Circulatory dynamics during periodic intracranial hypertension in fetal sheep.

The human fetal head is periodically compressed during labor. The resulting increase in intracranial pressure (ICP) may exceed the hydrostatic increase in mean arterial pressure (MAP), thereby decreasing cerebral perfusion pressure (CPP). We determined whether the cardiovascular system of near-term fetal sheep is capable of rapidly increasing MAP during periodic increases in ICP. In 12 chronically instrumented fetuses, we produced sinusoidal oscillations in ICP with a maximum of 52 +/- 1 mmHg (baseline MAP) and a minimum of 4 +/- 1 mmHg at a 3-min periodicity by ventricular fluid infusion and withdrawal. Phasic increases in MAP and decreases in electromagnetically determined renal blood flow tracked behind ICP by 0.3-0.5 min. By the sixth cycle, tonic peripheral vasoconstriction that occurred attenuated by the reduction in CPP during subsequent ICP oscillations. By the 10th cycle, plasma catecholamines and vasopressin increased 20-fold. To more closely simulate the pattern during labor, we produced an ICP triangular pulse train with 5-min periodicity and pulse duration of 1.5 min in six other fetuses. The MAP response was nearly out of phase with this more rapid rise of ICP. Thus the phasic component of the fetal pressor response is inadequate for maintaining CPP when ICP is increased to baseline MAP in less than 0.75 min. However, when the ICP pulse duration and frequency are sufficiently high, a tonic pressor response that may be humorally mediated acts to minimize transient cerebral ischemia.

Comparison of flow-resistive work load due to humidifying devices.

There are many kinds of humidifying devices. We evaluated six humidifiers from the viewpoint of AWLs. The AWL was obtained by calculating the area difference between pressure-volume tracings obtained without and with humidifiers. To examine the effect of pressure monitoring sites on AWL when a humidifier is placed, we measured AWL at three different pressure monitoring sites. The AWL was affected significantly by the pressure monitoring site for the ventilator. When a pressure monitor sensor was placed on the inspiratory limb between the inspiratory valve and humidifiers, the ventilator was not able to compensate for the pressure drop caused by impedance characteristics of the humidifier equipment. This resulted in significant inspiratory AWL on the patient. Thus, humidifying devices should be carefully selected from the viewpoint of not only humidifying capability but also AWL. Furthermore, we must recognize the importance of the pressure monitoring site for the ventilator.

Postischemic recovery rate of cerebral ATP, phosphocreatine, pH, and evoked potentials.

We tested the hypotheses that after complete cerebral ischemia, first, rate of recovery of ATP, phosphocreatine (PCr), and intracellular pH (pHi) varies with ischemic duration and second, rate of metabolic recovery is a more sensitive predictor of consequent electrophysiological deficit than steady-state metabolic recovery. With the use of transient intracranial hypertension in anesthetized dogs, ischemic duration was set for either 3, 12, or 30 min, which depressed somatosensory-evoked potential (SEP) recovery amplitude by 30, 59, and 88%, respectively. In contrast, ATP, PCr, and pHi, measured by 31P magnetic resonance spectroscopy, fully recovered. When ischemic duration was increased from 3 to 12 min, mean recovery time of ATP (6 min) remained rapid but that of pHi (12-28 min) was prolonged. After 30 min of ischemia, pHi recovery was not slowed further (25 min) but that of ATP was now markedly prolonged (36 min). PCr recovery time increased progressively with ischemic duration (5, 11, and 21 min, respectively) and correlated best with SEP recovery (r = 0.74). We conclude that the brain's ability to rapidly normalize pH is a sensitive predictor of electrophysiological recovery after short ischemia but that ATP regeneration becomes important with prolonged ischemia. PCr recovery rate was the best overall predictor, probably because it depends on both pHi and the ratio of ATP to ADP by the creatine kinase reaction.

Rapid screening for Staphylococcus aureus infection by measuring enterotoxin B.

We developed a simple, sensitive laser nephelometric assay (LNA) to detect circulating staphylococcal enterotoxin B (SEB). This assay yields the result within 2 h and needs no special treatment. Influence of protein A, a product generated by Staphylococcus aureus, was negligible in this assay. The levels of SEB in plasma were measured in 28 patients with and without S. aureus infection with the LNA. The levels of SEB in plasma increased significantly in patients with S. aureus infection. We also demonstrated that the levels of SEB in plasma were higher in patients with methicillin-resistant S. aureus infection than in patients with nonresistant staphylococcal infection. Our data indicate that LNA is a useful assay in the early diagnosis of methicillin-resistant S. aureus infection.

Regional adrenal blood flow during hypoxia in anesthetized, ventilated dogs.

The effect of hypoxic hypoxia (HH) and carbon monoxide hypoxia (COH) on adrenal medullary (MQ) and cortical (CQ) blood flow (radiolabeled microsphere technique) was studied in pentobarbital sodium-anesthetized, mechanically ventilated dogs. Animals were exposed to 60 min of hypoxia (arterial O2 content 8 vol%) induced by adding either nitrogen (HH, n = 6) or carbon monoxide (COH, n = 6) to the inspired gas. Whole adrenal Q and CQ increased by 70 and 50%, respectively, with HH but were unchanged during COH. MQ, however, increased threefold during both HH and COH. HH and COH both increased arterial levels of epinephrine, corticosteroids, and adrenocorticotropic hormone (ACTH). To determine whether the increase in CQ during HH was because of HH-induced increases in mean arterial blood pressure (MAP, approximately 20 mmHg), an additional group of animals (n = 6) was exposed to HH but had MAP maintained at control levels using a pressurized-bottle system. MAP control did not alter the CQ response to HH. We conclude that MQ appears to be associated with medullary secretory activity during hypoxia and that HH and COH stimulate adrenal medullary secretion equally. In contrast, CQ increases only with HH, despite similar increases in ACTH and corticosteroid levels during HH and COH, suggesting that an alternative mechanism is responsible for increased cortical blood flow during HH.

Effect of naloxone and ibuprofen on organ blood flow during endotoxic shock in pig.

The effects of an opiate antagonist naloxone and a cyclooxygenase inhibitor ibuprofen on organ blood flow during endotoxic shock were evaluated in a fluid-resuscitated porcine endotoxic shock model. Radiolabeled microspheres were used to measure regional blood flow. Escherichia coli endotoxin (0.1 mg/kg), infused intravenously over 40 min, reduced mean arterial blood pressure to 50 mmHg and systemic vascular resistance to 57% of control without affecting cardiac output. Endotoxin reduced blood flow to cerebrum (to 49% of control), kidney (to 25% of control), spleen, and skeletal muscle, while blood flow to left ventricle, stomach, and small and large intestines were unaffected. Sixty minutes after endotoxin administration, animals were randomized to one of three groups. Group I animals were controls and received no drug, group II animals received ibuprofen (12.5 mg/kg iv), and group III animals received naloxone (2 mg/kg iv) 60 min after endotoxin. Ibuprofen increased mean arterial blood pressure to 80 mmHg and increased blood flow to both cerebrum (to 92% of control) and kidney (to 47% of control). Plasma levels of thromboxane B2 and 6-ketoprostaglandin F1 alpha were increased 8- and 16-fold, respectively, after endotoxin, and both were decreased by ibuprofen. Naloxone increased mean arterial blood pressure to 62 mmHg but had no effect on regional blood flow or plasma cyclooxygenase metabolite levels. These data suggest that cyclooxygenase metabolites may contribute to decreased mean arterial blood pressure and reduced organ blood flow during endotoxic shock in the pig.

Serial changes in cellular immunity of septic patients with multiple organ-system failure.

Total lymphocyte count, lymphocyte cell-surface markers (OKT3, OKT4, OKT8, and B-1), serum complement factors (C3 and C4), immunoglobulins (IgG, IgA, and IgM), ceruloplasmin (Crl), and transferrin (Trf) were determined weekly for nine septic postoperative patients, all of whom had multiple organ-system failure. The peripheral blood total lymphocyte count, its subpopulation, T-cell subset, and proliferative responses of lymphocyte to phytohemagglutinin (PHA) and concanavalin A (Con A) decreased in all patients. OKT3 and B-1 decreased progressively in the four nonsurvivors compared with the five survivors. Although immunoglobulin levels were within the normal range in both groups, they tended to increase in survivors and decrease in nonsurvivors. Serial levels of C3, C4, Crl, and Trf increased in survivors but did not change in nonsurvivors. T-cell function and antibody-producing activity diminished progressively in nonsurvivors. These changes in cellular immunity may represent another manifestation of multiple organ-system failure during sepsis.

Elimination of false-positive limulus amebocyte lysate tests in patients with hyperlipidemia.

Varying concentrations of lipopolysaccharide (LPS) and mannan suspensions were mixed with either saline or plasma from normal volunteers, heated to 100 degrees C for 10 min, and then subjected to the limulus amebocyte lysate test (LAL). A positive LAL in saline required minimum LPS and mannan concentrations of 10(-11) and 10(-5) g/ml, respectively, while the minimum concentrations premixed with plasma were 10(-13) and 10(-9) g/ml, respectively. Thus, use of plasma instead of saline increased assay sensitivity 100-fold for LPS and 10,000-fold for mannan. In the second part of the experiment, normal plasma was separated into lipid and nonlipid phases by Folch's method. LAL analysis of each phase revealed equal sensitivity for LPS and mannan in the nonlipid phase, but no sensitivity in the lipid extract. Subsequently, 200 ml of a fat emulsion (Intralipos) was administered to the normal volunteers, and LAL and lipid analyses were performed. The LAL turned positive in all volunteers. When LAL was positive, triglycerides (TG), chylomicron (Chyl), and very low-density lipoprotein (VLDL) increased significantly compared with when LAL was negative. It is concluded that plasma lipids increase the sensitivity of LAL and directly activate LAL when TG, Chyl, and VLDL concentrations are high. This effect of plasma lipids on LAL can be eliminated by extracting LPS and mannan in the nonlipid phase.

Effects of driving pressure and respiratory rate on airway pressure and PaCO2 in rabbits during high-frequency jet ventilation.

The effects of driving pressure (DP) and respiratory rate (RR) on mean airway pressure (Paw), PaCO2, and other respiratory variables were studied during high-frequency jet ventilation (HFJV) in anesthetized rabbits. The animals were tracheotomized and paralyzed, and various combinations of RR (4, 8, 12, and 16 Hz) and DP (0.5, 1.0, and 2.0 kg/cm2) were applied randomly with an inspiratory/expiratory ratio of 1.0. HFJV was delivered via a 2.5-Fr catheter through a T-attachment, using 100% oxygen, and a hot-wire flowmeter was connected to the outlet of the T-attachment for measurement of the minute volume (MV). Heart rate, arterial BP and CVP, respiratory variables, and arterial blood gases were monitored during the study. There were no direct correlations between PaCO2 and DP, MV, or RR. However, there was an inverse correlation between PaCO2 and tidal volume, and linear correlations were found between Paw and DP, and between DP and MV. It is concluded that HFJV over an RR range of 4 to 16 Hz depends mainly upon tidal volume. When the desired PaCO2 and Paw are determined, DP and RR can be calculated following the equations established in this study.

High-frequency jet ventilation for differential lung ventilation.

High-frequency jet ventilation using a jet injector located at the right mainstem bronchus was superimposed on standard mechanical ventilation to ventilate the injured lung of a patient with unilateral massive atelectasis secondary to pulmonary hemorrhage. This technique of differential ventilation markedly improved arterial oxygenation in this patient and may prove to be a simpler modality of respiratory support in patients who have respiratory failure from unilateral lung disease.

Amino acids and thiobarbituric acid reactive substances in cerebrospinal fluid and plasma of patients with septic encephalopathy.

Amino acids and thiobarbituric acid reactive substances (TBARs) in the cerebrospinal fluid (CSF) and plasma were identified and assayed in 5 patients with septic encephalopathy. Levels of all the high molecular weight neutral amino acids (LNAAs) appeared to increase in the CSF. CSF levels of phenylalanine (PHE) and methionine (MET) increased significantly by factors of 20.9 and 9.5, respectively, and the plasma PHE level increased 7.5-fold. No significant changes in branched-chain amino acids were observed in either the CSF or plasma. The CSF/plasma ratios of valine (VAL), tyrosine (TYR), PHE, and MET significantly increased to 0.21, 0.46, 0.52, and 0.52, respectively. TBAR levels increased 4-fold in the CSF and also were slightly increased in the plasma, suggesting that lipid peroxidation in the central nervous tissues is markedly increased. We conclude that increases in LNAA levels and in lipid peroxidation in the central nervous tissues may play important roles in the development of septic encephalopathy.

Gabexate mesilate (FOY) therapy of disseminated intravascular coagulation due to sepsis.

Gabexate mesilate (FOY), a synthetic serine proteinase inhibitor, has an anticoagulant activity in the absence of antithrombin-III. We investigated FOY therapy for the treatment of disseminated intravascular coagulation (DIC) associated with sepsis in 15 patients (group F), and compared it with heparin therapy in 8 patients (group H). Successful treatment was observed in 13 patients in group F and in 4 patients in group H. The efficacy of the therapy in both groups was not significantly different. However, in patients whose antithrombin-III values were less than 20 mg/dl at the initiation of the therapy, FOY therapy was successful in 6 of 7 patients, whereas heparin therapy was not at all successful in 4 patients (rho less than 0.05). We conclude that FOY can be used as effectively as heparin for the treatment of DIC, and that FOY therapy is superior to heparin therapy in DIC associated with decreased antithrombin-III.

Application of HPLC measurement of plasma concentration of gabexate mesilate.

The plasma concentration of gabexate mesilate (ethyl-p-(6-guanidinohexanoyloxy) benzoate) methanesulfonate (GM), FOY, was measured on a high performance liquid chromatography. GM concentrations ranging from 1 to 50 micrograms/ml of whole blood were able to be determined with this method. The half-life of GM in plasma was 55 seconds and the minimum concentration of GM which affected the activated coagulation time of whole blood (ACT) was 10 micrograms/ml. This method is sensitive and accurate to provide us with the pharmacodynamic basis for the determination of the effective plasma concentration of GM with respect to its anticoagulant activity.