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PubMed1991

Postischemic myocardial "stunning". Identification of major differences between the open-chest and the conscious dog and evaluation of the oxygen radical hypothesis in the conscious dog.

Recent studies suggest that oxygen-derived free radicals contribute to the pathogenesis of postischemic myocardial dysfunction (myocardial "stunning"). This concept, however, is predicated exclusively on results obtained in open-chest preparations, which are subject to the confounding influence of many unphysiological conditions. The lack of supporting evidence in more physiological animal models represents a major persisting limitation of the oxy-radical hypothesis of myocardial stunning. The goal of this study was to address two fundamental (and related) questions: 1) Does the open-chest animal model alter the phenomenon of myocardial stunning? 2) If so, how valid are the concepts, derived from such a model, regarding the pathogenetic role of oxy-radicals? In part 1 of the study, myocardial stunning after a 15-minute coronary occlusion was compared in 30 pentobarbital-anesthetized open-chest dogs and in 19 conscious dogs. For any given level of collateral flow during occlusion, the recovery of systolic wall thickening after reperfusion was markedly less in open-chest animals. In an additional group of five open-chest dogs, a close inverse relation was noted between body temperature and postischemic wall thickening, indicating that the recovery of the stunned myocardium in acute experiments may vary markedly depending on how temperature is controlled. Because of these major differences between open-chest and conscious dogs, the oxy-radical hypothesis needs to be tested in the latter model. Thus, in part 2 of the study, conscious unsedated dogs undergoing a 15-minute coronary occlusion were randomized to an intravenous infusion of either saline (19 coronary occlusions) or superoxide dismutase (SOD) plus catalase (CAT) (21 coronary occlusions). Despite the fact that the plasma levels of SOD and CAT declined rapidly after reperfusion, postischemic wall thickening was significantly greater in treated compared with control dogs throughout the first 6 hours of reflow. Thus, a brief (60-minute) infusion of SOD and CAT produced a sustained improvement of recovery of contractility. The magnitude of this beneficial effect was a function of the severity of ischemia: the lower the collateral perfusion, the greater the improvement effected by the enzymes. The accelerated recovery produced by SOD and CAT was not followed by any deterioration of contractility, suggesting that postischemic dysfunction is not a teleologically "protective" phenomenon. In conclusion, the severity of myocardial stunning is greatly exaggerated by the unphysiological conditions present in the barbiturate-anesthetized open-chest dog.(ABSTRACT TRUNCATED AT 400 WORDS)

Anesthesia, General↗
PubMed2000

Pure consciousness: distinct phenomenological and physiological correlates of "consciousness itself".

This paper explores subjective reports and physiological correlates of the experience of "consciousness itself"--self awareness isolated from the processes and objects of experience during Transcendental Meditation practice. Subjectively, this state is characterized by the absence of the very framework (time, space, and body sense) and content (qualities of inner and outer perception) that define waking experiences. Physiologically, this state is distinguished by the presence of apneustic breathing, autonomic orienting at the onset of breath changes, and increases in the frequency of peak EEG power. A model, called the junction point model, is presented that integrates pure consciousness with waking, dreaming, or sleeping. It could provide a structure to generate a coherent program of research to test the full range of consciousness and so enable us to understand what it means to be fully human.

Adult↗
PubMed1997

Learning, action and consciousness: a hybrid approach toward modelling consciousness.

This paper is an attempt at understanding the issue of consciousness through investigating its functional role, especially in learning, and through devising hybrid neural network models that (in a qualitative manner) approximate characteristics of human consciousness. In doing so, the paper examines explicit and implicit learning in a variety of psychological experiments and delineates the conscious/unconscious distinction in terms of the two types of learning and their respective products. The distinctions are captured in a two-level action-based model CLARION. Some fundamental theoretical issues are also clarified with the help of the model. Comparisons with existing models of consciousness are made to accentuate the present approach.

Journal Article↗
PubMed1983

Ventricular refractory periods in relation to rate and test-site VT intervals in anesthetized and conscious dogs: a canine model for conscious state measurements.

The functional relationship of ventricular effective refractory period (ERP) with basic cycle length (BCL) of stimulated ventricular depolarization and VT intervals of test-site unipolar ventricular electrograms were studied in five conscious and eight anesthetized (sodium pentobarbital, 30 mg/kg) open-chested dogs. The range of BCLs studied was 300 to 1000 ms, achieved through ventricular stimulation following chemically-induced complete AV block. In the conscious animal model developed for this study, two-to-four ventricular electrode leads were exteriorized and the ventricular rate was maintained by an implanted programmable VVI pacemaker. In all animals studied, the BCL-ERP relation was closely represented by the empirical equation ERP = A-B.Exp(-k.BCL), and the VT-ERP relation over the same range of BCLs was linear: ERP = C + D.VT. The correlation coefficients were in the range of 0.991 to 0.999. The mean values of the parameters in the above equations determined by the appropriate non-linear or linear regression analysis showed significant differences between the two groups of animals studied. In three conscious animals a strong linear correlation between the test-site VT intervals and simultaneously measured QT intervals measured from the lead II surface electrogram was demonstrated (r = 0.993 to 0.998). For a fixed site of stimulation, the morphology of ventricular depolarization complexes as well as the corresponding T-waves remained essentially unaltered with BCL for both myocardial and surface electrograms. The possible applications of developed canine model and the results of the present study include: (1) the study of the rate-dependent effects of cardioactive drugs on ventricular electrophysiology and, (2) the improved design of electronic refractory periods of rate programmable pacemakers.

Anesthetics↗
PubMed1999

Pure Consciousness: Distinct Phenomenological and Physiological Correlates of "Consciousness Itself"

This paper explores subjective reports and physiological correlates of the experience of "consciousness itself" - self awareness isolated from the processes and objects of experience during Transcendental Meditation practice. Subjectively, this state is characterized by the absence of the very framework (time, space, and body sense) and content (qualities of inner and outer perception) that define waking experiences. Physiologically, this state is distinguished by the presence of apneustic breathing, autonomic orienting at the onset of breath changes, and increases in the frequency of peak EEG power. A model, called the junction point model, is presented that integrates pure consciousness with waking, dreaming, or sleeping. It could provide a structure to generate a coherent program of research to test the full range of consciousness and so enable us to understand what it means to be fully human.

Journal Article↗
PubMed1997

Safety and efficacy of flumazenil in reversing conscious sedation in the emergency department. Emergency Medicine Conscious Sedation Study Group.

OBJECTIVES: To evaluate the safety and efficacy of flumazenil vs placebo in reversing fentanyl and midazolam-induced conscious sedation in ED patients undergoing a short, painful procedure. METHODS: This was a multicenter, randomized, parallel, double-blind, placebo-controlled study conducted at 9 university-affiliated teaching hospitals. Patients > 18 years of age requiring conscious sedation for a painful procedure expected to last < 20 minutes were eligible for inclusion in the study. Patients received 2 micrograms/kg of fentanyl, followed by midazolam titrated to the desired level of sedation. Patients were then randomized to receive either flumazenil or placebo in a 3:1 ratio (flumazenil:placebo). Vital signs, O2 saturation, and alertness were recorded at regular intervals. Prior to ED release, patients were asked to rate the amount of discomfort they experienced and the level of relaxation achieved on a 10-cm visual analog scale (VAS). They also were questioned about their recall for the procedure and satisfaction with the drug regimen. Physicians also rated their satisfaction with the drug regimen on a 10-cm VAS. RESULTS: Overall, 133 patients received flumazenil and 46 patients received placebo. Patients in the 2 groups received similar doses of midazolam. The patients who received flumazenil returned to baseline alertness earlier (11.1 min vs 24.8 min, p < 0.001) and at a faster rate than did the patients given placebo. Actual intervals from procedure completion until release from the ED did not differ between the 2 groups (98.2 +/- 3.6 min flumazenil vs 96.9 +/- 5.8 min placebo; p = 0.89). The amounts of discomfort experienced, levels of relaxation achieved, recalls for the procedure, and both patient and physician satisfactions were also similar for the 2 groups. There were no serious adverse effects related to the study drug, and minor adverse effects were similar for the 2 groups. CONCLUSION: Flumazenil is safe and efficacious in reversing midazolam-induced sedation in ED patients given a combination of fentanyl and midazolam to facilitate the performance of a short, painful procedure. The patients given flumazenil returned to baseline alertness earlier and at a faster rate than did the patients given placebo. However, flumazenil did not alter the actual interval from procedure completion until ED release.

Adolescent↗
PubMed1985

Cognition and states of consciousness: the necessity for empirical study of ordinary and nonordinary consciousness for contemporary cognitive psychology.

Recent criticisms of the place and function of "consciousness" in "cognitive science" are considered and rejected. Contrary to current orthodoxy subjective experience during abstract cognitive activity, especially when placed in its natural series with phenomenal accounts of so-called "altered states of consciousness," can provide unique and crucial evidence concerning just that core of "semantics" which eludes the automatized "syntax" of computer simulation. The "noetic" aspect of extreme altered states can be placed in relation to introspective descriptions of "insight." Various altered state features--synaesthesias, geometric/mandala imagery, reorganizations of "perceptual" dimensions and enhanced "self-reference"--can be taken as direct "exteriorizations" of abstract symbolic processes as discussed by Neisser, Geschwind, Mead, and Arnheim. A genuine cognitive psychology cannot continue to ignore the qualitative-experiential bases of symbolization. More specifically, the sense that insight just comes to us as if from "outside," its preliminary microgenetic processes masked, does not show the failure of introspective phenomenology but rather offers a unique and positive clue to the imaginal dialogic structure of higher mental processes. Thinking, as one phase of imaginal "conversation," must be "sent" from the phenomenal "other" to an attenuated, receptive phenomenal "self." A reconsideration of the Würzburg controversy, adding closely related altered state phenomena to the transitional series between "impalpable awareness" and specific imagery, suggests that the normally masked processes underlying the "felt meaning" or "insight" state are most directly exteriorized as what Klüver termed "complex" or geometric-dynamic synaesthesias. Finally, a reinterpretation of classical introspectionism's "sensation" shows the "mechanism" by which the metaphorical/synaesthetic processes of cognition are generated. Titchener's "sensation" plays the crucial role in metaphor it so conspicuously lacked in functional perception.

Awareness↗
PubMed1984

Assessment of level of consciousness following severe neurological insult. A comparison of the psychometric qualities of the Glasgow Coma Scale and the Comprehensive Level of Consciousness Scale.

An alternative method of coma assessment is presented and compared with the Glasgow Coma Scale. The merits of the Comprehensive Level of Consciousness Scale as a research tool are presented. An analysis of 101 consecutive consciousness-impaired patients with their short-term outcome is presented.

Adolescent↗
PubMed1986

Contributions of glomerular and tubular mechanisms to antidiuresis in conscious domestic fowl.

Recently developed radioimmunoassay (RIA techniques were employed in a quantitative investigation of the renal actions of the avian antidiuretic hormone arginine vasotocin (AVT) in the conscious domestic fowl. Constant intravenous infusion of AVT at doses of 0.125-1.00 ng . kg-1 . min-1 was used to produce plasma AVT (PAVT) concentrations (verified by RIA) over the entire range of physiological PAVT levels in the domestic fowl. Comparison of the dose-response relationships between PAVT and glomerular and tubular mechanisms of antidiuresis revealed that tubular mechanisms are of primary importance and glomerular mechanisms of secondary importance in the conservation of water by the avian kidney. The greatest proportion of the total AVT-induced reduction in renal water excretion occurred at low physiological PAVT levels (less than 5 microU/ml), prior to any significant reduction in glomerular filtration rate (GFR), and appeared to be the exclusive result of tubular mechanisms of antidiuresis. At high PAVT levels (5-16 microU/ml), glomerular and tubular mechanisms overlapped, and their effects on water conservation could not be separated. Although GFR was reduced by nearly 30% at the highest dose of AVT, only minor additional amounts of water were conserved by the combined actions of glomerular and tubular mechanisms. The glomerular mechanisms appear to have only a minor secondary effect on water-conserving ability of the avian kidney.

Animals↗
PubMedDate not supplied

Reversal of central nervous system effects by flumazenil after intravenous conscious sedation with midazolam: report of a multicenter clinical study. The Flumazenil in Intravenous Conscious Sedation with Midazolam Multicenter Study Group I.

Flumazenil, a benzodiazepine antagonist, reverses the residual central nervous system effects of benzodiazepines. In this US double-blind, multicenter study, the efficacy of flumazenil was compared with that of placebo in antagonizing the effects of midazolam, a benzodiazepine used to induce intravenous conscious sedation. The mean dose of flumazenil was 0.7 mg, administered intravenously. At 5 minutes posttreatment, 82% of 131 flumazenil-treated patients, compared with 15% of 65 placebo-treated patients, demonstrated complete reversal of sedation. In 85% of patients who responded to flumazenil, this reversal of sedation was maintained throughout the 180-minute observation period. Psychomotor performance returned to prestudy levels 5 minutes posttreatment in 87% of the flumazenil-treated patients, compared with 28% of the placebo-treated patients. At the doses administered, flumazenil was less effective in reversing midazolam-induced amnesia, with only 60% of patients demonstrating partial recovery of memory. It was, nevertheless, more effective than placebo. Flumazenil was well tolerated. Dizziness (10%) and nausea (9%) were the most frequently reported adverse effects. Results of this study demonstrate that flumazenil antagonizes the central nervous system effects of midazolam after intravenous conscious sedation.

Adolescent↗
PubMedDate not supplied

Reversal of central benzodiazepine effects by flumazenil after conscious sedation produced by intravenous diazepam. The Flumazenil in Intravenous Conscious Sedation with Diazepam Multicenter Study Group I.

Flumazenil is a competitive benzodiazepine antagonist that rapidly reverses the residual effects of benzodiazepines following intravenous conscious sedation. In a double-blind, multicenter study, postoperative patients who had been sedated with intravenous diazepam were randomly allocated to receive intravenous doses of flumazenil (0.4 mg to 1 mg) or placebo. Levels of sedation and psychomotor impairment were evaluated prestudy, at baseline, and at 6 intervals from 5 to 180 minutes posttreatment. A global evaluation of effectiveness was made at the 5-minute assessment, and memory was assessed at the 180-minute assessment. Flumazenil (mean dose: 0.73 mg [7.3 ml]) was significantly more effective than placebo (mean dose: 8.9 ml) in reversing sedation, psychomotor impairment, and amnesia within 5 minutes after the start of administration. At the 5-minute posttreatment assessment, 84% of 102 flumazenil-treated patients (compared with 42% of 52 placebo-treated patients) experienced complete reversal of sedation. Ninety-two percent of 93 flumazenil-treated patients (compared with 41% of 46 placebo-treated patients) had normal psychomotor function. Reversal of amnesia at the 5-minute assessment was achieved in 75% of 101 flumazenil-treated patients and in 20% of 51 placebo-treated patients. Statistically significant differences between flumazenil and placebo were also observed at the 15-minute assessment. Thereafter there were no significant differences between the two treatment groups. Most (70%) flumazenil-treated patients exhibited no recurrence of sedation during the 180-minute assessment period. The most frequent adverse reaction in the flumazenil group was dizziness (6%). There were no serious adverse experiences related to the test drug. Flumazenil provided prompt, controlled reversal of residual effects, especially sedation, in the majority (84%) of patients recovering from intravenous conscious sedation induced by diazepam. For most (70%) of these flumazenil-treated patients, the reversal was maintained throughout the 180-minute assessment.

Adolescent↗
PubMed1995

Conscious and pre-conscious processes as seen from the standpoint of sleep-waking cycle neurophysiology.

The literature on state-dependent fluctuations in thalamocortical activities indicates that in electrophysiological terms, waking and paradoxical sleep are fundamentally identical states, with the provision that the handling of sensory information is altered in REM sleep. The central paradox of REM sleep, namely the apparent lack of cognitive responsiveness to sensory stimulation in spite of increased thalamocortical responsiveness to sensory stimuli, will lead us to hypothesize that the processing of sensory inputs in REM sleep is similar to that underlying preconscious processing of sensory inputs in the waking state. This will lead to a general discussion of the role of fast (approximately equal to 40 Hz) thalamocortical oscillations and temporal binding in sensory processing and conscious experience.

Arousal↗
PubMed1997

Looking for the agent: an investigation into consciousness of action and self-consciousness in schizophrenic patients.

The abilities to attribute an action to its proper agent and to understand its meaning when it is produced by someone else are basic aspects of human social communication. Several psychiatric syndromes, such as schizophrenia, seem to lead to a dysfunction of the awareness of one's own action as well as of recognition of actions performed by others. Such syndromes offer a framework for studying the determinants of agency, the ability to correctly attribute actions to their veridical source. Thirty normal subjects and 30 schizophrenic patients with and without hallucinations and/or delusional experiences were required to execute simple finger and wrist movements, without direct visual control of their hand. The image of either their own hand or an alien hand executing the same or a different movement was presented on a TV-screen in real time. The task for the subjects was to discriminate whether the hand presented on the screen was their own or not. Hallucinating and deluded schizophrenic patients were more impaired in discriminating their own hand from the alien one than the non-hallucinating ones, and tended to misattribute the alien hand to themselves. Results are discussed according to a model of action control. A tentative description of the mechanisms leading to action consciousness is proposed.

Adult↗
PubMed1991

Cardiovascular effects of elgodipine in conscious pigs with a normal coronary circulation and in conscious pigs with a healed myocardial infarction.

The cardiovascular effects of the phenyldihydropyridine derivative elgodipine (0.3, 1, 3, 10, and 30 microgram/kg/min) were studied in normal conscious pigs and in pigs with chronic left ventricular dysfunction (LVD, caused by coronary artery occlusion) without and after beta-adrenoceptor blockade with propranolol (0.5 mg/kg + 0.5 mg/kg/h). In normal pigs, elgodipine increased cardiac output from 2.57 +/- 0.09 to 5.21 +/- 0.24 L/min (p less than 0.05) as a result of a doubling of the heart rate. Mean arterial blood pressure decreased from 94 +/- 2 to 76 +/- 3 mm Hg (p less than 0.05) as a result of a decrease in systemic vascular resistance. Left ventricular (LV) dP/dtmax increased (by up to 78 +/- 9%), but left ventricular end-diastolic pressure (LVEDP) remained unchanged. After propranolol administration elgodipine did not increase LV dP/dtmax, and the increase in heart rate was attenuated, resulting in a smaller increase in cardiac output (from 2.11 +/- 0.13 to 3.09 +/- 0.23 L/min, p less than 0.05), but an unchanged vasodilator response. In pigs with LVD, elgodipine increased cardiac output and LV dP/dtmax less than in normal animals, but the vasodilator response was not affected. LVEDP decreased from 14.6 +/- 1.6 to 11.7 +/- 2.5 mm Hg (p less than 0.05). In animals with LVD, propranolol caused a more severe depression of systemic hemodynamics, but did not modify the cardiovascular responses to elgodipine. Its cardiovascular profile suggests that elgodipine may not only be useful in the treatment of cardiovascular disorders for which other dihydropyridines are already in use, but also in mild chronic heart failure.

Adrenergic beta-Antagonists↗
PubMed1999

[Time of consciousness, consciousness of time].

Time shapes our behavior: we must estimate the duration of events in our environment in order to anticipate changes and time our activity in function of these changes. However, there is no sensory modality devoted to the perception of time, therefore the question is to know which mechanisms underlie the consciousness that time flows and allow us to estimate time precisely. This article proposes a brief overview of psychological, neuropsychological and brain imaging studies which rely on theoretical models postulating the existence of an internal timer. These studies examine the different components--time base, counter and memory--of this timer: particularly they are aimed at characterising the relationships between the evolution of these components with age or their pathological alterations and changes in temporal judgements. They also attempt to specify the neural bases of these components. From this brief overview comes the idea that, if an internal timer exits, it does not mark objective time but a multitude of subjective times.

Biological Clocks↗
PubMed2001

Consciousness, the brain, and spacetime geometry: an addendum. Some new developments on the Orch OR model for consciousness.

Brain action is both physically controlled and beyond computational simulation. Accordingly, there is a strong case for examining brain organization in a way that specifically seeks out structures in the brain that might plausibly support such putative non-computational action at the ill-understood borderline between quantum and classical physics. Thus, we must seek out structures in the brain where the actual physics that operates at this level could plausibly have important influence on brain action. This is the basis of the Orch-OR model that Stuart Hameroff and I have been proposing, and which he describes in the foregoing article. The case is strongly put forward that the neuronal microtubules play a key role in the required quantum/classical borderline activities which might have an essential relevance to the phenomenon of consciousness. The exploration of such deeper level of neuronal structure and function is very much a continuation of the line of work so wonderfully initiated by Cajal.

Brain↗
PubMed1993

[Conscious, unconscious and not conscious in coma].

In this work, the relation between the consciousness and the unconsciousness was studied in patients presenting a neurosurgical coma state. The study includes 29 patients with clinical observations during their hospitalisation period and a follow up for one year after the emergence from the state of coma. The psychoanalytic methods were used, taking in consideration the emotional and personal history of each patient. We attempted to demonstrate the persistence of the unconscious psychic life during coma and the early period after awakening from the coma. In addition, we felt the existence of a sort of direct confrontation with the unconscious psychic life in some patients emerging from a comatose state. The question is also what are the effects of such experience and how would they affect the life of the patients in the future?

Coma↗
PubMedDate not supplied

Reversal of central benzodiazepine effects by intravenous flumazenil after conscious sedation with midazolam and opioids: a multicenter clinical study. The Flumazenil in Intravenous Conscious Sedation with Midazolam Multicenter Study Group II.

The efficacy and safety of flumazenil in antagonizing the central effects of the benzodiazepine midazolam was demonstrated in patients in whom conscious sedation was induced with midazolam plus an opioid (fentanyl, meperidine, or morphine). In a double-blind, multicenter study, 240 patients were administered flumazenil postoperatively at an average intravenous dose of 0.7 mg (7 ml) and 114 patients were administered an average dose of 9 ml placebo. Complete reversal of sedation was observed in 80% of flumazenil-treated patients and 30% of placebo-treated patients 5 minutes posttreatment. In 87% of patients who responded to flumazenil, the level of alertness was maintained throughout the 180-minute observation period. Midazolam-impaired psychomotor performance returned to normal 5 minutes posttreatment in 80% of the flumazenil-treated patients and 28% of the placebo-treated patients. Flumazenil was less effective in reversing midazolam-induced amnesia, with only 70% of flumazenil-treated patients (and 15% of placebo-treated patients) able to recall the picture shown them at the 5-minute assessment, and fewer patients able to recall pictures shown at later times. Flumazenil was well tolerated, although adverse effects were reported slightly more often than in the placebo group. The most frequent adverse events in both groups were dizziness and nausea. Vital signs were not affected.

Adolescent↗