Cortical Electroencephalogram Research Articles

Corticosterone and Growth Hormone Secretions during Long-Term Thiopental Anesthesia in the Male Rat

To study the temporal correlation of secretory profiles of corticosterone (CS) and growth hormone (GH) in adult male rats in the continuous-sleep state, CS and GH concentrations were measured in blood sampled at 10-min intervals through an intracardiac cannula for 11-12 h under long-term thiopental anesthesia. The cortical electroencephalogram (EEG) was monitored to maintain stable sleep during the sampling period. Sixteen rats were subjected to the experiment. By analysis of power spectrum and least-squares methods all the time series of CS and GH concentrations in blood were revealed to have three major ultradian rhythms with periodicities of 1.5 h and its multiples. Although there were no significant positive or negative cross-correlation coefficients between the periodicities of CS and GH, a tendency was evident for GH concentrations to be high when CS concentrations were low, and CS concentrations to be high when GH concentrations were low. The results demonstrate that CS and GH secretions are able to manifest the same ultradian rhythms as those in the unanesthetized, freely moving condition even in the continuous-sleep state due to thiopental anesthesia. Combined with our previous findings, the CS, GH and sleep-wakefulness rhythms appear to be governed by separate pacemakers, although sharing the same basic ultradian rhythm.

Genetics and the Risk for Alcoholism

The importance of genetic factors in alcoholism is supported by the familial nature of this disorder, the significantly higher concordance rate in identical than in fraternal twins, and the fourfold higher risk for children of alcoholics, even when adopted out at birth. Based on this evidence, the search is under way to identify possible genetically influenced factors that might contribute to the alcoholism risk. Studies of populations at high risk for the future development of alcoholism (eg, sons of alcoholics) have revealed a probable decreased intensity of reaction to modest doses of ethanol, a possible decreased amplitude of the P300 wave of the event-related potential, and a possible decreased amount of alpha-wave activity on the background cortical electroencephalogram. The implications of these and other findings and their impact on the practice of medicine are explored.

Tonic desynchronisation of cortical electroencephalogram by electrical and chemical stimulation of superior colliculus and surrounding structures in urethane-anaesthetised rats

Damage to the superior colliculus in rats impairs desynchronisation of the cortical electroencephalogram in response to light flashes. However, it is unclear which elements within the superior colliculus, and which efferent collicular pathways, might be involved in alerting cerebral cortex to visual stimuli. To investigate this problem, the superior colliculus and surrounding structures were stimulated either electrically (3 s trains of 0.2 ms 100 Hz cathodal pulses), or chemically (200 nl of 5 mM sodium L-glutamate), in rats anaesthetised with urethane. The cortical electroencephalogram was recorded bilaterally from frontal cortex. At each site tested with electrical stimulation the threshold current (up to 60 microA) required to produce tonic desynchronisation (outlasting stimulation-offset by at least 10 s) was determined. Comparison of the effects of electrical and chemical stimulation suggested the following: (1) stimulation of cells in the deep layers of the superior colliculus can desynchronise the cortical electroencephalogram. There may also be an additional effective area in the rostral part of the superficial layers, but this needs to be confirmed in unanaesthetised animals. (2) Stimulation of fibres in the deep white layers of caudal superior colliculus, and of cells in a wide area of caudal midbrain reticular formation, are also effective at desynchronising the cortical electroencephalogram. It is therefore possible that the ipsilateral descending pathway, that runs from the superior colliculus to terminate in the parabigeminal and cuneiform nuclei and surrounding reticular formation, is involved in mediating cortical desynchronisation initiated by the superior colliculus. Evidence from other studies indicates that some sites in this pathway may be part of a "defence arousal system". (3) Sites on the ascending pathways from the superior colliculus, to structures including dorsal thalamus, pretectum, zona incerta and rostral midbrain reticular formation, were relatively ineffective at tonically desynchronising the cortex. However, some of these pathways might mediate phasic, movement-related arousal of collicular origin.

The effect of high dose sodium thiopental on brain stem auditory and median nerve somatosensory evoked responses in humans.

Median nerve somatosensory evoked potentials (MnSSEPs), brain stem auditory evoked responses (BAERs), and the cortical electro-encephalogram (EEG) were recorded in six patients during a 62-min infusion of sodium thiopental (STP) at a rate of 1.25 mg X kg-1 X min-1 (total dose, 77.5 mg/kg). The EEG became isoelectric after 22 +/- 8 (SD) min of STP infusion. Dose-related changes in the latencies and amplitudes of various evoked response wave forms were observed. However, in no instance was any component of either the MnSSEP or the BAER rendered unobtainable by STP administration. For the MnSSEP, progressive increases in the central conduction time (5.33 +/- 0.41 ms preinduction vs. 7.46 +/- 1.2 ms at t = 60 min) and in the latency of the cortical primary specific complex were observed simultaneously with significant reductions in the amplitude of the latter (2.10 +/- 0.85 muV preinduction vs. 0.85 +/- 0.55 muV at t = 60 min). Changes in the latency and amplitude of the response recorded over the upper cervical spine (C2) were not statistically significant in this small population. For the BAER, progressive and significant increases in the latencies of Waves I, III, V (e.g., Wave V latency: 6.16 +/- 0.24 vs. 6.87 +/- 0.31 ms) and in the I-III, III-V, and the I-V interwave latencies were observed. The amplitudes of the BAER components were not significantly altered. The authors conclude that the administration of a dose of STP in excess of twice that required to produce EEG isoelectricity can be compatible with effective monitoring of MnSSEPs and BAERs. However, STP produces dose-related changes in both evoked response wave forms, which must be considered in the interpretation of responses elicited during STP anesthesia.

Responses of thalamic and hypothalamic neurons to scrotal warming in rats: Non-specific responses?

Activities of thalamic and hypothalamic neurons in response to scrotal temperature change were investigated in urethanized (1.2-1.5 g/kg) rats with special attention to changes in cortical electroencephalogram (EEG). Somatosensory relay neurons were identified electrophysiologically in the ventrobasal complex (VB) of the thalamus. These neurons had tactile receptive fields in areas outside the scrotum. Forty out of 44 of these neurons responded to scrotal warming by increase in firing rate. The responses occurred abruptly at threshold temperatures ranging from 31 to 40 degrees C (switching response) with simultaneous changes in EEG from high to low voltages (desynchronization). In both the thalamus and the hypothalamus, neurons excited or inhibited by scrotal warming were also excited or inhibited, respectively, by noxious stimulation that produced EEG desynchronization. Neurons showing no response to scrotal warming were not affected by noxious stimulation. In deeply anesthetized (2.5 g/kg urethane) rats, VB relay neurons responded to tactile stimulation of their receptive fields, but scrotal warming produced no change in either EEG or activities of thalamic and hypothalamic neurons. These facts suggest that the responses of thalamic and hypothalamic neurons to scrotal warming may be 'non-specific'. Most thalamic and hypothalamic neurons showing switching responses did not appear to mediate specific information concerning scrotal skin temperature.

Absence of Seizures During Induction of Anesthesia with High-Dose Fentanyl

Anesthesia was induced in six patients scheduled for elective aortocoronary bypass (ACB) surgery with intravenous fentanyl, either 50 (n = 2) or 150 micrograms/kg (n = 4) over 20 or 60 sec, respectively. Patients had been given their usual antianginal medications before surgery and were premedicated with morphine sulfate. Arterial plasma fentanyl levels were measured repetitively at frequent intervals, and eight leads of the cortical electroencephalogram (EEG) were recorded continuously. Peak plasma fentanyl concentrations exceeded 1750 ng/ml at the end of the injection of 150 micrograms/kg and then decreased by more than 75% within 3 min. In an additional two patients, incremental doses of fentanyl (25, 25, 50, 50 micrograms/kg; total 150 micrograms/Kg) maintained fentanyl concentrations between 30 and 650 ng/ml for the entire 15 min of the study. In all cases, diffuse slow-wave EEG activity, characteristic of fentanyl anesthesia, was seen. Motor activity, including wrist flexion and ocular movements, was observed during the onset of fentanyl-induced truncal rigidity, but no seizure-like activity was found in the EEG.

Visual desynchronization of cortical EEG impaired by lesions of superior colliculus in rats.

It is unclear whether rats with lesions of the superior colliculus (SC) neglect visual stimuli because a) they fail to notice the stimuli or b) they notice the stimuli but fail to make specific orienting movements of the eyes and head toward them. To investigate this issue, we used an index of "noticing" that does not involve overt orienting movements, namely, desynchronization of the cortical electroencephalogram (EEG) in drowsy animals. In the first experiment, large collicular lesions with some invasion of surrounding areas severely impaired EEG desynchronization to a brief overhead flash of light but did not significantly affect desynchronization to brief bursts of white noise. No impairment was found after control lesions of cerebral cortex overlying the superior colliculus or of striate cortex. A subsequent experiment found that the visual impairment was still present when lesions were confined to the superior colliculus. It appears that rats with lesions of the superior colliculus can, in certain circumstances, fail to notice visual stimuli and that in rats, the superior colliculus is concerned not only with specific orienting movements to visual stimuli but also with visual desynchronization of the cortical EEG.

Differential plasma corticosterone responses to hippocampal stimulation.

The effect of limbic forebrain stimulation on pituitary-adrenal function was assessed by evaluating plasma corticosterone obtained prior to and following sham or electrical stimulation of urethane (1.20 g/kg) anesthetized female rats. Cortical electroencephalogram (EEG), electrocardiogram (ECG), heart rate (HR), mean arterial blood pressure (MAP), and respiration were routinely monitored. Timed blood samples (0.25 ml) were obtained from a catheterized femoral artery. The HR (Bts/min), MAP (mm of Hg), and corticosterone levels (microgram/dl) for 7 non-stimulated rats averaged over 6 sampling periods were 385 +/- 19,95 +/- 6, and 70.3 +/- 5.8 respectively. In electrically or sham stimulated rats, blood samples were taken just prior to stimulation (biphasic square waves, 100 microA, 50 or 60 Hz, 1 ms, 1 s on/1 s off for 15 or 30 min) and 5, 10, 15, and 30 min after initiation of stimulation. Significant changes in plasma corticosterone levels were obtained following stimulation of hippocampal and amygdaloid areas. In contrast, no change in corticosterone concentration was observed following stimulation of cortex, corpus callosum, fornix and a variety of other CNS areas. Detailed analysis of hippocampal influence on urethane stimulated plasma corticosterone levels showed increased plasma corticosterone levels following stimulation of CA1. In contrast, stimulation of CA3, dentate (includes CA4) and the subiculum produced significant decreases in plasma corticosterone levels. No change in corticosterone levels was observed following sham stimulation. Collectively, these data indicate that consideration must be given to the possibility that differential neuroendocrine regulatory mechanisms reside within various limbic forebrain complexes and that electrical stimulation of limbic forebrain sites of urethane anesthetized rats may provide information regarding sites inhibitory to pituitary-adrenal activity.

Excitatory effect of intrahippocampal injection of glutamic acid on rabbit EEG.

Glutamic acid microinjection into the rabbit dorsal hippocampus was studied in its effects on hippocampal and cortical electroencephalogram (EEG). The studies were carried out on rabbits with chronically implanted electrodes and cannulae. Bipolar, silver recording electrodes and stainless steel cannulae were implanted into the hippocampus, and recording electrodes were placed on the surface of the frontal and cingular cortical areas. Low doses of glutamic acid (5-25 nM) induced EEG and behavioral arousal. Short lasting epileptiform-like seizures and behavioral convulsions were induced after injection of high doses of glutamic acid (100-500 nM). These findings suggest that glutamic acid in the hippocampus of the rabbit is involved in behavioral arousal and epileptiform-like disorders.

Electrographic, clinical and pathological alterations following systemic administration of kainic acid, bicuculline or pentetrazole: Metabolic mapping using the deoxyglucose method with special reference to the pathology of epilepsy

Abstract Kainic acid, bicuculline or pentetrazole have been injected systemically in rats. Clinical, electrographic and metabolic alterations (using the deoxyglucose method), have been studied in relation to subsequently demonstrated neuropathology using stains for degenerating nerve fibers or neurons. Twenty minutes after administration of the toxin (9–12 mg/kg i.p.), the animals displayed ‘wet shakes’; their frequency of occurrence was steadily increased before subsiding 60 min later when the overt typical limbic motor seizures started. The latter progressively evolved into status epilepticus. Epileptiform activity started (approximately 20 min after the injections) in the temporal pole of the hippocampal formation (in particular the entorhinal cortex) and propagated to the rostral Ammon's horn, the amygdala, medial thalamus and pre-frontal cortex and diffusely to the cortical electroencephalogram. Postictal depressions were exclusively seen in the hippocampal formation, thus further stressing the central position occupied by this structure in the electrographic effects of the toxin. At longer delays (3–6 days), rhythmic spikes were exclusively present in the amygdaloid complex. Less than l h after administration of kainic acid, i.e. before the occurrence of the first limbic motor seizure, the autoradiographic deoxyglucose maps revealed an increase in glucose consumption exclusively in the hippocampal formation and lateral septum. At longer delays (2–5 h) the increase in radioactive material progressively involved: (1) structures projected upon directly by the hippocampal formation through the pre- and post-commissural fornix system (in addition to the lateral septum, the infralimbic cortex, the nucleus accumbens, ventral putamen and antero-medial thalamic nuclei); (2) the rostral limbic cortex (in particular the deep layers of the pre-limbic and agranular insular cortices) and structures which have direct connections with the rostral limbic cortex including the cingulate, retrosplenial and perirhinal cortices as well as the claustrum; (3) the amygdaloid complex, the stria terminalis fiber tract and its bed nucleus. In contrast, there was a concomitant decrease in glucose consumption in ‘non-limbic’ cortical structures as well as in most regions of the forebrain, mesencephalon and brain stem. At longer delays (2–3 days) the metabolism was decreased in the entire brain with a few noticeable exceptions, including the amygdala. There is, therefore, a remarkable correlation between the electrographic changes and the rise in metabolism. Furthermore, the pathological alterations (signs of degeneration) were almost exclusively present in structures in which there had been a rise in metabolism (in particular the hippocampal formation, lateral septum, amygdala, medial thalamus and claustrum). In contrast, bicuculline (0.4–0.8 mg/kg i.v.) or pentetrazole (60 mg/kg i.p.) produced less than 1 min after the injection a typical tonico-clonic generalized convulsive seizure with severe post-ictal depressions in several brain structures including the frontal and occipital cortices. Short delays (less than 1 h) after single or a few generalized convulsive seizures, the most conspicuous rise in metabolism was noted in the cerebellum and vestibular nuclei, the red nucleus, substantia nigra, nucleus of the occulomotor nerve and the neocortex. In contrast, a decrease in glucose consumption was manifested in limbic structures, in particular, the hippocampal formation and the amygdala. Thus, in several respects, the image produced by the deoxyglucose maps and its electrographic correlates is the opposite of that obtained after kainic acid. After short delays, the most conspicuous brain damage seen with the FinkHeimer stain consists of fine argyorphilic grains surrounding the cerebellar Purkinje perikarya, which appear to reflect degenerative changes in basked cell innervation. It is suggested that the systemic administration of kainic acid may provide a useful animal model for the study of both the preferential susceptibility of limbic structures to epileptogenic procedures and their vulnerability to the pathological consequences of epilepsy.

Synchronization of hippocampal and cortical electroencephalogram by thyrotropin-releasing hormone

Abstract The septal region has recently been shown to be extremely sensitive to thyrotropin-releasing hormone (TRH)-induced antagonism of pentobarbital narcosis in the rat. As the septohippocampal system is thought to provide a neuroanatomical substrate mediating synchronization of the hippocampal EEG, we hypothesized that TRH would induce hippocampal synchrony. Animals were pretreated with pentobarbital and both hippocampal and cortical EEG monitored. By using spectral analysis of the EEG, it was shown that intracerebroventricular administration of TRH caused a significant increase in both hippocampal (3 to 7 Hz) and cortical (7 to 11 Hz) synchrony. It is postulated that TRH-induced hippocampal synchrony may play a role in TRH antagonism of pentobarbital narcosis.

Influence of electrical stimulation of the region of the area postrema/nucleus of the solitary tract on unit activity in the anterior raphe and the cortical electroencephalogram of the rat

Abstract Recent anatomical studies of the afferent fibers to the anterior raphe nuclei reported a projection originating in the region of the area postrema (AP) and nucleus tractus solitarius (NTS) in the rat. The present study examined the effects of stimulation of this projection on the spontaneous activity of individual neurons in the anterior raphe in urethane-anesthetized rats. Results from 42 raphe units from 14 rats showed that stimulation of the region of the AP/NTS at 1 or 10 Hz, 0.1 to 1.0 mA, had no effect on approximately 50% of the units, increased discharge rates in 10 to 20% and produced suppression of firing in 30 to 40%. The magnitude of these effects on raphe activity was substantially smaller than those seen in previous studies of stimulation of other afferents to the raphe, e.g., the lateral habenula or substantia nigra. No relationship was found in the present study between changes in raphe activity and the cortical EEG synchronization produced by the AP/NTS stimulation.

Genetically determined spontaneous and pentylenetetrazol-induced brief spindle episodes in mice

Abstract Regular 7 s , 1- to 5-s bursts of high-amplitude spindles were observed in the cortical electroencephalogram of DBA mice. We named these bursts “brief spindle episodes” (BSE). The BSEs were bilaterally symmetrical and could be seen to occur earlier in more frontal derivations. BSEs appeared to actively suppress overt body movement, though some facial twitching could be observed. Two convulsant agents, pentylenetetrazol (PTZ) and picrotoxin, provoked BSE activity; a third, nicotine, suppressed BSE activity at both sub- and supraconvulsant doses. Three other inbred mouse strains were also tested for BSE occurrence. Two, C57BL 6 and BALB c mice, failed to show BSE activity either spontaneously or after PTZ. The third strain, C3H, showed lower-amplitude, shorter-duration, and less well-organized BSE activity spontaneously and after PTZ. Juvenile DBA mice (21 to 25 days) showed slower, lower-amplitude, shorter-duration BSEs than did adults. Older mice (31 to 36 days) showed more adult BSEs. The possibility that BSEs are an epileptic phenomenon is discussed. It is clear that they are a genetically determined electroencephalographic characteristic that may provide a useful tool for studying genetic determination of nervous system functioning as well as mechanisms of cortical hypersynchrony.

Release of growth hormone in lactating and non-lactating goats in relation to behaviour, stages of sleep, electroencephalograms, environmental stimuli and levels of prolactin, insulin, glucose and free fatty acids in the circulation.

Recording electrodes were implanted in contact with the dura mater overlying the parietal cortex of six female goats, four of which were lactating. After recovery from surgery and complete familiarization with the housing conditions, the personnel and the recording technique, each goat was observed continuously for 24 h with simultaneous recording of the cortical electroencephalogram (EEG). Remote blood sampling was carried out every 30 min without disturbing the animal. Apart from the release of growth hormone (GH) associated with morning milking in two of the goats, there was no consistent relationship between the apparently spontaneous, episodic release of GH and behvaiour, stages of sleep, cortical EEG, air temperature, time of day or night, obvious environmental stimuli which arose from the normal husbandry routine, or the levels of porlactin, insulin, glucose or free fatty acids in the blood. There was also no relationship between the release of prolactin and the stages of sleep.

Effect of thyrotropin-releasing hormone, luteinizing hormone-releasing hormone, and somatostatin on neuronal activity of brain stem reticular formation and hippocampus in the female rat

Abstract Changes in the multiunit activity of the brain stem reticular formation and dorsal hippocampus were studied in environmentally habituated, freely moving, regularly cyclic female rats with chronically implanted “macro” and “semimicro” depth electrodes. Cortical electroencephalograms and multiunit activity were recorded continuously. An inverse relationship was observed between the brain stem reticular formation and the dorsal hippocampus multiunit activity. The multiunit activity in the brain stem reticular formation was variably high during attentive behavior, stable and low under slow-wave sleep, and reached very high values in paradoxical sleep (REM). Conversely, the dorsal hippocampus multiunit activity was high during slow-wave sleep and variably low during attentive behavior or REM sleep. Samples of raw multiunit activity were tape-recorded during slow-wave sleep for analysis of interspike intervals of amplitude-discriminated cell discharges prior to and after hormonal treatments. The analysis revealed that intraperitoneal injection of either thyrotropin-releasing hormone ( 3 μ g 100 g body weight) or luteinizing hormone-releasing hormone (500 ng/rat) resulted in a rapid decrease in interspike intervals of amplitude-discriminated spikes in the brain stem reticular formation and a concomitant increase in intervals between hippocampal cell discharges. Somatostatin ( 3 μ g 100 g body weight), on the other hand, resulted in a general depression of firing rates of neurons in both the brain stem reticular formation and the dorsal hippocampus. In the administered doses, none of the hormones interfered with the regular vaginal cycle of the rats.

Antiserum to brain gangliosides produces recurrent epileptiform activity.

A single injection of 10 microliters of antiserum to total brain ganglioside onto (and into) the sensorimotor cortex of the rat resulted in recurrent spiking in the cortical electroencephalogram, lasting from 7 to 17 days. Absorption of antibody with pure monosialoganglioside (GM1) completely abosished the effect. Spiking was reactivated after 4 weeks by intramuscular injection of pentylenetetrazole.

Central Nervous Regulation of Body Temperature During Sleep

The relationship between hypothalamic temperature and metabolic heat production was measured during wakefulness, slow-wave sleep, and paradoxical sleep in unrestrained kangaroo rats (Dipodomys). Hypothalamic temperature was manipulated with chronically implanted, water-perfused thermodes while cortical electroencephalogram, electromyogram, metabolic rate, and body movement were continuously recorded. During slow-wave sleep, in comparison to wakefulness, there is a lowered threshold hypothalamic temperature for the metabolic heat production response and a lowered proportionality constant relating rate of metabolic heat production to hypothalamic temperature. During paradoxical sleep no increase in metabolic heat production could be elicited by lowering hypothalamic temperature, which indicates that the thermoregulatory system is inoperative. These results provide a basis for explaining the changes in various body temperatures, metabolic rate, and other thermoregulatory responses during sleep in a variety of mammals.

Variability of skin temperature in the waking monkey.

Temperatures of the brain, skin, and nasal mucosa were recorded along with the cortical electroencephalogram (EEG) in chaired, conscious pigtail monkeys at 25 degrees C air temperature. In undisturbed animals, skin temperatures ranged from 34 to 37 degrees C. When the animal was alerted by visual or auditory stimuli, temperatures on the extremities, tail, nose, ears, and nasal mucosa dropped rapidly to 22-29 degrees C. Temperatures on the proximal limbs and trunk and most of the head remained steady at all times. Average hypothalamic temperature was 0.91 degrees C higher when the extremities, tail, nose, ears, and nasal mucosa were cool than when they were warm, the brain temperature change beginning 80-120 s after the change in peripheral temperatures. A slight decrease in EEG frequency, but no change in amplitude, occurred during skin warming. Anesthetic doses of barbiturate led to a rapid rise in temperature of the extremities, tail, nose, ears, and nasal mucosa and a drop in brain temperature. These large changes in skin temperature in conscious monkeys reflect changes in cutaneous blood flow, the resulting alteration in heat loss leading to a rapid change in deep body temperature. The experiments demonstrate the importance of the state of arousal on autonomic nervous control of peripheral vasomotor tone in the monkey.

Electroencephalographic Responses to 2500 Rads of Whole-Body Gamma-Neutron Radiation in the Monkey Macaca mulatta

Monkeys were trained on a behavioral task and instrumented with chronic EEG recording electrodes and systemic arterial catheters for blood pressure measurement. They were then exposed to a 2500-rad pulse of mixed gamma-neutron radiation. Spectral analysis of the cortical electroencephalogram revealed changes in both frequency content and amplitude of the EEG related to periods of behavioral incapacitation. Simultaneous measurements of systemic blood pressure did not show any close relationships with EEG or behavioral changes.

Cardiovascular and central nervous system effects of parenterally administered single doses of procarbazine (NSC-77,213)

Experiments were undertaken to determine the initial pharmacologic changes elicited by iv administration of procarbazine in the rhesus monkey (25–400 mg/kg) and the isolated, blood-perfused dog heart (25–400 mg/kg). In unanesthetized animals somnolence and synchronization of the electroencephalogram were noted after all doses. These effects were reversible within 15 min to 3 hr at doses up to 200 mg/kg. Over a 4 hr period, mean arterial blood pressure gradually decreased 10–40 mmHg, and some animals developed intermittent periods of ventricular ectopic beats. Two of 3 animals given 400 mg/kg died from severe hypotension and respiratory distress. In pentobarbital-anesthetized animals, procarbazine suppressed or eliminated cortical electroencephalogram activity for varying periods of time. All doses initially increased carotid artery blood flow, but by 15–30 min after injection mean arterial blood pressure had decreased below control levels. Within 6 hr, 6 of 9 animals given 100–400 mg/kg died from severe hypotension and respiratory arrest. All doses of procarbazine exerted positive inotropic and chronotropic responses in the isolated heart. These actions could be attenuated by pretreatment with reserpine (0.1 mg/kg) or dl-propranolol (0.125 mg), but not by d-propranolol (0.125 mg). The present results indicate that parenterally administered procarbazine causes both central nervous system and cardiovascular alterations.