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Biomedical subjects

G Edelman

Publications and source records attributed to G Edelman.

31 records · Page 2Linked to original sources

Brain tissue oxygen pressure, carbon dioxide pressure, and pH during hypothermic circulatory arrest.

BACKGROUND: This study evaluated brain tissue oxygen pressure (PO2), carbon dioxide pressure (PCO2), and pH in a patient during hypothermic circulatory arrest. METHODS: A combined PO2, PCO2, and pH sensor was placed in cortex tissue. Brain temperature was then decreased to 17 degrees C followed by circulatory arrest for 44 minutes during an endarterectomy of the M1 segment of the middle cerebral artery. RESULTS: Brain tissue PO2 increased during brain cooling from 10 mmHg-30 mmHg and decreased to zero following exsanguination. During circulatory arrest, tissue PCO2 increased to >200 mmHg and pH decreased to 6.0. Tissue PCO2 and pH recovered during circulatory rewarming but the increase in PO2 was delayed. Tissue parameters continued to improve during 2 days of postsurgical monitoring and were correlated with neurologic recovery. CONCLUSIONS: These results show that brain tissue PO2, PCO2, and pH measures indicate the severity of ischemia during hypothermic cardiac arrest and recovery in the postoperative period.

Arterial Occlusive Diseases↗

Brain tissue oxygen pressure, carbon dioxide pressure and pH during ischemia.

In this case we evaluated brain tissue pO2, pCO2 and pH during ischemia and arterial oxygen desaturation (hypoxia). In both situations brain pO2 decreased. During ischemia, tissue pCO2 increased while pH decreased; but both pCO2 and pH were stable during hypoxia. These results suggest that brain tissue pO2, pCO2 and pH measures provide information on tissue perfusion and oxygen availability during ischemia and hypoxia.

Brain↗

Brain tissue oxygen, carbon dioxide, and pH in neurosurgical patients at risk for ischemia.

A sensor that measures oxygen pressure (PO2), carbon dioxide pressure (PCO2), and pH was evaluated in brain tissue of patients at risk for ischemia. The sensor is 0.5 mm in diameter and was inserted into cortex tissue in 14 patients undergoing craniotomy for cerebrovascular surgery. A compromised cerebral circulation was identified in 8 of 14 patients by single photon emission computed tomography (SPECT) scan, cerebral angiography, and transient ischemic episodes before surgery. Under baseline conditions with isoflurane anesthesia and normal blood gases, tissue P02 was lower in the eight compromised compared to six noncompromised patients (noncompromised 37 +/- 12 mm Hg, compromised 10 +/- 5 mm Hg; P < 0.05), PCO2 was increased (noncompromised 49 +/- 5 mm Hg, compromised 72 +/- 23 mm Hg; P < 0.05), and pH was decreased (noncompromised 7.16 +/- 0.08, compromised 6.82 +/- 0.21; P < 0.05). Critical tissue values for the identification of ischemia were a P02 of 20 mm Hg, PCO2 of 60 mm Hg, and a pH of 7.0. These results suggest that brain tissue measures of P02, PCO2, and pH provide information on the adequacy of cerebral perfusion in neurosurgical patients.

Adult↗

Brain tissue response to CO2 in patients with arteriovenous malformation.

We tested whether cerebral arteriovenous malformations (AVM) alter brain tissue oxygen pressure, PO2, carbon dioxide pressure PCO2, and pH before, during, and after hypercapnia. A craniotomy was performed and a sensor inserted into normal brain tissue (control) (n = 7) or into tissue adjacent to an AVM (n = 9). Under baseline conditions, tissue PO2 was 80% lower in AVM compared to control patients, but PCO2 and pH were normal. During a 10 mm Hg increase in PaCO2, tissue PO2 increased only in AVM patients, PCO2 increased in both groups, and pH decreased only in controls. When hypercapnia was reversed, tissue PCO2 decreased below baseline and pH increased in AVM patients. Results suggest that tissue CO2 washout and elevated pH result from increases in blood flow during hypercapnia. This response may be related to symptoms of hyperperfusion during AVM resection.

Brain↗

Comparison of isoflurane and desflurane anesthetic depth using burst suppression of the electroencephalogram in neurosurgical patients.

We compared the anesthetic effects of desflurane and isoflurane using percent burst suppression of the electroencephalogram (EEG) as an end-point in 10 neurosurgical patients. The EEG was recorded from frontal leads and processed variables were analyzed as a function of increasing isoflurane and desflurane concentration with age and baseline delta EEG power (0.5-3.75 Hz) as independent variables. Isoflurane and desflurane (0.5, 1.0, 1.5, 2.0 minimum alveolar anesthetic concentration [MAC]) were incrementally administered until the EEG was quiesecent at least 40% of the time. Both anesthetics were evaluated separately in each patient. By analysis of variance, isoflurane and desflurane produced dose-related increments in burst suppression which were significantly affected by the age and baseline delta EEG of the patient. When isoflurane and desflurane were equated by MAC and adjusted for age, they produced statistically similar patterns of EEG burst suppression. Within subjects, a high degree of correlation was observed for percent burst suppression between equipotent levels of isoflurane and desflurane (r = 0.85; P < 0.05). Patients with baseline delta EEG power less than 80% of total power showed increases in delta EEG and decreases in median frequency with isoflurane and desflurane. Patients with baseline delta EEG power > 80% of total power produced no change in EEG frequency with increasing anesthesia but revealed a greater sensitivity to the development of burst suppression. These results show that isoflurane and desflurane produce similar EEG suppression in neurosurgical patients. If the EEG is initially slow, further slowing cannot be used to assess anesthetic depth.

Adult↗

Nitrous oxide added to isoflurane increases brain artery blood flow and low frequency brain electrical activity.

Although changes in cerebral blood flow (CBF) and the electroencephalogram (EEG) have been reported with nitrous oxide (N2O) administration, the interaction of these parameters is unclear. The purpose of this study was to measure CBF and EEG during N2O administration in eight patients. A craniotomy was performed and CBF was measured in major brain arteries using a transit time Doppler flowmeter. EEG was recorded bilaterally from frontooccipital leads. Power spectrum analysis was performed on the EEG and power for delta, theta, alpha, and beta frequency bands analyzed over time. Arterial blood pressure was recorded continuously. N2O (66%) was added to the inspired gases during isoflurane anesthesia (0.8% end tidal) under hypocapnic (Paco2 = 29 mm Hg) and normocapnic conditions (Paco2 = 39 mm Hg). During hypocapnia, N2O administration decreased alpha EEG activity and increased delta activity but did not change CBF. During normacapnia, N2O produced similar but greater changes in EEG and increased CBF 39%. In three patients, the isoflurane concentration was increased to 1.6% end tidal during normocapnia. N2O administration in these patients also enhanced delta EEG activity and increased CBF. The slowing of EEG activity with N2O is temporally related to increases in CBF during normocapnia. Hypocapnia abolished the increase in CBF during N2O and attenuated the shift of EEG to delta activity.

Adult↗

Brain tissue acid-base response to hypercapnia in neurosurgical patients.

These studies were conducted in neurosurgical patients to determine brain tissue nonbicarbonate buffering of pH changes during hypercapnia. Following a craniotomy, a sensor which continuously measures oxygen pressure, carbon dioxide pressure, pH and temperature was inserted into cortex tissue of nine subjects. Bicarbonate concentration was calculated from the Henderson-Hasselbach equation. Following baseline measures, PaCO2 was increased 10mmHg for 10 min. Tissue pCO2 increased 9 mmHg (p < 0.05) without a change in tissue pO2. In six patients, tissue bicarbonate concentration increased from 18 to 20 meq L-1 (p < 0.05), indicating a 40-50% attenuation of the increase in hydrogen ion (H+) by nonbicarbonate buffering mechanisms. Three patients showed no increase in tissue bicarbonate during hypercapnia; 2 had baseline tissue pH less than 6.5 and one displayed signs of tissue hypoxia during the CO2 challenge. In all patients, increases in tissue H+ during hypercapnia were related to baseline tissue bicarbonate concentration. Marked increases in H+ were seen when baseline bicarbonate decreased below 10 meq L-1. These results suggest that when tissue bicarbonate is depleted, the risk of H+ induced injury during hypercapnia is increased.

Acid-Base Imbalance↗

Cerebral and spinal cord blood flow in awake and fentanyl-N2O anesthetized rats: evidence for preservation of blood flow autoregulation during anesthesia.

Blood flow responses to alterations in mean arterial blood pressure (MABP) were measured in the cerebral cortex, subcortex, midbrain, and spinal cord of awake rats. Data were compared with those of rats anesthetized with an i.v. fentanyl infusion and inspired nitrous oxide (N2O). Regional cerebral blood flow was measured using radioactive microspheres in the following blood pressure ranges: (a) <40 mm Hg; (b) 40-60; (c) 60-80; (d) 80-100; (e) 100-120; (f) 120-140; (g) 140-160; and (h) >160. Blood pressure was increased with phenylephrine or decreased with trimethaphan combined with blood withdrawal. Cerebral blood flow was not measured when MABP was less than 60 mm Hg in awake rats. Autoregulation was seen in all brain areas between 60 and 140 mm Hg in both treatment groups. Although regional cerebral blood flow was not different between the two treatment groups, PaCO2 was 2-4 mm Hg lower in awake rats. This suggests that PaCO2-corrected cerebral blood flow may be 10-20% lower with fentanyl-N2O anesthesia.

Journal Article↗

Cerebral autoregulation in awake versus isoflurane-anesthetized rats.

We evaluated regional cerebral and spinal cord blood flow in rats during isoflurane anesthesia. Tissue blood flow was measured in cerebral cortex, subcortex, midbrain, and spinal cord using radioactive microspheres. Blood flow autoregulation was measured within the following arterial blood pressure ranges (mm Hg): 1 = less than 50, 2 = 50-90, 3 = 90-130, 4 = 130-170, 5 = greater than 170. Arterial blood pressure was increased using phenylephrine infusion and decreased with ganglionic blockade and hemorrhage. Three treatment groups were studied: 1 = awake control, 2 = 1.0 minimum alveolar anesthetic concentration (MAC) isoflurane, 3 = 2.0 MAC isoflurane. Autoregulation was seen in awake rats from 50 to 170 mm Hg in all tissues. The autoregulatory coefficient (change in blood flow/change in blood pressure) was increased in midbrain and spinal cord during 1.0 MAC isoflurane and in all tissues during 2.0 MAC isoflurane (P less than 0.05). Within the arterial blood pressure range of 90-130 mm Hg, isoflurane produced the following changes in tissue blood flow (percent of awake control): 1.0 MAC isoflurane: cortex = 87% +/- 8% (P greater than 0.30), subcortex = 124% +/- 11% (P greater than 0.05), midbrain = 263% +/- 20% (P less than 0.001), spinal cord = 278% +/- 19% (P less than 0.001); 2.0 MAC isoflurane: cortex = 137% +/- 13% (P less than 0.05), subcortex = 272% +/- 24% (P less than 0.001), midbrain = 510% +/- 53% (P less than 0.001), spinal cord = 535% +/- 50% (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗

Fetal islet allotransplantation in rabbits.

Haploidentical fetal rabbit islets were transplanted into the renal subcapsular space of outbred maternal hosts. Islets were prepared by a mild collagenase digestion and were cultured in air and a high oxygen environment for 10 days prior to implantation. Grafts were examined at 14 days and later. No grafts survived in the absence of host immunosuppression, even when treatment of the donor tissue included both culture and ultraviolet-B irradiation (groups 1 and 3). With a high dose of oral cyclosporine, 30 mg/kg/day on days 0-3, viable but disrupted islets were present in 1/7 recipients of islets treated by culture alone. Only with high-dose peritransplant cyclosporine or chronic low-dose immunosuppression, and islet treatment with UVB and culture, was regular graft survival achieved (groups 4A and 5). These results demonstrate that haploidentical outbred hosts can be made to accept fetal islet allografts pretreated by UVB irradiation and culture in a high oxygen environment only if the recipient is given a high peritransplant dose of oral cyclosporine (30 mg/kg/day) or chronic low-dose cyclosporine, (10 mg/kg/day).

Animals↗

A comparative study of electrocoagulation and tubal rings for tubal occlusion at laparoscopy.

The surgical and early postoperative complications and complaints associated with laparoscopic sterilization using electrocoagulation or tubal rings for tubal occlusion were evaluated in a comparative study. Procedures were randomly assigned to subjects (electrocoagulation to 151 subjects and tubal rings to 148 subjects). Difficulties in carrying out the sterillization procedures occurred more frequently when tubal rings were used (6.1%) than when electrocoagulation was used (2.0%). Rates of complications occurring at the time of surgery were similar for the two procedures. However, one patient in the electrocoagulation group had a bowel burn. Postoperative pelvic and abdominal pain were reported by a significantly higher proportion of the tubal ring cases (32.0%) than electrocoagulation cases (19.4%). It appears that although the incidence of surgical difficulties and pain may be somewhat more frequent with the tubal ring, the avoidance of such potentially serious complications as bowel burns may make femal sterilization by the tubal ring method preferable.

Electrocoagulation↗

Phase I trial of interferon-gamma (IFN-gamma) retroviral vector administered intratumorally to patients with metastatic melanoma.

BACKGROUND: Interferon-gamma (IFN-gamma) gene/retroviral vector cell vaccinations have generated protective responses from unmodified tumor cell challenges as well as a regression of established tumors in animal models. The purpose of this trial was to determine the feasibility and safety of a direct intratumoral injection of IFN-gamma retroviral vector in advanced melanoma patients. METHODS: This was a phase I study, in which 13 patients received a single daily injection of a retroviral vector with the IFN-gamma gene for 5 consecutive days (1.5 x 10(8) colony-forming units total dose); patients subsequently underwent resection of the injected lesion to confirm DNA transduction in situ. RESULTS: No toxicity related to the injected vector was observed. Replication competent retrovirus was not observed in any prepared samples (n = 65). IFN-gamma expression was confirmed in 3 of 10 harvested tumor samples; one was equivocal, and DNA transduction was unable to be confirmed by enzyme-linked immunospot assay in six samples. CONCLUSIONS: An injection of IFN-gamma gene/retroviral vector is well tolerated. DNA transduction was demonstrated in human subjects, confirming the feasibility of the direct injection approach for the gene therapy of solid tumors. Further trials to determine optimal schedule and potential efficacy are indicated.

Adult↗

Phase I trial of retroviral vector-mediated interferon (IFN)-gamma gene transfer into autologous tumor cells in patients with metastatic melanoma.

The purpose of this study was to determine the safety of treating melanoma patients with retroviral vector-mediated interferon (IFN)-gamma gene-transduced autologous tumor cells. We designed a phase I study, in which irradiated, autologous, transduced melanoma cells expressing the IFN-gamma gene were injected subcutaneously every 2 weeks with escalating cell doses for six injections. Tumor tissue was harvested from 58 patients with metastatic melanoma. Twelve patients had sufficient expansion of autologous tumor (0.56-160 x 10(7) cells) and adequate IFN-gamma expression after gene transduction (2-79,000 U/10(6) cells/24 hours) for injections. Five patients received injections. No toxicity was attributed to the IFN-gamma retroviral vector in the patients injected. One of the injected patients remains disease-free after 13 injections, following the surgical removal of brain, adrenal, and lung metastases. We found that injections of autologous tumor cells transduced by IFN-gamma gene were well tolerated. However, the ability to develop primary autologous melanoma cell lines was limited, and only a minority of patients were injected.

Adolescent↗