the first 12 hours following delivery compared with women in epoch 1 (51 [range, 28-125] minutes vs 102 [range, 32-320] minutes; P=.005). In addition, there was a significantly decreased variation in the time from the administration of uterotonic medications to transfusion of blood in epoch 2 (P=.035). Furthermore, women in epoch 2 had significantly lower estimated blood loss than women in epoch 1 (1250 [range, 1000-1750] mL vs 1500 [range, 1000-2000] mL; P=.032). CONCLUSION: The implementation of a multidisciplinary simulation program at a large academic center focusing on the management of postpartum hemorrhage was associated with an improved clinical response. Specifically, there were significantly faster times from the administration of uterotonic medications to transfusion of blood, decreased variance in the time from the administration of uterotonic medications to transfusion of blood, and lower estimated blood loss following the implementation of a simulation program. Because delay in treatment is a major cause of preventable maternal death in obstetrical hemorrhage, the results in our study provided clinical evidence that a simulation program may improve patient outcomes in such emergencies.

Analgesic utilization before and after rescheduling of hydrocodone in a large academic level 1 trauma center.

BACKGROUND: Hydrocodone-containing products were recently rescheduled from Drug Enforcement Agency (DEA) schedule III to schedule II due to concerns of abuse and misuse. These changes went into effect on October 6, 2014. OBJECTIVE: This quality improvement project involved a retrospective analysis to determine the effect of the DEA schedule change on prescribing habits of hydrocodone-containing products as well as the remaining schedule III and IV opioids, codeine (schedule III) and tramadol (schedule IV). METHODS: The authors performed a medication use evaluation at our academic level 1 trauma hospital system on outpatient use of hydrocodone-containing products, tramadol, and codeine-containing products for 6 months before and 6 months after the change to schedule II using our electronic record and pharmacy system. RESULTS: A total of 88,428 prescription orders were analyzed. Comparison of prescriptions before and after the DEA schedule changes showed hydrocodone prescriptions reduced from an average of 225.97 per day to 1.20 per day. In addition, tramadol increased from 60.04 per day to 91.85 per day and codeine from 6.81 per day to 98.94 per day. CONCLUSIONS: Our data show a very substantial decrease in utilization of hydrocodone-containing products and concomitant increase in the utilization of tramadol and codeine products at our hospital after the DEA schedule change.

Predicting protein aggregation during storage in lyophilized solids using solid state amide hydrogen/deuterium exchange with mass spectrometric analysis (ssHDX-MS).

Solid state amide hydrogen/deuterium exchange with mass spectrometric analysis (ssHDX-MS) was used to assess the conformation of myoglobin (Mb) in lyophilized formulations, and the results correlated with the extent of aggregation during storage. Mb was colyophilized with sucrose (1:1 or 1:8 w/w), mannitol (1:1 w/w), or NaCl (1:1 w/w) or in the absence of excipients. Immediately after lyophilization, samples of each formulation were analyzed by ssHDX-MS and Fourier transform infrared spectroscopy (FTIR) to assess Mb conformation, and by dynamic light scattering (DLS) and size exclusion chromatography (SEC) to determine the extent of aggregation. The remaining samples were then placed on stability at 25 °C and 60% RH or 40 °C and 75% RH for up to 1 year, withdrawn at intervals, and analyzed for aggregate content by SEC and DLS. In ssHDX-MS of samples immediately after lyophilization (t = 0), Mb was less deuterated in solids containing sucrose (1:1 and 1:8 w/w) than in those containing mannitol (1:1 w/w), NaCl (1:1 w/w), or Mb alone. Deuterium uptake kinetics and peptide mass envelopes also indicated greater Mb structural perturbation in mannitol, NaCl, or Mb-alone samples at t = 0. The extent of deuterium incorporation and kinetic parameters related to rapidly and slowly exchanging amide pools (Nfast, Nslow), measured at t = 0, were highly correlated with the extent of aggregation on storage as measured by SEC. In contrast, the extent of aggregation was weakly correlated with FTIR band intensity and peak position measured at t = 0. The results support the use of ssHDX-MS as a formulation screening tool in developing lyophilized protein drug products.

Freeze-drying simulation framework coupling product attributes and equipment capability: toward accelerating process by equipment modifications.

A physics-based model for the sublimation-transport-condensation processes occurring in pharmaceutical freeze-drying by coupling product attributes and equipment capabilities into a unified simulation framework is presented. The system-level model is used to determine the effect of operating conditions such as shelf temperature, chamber pressure, and the load size on occurrence of choking for a production-scale dryer. Several data sets corresponding to production-scale runs with a load from 120 to 485 L have been compared with simulations. A subset of data is used for calibration, whereas another data set corresponding to a load of 150 L is used for model validation. The model predictions for both the onset and extent of choking as well as for the measured product temperature agree well with the production-scale measurements. Additionally, we study the effect of resistance to vapor transport presented by the duct with a valve and a baffle in the production-scale freeze-dryer. Computation Fluid Dynamics (CFD) techniques augmented with a system-level unsteady heat and mass transfer model allow to predict dynamic process conditions taking into consideration specific dryer design. CFD modeling of flow structure in the duct presented here for a production-scale freeze-dryer quantifies the benefit of reducing the obstruction to the flow through several design modifications. It is found that the use of a combined valve-baffle system can increase vapor flow rate by a factor of 2.2. Moreover, minor design changes such as moving the baffle downstream by about 10 cm can increase the flow rate by 54%. The proposed design changes can increase drying rates, improve efficiency, and reduce cycle times due to fewer obstructions in the vapor flow path. The comprehensive simulation framework combining the system-level model and the detailed CFD computations can provide a process analytical tool for more efficient and robust freeze-drying of bio-pharmaceuticals.

Human collagen injections to reduce rectal dose during radiotherapy.

OBJECTIVES: The continuing search for interventions, which address the incidence and grade of rectal toxicities associated with radiation treatment of prostate cancer, is a major concern. We are reporting an investigational trial using human collagen to increase the distance between the prostate and anterior rectal wall, thereby decreasing the radiation dose to the rectum. METHODS: This is a pilot study evaluating the use of human collagen as a displacing agent for the rectal wall injected before starting a course of intensity-modulated radiotherapy (IMRT) for prostate cancer. Using a transperineal approach, 20 mL of human collagen was injected into the perirectal space in an outpatient setting. Computerized IMRT plans were performed pre- and postcollagen injection, and after a patient completed their radiotherapy, to determine radiation dose reduction to the rectum associated with the collagen injection. Computed tomography scans were performed 6 months and 12 months after completing their radiotherapy to evaluate absorption rate of the collagen. All patients were treated with IMRT to a dose of 75.6 Gy to the prostate. RESULTS: Eleven patients were enrolled into the study. The injection of human collagen in the outpatient setting was well tolerated. The mean separation between the prostate and anterior rectum was 12.7 mm. The mean reduction in dose to the anterior rectal wall was 50%. All men denied any rectal symptoms during the study. CONCLUSIONS: The transperineal injection of human collagen for the purpose of tissue displacement is well tolerated in the outpatient setting. The increased separation between the prostate and rectum resulted in a significant decrease in radiation dose to the rectum while receiving IMRT and was associated with no rectal toxicities.

Cerebral and somatic oxygen saturation decrease after delayed sternal closure in children after cardiac surgery.

OBJECTIVES: Delayed sternal closure after pediatric cardiac surgery can temporarily impair cardiac output. Cerebral and somatic regional oxygen saturation measured by using near-infrared spectroscopy (NIRS) have been used as potential surrogates of cerebral and somatic mixed venous oxygen saturation. We hypothesized that cerebral and somatic regional oxygen saturation correlate with indicators of hemodynamic compromise after delayed sternal closure in children undergoing cardiac surgery. METHODS: We studied 36 postoperative children (median age, 10 days; range, 1-510 days) undergoing delayed sternal closure 3.7 +/- 2 days after cardiac surgery. Twenty-five had biventricular physiology, whereas 11 had single-ventricle physiology. Cerebral regional oxygen saturation, somatic regional oxygen saturation, and other physiologic parameters (hemodynamic data, respiratory data, blood gas analysis, lactate levels, and inotrope scores) were analyzed at 16 different time points 24 hours before and after sternal closure. One-way analysis of variance and the paired t test were used for statistical comparisons. RESULTS: Cerebral and somatic regional oxygen saturation decreased after delayed sternal closure compared with preclosure levels (P = .02 and P = .01, respectively). Higher heart rate (P = .03), lactate levels (P = .02), and left atrial pressure (P = .001) were also noted, suggesting mild hemodynamic compromise. Arterial pressure and inotrope score were unchanged. Somatic regional oxygen saturation returned to preclosure levels earlier in the biventricular group than in the single-ventricle group, whereas cerebral regional oxygen saturation remained decreased after sternal closure with no evidence of return to preclosure levels during the observation period. Oxygen saturation, Pao(2), and Paco(2) levels were unaffected by sternal closure, although greater positive-pressure ventilation was required (P < .01), suggesting reduced lung compliance. CONCLUSION: Cerebral and somatic regional oxygen saturation decrease after delayed sternal closure in children recovering from congenital cardiac surgery. These indices are in agreement with other physiologic indicators of cardiac performance, suggesting mild and transient hemodynamic compromise after sternal closure. Cerebral and somatic regional oxygen saturation monitoring might be a useful adjunct during delayed sternal closure.

Association of rapid head growth in children following tracheostomy tube placement.

INTRODUCTION: Our clinical observation indicates that some children who have a tracheostomy may experience increasing head circumference as they grow and develop. Accurate assessment and interpretation of growth parameters is an essential component of following child development. Appreciation for variations in growth is especially important in special populations, such as children with a tracheostomy. The aim of this study is to define head growth in children with a tracheostomy. METHOD: This retrospective cohort study includes children who underwent tracheostomy tube placement prior to 2 years of age in a respiratory rehabilitation unit within a children's hospital. Serial head circumference measurements were plotted against age on growth charts adjusted for gestational age. The percentage of patients with accelerated head growth, defined as increased head circumference across two major percentiles within 6 months following tracheostomy, was determined. RESULTS: Fifty-seven percent (20 out of 35 children) demonstrated increased head circumference across two major percentiles within 6 months following tracheostomy. DISCUSSION: Accelerated head growth is associated with the presence of a tracheostomy tube in children in this study. Further investigation is warranted to establish the relationship of head circumference to other growth parameters. In addition, the etiology of this phenomenon requires additional study. Understanding head growth in children with a tracheostomy will promote adequate growth assessment and may lead to improved patient care.

Resuscitation with 100%, compared with 21%, oxygen following brief, repeated periods of apnea can protect vulnerable neonatal brain regions from apoptotic injury.

PURPOSE: To determine the effect of repeated intermittent apnea and resuscitation with 100% vs. 21% oxygen enriched gas on levels of key regulatory proteins contributing to cell death (Bax, Caspase-3) or protecting neurons from hypoxic/ischemic injury (Bcl-2, p-Akt, p-CREB). METHODS: The anaesthetized, mechanically ventilated newborn piglets underwent 10 episodes of apnea with resuscitation either with 100% or with 21% oxygen. Following 6h recovery the animals were sacrificed painlessly, the brain dissected out and used to determine levels of Bcl-2, Bax, Caspase-3, p-Akt and p-CREB in the striatum, frontal cortex, midbrain and hippocampus were studied. RESULTS: In hippocampus and striatum, Bcl-2 expression was higher with 100% vs. 21% group (173+/-29% vs. 121+/-31%, p<0.05 and 189+/-10% vs. 117+/-47%, p<0.01, respectively) whereas the Bax expression was lower (88+/-3% vs. 100+/-9%, p<0.05 and 117+/-5% vs. 133+/-10%, p<0.05, respectively). Expression of Caspase-3 in the striatum, was lower with 100% vs. 21% group (197+/-35% vs. 263+/-33%, p<0.05, respectively) but not different in the hippocampus. p-Akt expression was higher with 100% vs. 21% oxygen in the hippocampus and striatum (225+/-44% vs. 108+/-35%, p<0.01 and 215+/-12% vs. 164+/-16%, p<0.01, respectively). The p-CREB expression was higher with 100% vs. 21% oxygen resuscitation in the hippocampus (217+/-41% vs. 132+/-30%, p<0.01) with no changes in striatum. Much smaller or insignificant differences between 100% vs. 21% oxygen groups were observed in the frontal cortex and midbrain, respectively. CONCLUSION: In neonatal piglet model of intermittent apnea, selectively vulnerable regions of brain (striatum and hippocampus) are better protected from apoptotic injury when resuscitation was conducted with 100%, rather than 21%, oxygen.

Response of brain oxygenation and metabolism to deep hypothermic circulatory arrest in newborn piglets: comparison of pH-stat and alpha-stat strategies.

BACKGROUND: To determine the effect of pH-stat as compared with alpha-stat management on brain oxygenation, level of striatal extracellular dopamine, phosphorylation, and levels of protein kinase B (Akt) and cyclic adenosine 3', 5'-monophosphate response element-binding protein (CREB), and levels of extracellular signal-regulated kinase (ERK)1/2, Bcl-2, and Bax in a piglet model of deep hypothermic circulatory arrest (DHCA). METHODS: The piglets were placed on cardiopulmonary bypass (CPB), cooled with pH-stat or alpha-stat to 18 degrees C, subjected to 90 minutes of DHCA, rewarmed, weaned from CPB, and maintained for two hours recovery. The cortical oxygen was measured by: quenching of phosphorescence; dopamine by microdialysis; phosphorylation of CREB (p-CREB), ERK (p-ERK) 1/2, Akt (p-Akt), and level of Bcl-2, Bax by Western blots. RESULTS: Oxygen pressure histograms for the microvasculature of the cortex show substantially higher oxygen levels during cooling and during the oxygen depletion period after cardiac arrest (up to 15 minutes) when using pH-stat compared with alpha-stat management. Significant increases in dopamine occurred at 45 minutes and 60 minutes of DHCA in the alpha-stat and pH-stat groups, respectively. The p-CREB and p-Akt in the pH-stat group were significantly higher than in the alpha-stat group (140 +/- 9%, p < 0.05 and 125 +/- 6%, p < 0.05, respectively). There was no significant difference in p-ERK1/2 and Bax. The Bcl-2 increased in the pH-stat group to 121 +/- 4% (p < 0.05) compared with the alpha-stat group. The ratio Bcl-2:Bax increased in the pH-stat group compared with the alpha-stat group. CONCLUSIONS: The increase in p-CREB, p-Akt, Bcl-2, Bcl-2/Bax, and delay in increase of dopamine indicated that pH-stat, in the piglet model, prolongs "safe" time of DHCA and provides some brain protection against ischemic injury.

Brain oxygen and metabolism is dependent on the rate of low-flow cardiopulmonary bypass following circulatory arrest in newborn piglets.

OBJECTIVE: To determine the optimum rate of low-flow hypothermic cardiopulmonary bypass (LF), following circulatory arrest (DHCA) on brain oxygenation (bO(2)), extracellular dopamine (DA), phosphorylation of select neuroregulatory proteins responsible for neuronal injury, and survival following ischemic brain injury: CREB, Erk1/2, Akt, Bcl-2, and Bax. METHODS: The piglets were placed on cardiopulmonary bypass (CPB) and cooled to 18 degrees C. They were then subjected to 30 min of DHCA followed by 1h of LF at 20, 50, or 80 ml/(kg/min), rewarmed, separated from CPB, and maintained for 2h. The bO(2) was measured by quenching of phosphorescence; DA by microdialysis; phosphorylation of CREB, ERK1/2, Akt, Bcl-2, and Bax by Western blots. The results are means+/-SD for seven experiments. RESULTS: Pre-bypass bO(2) was 47.4+/-4.2 mmHg and decreased to 1.9+/-0.8 mmHg during DHCA. At the end of LF at 20, 50, and 80 ml/(kg/min), bO(2) was 11.8+/-1.6, 26+/-1.8, and 33.9+/-2.6 mmHg, respectively. The DA increased 510-fold relative to control (p<0.001) by 15 min of LF-20 with maximum increase occurring at 45 min. With LF-50, increase in DA was not statistically significant and no increase was observed when LF-80 was used. Bcl-2 immunoreactivity increased after LF-50 and LF-80 (140+/-14.5%, p<0.05 and 202+/-34%, p<0.05, respectively). Neither flow increased Bax immunoreactivity. The ratio of Bcl-2/Bax, pCREB, pAkt, pErk increased significantly with increasing the flow rate of LF. CONCLUSIONS: The protective effect of LF following DHCA on brain metabolism is dependent on the flow rate. Flow-dependent increase in pCREB, pErk1/2, pAkt, increase in Bcl-2/Bax, and decrease in DA indicated that to minimize DHCA-dependent neuronal injury, LF flow should be above 50 ml/(kg/min).

A second-generation cementless total hip arthroplasty mean 9-year results.

Two hundred fifty-eight primary total hip arthroplasties in 231 patients were implanted using a circumferentially, proximally porous-coated, collared femoral component and a cementless, hemispherical, porous-coated acetabular component and followed up for a mean of 9 years (5-14 years). Four femoral components were revised (2 stems for infection and 2 stems for aseptic loosening). One additional femoral component was radiographically loose at last follow-up. Nine hips underwent acetabular revision (4 for instability, 2 for infection, 2 for loosening, and 1 for osteolysis). Ten-year survivorship with revision or loosening of any component as the end point was 92%; with femoral component aseptic loosening as end point, survivorship was 98%; with acetabular aseptic loosening as the end point, survivorship was 99%. Osteolysis was identified in 26 hips (13%).

Regulation of brain cell death and survival after cardiopulmonary bypass.

BACKGROUND: This study investigated the effect of low flow cardiopulmonary bypass, circulatory arrest, and selective cerebral perfusion on expression and phosphorylation of selected regulators of cell death and survival in striatum of newborn piglets. METHODS: Animals were assigned to sham operation and three experimental groups. The experimental groups were placed on bypass, cooled to 18 degrees C, and subjected to 90 minutes of deep hypothermic circulatory arrest (DHCA), low-flow cardiopulmonary bypass (LFCPB) at mL/(kg x min), or selective cerebral perfusion (SCP) at 20 mL/(kg x min), followed by rewarming and 2 hours of recovery. The oxygen pressure in the microcirculation of the cortex was measured by quenching of phosphorescence. Levels of phosphorylated and total protein were determined by Western blot analysis. RESULTS: Control oxygen pressure was 55 +/- 9 mm Hg and decreased during DHCA, LFCPB, and SCP to 1.1 +/- 0.6 mm Hg, 9.8 +/- 2.3 mm Hg, and 9.3 +/- 1.9 mm Hg, respectively (p < 0.001). After DHCA, N-terminal of Bcl-2-associated X protein (N-Bax) levels increased (295% +/- 15%, p < 0.01), B-cell leukemia protein (Bcl-2) levels decreased (31% +/- 9%, p < 0.01), and phosphorylation level of protein kinase B (pAkt) and extracellular signal-regulated kinase 1/2 (pERK1/2) did not change. After LFCPB and SCP, N-Bax and Bcl-2 levels were unchanged, pAkt levels increased (367% +/- 122%, p < 0.05 and 337% +/- 47%, p < 0.01, respectively), pERK1 (484% +/- 70% and 501% +/- 255%, respectively; p < 0.01) and pERK2 (569% +/- 128%; p < 0.001 and 494% +/- 162%; p < 0.05, respectively) levels increased, and total ERK2 levels also increased (279% +/- 90% and 153% +/- 44%, respectively, p < 0.05). CONCLUSIONS: Stable levels of Bcl-2 and Bax and the increases in pAkt and pERK1/2 after LFCPB and SCP are likely indicators of improved chances for cell survival.

Brain oxygen and metabolism during circulatory arrest with intermittent brief periods of low-flow cardiopulmonary bypass in newborn piglets.

OBJECTIVE: We performed this study to determine whether brief intermittent periods of low-flow cardiopulmonary bypass during deep hypothermic circulatory arrest would improve cortical metabolic status and prolong the "safe" time of deep hypothermic circulatory arrest. METHODS: After a 2-hour baseline, newborn piglets were placed on cardiopulmonary bypass and cooled to 18 degrees C. The animals were then subjected to 80 minutes of deep hypothermic circulatory arrest interrupted by 5-minute periods of low-flow cardiopulmonary bypass at either 20 mL x kg(-1) x min(-1) (LF-20) or 80 mL x kg(-1) x min(-1) (LF-80) during 20, 40, 60, and 80 minutes of deep hypothermic circulatory arrest. All animals were rewarmed, separated from cardiopulmonary bypass, and maintained for 2 hours (recovery). The oxygen pressure in the cerebral cortex was measured by the quenching of phosphorescence. The extracellular dopamine level in the striatum was determined by microdialysis. Results are means +/- SD. RESULTS: Prebypass oxygen pressure in the cerebral cortex was 65 +/- 7 mm Hg. During the first 20 minutes of deep hypothermic circulatory arrest, cortical oxygen pressure decreased to 1.3 +/- 0.4 mm Hg. Four successive intermittent periods of LF-20 increased cortical oxygen pressure to 6.9 +/- 1.2 mm Hg, 6.6 +/- 1.9 mm Hg, 5.3 +/- 1.6 mm Hg, and 3.1 +/- 1.2 mm Hg. During the intermittent periods of LF-80, cortical oxygen pressure increased to 21.1 +/- 5.3 mm Hg, 20.6 +/- 3.7 mm Hg, 19.5 +/- 3.95 mm Hg, and 20.8 +/- 5.5 mm Hg. A significant increase in extracellular dopamine occurred after 45 minutes of deep hypothermic circulatory arrest alone, whereas in the groups of LF-20 and LF-80, the increase in dopamine did not occur until 52.5 and 60 minutes of deep hypothermic circulatory arrest, respectively. CONCLUSIONS: The protective effect of intermittent periods of low-flow cardiopulmonary bypass during deep hypothermic circulatory arrest is dependent on the flow rate. We observed that a flow rate of 80 mL x kg(-1) x min(-1) improved brain oxygenation and prevented an increase in extracellular dopamine release.

Effects of single-ventricle physiology with aortopulmonary shunt on regional myocardial blood flow in a piglet model.

OBJECTIVES: In single-ventricle physiology with aortopulmonary connection, diastolic hypotension could alter regional myocardial blood flow. Also, afterload increases could impair myocardial blood flow by increased wall tension and relative subendocardial malperfusion. This study explores the effects of acute single-ventricle physiology on regional myocardial blood flow distribution and investigates the consequences of moderate afterload augmentation on myocardial blood flow. METHODS: Single-ventricle physiology was created in 8 piglets without using bypass, and 8 animals served as a sham control group. Aortopulmonary shunt, echo-guided atrial septostomy, tricuspid valve avulsion, and pulmonary artery occlusion allowed the left ventricle to support systemic and pulmonary circulations. Afterload augmentation was produced by aortic balloon inflation. Physiologic recordings and stable-isotope microsphere determination of myocardial blood flow to the subepicardium and subendocardium were obtained at baseline and during single-ventricle physiology (at 30 minutes, 120 minutes, and afterload increase). RESULTS: Arterial oxygen content, diastolic pressure, and coronary perfusion pressure declined after creation of single-ventricle physiology (P < .05). Acute single-ventricle physiology resulted in higher myocardial blood flow (P < .05), unchanged subendocardial/subepicardial flow ratio and oxygen delivery, and lower coronary resistance (P < .01) as compared with biventricular physiology. Afterload augmentation increased coronary perfusion pressure, causing a trend for higher myocardial blood flow and oxygen delivery (P = NS), without affecting subendocardial/subepicardial flow distribution. Myocardial oxygen supply/demand balance fell in single-ventricle physiology, remaining unchanged during afterload augmentation. CONCLUSIONS: Our study demonstrates that, in acute single-ventricle physiology with aortopulmonary shunt, myocardial blood flow is maintained by lower coronary perfusion pressure. Further, single-ventricle physiology results in less favorable myocardial oxygen supply/demand balance, although normal transmural myocardial blood flow distribution is maintained. Avoidance of diastolic runoff (ventricle-pulmonary conduit) could improve coronary reserve. In our study, moderate afterload augmentation did not induce relative subendocardial malperfusion, nor did it worsen oxygen supply/demand balance.