Resuscitation
7, 237-248
Neurophysiological mechanisms of postresuscitation brain pathology
A. M. GURVITCH,
YU. V. ZARZHETSKY
and YEKATERINA
A. MUTUSKINA
Research Laboratory of General Reanimatology, U.S.S.R. Academy of Medical Science, Moscow, U.S.S.R.
Summary Two phenomena are described that occur in the post-resuscitation period after following l&l5 min circulatory arrest: electroshock and ventricular fibrillation. The first one manifests itself in generalized alpha-like activity on the electrocorticogram (ECoG) in the early post-resuscitation period. The probability of its registration increases with the prolongation of circulatory arrest. It is shown that alpha-like activity, which reflects excitation of the brain limbic system, delays recovery of normal forms of cerebral electric activity, thus making the prognosis worse. It is also demonstrated that the appearance of alpha-like activity to a certain extent depends on the artificial lung ventilation regime (ALVR) and on the intensity of excitation of the respiratory centre determined by ALVR. The second phenomenon is the connection of delayed depression of the ECoG high-frequency component appearing on days 4-7 after resuscitation with the augmentation of cerebral blood flow. This relationship led us to propose that overloading of the cortical neurons may be the reason for the depression of the ECoG high-frequency component. Both phenomena indicate that neurophysiological mechanisms make a significant, though as yet underestimated, contribution to the post-resuscitation pathology of the brain. In reanimatology the brain is usually considered to be passive, subject to pathogenic influences leading to changes in its tissue, circulation and functions. Research workers concentrate on elucidating the nature of tissue changes and disorders of the microcirculation. Study of the functional changes in the central nervous system is usually of a purely descriptive character. However, it is reasonable to surmise that brain function disorders during dying and resuscitation should be included in the post-resuscitation pathological process as the most important pathogenetic link. Some examples of the correctness of this approach are well known. Thus the development of convulsive attacks during the postresuscitation process is unfavourable, not only due to the functional disorders which occur during the attacks in the somatic systems and in the circulatory system in particular, but also because seizure discharges actively disturb cerebral physiology and change inter- and intra-central relationships, and delay or reverse the restoration processes. However, the role of neurophysiological mechanisms prober can also be detected outside the convulsive phenomena. Thus Negovsky (1943) discovered a 237
238
A. M. GURVITCH AND OTHERS
lB2dP.
MOT.n.CAUD.
AMYGD. * NCIK -.4-C-
/ I
.
H!rH.P. CmM.
MEs* *--
P
Fig. 1. Distribution of electrical activity from the amygdala in brain formations in the electroencephalogram of the dog. (a) Minute 36 after resuscitation from 9 min of circulatory arrest due to electroshock with cardiac fibrillation. Monopolar EEG leads, relative to the bones of the frontal sinuses. First four leads, from different areas of the cortex (epidural position of electrodes). Further, consecutively from n. caudatus, n. amygdalae, n. centro-medial thalami, posterior hypothalamus formation reticularis of the mesencephalon. Calibration: 1 s and 50 mV. (b) Minute 19 after resuscitation from 12 min of circulatory arrest due to electroshock with cardiac fibrillation. Leads, top, control (contr. between the bones of the frontal sinuses and ear). further monopolar, from three cortical areas, n. caudatus (n. caud.), n. amygdalae (amygd.), n. dorsomedialis thalami (n.DM.) and ECG. Time calibration: 1 s. Amplification scale: varying for different areas, corresponding to the note below at the right (l-7, leads consecutively from top down).
POST-RESUSCITATION
BRAIN PATHOLOGY
239
relationship between the post-resuscitation restoration of respiratory centre activity and functions of the central nervous system as a whole. Specifically, he was able to prove the stabilizing influence of the respiratory centre on the vasomotor centre. The disorders of general haemodynamics seen in the post-resuscitation period are neurogenically conditioned (Trubina & Volkov, 1976). The role of neuroendocrine disorders in the post-resuscitation period is self-evident. The purpose of this report is to attract attention of research workers to the role of neurophysiological mechanisms proper in developing post-resuscitation pathological processes in the brain. We have at our disposal two phenomena meriting attention from this point of view. The history of one of them dates back to the work of Van Harreveld, who in 1947 described in cats the appearance in the EEG after compression ischaemia of the central nervous system of generalized rhythmic alpha-like activity, uniformly present in all cortical areas. Later the same activity was confirmed by us in experiments with the resuscitation of dogs (Gurvitch, 1964). In recent years a number of descriptions have appeared of post-resuscitation coma in man with alpha-like activity on EEG (alphacoma: Chakraverty, 1975; Grindal, Suter & Maertinez, 1977). The activity resembles the activity seen in animal experiments in several respects. The following features are most typical of the activity commonly recorded in dogs after circulatory arrest: (ii) it appears in the initial stages of the post-resuscitation period, after the return of respiration and cornea1 reflexes, before, simultaneously or slightly later than, the appearance of the usual electrical activity (delta-waves); it can persist on the EEG for many minutes and even hours; (ii) it has a relatively regular sinusoidal form and frequency in the range of 6-12/s, sometimes with a component of 20-22/s (Fig. 1); (iii) it is recorded in the cortex mainly in the monopolar leads;
240 A. M. GURVITCH AND OTHERS
0
1
2-5
6-7
8-15
17-25
Duration of circulatory arrest (mid
Fig. 2. Probability in percentage of experiments of amygdalogenic activity depending on the duration and origin of circulatory arrest. 1, Mechanical asphyxia; 2, exsanguination; 3, cardiac librillation; 4, compression ischaemia.
(iv) it has maximum amplitude and first appears in the area of the amygdaloid nucleus (up to l-2 mV, average 360 mV), slightly less in hippocampus, in the other nuclei and in the cerebral cortex 20-40 mV. It is important that the probability of its appearing is the greater the longer the time of circulatory arrest. This is shown in Fig. 2, which demonstrates the possible activity as a percentage of the total number of experiments. A dependence also exists on the model of circulatory arrest: activity in the case of mechanical asphyxia appears after notably shorter periods of circulatory arrest than with compression ischaemia of the brain. Models with exsanguination and cardiac fibrillation occupy an intermediate place. The question arises as to whether this activity is just a sign of the severity of disorders in cerebral functions or whether it reflects the mechanisms actively participating in post-resuscitation processes. This is no idle question, as the generator of this activity, the amygdaloid nucleus, is part of a system connected directly with neurovegetative and neuroendocrine regulation. We have demonstrated that dogs resuscitated 14 min after circulatory arrest by cardiac fibrillation showed the interaction of this activity with slow-wave complexes for an hour. It was possible to establish statistically that this activity hindered the restoration of the usual slow activity, which is ‘normal’ for these conditions (Figs. 3,4). Fig. 3 shows a marked extension of the interval between the wave complexes of the
POST-RESUSCITATION BRAINPATHOLOGY 241
burstson intervalsbetweencomplexesof slow‘waveson EEG in the Fig. 3. Influenceof amygdalogenic experiment on the dog with circulatory arrest for 14 min (electroshock, cardiac fibrillation). I. Minute 38 after resuscitation. II. Minute 10 after latter. Leads: 1, control; 2 and 3, from the temporal and somatosensory cortex; 4, from n. amygdalae; 5, from thalamus0 6,7, bipolar -between two marked cortical areas (6) and between n. amygdalae and thalamus (7); 8, ECG, Calibration: 1 s and 100 mV.
restoring activity during the period of sinusoidal oscillation bursts. Fig. 4 shows the statistical treatment of this experiment. Such demonstrative observations are rare. But the influence of this activity on the dynamics of restoration of background activity was shown statistically by analysis of the data of a number of experimental groups, who revived dogs that had experienced different periods of circulatory arrest, due to cardiac arrest and blood loss. The influence of activity arising from the amygdala latency of recovery of background activity from which the usual post-resuscitation EEG with a predominance of delta- and theta- oscillations is formed, has been studied. A group of 21 experiments with clinical death from 4 to 10 min by exsanguination or electroshock with subsequent cardiac fibrillation with an average latency of restoration of background electrical activity of 24 min was divided into two subgroups: in one, amygdalogenic activity appeared before the background activity; in the other, simultaneously or later. It was found that when the activity from the amygdala appeared before background activity (the latency time of amygdalogenic electric activity was less than 24 min), then the recovery of the latter was delayed and developed later. If the activity studied appeared later (its latency being more than 24 min), then the latency in recovery of background activity on EEG was below average. That is, when
242
A. M. GURVITCH AND OTHERS
bef or.
-
d-6
8ft.r
Fig. 4. Diagram of dependence of intervals between complexes of slow waves on EEG and amygdalogenic bursts. Averaged data for 60 min (see Fig. 3) in seconds (M +m) befcrz, during and after volley; I and II, intervals after bursts. Difference between first and second columns and between second and third columns (P
7, 237-248
Neurophysiological mechanisms of postresuscitation brain pathology
A. M. GURVITCH,
YU. V. ZARZHETSKY
and YEKATERINA
A. MUTUSKINA
Research Laboratory of General Reanimatology, U.S.S.R. Academy of Medical Science, Moscow, U.S.S.R.
Summary Two phenomena are described that occur in the post-resuscitation period after following l&l5 min circulatory arrest: electroshock and ventricular fibrillation. The first one manifests itself in generalized alpha-like activity on the electrocorticogram (ECoG) in the early post-resuscitation period. The probability of its registration increases with the prolongation of circulatory arrest. It is shown that alpha-like activity, which reflects excitation of the brain limbic system, delays recovery of normal forms of cerebral electric activity, thus making the prognosis worse. It is also demonstrated that the appearance of alpha-like activity to a certain extent depends on the artificial lung ventilation regime (ALVR) and on the intensity of excitation of the respiratory centre determined by ALVR. The second phenomenon is the connection of delayed depression of the ECoG high-frequency component appearing on days 4-7 after resuscitation with the augmentation of cerebral blood flow. This relationship led us to propose that overloading of the cortical neurons may be the reason for the depression of the ECoG high-frequency component. Both phenomena indicate that neurophysiological mechanisms make a significant, though as yet underestimated, contribution to the post-resuscitation pathology of the brain. In reanimatology the brain is usually considered to be passive, subject to pathogenic influences leading to changes in its tissue, circulation and functions. Research workers concentrate on elucidating the nature of tissue changes and disorders of the microcirculation. Study of the functional changes in the central nervous system is usually of a purely descriptive character. However, it is reasonable to surmise that brain function disorders during dying and resuscitation should be included in the post-resuscitation pathological process as the most important pathogenetic link. Some examples of the correctness of this approach are well known. Thus the development of convulsive attacks during the postresuscitation process is unfavourable, not only due to the functional disorders which occur during the attacks in the somatic systems and in the circulatory system in particular, but also because seizure discharges actively disturb cerebral physiology and change inter- and intra-central relationships, and delay or reverse the restoration processes. However, the role of neurophysiological mechanisms prober can also be detected outside the convulsive phenomena. Thus Negovsky (1943) discovered a 237
238
A. M. GURVITCH AND OTHERS
lB2dP.
MOT.n.CAUD.
AMYGD. * NCIK -.4-C-
/ I
.
H!rH.P. CmM.
MEs* *--
P
Fig. 1. Distribution of electrical activity from the amygdala in brain formations in the electroencephalogram of the dog. (a) Minute 36 after resuscitation from 9 min of circulatory arrest due to electroshock with cardiac fibrillation. Monopolar EEG leads, relative to the bones of the frontal sinuses. First four leads, from different areas of the cortex (epidural position of electrodes). Further, consecutively from n. caudatus, n. amygdalae, n. centro-medial thalami, posterior hypothalamus formation reticularis of the mesencephalon. Calibration: 1 s and 50 mV. (b) Minute 19 after resuscitation from 12 min of circulatory arrest due to electroshock with cardiac fibrillation. Leads, top, control (contr. between the bones of the frontal sinuses and ear). further monopolar, from three cortical areas, n. caudatus (n. caud.), n. amygdalae (amygd.), n. dorsomedialis thalami (n.DM.) and ECG. Time calibration: 1 s. Amplification scale: varying for different areas, corresponding to the note below at the right (l-7, leads consecutively from top down).
POST-RESUSCITATION
BRAIN PATHOLOGY
239
relationship between the post-resuscitation restoration of respiratory centre activity and functions of the central nervous system as a whole. Specifically, he was able to prove the stabilizing influence of the respiratory centre on the vasomotor centre. The disorders of general haemodynamics seen in the post-resuscitation period are neurogenically conditioned (Trubina & Volkov, 1976). The role of neuroendocrine disorders in the post-resuscitation period is self-evident. The purpose of this report is to attract attention of research workers to the role of neurophysiological mechanisms proper in developing post-resuscitation pathological processes in the brain. We have at our disposal two phenomena meriting attention from this point of view. The history of one of them dates back to the work of Van Harreveld, who in 1947 described in cats the appearance in the EEG after compression ischaemia of the central nervous system of generalized rhythmic alpha-like activity, uniformly present in all cortical areas. Later the same activity was confirmed by us in experiments with the resuscitation of dogs (Gurvitch, 1964). In recent years a number of descriptions have appeared of post-resuscitation coma in man with alpha-like activity on EEG (alphacoma: Chakraverty, 1975; Grindal, Suter & Maertinez, 1977). The activity resembles the activity seen in animal experiments in several respects. The following features are most typical of the activity commonly recorded in dogs after circulatory arrest: (ii) it appears in the initial stages of the post-resuscitation period, after the return of respiration and cornea1 reflexes, before, simultaneously or slightly later than, the appearance of the usual electrical activity (delta-waves); it can persist on the EEG for many minutes and even hours; (ii) it has a relatively regular sinusoidal form and frequency in the range of 6-12/s, sometimes with a component of 20-22/s (Fig. 1); (iii) it is recorded in the cortex mainly in the monopolar leads;
240 A. M. GURVITCH AND OTHERS
0
1
2-5
6-7
8-15
17-25
Duration of circulatory arrest (mid
Fig. 2. Probability in percentage of experiments of amygdalogenic activity depending on the duration and origin of circulatory arrest. 1, Mechanical asphyxia; 2, exsanguination; 3, cardiac librillation; 4, compression ischaemia.
(iv) it has maximum amplitude and first appears in the area of the amygdaloid nucleus (up to l-2 mV, average 360 mV), slightly less in hippocampus, in the other nuclei and in the cerebral cortex 20-40 mV. It is important that the probability of its appearing is the greater the longer the time of circulatory arrest. This is shown in Fig. 2, which demonstrates the possible activity as a percentage of the total number of experiments. A dependence also exists on the model of circulatory arrest: activity in the case of mechanical asphyxia appears after notably shorter periods of circulatory arrest than with compression ischaemia of the brain. Models with exsanguination and cardiac fibrillation occupy an intermediate place. The question arises as to whether this activity is just a sign of the severity of disorders in cerebral functions or whether it reflects the mechanisms actively participating in post-resuscitation processes. This is no idle question, as the generator of this activity, the amygdaloid nucleus, is part of a system connected directly with neurovegetative and neuroendocrine regulation. We have demonstrated that dogs resuscitated 14 min after circulatory arrest by cardiac fibrillation showed the interaction of this activity with slow-wave complexes for an hour. It was possible to establish statistically that this activity hindered the restoration of the usual slow activity, which is ‘normal’ for these conditions (Figs. 3,4). Fig. 3 shows a marked extension of the interval between the wave complexes of the
POST-RESUSCITATION BRAINPATHOLOGY 241
burstson intervalsbetweencomplexesof slow‘waveson EEG in the Fig. 3. Influenceof amygdalogenic experiment on the dog with circulatory arrest for 14 min (electroshock, cardiac fibrillation). I. Minute 38 after resuscitation. II. Minute 10 after latter. Leads: 1, control; 2 and 3, from the temporal and somatosensory cortex; 4, from n. amygdalae; 5, from thalamus0 6,7, bipolar -between two marked cortical areas (6) and between n. amygdalae and thalamus (7); 8, ECG, Calibration: 1 s and 100 mV.
restoring activity during the period of sinusoidal oscillation bursts. Fig. 4 shows the statistical treatment of this experiment. Such demonstrative observations are rare. But the influence of this activity on the dynamics of restoration of background activity was shown statistically by analysis of the data of a number of experimental groups, who revived dogs that had experienced different periods of circulatory arrest, due to cardiac arrest and blood loss. The influence of activity arising from the amygdala latency of recovery of background activity from which the usual post-resuscitation EEG with a predominance of delta- and theta- oscillations is formed, has been studied. A group of 21 experiments with clinical death from 4 to 10 min by exsanguination or electroshock with subsequent cardiac fibrillation with an average latency of restoration of background electrical activity of 24 min was divided into two subgroups: in one, amygdalogenic activity appeared before the background activity; in the other, simultaneously or later. It was found that when the activity from the amygdala appeared before background activity (the latency time of amygdalogenic electric activity was less than 24 min), then the recovery of the latter was delayed and developed later. If the activity studied appeared later (its latency being more than 24 min), then the latency in recovery of background activity on EEG was below average. That is, when
242
A. M. GURVITCH AND OTHERS
bef or.
-
d-6
8ft.r
Fig. 4. Diagram of dependence of intervals between complexes of slow waves on EEG and amygdalogenic bursts. Averaged data for 60 min (see Fig. 3) in seconds (M +m) befcrz, during and after volley; I and II, intervals after bursts. Difference between first and second columns and between second and third columns (P
