Biomedical subjects

J L McNamara

Publications and source records attributed to J L McNamara.

9 recordsLinked to original sources

PubMed2001

Alternative methods for anticoagulation monitoring in pediatric patients with applicability to a patient with severe hemophilia A and circulating inhibitor.

Anticoagulation monitoring in pediatric patients can be problematic because of the immaturity of the coagulation system in this population. In addition, the hemodilution required to place a small patient on bypass can interfere with standard monitoring methods. In this institution, the Hemochron Jr. ACT (activated clotting time)+ assay has been the standard of care for anticoagulation monitoring since 1997. This assay, with a target ACT of 400 s for initiating bypass, was compared to both the Medtronic HMS system (N = 7) and the Hemochron HiTT assay (N = 6) in pediatric patients. All three assays were then employed to monitor a pediatric Hemophilia A patient (Factor VIII <1%) with high inhibitor titer. Both the HiTT clotting time and the HMS heparin level showed statistically significant correlation to the ACT+ (HiTT, N = 24, r = 0.761; HMS, N = 31, r = 0.818). An HMS target heparin level of 1.5 mg/kg and a HiTT target clotting time of 180 s were found to be clinically equivalent to the 400-s ACT+ as indicators of the need for additional heparin. When a 7-year-old male with severe hemophilia A and high inhibitor titer required tricuspid valve replacement, all three assays were used to ensure appropriate anticoagulation management. During bypass, this patient's ACT+ remained out of range (>1005 s). The HiTT was maintained at >180 s and the HMS heparin level at >1.5 mg/kg. Heparin was administered when any single parameter was below the cutoff value. The use of the combination of three distinct monitoring assays for this patient allowed the surgical team an added level of confidence that appropriate anticoagulation had been maintained.

Anticoagulants↗

PubMed2000

Acute hypoxia and reoxygenation impairs exhaled nitric oxide release and pulmonary mechanics.

OBJECTIVE: Changes in exhaled nitric oxide levels often accompany conditions associated with elevated pulmonary vascular resistance and altered lung mechanics. However, it is unclear whether changes in exhaled nitric oxide reflect altered vascular or bronchial nitric oxide production. This study determined the effects of acute hypoxia and reoxygenation on pulmonary mechanics, plasma nitrite levels, and exhaled nitric oxide production. METHODS: Ten piglets underwent 90 minutes of hypoxia (fraction of inspired oxygen = 12%), 1 hour of reoxygenation on cardiopulmonary bypass, and 2 hours of recovery. Five additional animals underwent bypass without hypoxia. Exhaled nitric oxide, plasma nitrite levels, and pulmonary mechanics were measured. RESULTS: Exhaled nitric oxide decreased to 36% of baseline by end hypoxia (34 +/- 14 vs 12 +/- 9 ppb, P =.005) and declined further to 20% of baseline at end recovery (7 +/- 6 ppb). Aortic nitrite levels decreased from baseline during hypoxia (from 102 +/- 13 to 49 +/- 7 micromol/L, P =.05) but returned to baseline during recovery. Pulmonary arterial nitrite also decreased during hypoxia (from 31.4 +/- 7.8 to 22.9 +/- 9.5 micromol/L, P =.04) and returned to baseline at end recovery. Decreased production of exhaled nitric oxide was associated with impaired gas exchange (alveolar-arterial gradient = 32 mm Hg at baseline and 84 mm Hg at end recovery), decreased pulmonary compliance (6.6 +/- 0.9 mL/cm H(2)O at baseline, 5.0 +/- 0.7 mL/cm H(2)O at end hypoxia, and 5.4 +/- 0.7 mL/cm H(2)O at end recovery), and increased inspiratory airway resistance (41 +/- 4 cm H(2)O. L(-1). s(-1) at baseline, 56 +/- 4.9 cm H(2)O. L(-1). s(-1) at end hypoxia, and 50 +/- 5 cm H(2)O. L(-1). s(-1) at end recovery). CONCLUSIONS: A decrease in exhaled nitric oxide persisted after hypoxia, and plasma nitrite levels returned to baseline on reoxygenation, indicating that alterations in exhaled nitric oxide during hypoxia-reoxygenation might be unrelated to plasma nitrite levels. Furthermore, decreased exhaled nitric oxide corresponded with altered pulmonary mechanics and gas exchange. Reduced exhaled nitric oxide after hypoxia-reoxygenation might reflect bronchial epithelial dysfunction associated with acute lung injury.

Acute Disease↗

PubMed1999

Effect of modified ultrafiltration on plasma thromboxane B2, leukotriene B4, and endothelin-1 in infants undergoing cardiopulmonary bypass.

BACKGROUND: Plasma thromboxane B2 (TXB2), leukotriene B4 (LTB4), and endothelin-1 (ET-1) levels increase on cardiopulmonary bypass (CPB). Elevated levels of TXB2 and ET-1 have been correlated with postoperative pulmonary hypertension in infants undergoing repair of congenital heart defects. LTB4 is a potent chemotactic cytokine whose levels correlate with leukocyte-mediated injury. Modified ultrafiltration (MUF) has been associated with improved hemodynamics and pulmonary function, in addition to its beneficial effects on fluid balance and blood conservation. Recent investigations have suggested that removal of cytokines may be the cause of the improved cardiopulmonary function seen with MUF. METHODS: Plasma TXB2, ET-1, and LTB4 levels were measured in 34 infants undergoing CPB: 22 underwent MUF (group 1), and 12 did not (group 2). Samples were obtained at various time points. All patients underwent conventional ultrafiltration during the rewarming phase of cardiopulmonary bypass. RESULTS: In group 1, mean end-CPB TXB2 level was 101.2 pg/mL versus 46.9 pg/mL post-MUF (p < 0.05). The mean TXB2 level 1 hour post-CPB (54.1 pg/mL) was not significantly different from the post-MUF level. In group 2, the mean end-CPB TXB2 level was 123.6 pg/mL versus 53.2 pg/mL 1 hour post-CPB. Hence, TXB2 levels decreased by similar amounts and to similar levels by 1 hour post-CPB in both groups. ET-1 levels increased after CPB and were unaffected by MUF: 1.45, 1.80, 2.55 pg/mL at end-CPB, post-MUF, and 1 hour post-CPB, respectively, in group 1; and 1.51, and 2.73 pg/mL at end-CPB and 1 hour post-CPB in group 2. LTB4 levels post-MUF were 119% of pre-MUF values, and were similar at 1 hour post-CPB in both groups. CONCLUSIONS: Despite reduction in TXB2 by MUF, values were similar and approached baseline 1 hour post-CPB in both groups. LTB4 levels increased slightly with MUF. ET-1 levels increased during and post-CPB and were unaffected by MUF. MUF does not appear to have a significant effect on post-CPB levels of TXB2, ET-1, and LTB4. Therefore, the improved hemodynamics observed with MUF do not appear to be related to removal of these cytokines.

Cardiopulmonary Bypass↗

PubMed1999

Bosentan prevents hypoxia-reoxygenation-induced pulmonary hypertension and improves pulmonary function.

BACKGROUND: Acute hypoxia results in increased pulmonary vascular resistance. Despite reoxygenation, pulmonary vascular resistance remains elevated and pulmonary function is altered. Endothelin-1 might contribute to hypoxia-reoxygenation-induced pulmonary hypertension and to reoxygenation injury by stimulating leukocytes. This study was carried out using an established model of hypoxia and reoxygenation to determine whether endothelin-1 blockade with Bosentan could prevent hypoxia-reoxygenation-induced pulmonary hypertension and reoxygenation injury. METHODS: Twenty neonatal piglets underwent 90 minutes of hypoxia, 60 minutes of reoxygenation on cardiopulmonary bypass, and 2 hours of recovery. Control animals (n = 12) received no drug treatment, whereas the treatment group (n = 8) received the endothelin-1 receptor antagonist, Bosentan, throughout hypoxia. RESULTS: In controls, pulmonary vascular resistance increased during hypoxia to 491% of baseline and remained elevated after reoxygenation; however in the Bosentan group, it increased to only 160% of baseline by end-hypoxia, then decreased to 76% at end-recovery. Arterial endothelin-1 levels in controls increased to 591% of baseline after reoxygenation. Arterial nitrite levels decreased during hypoxia in controls but were maintained in the Bosentan group. Consequently, animals in the Bosentan group had better postreoxygenation pulmonary vascular resistance, A-a gradient, and airway resistance along with lower myeloperoxidase levels than controls. CONCLUSIONS: Acute hypoxia and postreoxygenation pulmonary hypertension was attenuated by Bosentan, which maintained nitric oxide levels during hypoxia, decreased leukocyte-mediated injury, and improved pulmonary function.

Animals↗

PubMed1996

Comparison of the performance characteristics of three generations of membrane oxygenators: Univoxregistered, Univoxreqistered Goldtrademark and SpiralGoldtrademark.

With continuous enhancement in oxygenator design, the question is raised as to how these changes actually impact the performance of the oxygenator. The recent addition of two new oxygenators by the Bentley Division of Baxter Healthcare Corporation provided us with a unique opportunity to compare the performance of each device and isolate the impact of each design change on performance. While the basic design and flow patterns have remained the same, application of the Duraflo II treatment has produced the Univox Gold and a change in the fibre-winding technique has produced the SpiralGold. This study compared the effects of heparin coating (Univox to Univox Gold) and fibre-winding (Univox Gold to SpiralGold) on gas and heat transfer and resistance to blood flow (pressure drop). Six oxygenators of each model were evaluated utilizing an in vitro single pass circuit, which first conditioned bovine blood to the Association for the Advancement of Medical Instrumentation (AAMI) venous standards. Blood flows of 4.0, 5.0, 6.0 and 7.0 l/min, FiO2 values of 1.0, 0.8 and 0.6, and gas-to-blood flow ratios of 0.5, 1.0 and 1.5 were chosen as test variables. Data generated included oxygen transfer, carbon dioxide transfer, arterial pO2, resistance to blood flow, and coefficient of heat exchange. The results indicate that the Duraflo II treatment does not have a significant effect on gas and heat transfer or resistance to blood flow. The fibre-winding technique employed with the new SpiralGold, however, has improved significantly gas exchange and arterial pO2 when compared with the previous Univox models. Resistance to blood flow and coefficient of heat exchange were not affected significantly by the winding technique.

Carbon Dioxide↗

PubMed1995

Tibiotalar contact area. Contribution of posterior malleolus and deltoid ligament.

Sixteen fresh ankle specimens were tested under physiologic loads to evaluate the effect on the tibiotalar contact area of increasing-size posterior malleolar fracture fragments and disruption of the deltoid ligament. The tibiotalar joint was maintained in a neutral position, and contact areas were recorded on pressure sensitive film. Posterior malleolar fracture fragments of 25%, 33%, and 50% as visualized on lateral radiographs were created. The deltoid ligament was sectioned after the final fracture fragment was made. There was a corresponding decrease of 4%, 13%, and 22% in tibiotalar contact area with the increasingly larger fracture fragments. The final disruption of the deltoid ligament did not alter the contact area. Statistical analyses using Student's t-test showed a statistically significant decrease in tibiotalar contact area in the samples with a fracture fragment of 33% and 50% involvement of the joint as compared with the control samples. Transection of the deltoid ligament produced no statistically significant further change in contact area. Displaced posterior malleolus fractures produce a significant decrease in contact area with 33% or greater involvement of the joint, which may predispose the tibiotalar joint to degenerative changes that should be lessened by anatomic reduction and internal fixation. Disruption of the deltoid ligament does not appear to alter contact area further, supporting the concept of repair as optional.

Ankle Injuries↗

PubMed1994

A comparison of contact pressures in tibial and patellar total knee components before and after service in vivo.

Laboratory testing of total knee components indicates that many designs produce contact stresses that exceed the yield strength of ultra-high molecular weight polyethylenes (UHMWPEs). It is often assumed that the polyethylene component will creep and wear to become more conforming over time, thus reducing these stresses. To test this theory, retrieved polyethylene tibial and patellar components, which showed signs of increased contact area through in vivo deformation, were tested for contact stress against matching components using Fuji Prescale pressure-sensitive film. The results showed an inverse relationship between initial conformity and in vivo changes in contact stress. More conforming devices showed little or no change in contact stress, and less conforming components showed small decreases in contact stress as a result of creep and wear. Even with these changes, however, the contact stresses for nonconforming designs remained well above those for the more conforming devices as well as the uniaxial yield strength of UHMWPE.

Humans↗

PubMed1991

All-polyethylene patellar components are not the answer.

Recent reports of the high incidence of polyethylene failure of metal-backed patellar components have rekindled the interest in cemented, all-polyethylene designs. One hundred four retrieved patellar components of metal-backed and all-polyethylene designs were analyzed for wear. Additionally, patellofemoral contact stress as a function of flexion angle was measured for unused components using pressure-sensitive Fuji film. Significant wear (2+ on a 0-3 scale) was seen in 65% of metal-backed designs and in 78% of all-polyethylene components. Severe wear (3) was seen in 44% of all-polyethylene components and in 39% of metal-backed devices. The incidence of severe wear (3) of congruent designs was statistically significantly lower than that of the noncongruent designs. Contact stress analysis confirmed that dome-type geometries typically resulted in stresses that exceed the yield strength of the polyethylene, whereas the more congruent geometries generated significantly reduced stress levels.

Biomechanical Phenomena↗

PubMed1991

Analysis of the failure of 122 polyethylene inserts from uncemented tibial knee components.

The extent of wear of retrieved, polyethylene tibial components appears to be related to design. To test this observation, 122 tibial inserts were graded for wear, and new components of several designs were tested for contact stress using Fuji film. Finite element analysis provided insight into subsurface stresses. Significant wear was seen in 61.5% of the tibial inserts examined. The presence of unconsolidated polymer powder was seen in 44% of the tibial inserts and was found to be statistically correlated with severe wear of the articulating surface. Contact stress in several noncongruent designs was found to exceed the yield strength of polyethylene. There was a positive correlation between the intensity of wear and the level of contact stress, with noncongruent designs having greater wear than fully congruent geometries. In the noncongruent designs, the thinner polyethylene components showed greater wear than thicker polyethylene inserts of the same design.

Corrosion↗