Search

Membrane pressure monitoring during extracorporeal membrane oxygenation (ECMO) is integral to monitoring circuit health. We compared a disposable vascular pressure device (DVPD) to the transducer pressure bag arterial line (TPBAL) monitoring system to determine whether the DVPD can reliably and accurately monitor membrane pressures during venovenous extracorporeal membrane oxygenation (VV ECMO). We analyzed existing quality assurance data collected at a single center as part of routine circuit performance monitoring and process improvement on a convenience sample of four VV ECMO circuits. We placed and zeroed a DVPD in line with the pre- and postmembrane TPBAL setups in coordination with a standard transducer setup. We recorded DVPD and TPBAL pressure measurements every 4 hours for 2.5 days on the four separate VV ECMO circuits. We compared the standard and DVPD pressures using Bland-Altman plots and methods that accounted for repeated measures in the same subject. We recorded 58 pre/postmembrane pressures. Mean membrane pressure values were similar in the DVPD (pre: 208 mmHg [SD, 50.8]; post: 175 mmHg [46.3]) compared to the standard TPBAL setup (pre: 205 mmHg [52.0]; post: 177 mmHg [46.3]). Using Bland-Altman methods, premembrane pressures were found to be 2.2 mmHg higher (95% confidence interval [CI]: -5.3 to 9.7) in the standard TPBAL setup compared to DVPD and 1.8 mmHg higher (95% CI: -5.3 to 8.9) than the postmembrane pressures. The DVPD provided an accurate measurement of circuit pressure as compared to the TPBAL setup. Across the range of pre- and postmembrane pressures, both methods reliably agreed. Future trials should investigate DVPD accuracy in different environments such as prehospital field cannulation or critical care transport of ECMO patients., Competing Interests: Disclosures: The authors have no conflicts of interest to report., (Copyright © ASAIO 2022.)

Background: We have previously demonstrated that xenogeneic bone marrow engraftment and donor-specific tolerance can be induced in mice receiving anti-CD4, -CD8, -Thy-1.2, and -NK1.1 monoclonal antibodies (mAbs) on Days -6 and -1, 3 Gy total body irradiation (TBI), and 7 Gy thymic irradiation on Day 0, followed by injection of T-cell depleted (TCD) rat bone marrow cells. We have recently demonstrated that anti-CD40L mAb treatment is sufficient to completely overcome CD4 cell-mediated resistance to allogeneic marrow engraftment and rapidly induce CD4 cell tolerance in an allogeneic combination., Methods: We investigated the ability of anti-CD40L mAb to promote mixed xenogeneic chimerism and donor-specific tolerance in B6 mice receiving anti-CD8, -Thy1.2 and -NK1.1 mAbs and 3 Gy TBI followed by TCD bone marrow transplantation (BMT) from F344 rats., Results: Administration of anti-CD4 mAb in this model could be completely replaced by one injection of anti-CD40L mAb. Evidence for deletional tolerance was obtained in mixed chimeras prepared with this anti-CD40L-based regimen. However, anti-NK1.1 and anti-Thy1.2 mAb could not be replaced by anti-CD40L mAb., Conclusions: These results demonstrate that anti-CD40L in combination with xenogeneic BMT can tolerize preexisting peripheral and intrathymic CD4 cells to xenoantigens. However, anti-CD40L does not prevent NK cell and/or gammaDelta cell-mediated rejection of xenogeneic bone marrow.

We initiated a clinical trial of nonmyeloablative haploidentical stem-cell transplantation (SCT) using MEDI-507, an immunoglobulin-G1 monoclonal anti-CD2 antibody. The trial was based on a preclinical major histocompatibility complex-mismatched bone marrow transplant model in which graft-versus-host disease (GVHD) was prevented and mixed chimerism as a platform for adoptive cellular immunotherapy was reliably induced. Twelve patients (three cohorts of four patients each) received cyclophosphamide, MEDI-507, and haploidentical unmanipulated bone marrow (n=8) or ex vivo T-cell-depleted peripheral blood stem cells (n=4) for chemorefractory hematologic malignancy. A two-dose regimen and schedule modifications of MEDI-507 were undertaken because of graft loss in the first cohort of four patients and GVHD in the second cohort. With ex vivo T-cell-depleted peripheral blood SCT, mixed chimerism occurred in all four patients without GVHD. Two patients, however, subsequently lost their grafts. Nonmyeloablative preparative therapy with MEDI-507 and haploidentical SCT have led to the reliable induction of at least transient mixed chimerism as a potential platform for adoptive cellular immunotherapy.

We investigated the effects of hypoxia/reoxygenation exposure on the barrier function of endothelial cell monolayers. Bovine pulmonary microvessel endothelial cells were grown to confluence on microporous filters (0.8-microns pore diameter) and exposed to hypoxia (0.1% O2 or PO2 approximately 1 mm Hg) for 2, 4, 12, or 24 hours, followed by reoxygenation with room air for a period ranging from 16 seconds to 2 hours. The transendothelial clearance rate of 125I-albumin was measured to determine the permeability of endothelial monolayers. Permeability increased twofold or fivefold over control values after 1 hour of reoxygenation in monolayers that had been exposed to either 12 or 24 hours of hypoxia. The response occurred within 5 minutes of reoxygenation, increased maximally by 40 minutes, and remained elevated with continuous reoxygenation for up to 2 hours. The increase in permeability was associated with F-actin reorganization, a change to spindlelike cells, and injured mitochondria. Immunoblot analysis indicated that neither hypoxia alone nor reoxygenation changed CuZn superoxide dismutase (SOD), MnSOD, and catalase levels. However, release of superoxide anions (O2-) into the extracellular medium increased by twofold within 40-60 minutes of reoxygenation. Treatment of endothelial cells with CuZnSOD (100 units/ml) for the 24-hour hypoxia period prevented O2- generation and approximately 50% of the increase in permeability. Higher CuZnSOD concentrations (greater than or equal to 200 units/ml) were not protective. Treatment with catalase (100-1,000 units/ml) inhibited the reoxygenation-induced increase in permeability at the highest catalase concentration (1,000 units/ml), suggesting a critical role of hydrogen peroxide in mediating the response.(ABSTRACT TRUNCATED AT 250 WORDS)

ASL-8052, a novel beta-adrenergic receptor antagonist, was studied in isolated guinea pig cardiac and tracheal tissues, in isolated frog sciatic nerves, and in anesthetized dogs. The compound was a moderately potent beta-adrenoceptor antagonist in right atria (pA2 6.96) but was much less active in tracheal tissues (pA2 5.33), indicating cardioselective properties. ASL-8052 possessed a small degree of intrinsic sympathomimetic action in isolated guinea pig right atria and caused direct cardiac depression only at concentrations 1,000-fold higher than its cardiac pA2. Significant local anesthetic action in frog sciatic nerve occurred at extremely high concentrations of ASL-8052 (greater than 0.1 M). In anesthetized dogs, ASL-8052 produced steady-state levels of beta-blockade within 10 min during a 3-h intravenous infusion. In contrast, propranolol produced increasing levels of blockade throughout most of the infusion period. Recovery from beta-blockade occurred rapidly following termination of ASL-8052 infusion (80% recovery in approximately 12 min), whereas very little recovery occurred following cessation of propranolol infusion. Intravenous infusion of ASL-8052 produced dose-dependent blockade of cardiac responses to isoproterenol but only minimally decreased hindlimb vascular responses to isoproterenol. The results indicate that ASL-8052 is a novel cardioselective beta-blocker with an ultrashort duration of action.

The effects of halothane, enflurane, and isoflurane were studied at 0.5, 0.75, and 1 MAC in 60% N2O on subcortical sensory evoked potentials recorded at the popliteal fossa (PF), the spine (L-3, C-6) and on cortical potentials recorded at the scalp (SC) following bilateral posterior tibial nerve stimulations at the ankle in 28 patients undergoing scoliosis surgery. Latencies and amplitudes of the resulting potentials at each level were compared with postinduction control values. With increasing MAC, latency and amplitude changes seen at C6 (subcortical) were also compared with those at SC (cortical). Increasing the concentrations of each agent resulted in a graded increase in latency and a graded decrease in amplitude, at all levels. At SC each increase in MAC with each agent resulted in an increase in latency (P less than 0.05) and a decrease in amplitude (P less than 0.005), respectively. The increases in SC latency at 0.75, 1 MAC were larger than the increase in latency at C-6 (P less than 0.005) and the decreases in SC amplitudes at 0.5, 0.75 and 1 MAC were greater than the decrease in amplitude at C-6 (P less than 0.01). Halothane, enflurane, and isoflurane in 60% N2O altered subcortical potentials less than cortical potentials. Enflurane and isoflurane at 0.5, 0.75, and 1 MAC, and halothane at 0.5, 0.75 MAC maintained subcortical and cortical potentials that were adequate for evaluation. However, 1 MAC of halothane suppressed cortical potentials but maintained subcortical potentials. Subcortical C-6 potential may serve as an additional monitor.

Our purpose in this study was to evaluate the tensile properties of expanded skin. In five guinea pigs, 29-cc ovoid tissue expanders were placed and sequentially expanded every 4 days until maximum volume was achieved. Five control and five expanded skins were harvested. Using an Instron tensile testing apparatus, skins were evaluated for stress-strain, maximum stiffness, and tensile strength, and the results were statistically compared. Centrally located expanded specimens demonstrated significantly weaker stress-strain values: 9.51 in.lb/in3 for expanded versus 30.11 in.lb/in3 for control (p less than 0.001). Maximum stiffness was similarly reduced: 4.56 lb/mm2 for expanded vs. 12.98 lb/mm2 for control (p less than 0.001). This is a 67.4 and 64.9 percent reduction, respectively, for the stress-strain and maximum stiffness. No statistically significant difference was seen in peripherally located expanded specimens relative to the controls: stress-strain expanded, 28.7 in.lb/in3 (p greater than 0.5); maximum stiffness expanded, 12.84 lb/mm2 (p greater than 0.5). Expanded skin demonstrated an average 35 percent reduction in tensile strength. We conclude that the tensile properties of expanded skin are significantly less than unexpanded skin and are a function of the degree of expansion.

Eleven canine experiments were performed to demonstrate the advantages of immediate vascular preservation in ribs used to fill a surgically created osseous gap bridging three vertebral bodies. In the five vascular rib grafts, mean blood flow was retained and measured at .101/ml/min/ml bone tissue. At autopsy 3 months post-operatively, vascularized grafts were more robust and hypertrophic. Mechanical testing in six stiffness modes confirmed the advantage of vascularized grafts. The experimental results indicate that vascularized grafts retain greater viability and better mechanical properties during graft incorporation. Providing a vascularized construct may be helpful in reconstructing large vertebral osseous gaps.

The authors have previously reported work demonstrating the superiority of vascularized vs. nonvascularized rib grafts, which were inlaid to bridge three vertebral bodies studied at 3 months postoperatively. They questioned whether the mechanical and biologic properties of the nonvascular grafts would improve over time to approach the performance of the vascularized grafts by 6 months. They found that, with increased time, the vascularized grafts continued to improve, showing hypertrophy, maintenance of cortical integrity, and bonding to the recipient vertebral bodies. The nonvascularized grafts, however, showed porosity, fragmentation, and replacement by spongiosa. Mechanical properties showed increased performance in the vascularized vs. nonvascularized grafts, and no improvement was seen between the nonvascularized grafts from 3 to 6 months.

We have studied the effect of angiotensin II and bradykinin on prostaglandin output and vascular tone during extracellular calcium depletion and administration of calcium antagonists and calmodulin inhibitors to elucidate the mechanism of action in the isolated rat kidney perfused with Tyrode's solution. Administration of angiotensin II (0.028-0.28 nmol) or bradykinin (0.28-2.8 nmol) enhanced the output of prostaglandin E2 and 6-keto-prostaglandin F1 alpha in a dose-dependent manner. Angiotensin II, but not bradykinin, produced renal vasoconstriction. Omission of calcium from the medium or infusion of calcium entry blockers, diltiazem (60 microM), or nimodipine (47 microM), failed to alter prostaglandin output elicited by angiotensin II or bradykinin; however, the effect of angiotensin II to produce renal vasoconstriction was inhibited. If calcium was omitted from the medium, the intracellular calcium antagonists, 8-(diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride (23 microM), dantrolene sodium (31 microM), or ryanodine (2 microM), attenuated prostaglandin output caused by angiotensin II but not bradykinin. Calmodulin inhibitors, trifluoperazine (2 microM), napthalene sulfonamide hydrochloride (2 microM), or calmidazolium (2 microM), diminished prostaglandin output elicited by angiotensin II, but not that caused by bradykinin. Trifluoperazine, but not naphthalene sulfonamide or calmidazolium, attenuated the renal vasoconstrictor effect of angiotensin II. Prostaglandin output induced by angiotensin II and bradykinin were inhibited by mepacrine and indomethacin, whereas, the prostaglandin output caused by exogenous arachidonic acid (33 nmol) was abolished by indomethacin but was unaltered by mepacrine, calcium antagonists, and calmodulin inhibitors. From these data, we conclude that angiotensin II produces renal vasoconstriction by a mechanism dependent on extracellular calcium but not calmodulin, whereas angiotensin II-induced prostaglandin output depends on intracellular calcium and calmodulin. In contrast, bradykinin appears to stimulate prostaglandin synthesis by a calcium/calmodulin-independent mechanism.

The cardiac effects of berberine were studied in isolated right and left atrial preparations from guinea pigs. In spontaneously beating right atria, berberine (1 X 10(-5) -3 X 10(-4) M) caused bradycardia, which was not prevented by atropine (1 X 10(-7) M). Over the same concentration range, berberine increased developed force (dF) in left atria electrically driven at 1.5 Hz. This occurred in both untreated and reserpine-treated tissues as well as in the presence of 5 X 10(-7) M propranolol and 1 X 10(-5) M phentolamine. At a stimulation frequency of 1.5 Hz, left atrial responses to each concentration of berberine reached steady state in approximately 10 min. Concentrations of berberine greater than 3 X 10(-4) M depressed dF and increased resting tone until eventually the left atria failed to contract. Analysis of the effects of berberine on the contractile waveform of left atria showed a concentration-dependent increase in maximal positive dF/dt, maximal negative dF/dt, time to peak tension, and relaxation time. When maximal negative dF/dt was normalized for changes in dF (-dF/dt/dF), berberine showed inhibition of the relaxation process. Berberine had only slight effects on post-rest potentiation and paired pulse stimulation, but enhanced the response of left atria to increases in stimulation frequency. From these results, it appears that berberine has a unique profile of action in isolated guinea pig atrial tissue, showing both positive inotropic and negative chronotropic activity. Berberine produces its positive inotropic effect by enhancing both the force-velocity relationship and the duration of the active state.(ABSTRACT TRUNCATED AT 250 WORDS)

The beta-adrenoreceptor antagonist properties of ASL-8123, the primary metabolite of esmolol, were determined in vitro and in vivo. ASL-8123 demonstrated weak competitive beta-adrenoreceptor blocking activity in isolated guinea pig right atria with a pA2 of 3.73 +/- 0.07; no agonist-like activity was observed in this tissue at concentrations of ASL-8123 from 3 X 10(-5) to 1 X 10(-2) M. In anesthetized dogs, ASL-8123 was infused at increasing dosages from 0.2-25.6 mg/kg/min, each dose rate maintained for 20 min. The compound produced a slight decrease in heart rate of 15-22 beats/min at cumulative doses of 508-1,020 mg/kg and decreased diastolic blood pressure by 14-47 mm Hg at cumulative doses of 252-1,020 mg/kg. ASL-8123 dose-dependently inhibited the heart rate and diastolic blood pressure responses to isoproterenol (0.5 micrograms/kg i.v.). Blood levels of ASL-8123 were linearly correlated with inhibition of the heart rate response to isoproterenol (r = 0.95-0.99 for each dog, n = 6). The blood level of ASL-8123 that produced a 50% inhibition of isoproterenol-induced tachycardia averaged 293 +/- 65 micrograms/ml. Recovery from beta-adrenoreceptor blockade after terminating the infusion of ASL-8123 occurred slowly, decreasing from 81% at the end of the infusion to 55% 60 min later, and was paralleled by a slow decrease in blood levels of ASL-8123. Thus, ASL-8123 is a weak beta-adrenoreceptor antagonist which is approximately 1,600-1,900 times less potent than its parent, esmolol.

The effects of 0.5, 0.75, and 1 MAC of halothane, enflurane, and isoflurane in 60% nitrous oxide on somatosensory cortical evoked potentials were studied in 30 patients undergoing corrective surgery for scoliosis. The evoked potentials were averaged at the scalp from the electroencephalogram following repeated bilateral posterior tibial nerve stimulation at the ankle. Latencies and amplitudes of the resulting potentials were measured and compared with the post-induction control values. Graded increase in latencies and graded decrease in amplitudes were found with increasing concentrations of all the three agents (P less than 0.05), confirming that the effects were dose related. Reductions in amplitudes were more marked than increase in latencies. The authors conclude that, during nitrous oxide-based anesthesia, enflurane, and isoflurane resulted in less alteration of somatosensory cortical evoked potentials than halothane. In conjunction with 60% nitrous oxide, 0.5 and 0.75 MAC of halothane, 0.5, 0.75, and 1.0 MAC of isoflurane and enflurane, respectively, were found to be compatible with the generation of waves adequate for evaluation.

Eighty-six patients with idiopathic scoliosis who underwent a posterior spinal fusion using sublaminar segmental spinal instrumentation were analyzed retrospectively. There were two operative groups: group 1, 66 patients who had Harrington rod instrumentation and segmental wiring, and group 2, 20 patients who had Luque rod instrumentation. The clinical and radiographic data of the two groups were similar except for the passage of more sublaminar wires and increased intraoperative blood loss in group 2. Twenty intraoperative or postoperative complications occurred in 19 patients (22%) including 14 neurologic complications. Three patients (3%) had major spinal cord injuries, while 11 patients (13%) had transient sensory changes. There was no significant difference in the incidence of neurologic complications between group 1 or group 2. The remaining intraoperative complications were due either to anesthesia, positioning during surgery, or technique (dural tear). Late complications occurred in two patients in group 1 only: one each with rod breakage and hook displacement. Only one patient (1%) has required additional surgery. Our results indicate that although segmental instrumentation can be beneficial in idiopathic scoliosis, the incidence of complications, primarily neurologic, will be higher than expected. The major reason appears to be surgeon inexperience with passage of sublaminar wires. As experience increases, the incidence of complications declines and becomes comparable with conventional Harrington rod instrumentation alone.

Twelve canine rib transposition grafts were harvested and evaluated for preservation of subperiosteal and medullary canal blood flow using the hydrogen washout technique. Blood flow using hydrogen washout technique also was studied in the T11 vertebral body. The mean hydrogen washout blood flow was 0.201 ml/min/ml tissue for the subperiosteal rib measurement, 0.058 ml/min/ml tissue for a rib medullary measurement, and 0.085 ml/min/ml tissue for the vertebral body. The medullary canal hydrogen washout values were consistently less than the subperiosteal values. The results have demonstrated that the blood supply to the vascularized rib pedicle can be retained and quantitated in harvesting the rib graft using the hydrogen washout technique.