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Biomedical subjects

E H Rubinstein

Publications and source records attributed to E H Rubinstein.

At least 19 recordsLinked to original sources

Physiologic responses to mild perianesthetic hypothermia in humans.

To evaluate physiologic responses to mild perianesthetic hypothermia, we measured tympanic membrane and skin-surface temperatures, peripheral vasoconstriction, thermal comfort, and muscular activity in nine healthy male volunteers. Each volunteer participated on three separate days: 1) normothermic isoflurane anesthesia; 2) hypothermic isoflurane anesthesia (1.5 degrees C decrease in central temperature); and 3) hypothermia alone (1.5 degrees C decrease in central temperature) induced by iced saline infusion. Involuntary postanesthetic muscular activity was considered thermoregulatory when preceded by central hypothermia and peripheral cutaneous vasoconstriction. Tremor was considered normal shivering when electromyographic patterns matched those produced by cold exposure in unanesthetized individuals. During postanesthetic recovery, central temperatures in hypothermic volunteers increased rapidly when residual end-tidal isoflurane concentrations were less than or equal to 0.3% but remained 0.5 degree C less than control values throughout 2 h of recovery. All volunteers were vasodilated during isoflurane administration. Peripheral vasoconstriction occurred only during recovery from hypothermic anesthesia, at end-tidal isoflurane concentrations of less than approximately 0.4%. Spontaneous tremor was always preceded by central hypothermia and peripheral vasoconstriction, indicating that muscular activity was thermoregulatory. Maximum tremor intensity during recovery from hypothermic anesthesia occurred when residual end-tidal isoflurane concentrations were less than or equal to 0.4%. Three patterns of postanesthetic muscular activity were identified. The first was a tonic stiffening that occurred in some normothermic and hypothermic volunteers when end-tidal isoflurane concentrations were approximately 0.4-0.2%. This activity appeared to be largely a direct, non-temperature-dependent effect of isoflurane anesthesia. In conjunction with lower residual anesthetic concentrations, stiffening was followed by a synchronous, tonic waxing-and-waning pattern and spontaneous electromyographic clonus, both of which were thermoregulatory. Tonic waxing-and-waning was by far the most common pattern and resembled that produced by cold-induced shivering in unanesthetized volunteers; it appears to be thermoregulatory shivering triggered by hypothermia. Spontaneous clonus resembled flexion-induced clonus and pathologic clonus and did not occur during hypothermia alone; it may represent abnormal shivering or an anesthetic-induced modification of normal shivering. We conclude that among the three patterns of muscular activity, only the synchronous, tonic waxing-and-waning pattern can be attributed to normal thermoregulatory shivering.

Adult

Lidocaine accelerates neuroelectrical recovery after incomplete global ischemia in rabbits.

The use of high-dose lidocaine for cerebral protection during ischemia has produced varied results. Our study uses a new, single carotid artery preparation in the rabbit to produce incomplete global ischemia by graded carotid occlusion; specific electroencephalographic changes are used as the end point for the extent of blood flow reduction sustained during 20 minutes. We monitored arterial pressure, intracranial pressure, and internal carotid blood flow that were recorded with an electromagnetic flowmeter after surgical ligation of the opposite internal and the two vertebral arteries, and we studied the electroencephalogram and somatosensory-evoked potentials elicited by stimulation of the sciatic nerve. Low-dose lidocaine (0.2 mg/kg/min) infused throughout the experiment significantly accelerated the time course of the return of electroencephalographic and evoked-potential amplitudes toward control. Deep halothane anesthesia alone elicited the slowest recovery, suggesting that the action of lidocaine was independent of its general anesthetic effect. There were very small differences among the groups in the measured arterial pressure, intracranial pressure, and cerebral blood flow, suggesting that lidocaine changed recovery rate without markedly modifying any characteristic of the postischemic cerebral perfusion. The protective effect of lidocaine may be the result of a specific blockade of Na+ channels or a decrease in excitatory neurotransmitter release, either of which would cause a delay in the onset of the events that lead to neuronal damage during ischemia.

Animals

Skin-surface temperature gradients correlate with fingertip blood flow in humans.

Skin-surface temperature gradients (forearm temperature - fingertip temperature) have been used as an index of thermoregulatory peripheral vasoconstriction. However, they have not been specifically compared with total finger blood flow, nor is it known how long it takes fingertip temperature to fully reflect an abrupt change in finger blood flow. Steady-state skin-temperature gradients were compared with total fingertip blood flow in 19 healthy volunteers. There was an excellent correlation between steady-state skin-surface temperature gradients and total fingertip blood flow measured with venous-occlusion volume plethysmography: gradient = 0.2-5.7.log(flow), r = 0.98. The half-time for fingertip cooling after complete arterial obstruction (in 8 volunteers) was 6.6 +/- 1.2 min. The authors conclude that skin-temperature gradients are an accurate measure of thermoregulatory peripheral vasoconstriction.

Adult

The thermoregulatory threshold in humans during halothane anesthesia.

Although suppression of thermoregulatory mechanisms by anesthetics is generally assumed, the extent to which thermoregulation is active during general anesthesia is not known. The only thermoregulatory responses available to anesthetized, hypothermic patients are vasoconstriction and non-shivering thermogenesis. To test anesthetic effects on thermoregulation, the authors measured skin-surface temperature gradients (forearm temperature--finger-tip temperature) as an index of cutaneous vasoconstriction in unpremedicated patients anesthetized with 1% halothane and paralyzed with vecuronium during elective, donor nephrectomy. Patients were randomly assigned to undergo maximal warming (warm room, humidified respiratory gases, and warm intravenous fluids; n = 5) or standard temperature management (no special warming measures; n = 5). Skin-surface temperature gradients greater than or equal to 4 degrees C were prospectively defined as significant vasoconstriction. Normothermic patients [average minimum esophageal temperature = 36.4 +/- 0.3 degrees C (SD)] did not demonstrate significant vasoconstriction. However, each hypothermic patient displayed significant vasoconstriction at esophageal temperatures ranging from 34.0 to 34.8 degrees C (average temperature = 34.4 +/- 0.2 degrees C). These data indicate that active thermoregulation occurs during halothane anesthesia, but that it does not occur until core temperature is approximately equal to 2.5 degrees C lower than normal. In two additional hypothermic patients, increased skin-temperature gradients correlated with decreased perfusion as measured by a laser Doppler technique. Measuring skin-surface temperature gradients is a simple, non-invasive, and quantitative method of determining the thermoregulatory threshold during anesthesia.

Anesthesia, Inhalation

Spontaneous post-anesthetic tremor does not resemble thermoregulatory shivering.

Spontaneous post-anesthetic tremor that resembles shivering is common during recovery from anesthesia. Risks to postoperative patients include an increase in metabolic rate of up to 400%, hypoxemia, wound dehiscence, dental damage, and disruption of delicate surgical repairs. The etiology of spontaneous post-anesthetic tremor is most commonly attributed to normal thermoregulatory shivering in response to intraoperative hypothermia. However, the mechanism of this tremor remains unknown, hampering prevention and treatment. The present study was designed to determine whether mechanisms other than thermoregulation contribute to the tremor. The electromyograms (EMGs) of eight muscles were observed in nine women during recovery from isoflurane anesthesia. Signals from each muscle were compared to those of pathologic clonus induced by plantar flexion in unanesthetized patients with spinal cord transections and to those of cold-induced shivering in normal, unanesthetized subjects. Two distinct EMG patterns were identified: 1) regular, bursting signals of 5-7 Hz similar to those produced by pathologic clonus in patients with spinal cord transections; and 2) tonic, irregular signals of 5-15 Hz which had poorly defined bursts that did not demonstrate the synchronous 4-8-cycle/min waxing and waning pattern typical of normal shivering. EMG activity occurred most often at expired isoflurane concentrations of 0.1-0.19%, and was not related to rectal temperature. During the later part of recovery when isoflurane concentrations were less than or equal to 0.1%, hypothermic patients frequently demonstrated no clinical or EMG evidence of muscular activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

The thermoregulatory threshold in humans during nitrous oxide-fentanyl anesthesia.

Narcotics and nitrous oxide (N2O) inhibit thermoregulatory responses in animals. The extent to which N2O/fentanyl anesthesia lowers the thermoregulatory threshold in humans was tested by measuring peripheral cutaneous vasoconstriction using skin-surface temperature gradients (forearm temperature-fingertip temperature) and the laser Doppler perfusion index. Fifteen unpremedicated patients were anesthetized with N2O (70%) and fentanyl (10 micrograms/kg iv bolus followed by 4 micrograms.kg-1.h-1 infusion) during elective, donor nephrectomy. Patients were randomly assigned to undergo additional warming (humidified respiratory gases, warmed intravenous fluids, and a heating blanket over the legs; n = 5) or standard temperature management (no special warming measures; n = 10). Significant vasoconstriction was prospectively defined as a skin-surface temperature gradient between forearm surface and finger-tip surface greater than or equal to 4 degrees C, and the thermoregulatory threshold was defined as the esophageal temperature at which such vasoconstriction occurred. Vasoconstriction did not occur in the patients who received additional warming and thus remained nearly normothermic [average minimum esophageal temperature = 35.8 +/- 0.4 degrees C (SD)] but did in six hypothermic patients at a mean esophageal temperature of 34.2 +/- 0.5 degrees C. Four hypothermic patients developed a passive thermal steady state without becoming sufficiently cold to trigger vasoconstriction. Thus, active thermoregulation occurs during N2O/fentanyl anesthesia but does not occur until core temperatures are approximately 2.5 degrees C lower than normal. The thermoregulatory threshold during N2O/fentanyl anesthesia is similar to that previously determined during halothane (34.4 +/- 0.2 degrees C).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation

Comparison of ketamine, physical restraint, halothane and pentobarbital: lack of influence on serotonergic measures in monkeys and rats.

The consequences of the use of ketamine for immobilization have been examined on the concentration of whole blood serotonin, concentrations of neurotransmitters and metabolites in CSF and brain, and specific binding of ligands related to neurotransmitters in brain. Vervet monkeys (Cercopithecus aethiops sabaeus) were examined under conditions which compared ketamine with physical restraint and with halothane. It was found that ketamine, used acutely in monkeys for restraint, had no influence on the concentration of serotonin in whole blood or the concentration of 5-hydroxyindoleacetic acid or homovanillic acid in the CSF. In rats, untreated animals were compared with those treated with ketamine alone, or in conjunction with pentobarbital. Treatment with ketamine had no influence on the specific binding of ketanserin, imipramine, prazosin or dihydroalprenolol in brain of rat, nor any influence on the concentrations of serotonin, 5-hydroxyindoleacetic acid, norepinephrine, epinephrine, dopamine, or dihydroxyphenylacetic acid in brain. A moderately increased concentration of homovanillic acid was observed in several areas of the brain of the rat after ketamine alone or paired with pentobarbital.

Animals

Cerebrovascular reactivity to CO2: modulation by arterial pressure.

Cerebrovascular reactivity to CO2 (CO2R), measured in halothane-anesthetized rabbits, decreased as arterial pressure was increased either pharmacologically or mechanically. On the other hand, hypotension, induced by bleeding, led to an increase in CO2R. These responses were unaffected by denervation of baroreceptors.

Animals

Cholinergic cerebral vasodilatation: lack of involvement of cranial parasympathetic nerves.

Cerebral blood flow (CBF) was estimated by measurement of internal carotid blood flow (ICBF) and sagittal sinus blood flow (SSBF) in mechanically ventilated rabbits under 70% N2O/30% O2. Electrical stimulation of cranial nerves III, VII, IX, or X, with stimulus parameters adequate to excite other visceromotor outflows of these nerves, failed to elicit change in CBF. Combined bilateral section of nerves VII, VIII, IX, X, and XI had no effect on the reactivity of CBF to CO2, nor did the sectioning of these nerves affect the increases in CBF induced by physostigmine. Division of the sinus and aortic nerves and of the vagi in the neck failed to change CO2 reactivity, even though normocapnic CBF was reduced. Pentobarbital blocked the increase in CBF produced by physostigmine, but had no effect on that produced by pilocarpine. The results indicate that cranial parasympathetic nerves do not contain cerebral vasodilator fibers, and that they are not the source of acetylcholine which is presumably involved in CBF regulation.

Animals

Cholinergic cerebral vasodilatation in the rabbit: absence of concomitant metabolic activation.

Cerebral blood flow (CBF) was estimated from measurements of internal carotid blood flow and sagittal sinus blood flow in mechanically ventilated rabbits under 70% N2O-30% O2. Intravenously administered physostigmine, a cholinesterase inhibitor, increased CBF under normocapnia and enhanced the cerebral vasodilatation of hypercapnia, but did not alter the cerebral metabolic rate of oxygen (CMRO2). The cerebrovascular effects of physostigmine were antagonized by atropine but not by dihydro-beta-erythroidine, a nicotinic blocker. Neostigmine, a quaternary cholinesterase inhibitor that does not cross the blood-brain barrier, showed no cerebrovascular effects. It is concluded that the cholinergic cerebral vasodilatation does not depend on cerebral metabolic activation, and that the cholinergic receptors involved are muscarinic and located beyond the blood-brain barrier.

Animals

Abolition of hypoxic vagal bradycardia by lateral mesencephalic lesions in spinal cats.

To examine central sites that integrate the vagal bradycardia induced by hypoxia, heart rates were recorded continuously in spinal, precollicular, decerebrated cats during transient hypoxia induced by ventilation with 100% nitrogen. Bilateral lesions in the lateral mesencephalic reticular formation either decreased the extent of bradycardia or caused a reversal to tachycardia; anesthesia induced the same change. In contrast, bilateral lesions in the medial mesencephalic reticular formation failed to alter the bradycardia. Hence, the lateral mesencephalic reticular formation is essential for the appearance of hypoxia-induced vagal bradycardia.

Anesthesia

Mechanisms of vascular changes in skeletal muscle during asphyxia in the cat.

Vascular responses in the hindlimb muscles of anesthetized paralyzed cats during systemic asphyxia were studied. The cats were ventilated with 10% O2-10% CO2-80% N2 for 10-20 min periods, while blood flow to the skinned hindlimb was monitored (electromagnetic flowmeter). Mean arterial pressure rose and hindlimb flow typically fell during asphyxia, implying increased vascular resistance. After sympathetic denervation of the hindlimb, resistance increased in some groups of animals, and did not change in others during asphyxia. Functional adrenalectomy did not alter these response characteristics. Resistance also did not changes significantly if the control resistance was first increased to the predenervation level by electrically pacing the lumbar sympathetic chain. In contrast, pronounced vasodilatation occurred during asphyxia after blocking of the alpha receptors in the hindlimb (phenoxybenzamine) or after systemic catecholamine depletion (reserpine). We conclude that the vasoconstriction in innervated muscle during asphyxia was caused in part by increased discharge of sympathetic constrictor nerves to the muscle vasculature, with augmentation from a humoral alpha agonist of nonadrenal origin, possibly norepinephrine released from sympathetic nerves throughout the body.

Adrenal Medulla

Vascular response to short-term systemic hypoxia, hypercapnia, and asphyxia in the cat.

Acute systemic hypoxia, hypercapnia, or asphyxia was produced in ketamine-anesthetized, paralyzed cats by ventilating them for 2-4 min with appropriate gas mixtures. A sustained rise in arterial pressure occurred in all cases. Vascular responses to hypoxia (7% O2, 10% 02, or 14% O2) included muscle constriction, cutaneous (hindpaw) dilatation (no change with 14% O2), renal constriction (unchanged flow), and unchanged intestinal resistance. Asphyxia (hypoxia + 10% CO2) produced a similar pattern, except that intestinal dilatation occurred. Hypercapnia (10% CO2 + 21% O2) produced muscle constriction, renal constriction (unchanged flow), intestinal dilatation, and no change in cutaneous resistance. Intestinal dilatation seemed in all cases a response to elevated CO2 only. Hypercapnia augmented the effects of hypoxia in skin and skeletal muscle. The variation of responses in different vascular beds suggests a patterning of sympathetic discharge, and varying responsivity to local and humoral factors.

Animals

Reversal of hypoxic bradycardia by halothane or midcollicular decerebration.

Previous work suggests a primary vagal bradycardia during hypoxic excitation of the arterial chemoreceptors. In this study we examined whether tachycardia, resulting from withdrawal of vagal inhibition of the cardiac pacemaker, may also occur during hypoxia. Cats with cervical spinal section were ventilated with hypoxic gas mixtures or allowed to remain apneic in expiration while heart rate was continually monitored. During recovery from halothane anesthesia or following electrolytic midcollicular decerebration, the bradycardic response to hypoxic or asphyxic stimulation was reduced or was reversed to tachycardia. The extent of reduction or reversal of the bradycardia was positively correlated with the level of the arterial pressure which was adjusted by either hemorrhage or infusion of phenylephrine. These findings indicate a tachycardic component of the vagal response to hypoxia, integrated in the pontomedullary region of the brainstem and resulting from interaction between the chemoreceptor and baroreceptor reflexes.

Animals