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Biomedical subjects

A W Gelb

Publications and source records attributed to A W Gelb.

At least 19 recordsLinked to original sources

Hemorrheological changes associated with brain death and their implications for potential organ donors.

Successful transplantation of donor organs from brain-dead patients requires adequate maintenance of hemodynamic parameters. Blood flow and tissue perfusion are highly dependent upon hemorrheology. The aim of the present study was to evaluate hemorrheological parameters in potential organ donors compared to healthy volunteers. Whole blood-, plasma- and corrected blood viscosity, hematocrit, erythrocyte deformability, and erythrocyte aggregation were obtained in ten consecutive brain-dead patients and ten matched volunteers. Compared to controls, hematocrit and whole blood viscosity at high and medium shear rates and erythrocyte deformability were significantly decreased. Plasma viscosity was significantly increased in all patients. In the same group, a highly significant increase was observed at all shear rates when viscosity was corrected for hematocrit. Definite rheological abnormalities were found in the blood of brain-dead patients, something which might lead to impaired organ function after transplantation. Therefore, optimizing such parameters by special fluid management may be of importance in potential organ donors.

Adolescent

Actions of propofol on pontine neurons controlling arterial pressure in rats.

Tonic firing of pontine neurons provides excitatory input to the vasomotor centre in the ventrolateral medulla. To increase our understanding of the actions of propofol on CNS neurons controlling the cardiovascular system, we evaluated the effects of propofol on this tonic firing of pontine neurons. The actions of propofol (doses 1-4, respectively: 24 +/- 2, 40 +/- 4, 65 +/- 3 and 104 +/- 3 mg.kg-1.hr-1) on the pontine neurons were studied using eight atropinized Wistar rats. Electrical activity of renal sympathetic nerves, systemic arterial blood pressure and heart rate were recorded. Propofol decreased renal nerve activity by 3 +/- 2%, 23 +/- 3%, 33 +/- 3% and 52 +/- 4% at the four doses. Arterial pressure and heart rate decreased similarly in a dose-dependent manner. Sympathetic and cardiovascular responses to blocking neurons in the pontine reticular formation by microinjection of glycine were depressed by propofol. Renal nerve activity was decreased by 44 +/- 5% 41 +/- 4%, 28 +/- 3% and 13 +/- 2% after pontine blockade during infusion of doses 1 to 4, respectively. Similarly, arterial pressure was decreased by 25 +/- 3, 15 +/- 2, 12 +/- 1 and 5 +/- 2 mmHg. Finally, heart rate decreased by 27 +/- 6, 20 +/- 4, 18 +/- 4 and 13 +/- 5 heats per min as the propofol dose increased. The tonic firing of pontine neurons was minimally depressed by the lower two doses of propofol but higher doses did appear to depress their firing, demonstrating dose-dependence of actions of this anaesthetic.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Propofol differentially attenuates the responses to exogenous and endogenous norepinephrine in the isolated rat femoral artery in vitro.

Propofol causes a decrease in vascular resistance mediated in part by a decrease in sympathetic output. To determine whether attenuation of norepinephrine release from sympathetic perivascular nerve terminals could contribute to decreased vascular resistance, we examined the effects of propofol on the contractile responses to exogenous and endogenous norepinephrine in the rat femoral artery. Endogenous norepinephrine was released from sympathetic nerve terminals using electrical field stimulation. The responses to both exogenous norepinephrine and neurally released norepinephrine were attenuated by propofol in concentrations from 1.0 to 10.0 micrograms/mL. At 50% of maximal and at maximal contractile responses to norepinephrine and electrical field stimulation, the response to electrical field stimulation was inhibited to a greater extent than the response to exogenous norepinephrine. This suggests that, in addition to direct postsynaptic vasodilation, propofol has the presynaptic effect of inhibiting norepinephrine release from perivascular nerves.

Animals

Association between electrocardiographic abnormalities and intracranial blood in patients following acute subarachnoid hemorrhage.

The etiological factors that influence the development of electrocardiographic (ECG) abnormalities following a subarachnoid hemorrhage are not fully understood. The purpose of this study was to assess if there was an association between ECG abnormalities and the amount of intracranial blood seen on computerized tomographic (CT) scanning following an acute bleed in patients with a cerebral aneurysm. The charts of 70 patients who had had a preoperative CT scan and a preoperative ECG within 96 h of bleed were reviewed. The neurological status of the patients was graded according to the Botterell classification and the amount of blood seen on the CT scan was graded by the Fisher classification. Thirty patients had an abnormal ECG. Seventy percent of these abnormalities involved the T wave or the ST segment. The incidence of ECG abnormalities was statistically greater for patients who had an increased amount of intracranial blood or an intracerebral clot, as seen on CT scan. All patients had treatment (surgical n = 69, embolization n = 1) of the aneurysm. Neither the amount of blood seen on CT scan nor the incidence of ECG abnormalities was useful in predicting patient outcome. In conclusion, an increased quantity of intracranial blood was associated with an increased incidence of ECG abnormalities.

Acute Disease

Predicting perioperative stroke.

The purpose of this review is to examine the incidence and mechanisms of perioperative stroke and to identify possible associated risk factors. The perioperative period can be subdivided into preoperative, intraoperative, and postoperative periods; we focus here on assessment in the preoperative period, as this is the time when risk prediction usually occurs. Surgical technique itself will not be considered, nor will intraoperative monitoring to detect cerebral ischemia be considered. This review will examine perioperative stroke in relation to general surgical procedures, including peripheral vascular reconstruction, orthopedic, gynecologic, and head and neck surgery.

Anesthesia

Evoked potential monitoring during posterior fossa aneurysm surgery: a comparison of two modalities.

The purpose of this study was to compare and assess the ability of two different evoked potential (EP) modalities, median nerve somatosensory evoked potentials (SSEP) and brainstem auditory evoked potentials (BAEP) in monitoring for cerebral ischaemia and in predicting neurological outcome during posterior fossa aneurysm surgery. During 70 procedures, patients were monitored with both SSEP and BAEP. Temporary occlusion of an artery was used in 52 patients and permanent occlusion in 21 patients. A change was defined as a greater than 50% decrease in amplitude and/or an increase in latency greater than 1 msec of the N20 (cortical waveform) for SSEP monitoring and of the fifth peak for BAEP monitoring. Neurological assessment of the patient was performed immediately on emergence, after 24 hr and at the time of discharge. In total, 14 patients had an SSEP change which predicted a neurological deficit in eight patients (57%). Ten patients had a change in BAEP; six had a neurological deficit (60%). Five patients had a change in both, two had a deficit (40%). The incidence of false negative results (a neurological deficit but no EP change) for both modalities was 20% (SSEP 47%, BAEP 60%). The incidence of false positive results (an EP change but no deficit) was 13% overall (SSEP 11%, BAEP 7%). All patients who had a permanent EP change developed a neurological deficit. We did not find a difference in the ability of SSEP compared with BAEP in predicting neurological deficits but, using both modalities, the incidence of false negative results was decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Cerebrovascular and cerebral metabolic effects of commonly used anaesthetics.

It is important to know the effects of anaesthetics on cerebral blood flow and cerebral metabolism to enable appropriate selection of agents for the brain injured patient. Thiopental possesses favourable cerebrovascular and metabolic properties but has not been shown to improve outcome in head injured patients. Propofol has properties similar to thiopental. Its rapid metabolism as well as its ability to reduce intracranial pressure and its antiemetic properties render it a very favourable drug. Despite controversies surrounding the effects of short-acting narcotics on intracranial pressure, they continue to be used because they provide stable haemodynamic conditions when used with care. Isoflurane is currently advocated as the best inhalational agent for neuroanaesthesia because of its lesser effects on cerebral blood flow and intracranial pressure. The effects of nitrous oxide on cerebral blood flow and intracranial pressure appear to vary according to the background anaesthetic used. Nitrous oxide is still widely used in most neuroanaesthetic practices, as its effects can be blunted by barbiturates, narcotics and/or hypocapnia. There is no convincing human study on the cerebral protective properties of anaesthetic agents although mild hypothermia has been shown experimentally to offer significant protection against global and focal ischaemia.

Anesthetics, Inhalation

Comparison of fentanyl, sufentanil and alfentanil during awake craniotomy for epilepsy.

Neurolept anaesthesia is used during awake craniotomy for epilepsy surgery. This study compares analgesia, sedation and the side effects of the newer opioids sufentanil and alfentanil, with those of fentanyl in patients undergoing awake craniotomy. Thirty patients were randomized into three groups, each received droperidol, dimenhydrinate and the chosen opioid as a bolus followed by an infusion. The opioid doses used were fentanyl 0.75 microgram.kg-1 plus 0.01 microgram.kg-1 x min-1; sufentanil 0.075 microgram.kg-1 plus 0.0015 microgram.kg-1 x min-1, and alfentanil 7.5 micrograms.kg-1 plus 0.5 microgram.kg-1 x min-1. There were no differences in the requirements for droperidol, dimenhydrinate or in the incidence of complications among the three groups. The total doses of the opioids required were fentanyl 4.9 +/- 1.3 micrograms.kg-1, sufentanil 0.6 +/- 0.2 microgram.kg-1 and alfentanil 149 +/- 36 micrograms.kg-1. Two patients became uncooperative requiring general anesthesia. The conditions for surgery, electrocorticography and for stimulation testing were satisfactory in all other patients. We conclude that the newer opioids did not offer any benefit over fentanyl.

Adult

Action of propofol on central sympathetic mechanisms controlling blood pressure.

This study was done using Wistar rats to determine if the actions of propofol (22 +/- 1, 40 +/- 2, 64 +/- 3 and 103 +/- 3 mg.kg-1 x hr-1) decreased blood pressure and heart rate through depression of brain stem vasomotor centres. All rats were given atropine to block vagal influences on the heart. Propofol decreased renal nerve activity as well as blood pressure and heart rate in a dose-dependent manner. Infusion of the lowest dose of propofol (22 +/- 1 mg.kg-1 x hr-1) had no effect on blood pressure, heart rate and renal nerve activity. Infusion of propofol at 40 +/- 2 mg.kg-1 x hr-1 decreased renal activity by 22 +/- 4% (mean +/- SEM) and at 64 +/- 3 mg.kg-1 x hr-1 it decreased renal nerve activity by 36 +/- 6%. Finally, infusion of the largest dose of propofol (102 +/- 3 mg.kg-1 x hr-1) decreased nerve activity by 50 +/- 5%. The haemodynamic changes observed in our experiments during the infusion propofol paralleled the changes in sympathetic firing, suggesting that hypotension was caused by central actions of propofol to depress sympathetic firing. In experiments with bolus injections of propofol, the renal nerve activity returned to normal before arterial pressure and heart rate recovered. Because decreases in blood pressure and heart rate were longer-lasting than changes in renal nerve activity, a part of the vasodepression and bradycardia caused by propofol likely resulted from direct actions on blood vessels and the heart. Sympathetic and cardiovascular responses to blocking neurons in the ventrolateral medulla with microinjection of glycine were depressed by propofol.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials

The effects of propofol compared to high-dose fentanyl anesthesia on rheologic parameters in coronary artery surgery.

Propofol has previously been found to decrease hematocrit values. Because hematocrit is an important determinant of blood viscosity, lower hematocrits may cause a decrease in blood viscosity, improving blood flow and oxygen delivery. This phenomenon may be beneficial in certain intraoperative situations. To study the influence of two anesthetic techniques on a variety of rheologic parameters, 32 patients scheduled for coronary artery bypass grafting (CABG) were divided into two groups. Group I (n = 18) was induced with high-dose fentanyl anesthesia (100 micrograms/kg), and group II (n = 16) with a combination of propofol and fentanyl anesthesia (1 to 1.5 mg/kg and 35 to 50 micrograms/kg, respectively). Maintenance anesthesia continued with infusions of the same drugs. Blood and plasma viscosity, hematocrit, erythrocyte aggregation factor, and erythrocyte deformability were measured preoperatively, intraoperatively, and up to 48 hours postoperatively. Whole blood viscosity was corrected to a standard hematocrit of 0.45. The two groups were comparable with respect to age, bypass duration, blood loss, urine output, transfusions, and fluid management. Erythrocyte deformability did not decrease during or after cardiopulmonary bypass (CPB). In both groups, hematocrit and blood and plasma were decreased significantly during and after CPB (P < 0.01) and returned to baseline levels 48 hours after surgery. After induction and before CPB, blood viscosity was only decreased in group II. However, the corrected blood viscosity was significantly elevated at all shear rates in group II compared to group I at 24 and 48 hours postoperatively (P < 0.01). In group II at these sampling times, this parameter was also significantly elevated compared to preoperative values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The clinical importance of erythrocyte deformability, a hemorrheological parameter.

Hemorheology, the science of the flow behavior of blood, has become increasingly important in clinical situations. The rheology of blood is dependent on its viscosity, which in turn is influenced by plasma viscosity, hematocrit, erythrocyte aggregation, and erythrocyte deformability. In recent years it has become apparent that the shape and elasticity of erythrocytes may be important in explaining the etiology of certain pathological situations. Thus, clinicians have become increasingly interested in hemorheology in general and erythrocyte deformability in particular. In the course of time, many clinical studies have been performed, but no concise review has thus far been published. This article encompasses a review of the clinically based literature on this subject.

Blood Viscosity

Methylparaben and propylparaben do not alter cerebral blood flow in humans.

In vitro studies suggest that the preservatives methylparaben and propylparaben included in some multidose vials of succinylcholine are the cerebral vasodilators responsible for the increases in intracranial pressure (ICP) documented after succinylcholine administration. To test this hypothesis, we measured cerebral blood flow (CBF) and cerebral blood flow velocity (CBFV) with inhaled 133Xenon and transcranial Doppler respectively in healthy humans before and after the intravenous administration of methylparaben and propylparaben. We found no change in either CBF or CBFV after the paraben injections and therefore conclude that it is unlikely that the rise in ICP seen with succinylcholine is caused by cerebral arterial vasodilatation from the preservatives methylparaben and propylparaben.

Cerebrovascular Circulation

The responsiveness of cerebral blood flow to changes in arterial carbon dioxide is maintained during propofol-nitrous oxide anesthesia in humans.

Because it is common to manipulate PaCO2 during neurosurgery, it is essential to characterize the relationship between cerebral blood flow (CBF) and changes in PaCO2. The purpose of this study was to investigate the effects of propofol-N2O anesthesia on the CBF response to changes in PaCO2 in healthy subjects. In seven patients, anesthesia was induced with propofol 2.0-2.5 mg/kg and then maintained with a propofol infusion of 12 mg.kg-1.h-1 for 10 min and then 9 mg.kg-1.h-1 for 10 min and then was reduced to 3-6 mg.kg-1.h-1 for the remainder of the study. The subjects' lungs were ventilated with N2O in O2 (FIO2 0.3) to the end-tidal CO2 present before anesthesia, and then CBF was measured using intravenous 133Xe and ten scintillation counters, five over each cerebral hemisphere. ETCO2 then was increased to 50 mmHg and CBF measurement repeated; ETCO2 then was reduced to 30 mmHg and CBF measurement repeated. Concurrent with each CBF measurement, arterial blood was sampled for PaCO2 and hemoglobin measurement. CBF at normocapnia (PaCO2 42 +/- 2 mmHg) was 33 +/- 7 ml.100 g-1.min-1, which increased to 58 +/- 10 ml.100 g-1.min-1 and decreased to 19 +/- 4 ml.100 g-1.min-1 on increasing PaCO2 (53 +/- 4 mmHg) and decreasing PaCO2 (31 +/- 2 mmHg), respectively. Both the PaCO2 and CBF values were statistically different from those measured at any other time (CBF P less than 0.002, PaCO2 P less than 0.001). The slope of CBF versus PaCO2 was 1.56 ml.100 g-1.min-1.mmHg.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Monitoring of brainstem function during vertebral basilar aneurysm surgery. The use of spontaneous ventilation.

Monitoring of cardiovascular, respiratory, and evoked potential parameters has been advocated during posterior fossa surgery to detect brainstem ischemia that may result from surgical manipulations. We report here our retrospective and smaller prospective experience of spontaneous ventilation as a monitor in patients undergoing vascular surgical procedures in the posterior fossa. Forty patients' charts were reviewed retrospectively, and 10 patients were studied prospectively. Respiratory changes in the retrospectively studied group occurred in 9 patients. Four patients developed apnea during temporary occlusion of the vertebral artery. These respiratory changes were associated with simultaneous cardiovascular changes in only 2 patients, and of the 13 patients monitored with evoked potentials, only 2 had simultaneous evoked potential changes. In the prospectively studied group, respiratory changes occurred in 4 patients. Three patients (2 with apnea during temporary occlusion) had a simultaneous change in evoked potentials but no cardiovascular changes. One patient had a change in all three parameters. Allowing our patients to breathe spontaneously provided an early and rapid indication of brainstem ischemia, especially during the temporary occlusion of the vertebral basilar artery system.

Adult

Cardiac function in aneurysmal subarachnoid haemorrhage: a study of electrocardiographic and echocardiographic abnormalities.

Electrocardiographic (ECG) changes are reported frequently after subarachnoid haemorrhage (SAH). The aim of this study was to investigate the functional significance of ECG changes by echocardiographic assessment of cardiac function. Forty-five patients with intracranial aneurysms were studied. All patients had a 12-lead ECG and a two-dimensional echocardiogram. After patients with an history of chronic cardiac disease (n = 4) were excluded, only four patients were found to have wall motion abnormalities. These patients had only minor ECG abnormalities, but severe neurological dysfunction. Conversely, patients with other ECG abnormalities including the deep inverted T waves associated usually with SAH, had normal echocardiograms. We conclude that the ECG is not an accurate predictor of myocardial function after SAH and that myocardial dysfunction is related more closely to severity of neurological condition.

Adolescent

Effects of fentanyl, sufentanil, and alfentanil on brain retractor pressure.

Sufentanil and alfentanil have been reported to increase cerebral blood flow and intracranial pressure. Agents producing these effects may adversely affect the relationship between brain retractors and underlying cerebral tissues during craniotomy, potentially predisposing the patient to brain retractor injury. The effects of fentanyl, sufentanil, alfentanil, and a placebo (saline) on brain retractor pressure were therefore evaluated prospectively in 24 adults undergoing elective craniotomy. None of these narcotics significantly affected brain retractor pressure. Each significantly and similarly decreased arterial pressure and cerebral perfusion pressure. If these narcotics are administered in doses that avoid adverse hemodynamic changes that could compromise cerebral tissues indirectly, each of the narcotics studied appears safe for intraoperative administration once the cranium is open.

Adult