Euro-Ps~chopi2arnraeo Press Ltd, 1981.
1. vo1.5, pp. 99-104 Printed in Great Britain.
GIOVANNI BATTISTA CASSANO, CARLO -MAGGINI and MARIO GUAZZELLI Psychiatric
Abstract 1. Nocturnal sleep and electro cardiographic patterns ware continously investigated in 20 male patients suffering frcm nocturnal angina attacks. Sleep pattern was severely disturbed regardless of the presence of ischenic episodes. Sleep Time was reduced because of a large Awakening Time and an Early Final Awakening. Stages 1 and 2 were increased and stages 3, 4 and, less markedly, REhlwere reduced. 2. Ischemic episodes were more frequently observed between 24:00 and 04:OO without any significant relationship to the sleep stages, thus suggesting the influence of a cronobiologic factor on the distribution of ischemic attacks during the night. 3. Ischemic episodes observed during the hemodynamic monitoring did not show any significant relation to the increase of myocardial oxygen consumption. This observation,together with the lack of relation between REM sleep and ischemic episodes during the night, seem to support the hypothesis of a reversible coronary spasm in the pathogenesis of nocturnal angina. Keywords: chest pain, hemodynamic angina, REM sleep, sleep stages. Abbreviations: ventricular:
LV: left ventricular: REM: rapid S-T: segment of the electrocardiogram.
nocturnal RV: right
Introduction In previous studies a correlation between sleep stages and ischemic episodes (Shapiro , 1962; has not been constantly found. Though, in early investigations Nowlin et al., 1965) the correlation between sleep and angina was emphasized, later studies did not support these results (Kales and Tan, 1969; Katayama et al., 1973). Moreover the increase of oxygen demands due to the psychophysiological involvement of rapid eye movements sleep (REM), up to date, is not conskdered the only triggering factor of nocturnal angina (Maseri et al,, 1975). On the * This paper is Part of the special topic "Psychopharmacology of the Circulatory System", published in vol 4, no 415, pp.521-544.
G. B. Cassano <'t (IL.
100 other hand polygraphic activation may occur (Molinari, 1968).
sleep studies have shown that intense the other sleep stages as frequently
autonomic as in REM sleep
The present investigation is aimed at exploring the possible relationship between ischemic attacks and sleep stages and to determine whether a characteristic sleep pattern could be found in patients suffering from "primary angina". Material
Twenty male patients (aged from 49 to 75 years; mean age: 58.3) sufferkng from nocturnal angina attacks were continuously monitored for 8 hours during the night for Electroencephalogram, Electrooculogram, Electromyogram and Electrocardiogram. The number of sleep recordings per subject, after one adaptation night, ranged from one to six for each patient, Ischemkc episodes, according to transient modifications with or without chest pain, were detected of the S-T segment of the electrocardiogram. Fourteen patients had S-T elevation, three S-T depression and three both. In eight patients recordings were also performed during hemodynamfc monitoring (left ventricular (LV) and right ventricular (RV) pressures in 7 patrents; aorti'c pressure in 2; pulmonary pressure in 2). Serum glutamic oxalacetic transaminase, serum glutamic pyruvic transaminase, lactic dehydrogenase and creatine Ilhosphokinase levels were investigated before and throughout the study, Therapy was discontinued 2 days before the study, giving only nitroglycerin during angina1 episodes. Thirty min. before the recording Diazepam 10 mg, was orally administered. Results Ischemic episodes were observed durrng 30 of the 45 recordings (153 with elevation and 15 with S-T depression). Chest pain was reported during 48 percent of the episodes without any relatron to the type of S-T changes, Ischemic episodes were most frequently reached a peak between 03:OO and 04:OO.
Table 1 shows the average numbers of fschemic episodes and Wake Time. The number of episodes was higher during REM, though not significantly.
and 04:OO and
during Sleep Stages Wake Time, Stage 1 and
Table 2 shows the mean values of the Sleep parameters recorded during the nights with and wit;hout ischanic episodes was higher during Wake Time. Stxp;e 1 and REX, though not significantly. The sleep pattern recorded during all 45 nrghts showed a short Sleep Time, related to a large Awakening Time and to an Early Final Awakening, Stage 1 and 2 were increased and Stage 4 and REM were reduced. The sleep pattern on the nights when ischemic episodes occurred, appeared to be more severely disturbed, However, the differences between nights wfth and those without ischemic
Nocturnal angina and sleep
episodes were not significant. The most severely disiurbed sleep pattern was observed during the nights when patients were hemodynamically monitored: comparing these nights with 8 of the sample, randomly selected, Awakening Time (pcn.05) and Stage 1, as oercent of Sieep Time (pLO.011, were increased and Stage REM, duration and as percent of Sleep Time (~40.01) was decreased.(Fig. 2). In the nights with hemodynamic monitoring, 48 ischemic episodes were observed (41 with S-T elevation and 7 with S-T depression); none of these episodes was preceded by an increase in the indices of myocardial oxygen consumption (heart rate, systolic and diastolic pressures, aortic and pulmonary pressures, LV and RV contractility parameters). On the contrary all the angina1 episodes were preceded by or concurrent with acute LV failure, as shown by the sudden decrease of LV contractility (dp/dt) associated with or followed by the decrease of systolic pressure and the increase of LV telediastolic pressure. Discussion
The results of this investigation allow us to draw the following conclusions: 1. Ischemic episodes mostly occur between 24:00 and 04:OO with a peak between 03:OO and 04.00. These data are in accordance with those previously reported (Katayama et al., 1973; Shappel and Orr, 1975). This temporal pattern is not consistent with the hypothesis that ischemic episodes are associated with the REM Stage, though this Stage is usually present during the last part of the night. The results of this study do not support this suggestion, since no significant correlation was found between ischemic episodes and the REM sleep. 2. Ischemic episodes appear to be unrelated to Sleep Stages and Wake Time. In fact, though a greater incidence was observed during Wake Time, Stage 1 and REM, the episodes occurred during all the Sleep Stages. These data do not give a conclusive answer to the problem of how Sleep dtages are related to ischemic episodes. Moreover, these results disagree with those reported by some authors 1965) who found a close relatron between the (Shapiro, 1962; Nowlin et al., REM Stage and ischemic attacks. The different characteristics of the sample studied and possible differences between the psysiopathological mechanrsms responsible for angina might explain these divergences. 3. The hemodynamic monitoring showed that none of the ischemic eprsodes recorded were preceded by an increase in the myocard~al consumptfion of oxygen, thus suggesting the pathogenetic hypothesis of a reversible coronary spasm, 4. The sleep pattern of these patients appeared to be severely dtsturbed. Even more marked disturbances were observed when patients were hemodynamically monitored. It is not possible to rule out that the quantitative changes in sleep patterns observed in these patients may have been due to the Coronary Core Unit setting (Lester et al,, 1969; Kales, 1972) since we have no control series. However, several authors (Shappel and Orr, 1975; Lester et al,, 1969; Rosenblatt et al., 1973) have reported in angrnal patients a light sleep, wrth frequent sleep wake shifts. The importance underestimated.
of treating insomnia in these patients should Benzodiazepines appear to be the best available
not be drugs for
besides their sleep-inducing and maintaining type of insomnia: in fact, properties they tend to inhibit the REM Stage and Stage 4; these stages have been shown to be positively correlated with nocturnal arhythmias. Great of these drugs. In fact, caution, however, must be devoted to the withdrawal their tendency to inhibit the REM Stage may when they are discontinued, characterized by an increase of dream activity, produce a rebound effect, which is often responsible for the onset of arhythmias and sudden deaths, Kales et al. (1969) therefore suggest a gradual withdrawal period, the last phase before definitive withdrawal calling for the use of an active dose every 5 days. 5.. The sleep pattern of the patients studied when compared with that of normal subjects, showed an increase in Wake Time and a marked decrease in Stages 3, 4 and REM. These structural modifications are similar to those observed in anxious and depressed patients (Maggini et al., 1974). These findings suggest that there may be some connection between angina and affective disorders. In particular, they support the hypothesis that this coronary disease is a psychosomatic phenomenon, equivalent to depression; and therefore sharing some important etiopathogenetic factors with it, This hypothesis further confirms the need for a multidisciplinary approach to this area of pathology. References KALES, A. and TAN, T.L. (1969). Sleep alterations associated with medical and Pathology. A. Kales (Ed), pp. 148-157, illnesses. In: Sleep, Physiology Lippincott Co. Philadelphia. KALES, A. (1972). The evaluation and treatment of sleep disorder: Pharmacological and psychological studies. Tn: The Sleeping Brain M,H, Chase (Ed) pp. 447-491. Brain Information Service - Brain Research Institute, Los Angeles. KATAYAMA, S., HARUMI, K., SHXMORUMA, K. and MURAO, S. (1973). Nocturnal attacks of angina pectoris in relation of sleep stages and sleep characteristics: A Polygraphic study. 7 Int. Congr. of EEG, Marseille, LESTER, B.K., BLOK, L. and GUN, C.G. (1969). The relation of cardiac arhythmia to phases of sleep, Clin. Res., 17: 456, MAGGINI, C., CASTROGIOVANNI, P. andGUAZZELLT, M. (1974). Studio poligrafico de1 sonno nelle sindromi depressive, Impiego di analisi statistiche multivavariate. In: Le Insonnie, Clinica e Terapia, E. Longanesi, G. Coccagna (Eds). Bologna. MASERI, A., MIMMO, R., CHIERCHIA, S., MARCHESI, C., PESOLA, A, and L'ABBATE, A. (1975). Coronary artery spasm as a cause of acute myocardial ischemia in man. Chest 68-5: 623-633. MOLINARI, S. (1968). La psicofisiologia de1 sonno e de1 sogno. I, Una selettiva rassegna di aggiornamento. Aggiornamenti di Psicologia, IstLtuto di: pskcologia, Universita di Bologna. NOWLIN, J.B., TROYER, W.G.Jr., COLLINS, W.S., SILVERMAN, G., NXCHOLAS, C,R,, MC INTOSH, H.D., ESTES, E.H.Jr. and BOGDONOPF,M.D. (1965). The association of nocturnal angina pectoris with dreaming. Ann, Tnternal. Med., 3: 10401046. ROSENBLATT, G., HARTMANN, E. and ZWILLING, G.R. (1973). Cardiac irritability during sleep and dreaming. J. Psychosom. Res., JJ: 129-134,
SHAPIRO, A. (1975). Observations on some periodic and non periodic phenomena in normal human sleep. Ann. New YorK Acad. SC., 98: 1139-1143. SBAPPELL, S.D. and ORR, W.C. (1975). Variant anginaand sleep: A case report with therapeutic considerations. Dis. Nerv. System., 285: 259-298. Inquiries
Dr. G.B. Cassano Psychiatric Clinic University of Pisa I-56100 Pisa Italy. Table Average distribution stage and wake time
of the (1).
Duration (min) WAKE TIME SLEEP STAGES (1)
Ischemic n./period 2.10 0.66 1.75 0.50 0.60
111 44 141 47 42
1 2 3+4 REM latency
episodes n.h 1.13 0.90 0.73 0.64 0.85
%ST min XST min %ST min %ST min %ST min n
min n min min min
of the monitoring
22 3.8 78 100 280 41 17.1 151 52.3 46 14.6 5 1.8 43 14.2 115 3.8
whole sample 45
sample (45) of the and of 8 recordings
Student's test applied between all sample group without and with ischemic episodes did not show ** : p < 0.01: significance levels * : p q 0.05;
1st REM latency REM periods
Sleep latency Awakening Awakening Time Final Awakening Sleep Time 1
and any of
group of significant student's
24 2.8 57 106 293 35 13.5 171 56.4 35 14.2 6 1.9 46 14.0 106 3.6
without ischemic (15)
21 4.7 90 95 274 44 18.8 141 50.2 42 14.9 5 1.5 42 14.6 118 3.8
20 3.5 67 87 306 42 14.9 166 52.9 39 13.2 5 2.0 54 17.0 104 3.8
29 6.1 156* 79 215 48 26.4** 111 47.9 39 19.1 2 1.1 15"" 5.5** 212 2.6
without ischemic the sample.
with episodes (30)
recordings without and difference. test between recordings
with (30) selected