Search PubMed⌕ Search

Biomedical subjects

K Oku

Publications and source records attributed to K Oku.

At least 37 records · Page 2Linked to original sources

Cerebral and systemic arteriovenous oxygen monitoring after cardiac arrest. Inadequate cerebral oxygen delivery.

BACKGROUND: After prolonged cardiac arrest, under controlled normotension, cardiac output and cerebral blood flow are reduced for several hours. This dog study documents for the first time the postarrest reduction in oxygen (O2) delivery in relation to O2 uptake for brain and entire organism. METHODS: In eight dogs we used our model of ventricular fibrillation (VF) cardiac arrest of 12.5 min, reperfusion with brief cardiopulmonary bypass, and controlled normotension, normoxemia, and mild hypocapnia to 24 h. RESULTS: Between 4 and 24 h after cardiac arrest, cardiac output decreased by about 25% and the systemic arteriovenous O2 content difference doubled, while the calculated systemic O2 utilization coefficient (O2 UC) increased and the systemic venous PO2 decreased, both not to critical levels. The cerebral arteriovenous O2 content difference however, which was 5.6 +/- 1.7 ml/dl before arrest, increased between 1 and 18 h, to 10.8 +/- 3.2 ml/dl at 4 h. The cerebral O2 UC increased and the cerebral venous PO2 decreased, both to critical levels. CONCLUSIONS: After prolonged cardiac arrest in dogs with previously fit hearts, the reduction of O2 transport to the brain is worse than its reduction to the whole organism. Monitoring these values might help in titrating life-support therapies.

Animals↗

Mild hypothermia after cardiac arrest in dogs does not affect postarrest cerebral oxygen uptake/delivery mismatching.

PURPOSE: To compare measurements of cerebral arteriovenous oxygen content differences (oxygen extraction ratios, oxygen utilization coefficients) in dogs after cardiac arrest, resuscitated under normothermia vs. mild hypothermia for 1-2 h or 12 h. METHODS: In 20 dogs, we used our model of ventricular fibrillation (no blood flow) of 12.5 min, reperfusion with brief cardiopulmonary bypass, and controlled ventilation, normotension, normoxemia, and mild hypocapnia to 24 h. We compared a normothermic control Group I (37.5 degrees C) (n = 8); with brief mild hypothermia in Group II (core and tympanic membrane temperature about 34 degrees C during the first hour after arrest) (n = 6); and with prolonged mild hypothermia in Group III (34 degrees C during the first 12 h after arrest) (n = 6). RESULTS: In Group I, the cerebral arteriovenous O2 content difference was 5.6 +/- 1.6 ml/dl before arrest; was low during reperfusion (transient hyperemia) and increased (worsened) significantly to 8.8 +/- 2.8 ml/dl at 1 h, remained increased until 18 h, and returned to baseline levels at 24 h after reperfusion. These values were not significantly different in hypothermic Groups II and III. The cerebral venous (saggital sinus) PO2 (PssO2) was about 40 mmHg (range 29-53) in all three groups before arrest and decreased significantly below baseline values, between 1 h and 18 h after arrest; the lowest mean values were 19 +/- 19 mmHg in Group I, 15 +/- 8 in Group II (NS), and 21 +/- 3 in Group III (NS). Postarrest PssO2 values of < or = 20 mmHg were found in 6/8 dogs in Group I, 5/6 in Group II and 4/6 in Group III. Among the 120 values of PssO2 measured between 1 h and 18 h after arrest, 32 were below the critical value of 20 mmHg. CONCLUSIONS: After prolonged cardiac arrest, critically low cerebral venous O2 values suggest inadequate cerebral O2 delivery. Brief or prolonged mild hypothermia after arrest does not mitigate the postarrest cerebral O2 uptake/delivery mismatching.

Animals↗

Growth-regulatory mechanism of two human esophageal-cancer cell lines in protein-free conditions.

We investigated the growth-regulatory mechanism of 2 esophageal squamous-cancer cell lines, TE2-NS and TE3-OS cells, both of which can grow stably in protein-free conditions in vitro. Protein-free conditioned media from TE2-NS and TE3-OS cells stimulated the growth of these cells. Exogenous epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), insulin-like growth factor (IGF)-I and -II enhanced cell proliferation by 2.2- to 3.8-fold in protein-free conditions, as compared with an untreated control. Receptor-binding assays showed that both TE2-NS and TE3-OS cells possessed a single class of high-affinity binding sites for IGF-I and 2 classes of binding sites for TGF-alpha, as confirmed on the cell membrane by immunochemistry. These results suggest that EGF, TGF-alpha and IGFs are candidates for the autocrine growth factor in cancer cells. The addition of inhibitory monoclonal antibodies against TGF-alpha and EGFR, but not those against either EGF or IGF-IR, significantly inhibited growth of the cells. Immunocytochemical staining and ELISA of the conditioned media both confirmed the production of TGF-alpha protein, but not EGF protein, in these cell lines. The data for a protein-free culture system strongly suggested that TGF-alpha, but not EGF or IGF, is biologically important as an autocrine growth factor in the growth of these cell lines in vitro.

Antibodies, Monoclonal↗

Systematic development of cerebral resuscitation after cardiac arrest. Three promising treatments: cardiopulmonary bypass, hypertensive hemodilution, and mild hypothermia.

Since 1970 we have investigated postischemic anoxic encephalopathy and potential treatments for cerebral resuscitation after cardiac arrest by cardiopulmonary-cerebral resuscitation (CPCR). The post-resuscitation syndrome has been studied at the levels of cell, organ, organism and community. Short-term and long-term models in rats, dogs, and monkeys have been developed, and an international multicenter randomized clinical trial mechanism was established. Clinical studies disproved the 5-min limit of reversible cardiac arrest and yielded other valuable data on treatments and prognostication. Thiopental loading or calcium entry blocker therapy (lidoflazine) gave no significant improvement in patients. Free radical scavengers are under investigation in the laboratory. We hypothesize that post-arrest perfusion failure and necrotizing cascades require etiology-specific combination treatments. Standard (control) therapy in a current dog model of cardiac arrest (no flow) of 12.5-20 min, reperfusion with cardiopulmonary bypass, and intensive care for 72-96 h has consistently resulted in survival with brain damage. After ventricular-fibrillation (VF) arrest of 17 min, moderate hypothermia (28-32 degrees C) inconsistently improved cerebral outcome. After VF arrest of 12.5 min, hypertension plus hemodilution normalized the local (multifocal) cerebral hypoperfusion post-arrest and, again, inconsistently improved cerebral outcome. Additional mild hypothermia (34-36 degrees C), however, consistently improved cerebral outcome, whether induced before or during and after arrest.

Animals↗

Detoxification with hemabsorption after cardiac arrest does not improve neurologic recovery. Review and outcome study in dogs.

We and others hypothesized that noxious substances released after prolonged cardiac arrest from malfunctioning liver, kidneys, or intestine (e.g. bacterial toxins, aromatic amino acids), might hamper recovery of the brain. The highly detoxifying effect of hemabsorption (i.e. hemoperfusion) with microencapsulated activated carbon has been demonstrated in other diseases. We used our dog model of ventricular fibrillation cardiac arrest of 15 min (n = 2 x 4) or 12.5 min (n = 2 x 6), reversed by brief (high flow) cardiopulmonary bypass (CPB). In half of the dogs in each insult group, a charcoal filter (HemoKart) was inserted into the circuit of CPB at low flow, from start of reperfusion to 4 h. Intermittent positive pressure ventilation was to 20 h and intensive care to 96 h after cardiac arrest. Bacterial blood cultures were positive in most of the dogs in both groups 30 min to 20 h after cardiac arrest (but not later) and were uninfluenced by hemabsorption. In the control groups to 4 h after cardiac arrest, serum levels of potentially injurious aromatic amino acids (e.g. phenylalanine, tyrosine) and of branched-chain/aromatic amino acid ratios, remained unchanged. From 12 to 48 h after cardiac arrest, aromatic amino acid levels increased (worsened). The branched-chain/aromatic amino acid ratios changed accordingly in the opposite direction. In the hemabsorption groups to 4 h after cardiac arrest, all amino acid levels were reduced, aromatic amino acids more so than branched-chain amino acids, thus increasing (improving) the ratio, compared with controls (P < 0.01). There was no group difference after discontinuance of hemabsorption at 4 h. Outcome in terms of overall performance categories and neurologic deficit scores from 24 to 96 h and brain histopathologic damage scores 96 h after cardiac arrest, were not significantly different between groups. The lack of a beneficial outcome effect of hemabsorption to 4 h after cardiac arrest does not support the self-intoxication hypothesis. The amino acid levels later after cardiac arrest suggest that more prolonged hemabsorption and more encompassing detoxification treatments, such as plasma phoresis or total body blood washout, might be evaluated.

Amino Acids↗

Mild hypothermia after cardiac arrest in dogs does not affect postarrest multifocal cerebral hypoperfusion.

BACKGROUND AND PURPOSE: Although mild resuscitative hypothermia (34 degrees C) immediately after cardiac arrest improves neurological outcome in dogs, its effects on cerebral blood flow and metabolism are unknown. METHODS: We used stable xenon-enhanced computed tomography to study local, regional, and global cerebral blood flow patterns up to 4 hours after cardiac arrest in dogs. We compared a normothermic (37.5 degrees C) control group (group I, n = 5) with a postarrest mild hypothermic group (group II, n = 5). After ventricular fibrillation of 12.5 minutes and reperfusion with brief cardiopulmonary bypass, the ventilation, normotension, normoxia, and mild hypocapnia were controlled to 4 hours after cardiac arrest. Group II received (minimal) head cooling during cardiac arrest, followed by systemic bypass cooling (to 34 degrees C) during the first hour of reperfusion after cardiac arrest. RESULTS: The postarrest homogeneous transient hyperemia was followed by global hypoperfusion from 1 to 4 hours after arrest, with increased "no-flow" and "trickle-flow" voxels (compared with baseline), without group differences. At 1 to 4 hours, mean global cerebral blood flow in computed tomographic slices was 55% of baseline in group I and 64% in group II (NS). No flow (local cerebral blood flow < 5 mL/100 cm3 per minute) occurred in 5 +/- 2% of the voxels in group I versus 9 +/- 5% in group II (NS). Trickle flow (5 to 10 mL/100 cm3 per minute) occurred in 10 +/- 3% voxels in group I versus 16 +/- 4% in group II (NS). Cerebral blood flow values in eight brain regions followed the same hyperemia-hypoperfusion sequence as global cerebral blood flow, with no significant difference in regional values between groups. The global cerebral metabolic rate of oxygen, which ranged between 2.7 and 4.5 mL/100 cm3 per minute before arrest in both groups, was at 1 hour after arrest 1.8 +/- 0.3 mL in normothermic group I (n = 3) and 1.9 +/- 0.4 mL is still-hypothermic group II (n = 5); at 2 and 4 hours after arrest, it ranged between 1.2 and 4.2 mL in group I and between 1.2 and 2.6 mL in group II. CONCLUSIONS: After cardiac arrest, mild resuscitative hypothermia lasting 1 hour does not significantly affect patterns of cerebral blood flow and oxygen uptake. This suggests that different mechanisms may explain its mitigating effect on brain damage.

Animals↗

Hypertension with hemodilution prevents multifocal cerebral hypoperfusion after cardiac arrest in dogs.

BACKGROUND: Improved neurological outcome with postarrest hypertensive hemodilution in an earlier study could be the result of more homogeneous cerebral perfusion and improved O2 delivery. We explored global, regional, and local cerebral blood flow by stable xenon-enhanced computed tomography and global cerebral metabolism in our dog cardiac arrest model. METHODS: Ventricular fibrillation cardiac arrest of 12.5 minutes was reversed by brief cardiopulmonary bypass, followed by life support to 4 hours postarrest. We compared control group I (n = 5; mean arterial blood pressure, 100 mm Hg; hematocrit, greater than or equal to 35%) with immediately postarrest reflow-promoted group II (n = 5; mean arterial blood pressure, 140-110 mm Hg; hypervolemic hemodilution with plasma substitute to hematocrit, 20-25%). RESULTS: After initial hyperemia in both groups, during the "delayed hypoperfusion phase" at 1-4 hours postarrest, global cerebral blood flow was 51-60% of baseline in group I versus 85-100% of baseline in group II (p less than 0.01). Percentages of brain tissue voxels with no flow, trickle flow, or low flow were lower (p less than 0.01) and mean regional cerebral blood flow values were higher in group II (p less than 0.01). Global cerebral oxygen uptake recovered to near baseline values at 3-4 hours postarrest in both groups. Postarrest arterial O2 content, however, in hemodiluted group II was 40-50% of that in group I. Thus, the O2 uptake/delivery ratio was increased (worsened) in both groups at 2-4 hours postarrest. CONCLUSIONS: After prolonged cardiac arrest, immediately induced moderate hypertensive hemodilution to hematocrit 20-25% can normalize cerebral blood flow patterns (improve homogeneity of cerebral perfusion), but does not improve cerebral O2 delivery, since the flow benefit is offset by decreased arterial O2 content. Individualized titration of hematocrit or hemodilution with acellular O2 carrying blood substitute (stroma-free hemoglobin or fluorocarbon solution) would be required to improve O2 uptake/delivery ratio.

Animals↗

Prenatal and postnatal development of the large intestine in the insectivore Suncus murinus, the laboratory shrew.

Development of the large intestine in the insectivore Suncus murinus (the laboratory shrew) was investigated from day 21 to 30 of gestation and from birth to 20 days of age. Two days before birth, the stratified epithelium in the large intestine changed into a single layer. Although neither villi nor villus-like structures were ever present, fissures, corresponding to openings of the crypts, appeared on the mucosal surface before birth. These increased in number as well as in width and depth, connected with each other, and gave the mucosal surface a ridge-like appearance by 20 days of age. An elevation containing submucosae appeared shortly after birth and formed a large circular fold during the neonatal period. Goblet cells were the predominant epithelial cell type. Individual epithelial cells were mature-looking a few days before birth; goblet cells contained numerous mucous globules and absorptive cells possessed well-developed organelles. However, although goblet cells increased in number and exhibited active mucous-releasing forms after birth, absorptive cells never showed morphologic evidence of active endocytosis, such as apical endocytotic complexes and large supranuclear vacuoles. Each epithelial cell was similar in ultrastructure to that of the adult shortly after birth.

Age Factors↗

Gd-DTPA-enhanced MR imaging of cryptococcal meningoencephalitis.

This report describes magnetic resonance (MR) imaging of biopsy-proved cryptococcal central nervous system (CNS) infection in a 31-year-old HIV negative man. Initial MR imaging revealed multi-focal Gd-DTPA enhancement and showed more lesions than contrast enhanced CT. The lesions regressed after antifungal therapy. MR imaging aids in diagnosis as well as helps to monitor the response to the pharmacological therapy of cryptococcal meningoencephalitis and possibly provides valuable insights into the pathophysiology of this condition.

Adult↗

Mild hypothermic cardiopulmonary resuscitation improves outcome after prolonged cardiac arrest in dogs.

BACKGROUND AND METHODS: This study was designed to explore the effect of mild cerebral and systemic hypothermia (34 degrees C) on outcome after prolonged cardiac arrest in dogs. After ventricular fibrillation with no flow of 10 min, and standard external CPR with epinephrine (low flow) from ventricular fibrillation time of 10 to 15 min, defibrillation and restoration of spontaneous normotension were between ventricular fibrillation time of 16 and 20 min. This procedure was followed by controlled ventilation to 20 hr postarrest and intensive care to 72 hr postarrest. In control group 1 (n = 10), core temperature was 37.5 degrees C; in control group 2 (n = 10), cooling was started immediately after restoration of spontaneous normotension; and in group 3 (n = 10), cooling was initiated with start of CPR. Cooling was by clinically feasible methods. RESULTS: Best overall performance categories achieved (1 = normal; 5 = brain death) were better in group 2 (p = .012) and group 3 (p = .005) than in group 1. Best neurologic deficit scores were 36 +/- 14% in group 1, 22 +/- 15% in group 2 (p = .02), and 19 +/- 18% in group 3 (p = .01). Brain histopathologic damage scores were also lower (better) in groups 2 (p = .05) and 3 (p = .03). Myocardial damage was the same in all three groups. CONCLUSION: Mild cerebral hypothermia started during or immediately after external CPR improves neurologic recovery.

Animals↗

Clinical significance of new coagulation and fibrinolytic markers in ischemic stroke patients.

BACKGROUND AND PURPOSE: We investigated plasma levels of D-dimer products of crosslinked fibrin degradation products, thrombin-antithrombin III complex, and plasmin-alpha 2-antiplasmin complex for detecting coagulation system activation in ischemic stroke patients to determine the possible effect of age on these marker levels. METHODS: We measured plasma levels of these three markers in 54 acute ischemic stroke patients within 5 days of stroke onset, in 44 chronic ischemic stroke patients over 3 months from onset, and in 50 age-matched healthy subjects. We divided the stroke patients into two subgroups, those with visible occlusion and those with nonvisible occlusion having obstruction of the major cerebral artery. RESULTS: The plasma levels of these three markers were significantly (p less than 0.01) higher in the stroke patients than in controls. Significant differences did not exist at any level between the patients and controls in the younger-aged subjects (less than or equal to 64 years of age), but did exist in the older-aged subjects (greater than or equal to 75 years of age). An age-related increase of the marker levels was noted between stroke patients and controls. No significant difference in the three markers was found among any of the stroke patients. CONCLUSIONS: Increased levels of these markers in stroke patients seem to be related mostly to age.

Aged↗

Effects of U74006F on multifocal cerebral blood flow and metabolism after cardiac arrest in dogs.

Lipid peroxidation reactions during reperfusion after cardiac arrest may contribute to postischemic cerebral hypoperfusion, which in turn can contribute to permanent neurological dysfunction. We designed this study to determine whether the aminosteroid U74006F, a putative inhibitor of lipid peroxidation, mitigates cerebral multifocal hypoperfusion after cardiac arrest. We used our established dog model of ventricular fibrillation cardiac arrest (no blood flow) of 12.5 minutes, reperfusion by cardiopulmonary bypass of less than or equal to 5 minutes, and control of extracerebral variables during 4 hours postarrest. Cerebral blood flow was monitored by the stable xenon computed tomography method. Changes in cerebral oxygen consumption were obtained from mean blood flow values of coronal slices and the cerebral arteriovenous (sagittal sinus) oxygen content difference. A treatment group (n = 5) received U74006F starting with reperfusion (1.5 mg/kg i.a. plus 1.5 mg/kg i.v.) and three additional (graded) doses over 4 hours (total dose 4.5, 7.5, or 14.5 mg/kg). The U74006F-treated group showed the same postarrest transient hyperemia and protracted hypoperfusion in terms of global (computed tomography slice), regional, and local (multifocal) cerebral blood flow values and the same global cerebral oxygen consumption pattern as a concurrent control group (n = 5). At 1-4 hours postarrest, in both groups there was mismatching of global cerebral oxygen consumption, which reached baseline values, in relation to global cerebral blood flow and oxygen delivery, which remained at 50% of baseline. We conclude that treatment with U74006F after prolonged cardiac arrest causes no deleterious side effects and does not seem to alter multifocal postarrest cerebral blood flow and oxygen consumption.

Animals↗

Endoscopic screening of early esophageal cancer with the Lugol dye method in patients with head and neck cancers.

The poor prognosis for esophageal cancer could be improved if lesions were detected at an early stage. To detect early esophageal cancer, endoscopic screening of the esophagus with the Lugol dye method was performed in patients with head and neck cancers who were asymptomatic but regarded as being at high risk for synchronous or metachronous esophageal cancer. Of 178 patients screened, 9 had esophageal cancer (5.1%). Eight of these patients (89%) were at early stages with no lymph node metastasis. Most of the lesions (9 of 13 lesions) were not detectable by barium studies or ordinary endoscopic study. The epidemiologic statistical analysis of the patients confirmed that they had a significantly high observed and expected number (O/E) ratio (39.7; P less than 0.001). These results demonstrate the value of endoscopic screening of the esophagus with the Lugol dye method in patients with head and neck cancers and imply that endoscopic screening with the Lugol dye method may be useful for detecting early esophageal cancer in individuals at risk for other causes.

Aged↗

Phenotypic characteristics of tumour-infiltrating lymphocytes in human oesophageal cancer tissues defined by quantitative two-colour analysis with flow-cytometry.

Phenotypic subpopulations of tumour-infiltrating lymphocytes (TIL) separated from human oesophageal cancer tissues were defined by quantitative two-colour analysis with flow-cytometry (FACScan), and their characteristics were investigated by comparison with peripheral blood lymphocytes (PBL) and intra-oesophageal lymphocytes from noncancerous tissue (IEL) as the controls. Fifteen patients (13 males and 2 females) with squamous cell carcinoma of the oesophagus were entered into the study. Lymphocytes were analyzed by FACScan and the frequencies of the subpopulations were determined using monoclonal antibodies for surface markers. Single colour analysis revealed a predominance of T cells among TIL and a significant reduction of natural killer (NK) cells compared with the controls. Two-colour analysis showed that CD4+ Leu8- (helper T cells) and CD8+ CD11b- (cytotoxic T cells) were significantly increased among TIL when compared with the controls. This significant increase of both helper and cytotoxic T cells, which are indispensable components of cellular immunity, strongly implies that TIL are performing a role in the expression of antigen-specific cellular immunity against the tumours. This is the first report of a phenotypic study of human oesophageal cancer that clearly indicates the significance of the TIL and suggests their potential for use as a source of adoptive immunotherapy.

Adult↗

Hypoplastic left heart syndrome with premature closure of foramen ovale: report of an unusual type of totally anomalous pulmonary venous return.

We report on a case of hypoplastic left heart syndrome (HLHS), associated with premature closure of the foramen ovale and an unusual type of totally anomalous pulmonary venous return. The existence of an anomalous connection of the right upper pulmonary vein to the superior vena cava-right atrial (SVC-RA) junction and the existence of the anomalous intrapulmonary venous channel between right upper and lower pulmonary vein allowed all the pulmonary blood to drain into the SVC-RA junction, whereas she had only partially anomalous pulmonary venous connection. The several intrapulmonary venous channels helped to delay the progression of pulmonary venous obstruction. Chromosomal analysis revealed that the patient had XO Turner syndrome. We conclude that all infants with HLHS should be carefully evaluated for the existence of anomalous pulmonary venous return. Two-dimensional Doppler echocardiography is one of the most useful techniques for evaluating such anomalies.

Abnormalities, Multiple↗

Mild cerebral hypothermia during and after cardiac arrest improves neurologic outcome in dogs.

We previously found mild hypothermia (34-36 degrees C), induced before cardiac arrest, to improve neurologic outcome. In this study we used a reproducible dog model to evaluate mild hypothermia by head cooling during arrest, continued with systemic cooling (34 degrees C) during recirculation and for 1 h after arrest. In four groups of dogs, ventricular fibrillation (no flow) of 12.5 min at 37.5 degrees C was reversed with cardiopulmonary bypass and defibrillation in less than or equal to 5 min, and followed by controlled ventilation to 20 h and intensive care to 96 h. In Study A we resuscitated with normotension and normal hematocrit; Control Group A-I (n = 12) was maintained normothermic, while Treatment Group A-II (n = 10) was treated with hypothermia. In Study B we resuscitated with hypertension and hemodilution. Control Group B-I (n = 12) was maintained normothermic (6 of 12 were not hemodiluted), while Treatment Group B-II (n = 10) was treated with hypothermia. Best overall performance categories (OPCs) achieved between 24 and 96 h postarrest were in Group A-I: OPC 1 (normal) in 0 of 12 dogs, OPC 2 (moderate disability) in 2, OPC 3 (severe disability) in 7, and OPC 4 (coma) in 3 dogs. In Group A-II, OPC 1 was achieved in 5 of 10 dogs (p less than 0.01), OPC 2 in 4 (p less than 0.001), OPC 3 in 1, and OPC 4 in 0 dogs. In Group B-I, OPC 1 was achieved in 0 of 12 dogs, OPC 2 in 6, OPC 3 in 5, and OPC 4 in 1 dog. In Group B-II, OPC 1 was achieved in 6 of 10 dogs (p less than 0.01), OPC 2 in 4 (p less than 0.05), and OPC 3 or 4 in 0 dogs. Mean neurologic deficit and brain histopathologic damage scores showed similar significant group differences. Morphologic myocardial damage scores were the same in all four groups. We conclude that mild brain cooling during and after insult improves neurologic outcome after cardiac arrest.

Animals↗

Hypertension with or without hemodilution after cardiac arrest in dogs.

We studied blood flow-promoting therapies after cardiac arrest in 18 dogs. Our model consisted of ventricular fibrillation (no blood flow) lasting 12.5 minutes, controlled reperfusion with cardiopulmonary bypass and defibrillation within 5 minutes, controlled intermittent positive-pressure ventilation to 20 hours, and intensive care to 96 hours. Group I (control, n = 6) dogs were reperfused under conditions of normotension (mean arterial blood pressure 100 mm Hg) and normal hematocrit (greater than or equal to 35%). Group II (n = 6) and III (n = 6) dogs were treated with norepinephrine at the beginning of reperfusion to induce hypertension for 4 hours. In addition, group III dogs received hypervolemic hemodilution to a hematocrit of 20% using dextran 40. There were no differences in the time to recovery of electroencephalographic activity among groups. All six group I dogs remained severely disabled; in groups II and III combined, six of the 12 dogs achieved good outcome (p less than 0.01). Some regional histopathologic damage scores at 96 hours were better in groups II and/or III than in group I (neocortex: p less than 0.05 group II different from group I; hippocampus: p less than 0.01 both groups II and III different from group I). Total histopathologic damage scores were similar among the groups. A hypertensive bout with a peak mean arterial blood pressure of greater than or equal to 200 mm Hg beginning 1-5 minutes after the start of reperfusion was correlated with good outcome (p less than 0.01). Our results support the use of an initial bout of severe hypertension, but not the use of delayed hemodilution.

Animals↗