Recommended dose of arbekacin, an aminoglycoside against methicillin-resistant Staphylococcus aureus, does not achieve desired serum concentration in critically ill patients with lowered creatinine clearance.

OBJECTIVE: To define the pharmacokinetics of arbekacin (ABK), an aminoglycoside, in patients with acutely lowered renal function. METHODS: We measured the serum concentrations of ABK, using fluorescence polarization immunoassay, in 10 critically ill patients (patient group) and six healthy volunteers (control group). Data were analysed with a two-compartment model and parameters were estimated by the Bayesian method. The Mann-Whitney U-test or chi-squared test was used as appropriate (P < 0.05). RESULTS: Creatinine clearance (CCR), measured or estimated using Cockcroft and Gault's formula of the patient group (CCR: 58 +/- 13 mL/min), was significantly lower than that of the control group (CCR: 99 +/- 8 mL/min). However, despite the low CCR, even the maintenance ABK dosage for normal CCR did not elevate the highest serum level (C(max)) to the effective range in the patient group. Although the ABK clearance (CL) did not differ between the groups, the patients' distribution volume (V(d)) increased significantly compared with the control. The transfer rate constant from central to peripheral compartment (k(12)) in the patient group was much higher than that in the control. CONCLUSION: In critically ill patients with lowered CCR, the ABK dose for normal CCR subjects does not elevate its serum concentration to effective levels because of augmented V(d) caused by increased k(12). The present results hypothesize that adjustment of antibiotic dosing according to CCR further lowers C(max) in critically ill patients with reduced CCR.

Reversible hypophosphatemia during moderate hypothermia therapy for brain-injured patients.

OBJECTIVE: Because plasma potassium, which may similarly change as plasma phosphate (P), decreases during moderate hypothermia, plasma P, a requisite electrolyte for the cell function, may alter during therapeutic moderate hypothermia for brain-injured patients. In 22 such patients who underwent moderate hypothermia or were treated with normothermia, plasma concentrations of P and other chemicals were examined. DESIGN: A prospective study. SETTING: The intensive care unit of a medical university hospital. PATIENTS AND INTERVENTIONS: In 15 consecutive patients with brain injury who underwent moderate hypothermia and 7 serial patients treated with normothermia, plasma concentrations of P, potassium, glucose, blood gas tension and pH, daily urine volume, and water balance were examined. Inequality in the numbers of patients of the two groups was the result of patient exclusion because of multiple trauma, aluminum hydroxide administrations, hyperventilation, preexisting diabetes mellitus, or administration of insulin. Daily blood sampling was done around 8 am. Inclusion criteria included a Glasgow Coma Scale score assessment < or = 8 at admission to the emergency room and evidence of injury on computerized tomography scanning of the brain. MEASUREMENT AND MAIN RESULTS: Hypothermia decreased plasma P levels as compared with those of normothermia within 4 days after the injury (this period was similar to the duration of the hypothermic phase in the hypothermia group). Such reduction related to changes in blood glucose levels, but not to any in the urine volume, or water balance. The P decrease occurred during the hypothermic phase, but subsequently there was a recovery of P after the rewarming phase. The changes in plasma potassium levels were similar to those in plasma P concentrations during the course. Such changes were accompanied by a recovery of decreased heart rate that occurred during the hypothermic phase. CONCLUSION: The results suggest that moderate hypothermia of 32-33 degrees C decreases plasma P levels. Further studies are required to examine whether P repletion may overcome certain hemodynamic derangements during moderate hypothermia in brain-injured patients.

Dose-dependent effects of propofol on renal sympathetic nerve activity, blood pressure and heart rate in urethane-anesthetized rabbits.

To evaluate the role of the autonomic nervous system in hemodynamic changes after propofol bolus injection, we used direct recordings of renal sympathetic nerve activity to examine the dose-dependent effects of propofol (2.5, 5, 10, and 20 mg/kg) on heart rate, mean blood pressure and renal sympathetic nerve activity in urethane-anesthetized rabbits. The animals were divided into four groups: animals with an intact neuraxis (intact group), cervical vagal nerve-sectioned animals (vagotomy group), carotid sinus and aortic-nerve sectioned animals (SAD group), and animals with SAD plus vagotomy (SADV group). Heart rate did not change significantly even after administration of 2.5 and 5 mg/kg but decreased markedly on 20 mg/kg injection in all groups. The intact and vagotomy groups had augmented renal sympathetic nerve activity with insignificant changes in mean blood pressure after 5 mg/kg injection of the agent. Insignificant changes of renal sympathetic nerve activity but a remarkable decrease of mean blood pressure appeared after 10 mg/kg propofol. Sustained hypotension in parallel with a profound depression of renal sympathetic nerve activity developed at the dose of 20 mg/kg. In SAD and SADV groups, however, dose-dependent depressions of renal sympathetic nerve activity were accompanied by decreases of mean blood pressure. These results suggest the following: (1) propofol-induced hypotensive effects are probably produced by the central-mediated sympathetic depression. (2) The baroreceptor reflex may be preserved at the lower dose of the agent. (3) Heart rate does not change significantly unless a large dose of propofol is used. The difference in effects on heart rate and on mean blood pressure may denote a greater inhibition of sympathetic vascular outflow than of the cardiac sympathetic outflow regulating cardiac rate and contractility. This hypothesis needs further clarification.

Effects of induced hypothermia on renal sympathetic nerve activity and baroreceptor reflex in urethane-anesthetized rabbits.

OBJECTIVE: To evaluate the role of the autonomic nervous system in hemodynamic changes during induced hypothermia. DESIGN: Prospective, randomized animal study. SETTING: An animal research laboratory in a medical university. SUBJECTS: A total of 29 anesthetized rabbits. INTERVENTIONS: Animals were anesthetized by intraperitoneal urethane. After tracheostomy and administration of gallamine, respiration was maintained by mechanical ventilatory support. The animals were divided into five groups (one control and the four experimental groups); animals were treated with an intact neuraxis and normothermia (control group), animals with an intact neuraxis (intact group), cervical vagotomized animals (vagotomy group), the carotid sinus and aortic nerves denervated animals (SAD group), and animals with SAD plus vagotomy (SADV group). The left renal sympathetic nerves were exposed by a retroperitoneal approach. MEASUREMENTS AND MAIN RESULTS: We examined the effects of surface cooling on HR, mean arterial pressure, central venous pressure, and renal sympathetic nerve activity (RSNA) in the animals. Changes of baroreflex sensitivity and plasma catecholamines were also measured simultaneously. Surface cooling caused progressive and profound decreases in HR in all experimental groups. In all groups, RSNAs increased at the early phase, which were followed by return to the precooling level. CONCLUSIONS: Hemodynamics and RSNA during induced hypothermia are regulated by mechanisms other than the baroreceptor reflex system, possibly the dermal cold receptors. Suppression of the baroreflex occurred on HR but not on RSNA during hypothermia, which may indicate direct effects of hypothermia on the heart. RSNA responses may be activated earlier than systemic catecholamine responses during induced hypothermia.

Moderate hypothermia improves imbalances of thromboxane A2 and prostaglandin I2 production after traumatic brain injury in humans.

OBJECTIVE: To examine the levels of thromboxane B2 (TXB2) and 6-keto prostaglandin F1alpha (6-keto PGF1alpha) production in arterial and internal jugular bulb sera in patients with traumatic brain injury (TBI). TBI is associated with arachidonate release and may be associated with an imbalance of vasoconstricting and vasodilating cyclooxygenase metabolites. DESIGN: A prospective, randomized study. SETTING: The intensive care unit of a medical university hospital. INTERVENTIONS: Twenty-six ventilated TBI patents (Glasgow Coma Scale score on admission, < or = 8 points) were divided randomly into two groups: a hypothermic group (n = 15), in which the patients were cooled to 32 to 33 degrees C after being giving vecuronium, midazolam, and buprenorphine; and a normothermic group (n = 11), in which the patients' body temperature was controlled at 36 to 37 degrees C by surface cooling using the same treatment as the hypothermic group. Body temperature control including normothermia was started 3 to 4 hrs after injury. The duration of hypothermia usually lasted for 3 to 4 days, after which the patients were rewarmed at a rate of approximately 1 C per day. MEASUREMENTS AND MAIN RESULTS: Blood sampling for TXB2 and 6-keto PGF1alpha was started shortly after admission in both groups. Arterial TXB2 levels on admission in both groups were elevated remarkably, but not 6-keto PGF1alpha, thereby causing an imbalance of the prostanoids after injury. In the normothermic group, TXB2 decreased transiently, but this prostanoid increased again 3 days after the injury. In the hypothermic group, such prostanoid differences disappeared shortly after therapy, and the condition was sustained for 10 days. Hypothermia attenuated differences in TXB2 levels between arterial and internal jugular bulb sera, which may reflect reduced cerebral prostanoid production. The Glasgow Outcome Scale score 6 months after the insult in the hypothermic group was significantly higher than that in the normothermic group (p = .04). CONCLUSION: The current results from a limited number of patients suggest that moderate hypothermia may reduce prostanoid production after TBI, thereby attenuating an imbalance of thromboxane A2 and prostaglandin I2. However, it must be clarified whether the changes in the prostanoid after moderate hypothermia are a secondary effect of other mediator changes or whether they simply represent an epiphenomenon that is mechanistically unrelated to damage in TBI.

Activated cytokine production in patients with accidental hypothermia.

We have demonstrated recently that therapeutic moderate hypothermia of 32-33 degrees C, induced by surface cooling under the administration of narcotics, sedatives and muscle relaxant, suppresses cytokine production after traumatic brain injury. We present here the first documented case report of augmented cytokine production in two accidental hypothermia patients, unconscious 84- (acute immersion) and 87- (non-immersion) year-old women, whose rectal temperatures were below 28 degrees C. The victims were artificially ventilated after sedation with midazolam and buprenorphine in accordance with our protocol. Rewarming at the rate of approximately 1 degrees C/h was done by blowing forced-air with appropriate fluid resuscitation. Plasma interleukin(IL)-6 and/or IL-8 levels were measured using ELISA in the patients. In both patients, plasma IL-6 levels on admission were already elevated and the cytokine levels further increased during and after the rewarming period. In the patient with the poorer prognosis, the plasma IL-8 level on admission was not elevated remarkably but after rewarming the level rose significantly. Augmented IL-6 production in accidental hypothermia was sustained for 6 days in the patient with the poorer prognosis but not in the subject with good recovery, who was treated with anti-thrombin III in the early phase. Since the mechanisms for developing accidental hypothermia were different, simple comparisons between the two cases should be limited. But, these findings may suggest a need for testing a hypothesis whether cytokine modulation could be a therapeutic approach worthy of consideration. The results presented here also suggest that in hypothermia, changes in cytokine release may vary depending on procedures such as the anesthetic drugs used, the duration of the therapy, or the rate of rewarming from hypothermia.

Effect of moderate hypothermia on systemic and internal jugular plasma IL-6 levels after traumatic brain injury in humans.

Moderate hypothermia may reduce subsequent neuronal damage after traumatic brain injury. Interleukin (IL)-6 may have a role in the pathogenesis of traumatic neuronal damage or repair. Using the enzyme-linked immunological sorbent assay (ELISA), we serially measured IL-6 levels in plasma obtained from the radial artery (systemic) and internal jugular vein (regional) in 13 cerebral trauma patients who underwent hypothermia of 32-33 degrees C ranged from 4-9 days postinjury and 10 head-injured patients who were maintained at normothermic levels (36-37 degrees C). In both patient populations, surface cooling was used since even in the normothermic group, cooling was needed to maintain patient temperature in the normothermic range. All patients were mechanically ventilated after injection of midazolam and vecuronium. The administration of these agents were continued until the end of the study. Hypothermia was typically maintained for four days, however, in some cases based upon CT findings and/or intra-cranial pressure change, the duration was prolonged. No significant differences were found between the two groups in age, gender and Glasgow Coma Scale upon admission. Further, no differences were found in terms of the classification of computed tomography findings or the occurrence of pupillary abnormalities on admission. The patients in this study had not sustained either abdominal or thoracic trauma. Before inducing hypothermia, IL-6 levels in the arterial and internal jugular venous blood exceeded the normal range. Specifically, the internal jugular plasma levels were significantly higher than those in the arterial plasma. While IL-6 levels in the normothermic group did not decrease even at 4 days postinjury, the plasma cytokine levels fell at both sites sharply after moderate hypothermia. The cytokine suppression found in the hypothermic group continued even after rewarming in these patients showing an improved clinical course, but not in those whose condition worsened. In addition to these changes in cytokine levels, the Glasgow Outcome Scale at 6 months postinjury was significantly higher in the hypothermic group than in the normothermia group. Based on the above, this clinical study with its small patient sample size suggests the need for further prospective randomized studies to examine the role of cytokine suppression in the beneficial effects of moderate hypothermia in patients with traumatic brain injury.

Effects of dexmedetomidine, an alpha2-adrenoceptor agonist, on renal sympathetic nerve activity, blood pressure, heart rate and central venous pressure in urethane-anesthetized rabbits.

To clarify the role of the neural blood pressure control system in hemodynamic changes after dexmedetomidine (DXM) administration, we examined the effects of an intravenous injection of DXM (10 microg/kg) on heart rate (HR), mean blood pressure (MBP), central venous pressure (CVP) and renal sympathetic nerve activity (RNA) in urethane-anesthetized rabbits using direct recordings of RNA. The animals were divided into four groups: animals with an intact neuraxis (intact group; n = 12), cervical vagotomized animals (vagotomy group; n = 5), sino-aortic denervated animals (SAD group; n = 5), and animals with SAD plus vagotomy (SADV group; n = 5). An initial HR decrease, which occurred in the intact group, did not occur in the other three groups, suggesting the mediation of the baroreflex. A subsequent HR decrease occurred in the three groups other than the vagotomy group, in which RNA recovered earlier than in the other groups. RNA in the intact group, associated with transient hypertension, was suppressed shortly after the injection. Such an RNA drop was not eliminated even in the SADV group. Despite recovery of RNA, hypotension lasted until the end of experiment in the intact and vagotomy groups. However, sustained depression of RNA associated with lasting hypotension was found in the SAD and SADV groups. CVP in all groups did not change significantly after the injection. These results suggest the following: (1) Initial bradycardia after DXM is mediated via the baroreflex. Subsequently, HR reductions may result mainly from central sympathetic depression. (2) An initial reduction in RNA is not mediated via the baroreceptor reflex, unlike HR responses, but by central sympatho-inhibitory effects. (3) Long-lasting hypotension after DXM is likely to be attributable to its peripheral vascular effects including the stimulation of pre-synaptic alpha2-adrenoceptors, rather than to central sympathetic depression.

Haemodynamic and catecholamine changes during rapid sevoflurane induction with tidal volume breathing.

PURPOSE: To compare haemodynamic and plasma catecholamine changes with rapid (three minute) inhalational anaesthesia induction with tidal volume breathing of sevoflurane 7%, conventional (seven minute) slow inhalation induction with increasing sevoflurane concentration up to 5%, and induction with thiamylal i.v. METHODS: Twenty-four patients were randomly divided into three groups of eight. In Group A, anaesthesia was induced with tidal volume breathing of sevoflurane 7% (inspiratory concentration) and nitrous oxide 50% in oxygen (total flow; 6 l.min-1) for three minutes: Group B received conventional slow induction for seven minutes and increasing sevoflurane concentration by 0.5% every two or three breaths up to 5% with nitrous oxide 50% in oxygen: and Group C received 5 mg.kg-1 thiamylal with an inhalation of 100% oxygen. Blood pressure, heart rate, rate pressure product, and plasma concentrations of epinephrine and norepinephrine were measured. RESULTS: There were no changes in blood pressure before or after intubation in Group A (sevoflurane 7%) whereas both were increased in patients in Group C (thiamylal). Changes in heart rate and rate pressure product were not different for the two inhalation groups. Plasma epinephrine concentrations decreased in all the three groups. Norepinephrine concentrations were increased before intubation in both inhalation groups but not in the thiamylal group. CONCLUSION: Rapid induction of anaesthesia with sevoflurane 7% and tidal volume breathing for three minutes induced less haemodynamic changes than the other methods studied and has no inhibitory effect on sympathetic activity.

3.5% hypertonic saline produces sympathetic activation in hemorrhaged rabbits.

The neural mechanisms for pressor effects after hypertonic saline infusion are still unclear. Using direct measurement of the renal sympathetic nerve activity (RNA), we tested the hypothesis that the autonomic nervous system is involved in an acute blood pressure elevation produced by hypertonic saline (HTS) in anesthetized rabbits subjected to hemorrhage. Twenty urethane-anesthetized rabbits were ventilated mechanically after a tracheostomy and paralyzed with gallamine triethiodide. Heart rate (HR), mean blood pressure (MBP) and central venous pressure (CVP) were measured simultaneously with RNA. The animals were divided into the following four groups: (1) animals with intact baroreceptors that received HTS (intact HTS group, N = 5); (2) those with intact baroreceptors that received normal saline (intact NS group, N = 5); (3) those that underwent selective cervical vagotomy (vagotomy group, N = 5); (4) those with sino-aortic denervation (SAD group, N = 5). The last two groups were given HTS only. After inducing hemorrhagic hypotension to 40 mmHg over 10 min, 3.5% HTS at half the volume of shed blood was infused over approximately 120 s. In the intact HTS group, sympathetic activation, associated with tachycardia and pressor effects, developed. This enhancement of RNA was followed by a return to the pre-infusion level, but the increased blood pressure and tachycardia lasted until the end of the experiment. These levels of MBP and HR were significantly higher than those of the intact NS group. In the vagotomized animals, HTS resuscitation also increased RNA and systemic blood pressure. In contrast, in the SAD group, neither sympathetic activation nor an early phase increase in systemic blood pressure occurred. These results indicate that in hemorrhaged rabbits, 3.5% HTS produces sympathetic activation along with an acute pressor effect and that this is likely to be mediated through the sino-aortic nerves, possibly the peripheral chemoreceptors, but not through the vagal nerves.

Ulinastatin, a human trypsin inhibitor, inhibits endotoxin-induced thromboxane B2 production in human monocytes.

OBJECTIVES: Ulinastatin has an inhibitory effect on certain cytokines produced from lipopolysaccharide (endotoxin)-stimulated human monocytes. However, the effects of ulinastatin on arachidonic acid metabolism in monocytes have not been determined. This study examined the effects of ulinastatin on the arachidonic acid metabolite, thromboxane B2, in response to endotoxin-, phorbol 12-myristate 13-acetate-, or arachidonic acid-stimulated human peripheral blood monocytes. DESIGN: Controlled, human laboratory investigation of monocyte function in vitro. SETTING: Research facility of a health science university. SUBJECTS: Five normal volunteers. INTERVENTIONS: Mononuclear cells were separated from blood using Histopaque. Monocytes were stimulated with endotoxin (0.1 to 10 micrograms/mL) or other stimulatory agents, which were added simultaneously with or without ulinastatin (25 to 1000 U/mL). None of the compounds in this study altered the cell viability of adherent cellular protein content. Ulinastatin alone did not affect basal thromboxane B2. MEASUREMENTS AND MAIN RESULTS: Endotoxin induced dose-dependent increases in thromboxane B2 production by the monocytes. Ulinastatin (100 U/mL) maximally decreased endotoxin (1.0 microgram/mL)-stimulated thromboxane B2 production, which was not further suppressed with higher ulinastatin concentrations. Increases in thromboxane B2, stimulated by phorbol myristic acid (10 nM) or arachidonic acid (16 microM), were also suppressed by ulinastatin at 100 to 1000 U/mL. CONCLUSIONS: These results indicate that ulinastatin may nonspecifically but moderately down-regulate stimulated arachidonic acid metabolism in human monocytes. Therefore, the present results warrant further clinical studies to examine the beneficial effects of ulinastatin in the treatment of patients with sepsis syndrome.

Inorganic fluoride kinetics and renal tubular function after sevoflurane anesthesia in chronic renal failure patients receiving hemodialysis.

Although sevoflurane is used in clinical anesthesia, its effects on renal function and inorganic fluoride (F-) kinetics in patients with chronic renal failure (CRF) have not been determined. We investigated F- kinetics and renal tubular function in sevoflurane anesthesia in CRF patients having hemodialysis. Five patients dialyzed and five with normal renal function undergoing parathyroidectomy or thyroidectomy were anesthetized with sevoflurane (1.0%-2.5%) and nitrous oxide in oxygen. Serum and urine levels of F-, blood urea nitrogen (BUN), serum creatinine (Cr), serum and urine beta 2-microglobulin (BMG) levels, and urine N-acetyl-beta-D-glucosaminidase (NAG) level were measured. BUN, Cr, and serum and urine BMG levels were significantly higher in the CRF patients than in the controls. There were no differences in serum F- level, rate of elimination, and area under the curve of serum F- levels between the two groups. However, the CRF patients had a significantly lower level of urine F- than control subjects. These data suggest that the F- kinetics in the CRF patients is different from that in normal renal function subjects. This clinical study with a limited number of patients may facilitate further studies to define the mechanisms of differences in the F- kinetics between normal subjects and CRF patients having hemodialysis after sevoflurane anesthesia.

The effect of ulinastatin, a human protease inhibitor, on the transfusion-induced increase of plasma polymorphonuclear granulocyte elastase.

Ulinastatin (UTI), a human protease inhibitor, inhibits polymorphonuclear granulocyte elastase (PMNE) release from granulocytes stimulated by several pathologic inflammatory processes. Blood transfusions increase plasma PMNE concentrations. We evaluated the effects of UTI on the transfusion-induced increase in PMNE. Thirty-nine patients undergoing gastrectomy were divided into four groups: Group A (n = 8), blood transfusion (-), UTI (-); Group B (n = 9), blood transfusion (+), UTI(-); Group C (n = 12), blood transfusion (-), UTI(+); and Group D (n = 10), blood transfusion (+), UTI(+). UTI of 300,000 U was infused in Groups C and D. White blood cell count (WBC), segmented cell count, plasma PMNE concentration, and PMNE release (PMNE concentration/segmented cell) were measured before, at the end of, and at 1 and 3 days after the operation. Although no significant differences were seen in WBC and segmented cell count among the groups, plasma PMNE concentration and PMNE release in Group B (transfusion without UTI) were significantly more than in Group A (no treatment) and Group D (transfusion with UTI) at the end of the operation, but the concentrations of the variables were not significantly different between Groups A and C (only UTI treatment). These results indicate that a single injection of 300,000 U of UTI inhibited transfusion-induced PMNE increase at the end of the operation. Thus, the present results may facilitate future studies testing the effects of UTI given at larger doses, or by a continuous administration, on the prevention of organ derangement after blood transfusion.

[Effects of fentanyl on renal sympathetic nerve activity, heart rate and systemic blood pressure in anesthetized rabbits--an evaluation in both rabbits and human].

This study was designed to evaluate effects of fentanyl (F) on heart rate (HR), systemic blood pressure (SBP) and renal sympathetic nerve activity (RNA) in urethane- or halothane-anesthetized rabbits. Twenty three urethane-anesthetized rabbits were divided into the following four groups: animals with neuraxis intact (Intact group, N = 8), cervical vagotomized animals (Vagotomy group, N = 5), animals treated with sino-aortic denervation (SAD group, N = 5), and those with sino-aortic denervation with vagotomy (SADV group, N = 5). In the intact group, administration of F (20 micrograms.kg-1, i.v.) caused a significant decrease in HR, but not in SBP, even in the presence of increase in RNA. In the Vagotomy group, no significant alterations in HR and SBP occurred despite activation of RNA. In the SAD group, F caused a significant decrease in HR and an increase in both SBP and RNA. In the SADV group, a decrease in HR disappeared but a significant increase in both SBP and RNA developed. In halothane-anesthetized rabbits having intact baroreceptors (N = 5), similar hemodynamic and sympathetic responses to F were observed. In human (N = 5), F (6 micrograms.kg-1, i.v.) caused a decrease in HR but the effect was not significant on SBP. Thus similar hemodynamic changes occurred in both human and in the animals. These results suggest that F may cause a simultaneous activation of vagal nerve and sympathetic nervous system, which might contribute to the hemodynamic stability when F is administered in human.

Role of vagal afferents in hypotension induced by venous air embolism.

To evaluate the role of the autonomic nervous system in the development of hypotension during air embolism, we studied the effects of an intravenous bolus injection of air (0.5 ml/kg) on mean blood pressure (MBP), central venous pressure (CVP), and renal nerve activity (RNA) in urethan-anesthetized rabbits of three groups: animals with an intact neuraxis (intact group; n = 5), cervical-vagotomized animals (vagotomy group; n = 5), and sinoaortic-denervated animals (SAD group; n = 5). In the intact group, despite a significant decrease in MBP at 10 s after air injection, RNA did not increase from the preinjection level. This response of RNA was associated with a significant increase in CVP and lasted for 20 s after the injection. Vagotomized animals, however, exhibited a significant augmentation in RNA in response to a drop in MBP at 10 s after the injection. In the SAD group, profound declines in both MBP and RNA were observed at 10 s after the injection of air. Animals in these two groups showed remarkable increases in CVP. At 5 min after the air administration, MBP in the vagotomy group was significantly higher than that in the intact group. All animals in the SAD group died within 5 min of the injection. These results indicate that during hypotension induced by air injection, sympathetic activation through arterial baroreceptors may be depressed by vagal afferents emanating from cardiopulmonary receptors; the results also suggest that the arterial baroreceptor nerves may be required to overcome the lethal events that should occur during venous air embolism.

Thyrotropin-releasing hormone produces different hemodynamic effects in vegetative and brain-dead patients.

To define a mechanism for the pressor effects of thyrotropin-releasing hormone (TRH), we evaluated changes in mean blood pressure (MBP) when a synthetic form of TRH (0.1 mg/kg, i.v.) was injected into two types of comatose patients: vegetative and brain dead. The patients in the vegetative group (n = 7, age 58 +/- 6) retained spontaneous respiration and brainstem function, whereas the brain-dead (BD) patients (n = 7, age 68 +/- 4) lacked these functions. In the vegetative group, TRH caused significant increases in MBP (from 91 +/- 8 mm Hg to 110 +/- 10 mm Hg) at 2 min after the injection [p < 0.05, analysis of variance (ANOVA) with a Scheffé F-test]. In contrast, five of the seven BD patient showed no alterations in the measured parameter in response to the TRH injection. However, the remaining two BD patients, who had spinal reflexes, exhibited an elevation in MBP. In such BD patients, baroreceptor reflex function was virtually absent, suggesting that the blood pressure regulation mediating through the baroreceptor reflex system might be abolished. These results indicate that in comatose patients, the hemodynamic effects of TRH may differ depending on impairments in the central nervous system; the results support previous reports indicating a mediation of the central sympathetic nervous system in the development of pressor effects of TRH. Furthermore, because brain-dead patients with spinal reflexes showed hypertensive responses to TRH, there is a possibility that these responses may have resulted from an activation of TRH receptors in the spinal cord.

[Effects of air injection on hemodynamics and sympathetic nerve activity in urethane-anesthetized rabbits].

We designed this experiment to evaluate effects of intravenous bolus injection of air (0.5 ml.kg-1) on systemic blood pressure (SBP), central venous pressure (CVP), and renal nerve activity (RNA) in urethane-anesthetized rabbits. Animals were divided into the following three groups: animals with neuraxis intact (I group, N = 5), cervical vagotomized animals (V group, N = 5) and sinoaortic denervated animals (SAD group, N = 4). All animals were placed on the right-side down position to avoid effects of the posture throughout the experiments of air embolism. In the I group, air caused profound hypotension (from 95 +/- 10 to 54 +/- 15 mmHg) associated with a significant increase in CVP (from 2 +/- 2 to 7 +/- 3 mmHg) twenty seconds after the injection of air. In spite of the significant hypotension, RNA response did not show any increase for twenty seconds. This response was followed by an augmentation in RNA thirty seconds after air injection. In contrast, vagotomized animals exhibited a significant RNA increase (147 +/- 11% of the control) in response to a decrease in SBP (from 93 +/- 6 to 78 +/- 5 mmHg) and an increase in CVP ten seconds after the administration of air. In SAD group, a rapid and remarkable decline in SBP (from 85 +/- 13 to 47 +/- 12 mmHg) occurred ten seconds after the injection of air. Despite this hypotension, RNA decreased nearly to a noise level after administration of air.(ABSTRACT TRUNCATED AT 250 WORDS)