Acta Physiol Scand 1992, 146, 155-164

Power spectral analysis of heart rate and blood pressure variability in anaesthetized dogs A. E. HEDMAN", J. E. K. H A R T I K A I N E N t , K. U. 0. T A H V A N A I N E N f and M. 0. K. HAKUMAKI"

t

*Department of Physiology, University of Kuopio, Departments of Medicine and f Clinical Physiology, Kuopio University Hospital, Finland

HEDMAN,A. E., HARTIKAINEN, J. E. K., TAHVANAINEN, K. U. 0. & HAKUMAKI, M. 0. K. 1992. Power spectral analysis of heart rate and blood pressure variability in anaesthetized dogs. Acta Physaol Scand 146, 155-164. Received 3 February 1992, accepted 24 April 1992. ISSN 0001-6772. Department of Physiology, University of Kuopio and Departments of Medicine and Clinical Physiology, Kuopio University Hospital, Finland. Short-term oscillation of heart rate and blood pressure are mainly regulated by the automatic nervous system. It has been proposed that non-neural factors, such as changes in intrathoracic pressure, can strongly modulate this rhythmicity. Our aim was to evaluate the effect of changing intrathoracic pressure and central autonomic nervous activity on heart rate and blood pressure variability. Evaluation was performed by using spectral analysis techniques with autoregressive modelling. The variability in heart rate and blood pressure remained in animals with open chest or paralysed respiratory muscles. After vagotomy, the variability in heart rate decreased, but not that of blood pressure. Total spinal anaesthesia elicited a decrease in the variability in blood pressure. The pharmacological blockade of a- and /%receptors further decreased both variabilities. It was concluded that in anaesthetized dogs heart rate and blood pressure variability are mainly of central origin and non-neural factors have only minor effect on these central rhythms. High (> 0.15 Hz), medium (0.07-0.15 Hz) and, obviously low (0.00-0.07 Hz) frequency variations in heart rate are mostly mediated vagally. In blood pressure, medium and obviously low frequency variations are modulated by sympathetic nervous system, whereas high frequency variations are secondary to the heart rate variation. Key mords: autonomic nervous system, blood pressure variability, intrathoracic pressure, heart rate variability, power spectral analysis, respiratory sinus arrhythmia.

T h e autonomic nervous system is the main regulator of short-term oscillation in heart rate (HR) and blood pressure (BP). Spectral analysis methods have made it possible to analyse these oscillations, and may provide a method to quantify the function of the autonomic nervous system. Evaluation of H R variability (HRV) by using power spectral analysis has already proved to be useful in diagnosing brain death (Kero et al. 1978) or diabetic neuropathy (Pagani et al. 1988, Weise et al. 1990), in evaluating high-risk Correspondence : Antti Hedman, Department of Physiology, University of Kuopio, P.O. Box 1627, SF-7021 1 Kuopio, Finland.

patients for sudden cardiac death after acute myocardial infarction (Mayers et al. 1986, Malik & Camm 1990) and in evaluating cardiorespiratory adaptation of newborn babies (Aarimaa et al. 1988). T h e power spectral analysis of R-R intervals (RRI), systolic (SAP) and diastolic (DAP) arterial pressure constitute of three typical components : a high frequency (HF, about 0.25Hz) component, which mainly consists of respiratory activity, a medium frequency (MF, about 0.1 Hz) component and a low frequency (LF, < 0.07 Hz) component. Changes in the variability in the HF component are thought to reflect changes in the parasympathetic nervous activity (Akselrod et al.

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flow transducer connected to the intubation tube. T h e oesophageal temperature was monitored and adjusted to 3 7 . 5 + 0 . 5 "C by an operation table heated hy a water bath. The arterial oxygen saturation \+as continuously monitored from the under both s! mpathetic and paras!-mpathetic tongue with a pulse osimetcr (Model 405, Criticontrol (r2liselrod et i i / . 1981, Porneranz r t (11 care S p t e m s Inc., \l,~aukasha,WI, USA). Between 1985, Rimoldi et I [ / . 1990, Siimes et (11. 1990, the recordings, the acid-base balance was determined Randall et a / . l991), onl! under s!-mpathetic b!- the Astrup technique (Siggaard Andersen et a/. control (Pagani r / N/. 19x6, Inoue et al. 1990) or 1960) from arterial blood samples taken from a to reflect mainly vagal modulation (Kleiger et r i l catheter inserted into the right femoral artery. The 1991). 'The lariahilit!. in the LF component has minute \-ohme of ventilation and concentration of been thought to arise d u e to the 1-ascular x-- o n g e n in inspired gas were adjusted in order to keep Pao, between 12 and 16 kPa and Pace? between 4 and adrenergic effector mechanism (XIadwed t't a / 6 kPa. Doses of 7.j0,, sodium bicarbonate were given 1989), d u e to regulation b!- the renin-angiotensin sy5teni (.4kselrod t t ( i / . 1981, 198.5) or d u e trl i.\-. to keep the pH between 7 . 3 5 and 5.45. '10 estimate the loss of fluid during the experiment, thermoregulation (Kitne! 1974). the urinary bladder was cannulated and the fluid Se\ era1 authors have suggested, that alterna- balance was corrected by infusion of 0,9(?" sodium tions in intrathoracic pressure could h e the caust chloride 4 ml kg-' h '. If bleeding was detected, an of oscillations i n H K and i n BP o r could a t least additional dose of fluid corresponding to the estimated strongl! modulate these rh!-thms 1-ia baroblood loss was administered. receptors and atrial receptors (Bainbridge 1920. SurgciiI procedure. For sympathetic blockade, an SaJers 1st ill. 1973, Kitney et ill. 1982, deBoer epidural catheter was inserted into the spinal space through the fourth or fifth lumbar intervertebral space 6'1 [ti. 1087) or via thoracic stretch receptors rt N / . 1984). For vagotomy, a middle (Feldman (Cl!-nes 1060, Dale? rt ol. 1083). On the other hand, in recent studies, it has been presumed incision was made in the neck and the sgnipathicolagal trunks were exposed. Silk sutures were bound that these oscillations are of central origin around the nerves so that they could be cut later. (Koepchen et al. 1981, 1986, Kuwahara r t ( I ) . T o record aortic pressure, a micro-tip catheter 1990, Shl-hoff Pt I [ / . 1991). In addition, intrinsic pressure transducer (Model PC-350, Millar Instruproperties of heart muscle can also modulate ments, Houston, TX, US4) was introduced through these oscillations (Bernardi zt ill. 1990). the left femoral artery into the aorta so that the tip T h e aim of this stud!- was t o evaluate the reached the aortic arch. For infusions, thc adjacent eRect of changing intrathoracic pressure and femoral vein was cannulated with a polyethylene mpathetic modulation on catheter. 1'0 record ECG, needle electrodes were central vagal a n d IIR and BP 1-ariab t!- (BPI') h!- using power inserted into the skin and connected to a preamplifier (High/Z/hlodel 432, Brookdeal, Bracknell, UK). spectral analysis. E . \ ; D P I . I N I Lsrt-up. ~ I ~ ~ ~ IDuring / the instrumentation and esperiment, animals were mainly artificially l-entilated. During each registration, the respirator 15 a 5 disconnected for 2-4 niin. Between the registra. - t t i i t t i ~ l . c , ~ r t / i r c . i t / / c ~ . i / crnif (/ I ~ I I I I I I I C I I ~ I NSix ~ ~ ~ . laborations animals were reconnected to the respirator and tor!--bred beagle dogs of' both sexes (weight the acid-base balance \\as corrected. 10.82 2.8 kg, age X i 3 32 da! s) Mere pre-medicated The esperiment consisted of the following pronith morphine h!drochloride (1 mg kg I ) s.c.) and cedures: ( I ) in the control, the dog breathed anaesthetized with r-chloralose (Z-D( + )gluco- spontaneousl!- so that intrathoracic pressure changed chloralosc, 100 mg bg-' i.\-.). .\dditional doses of' normally during respiration; ( 2 ) to abolish changes in chloralose (LO mg kg- h-') were administered intrathoracic pressure and to eliminate stimulation of during the operation. Buprenorphine n a5 com- the intrathoracic stretch receptors during respiration, bined with anaesthesia to ensure analgesia. Doses the respirator!. muscles \\-ere paralysed with succinyl(0.01 mg kg ' s.c.) were gken a t the beginning of' choline (1 mg kg-' i.v.); ( 3 ) after 30 min recovery anaesthesia and before surgery. The animals 15 cre from respiratory muscle paralysis, a left thoracotomy intuhated, connected to a posithe pressure res- was done and the right pleura was also incised. This pirator (Harvard Dual Phase Pump, Illode1 613, \\as performed to abolish changes in intrathoracic pressure but still allowing the thoracic stretch H a n a r d C:o. I h v e r , X1.1, CS.1) and wntilated \\ith a mixture of' room air and oxygen. T h e receptors to function when the animal tried to breathe; frequency of breathing n a s estimated with an air (4)the respiratory muscles were again paralysed with

1981, 108i, Pomeranz t't ( I / . 198.5, Pagani et u l . 1986, Rimoldi ct i t ) . 1990, Siimes rt i i / . 1990, Randall et (il. 1991). Accordingl!-, t h e L-ariabilitJin %IF component has been proposed to be

-

Heart rate and blood pressure variability succinylcholine ; ( 5 ) parasympathetic efferent nerve activity to the heart was eliminated by cutting the cervical vago-sympathetic trunks; (6) sympathetic efferent activity was blocked with total spinal an(8 ml, aesthesia. Bupivacaine hydrochloride 5 mg m1-l) was injected via the spinal catheter into the spinal space. It blocked the sympathetic activity as well as possible spinal reflexes. The blockade was confirmed in two animals by recording sympathetic nerve activity on left stellate nerves before and after the spinal anaesthesia. After total spinal anaesthesia, sympathetic burst disappeared and only background noise remained; and (7) the influence of humoral factors such as catecholamines were eliminated by blocking the a- and ,&receptors with labetalolhydrochloride (2.5 mg kg-' i.v.). Muscarine receptors were also blocked with atropine (0.1 mg kg-'). At the end of the experiment the animal was anaesthetized deeply and killed. Data acquisition and analysis. ECG, aortic pressure and tracheal air flow signals were stored into an instrumentation tape recorder. The ECG and aortic blood pressure signals were analogue-to-digital converted (200 Hz channel-', 12 bits) off-line and stored in an IBM PC/AT compatible microcomputer. All data acquisition and analysis were performed using a menu-driven software package (CAFTS, Medikro Oy, Kuopio, Finland). The software package utilizes a modified single-scan algorithm for QRS detection described by Engelese & Zeelenberg (1979) followed by a second order polynomial interpolation of each R wave. The accuracy of better than 2 ms is obtained in QRS detection. Mean values and standard deviations of RRI, HR, SAP and DAP were calculated. In addition, spectral density estimates of RRI, SAP and DAP signals in the frequency domain were calculated from a user-defined stationary region with 256 R-R intervals at maximum. An adaptive least-mean-square (LMS) autoregressive modelling algorithm based on gradient approximation was used for the estimation of power spectral density functions (Marple 1987). The model order of 18 was used. After linear (LMS) detrending of the RRI, SAP and DAP time series, each spectral density function was divided into three frequency bands: low frequency band (LF, 0.0k0.07 Hz), medium frequency band (MF, 0.07-0.15 Hz) and high frequency band [HF, 0.15 Hz-0.5 (frequency equal to mean RRI)]. The total power of RRI, SAP or DAP, expressed as variance ( r = 1 SD2), was divided by numerical integration into the corresponding three frequency bands. In addition, the frequencies corresponding maximum spectral powers in the M F and H F bands were calculated by the software package. In the LF band the frequency was estimated manually. Statistical analysis. Data are presented as meanf SEM. A Mann-Whitney U-test was used to compare the control, i.e. closed thorax condition, to

157

other conditions. In addition, differences between conditions after vagotomy, total spinal anaesthesia and pharmacological receptor blockade were tested with Kruskal-Wallis analysis of variance followed by Mann-Whitney U-test with Bonferroni correction, if significant effect was found. A P-value of less than 0.05 was considered to be statistically significant.

RESULTS Control period Anaesthetized dogs with intact thorax breathed spontaneously (Figs 1a, 2a). T h e mean length of RRI was 594k82 ms. The RRI variability was 6452 f2780 ms'. T h e breathing frequency (0.09_+0.01 Hz) was within the MF band, and accordingly, the MF component was dominating (3587&1767msz) (Fig. 3). T h e LF and HF components were 1936k 1051 and 929 f254 ms', respectively. SAP and DAP were 148f6 and 100 f9 m m H g , respectively. Variabilities in SAP and DAP were 35.9k10.7 and 47.8 10.8 mmHg2, respectively (Table 2 ) .

6

0

TIME (51

20

Fig. 1. An authentic recording of aortic pressure, ECG and tracheal air flow during spontaneous breathing in a dog with closed chest (a) and after the changes in intrathoracic pressure were eliminated by paralysis of respiratory muscles and thoracotomy (b). 6-2

.4. E. Hedman et al.

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& 2 ) . T h e frequency of maximal spectral power

of Bpi- also shifted from the lower frequencies to the H F band. 1000

\

b)

10000 1000 100 10

p v W % w 3L 1000

(cl

10000 1000 100 10

10000 1000 100

-4niniuls mith open thorrtr

-4fter thoracotomy, the animals were again disconnected from the respirator and allowed to make respirator). efforts (Fig. 2c). T h e mean length of the RRI and the RRI variability did not change significantly as compared to the control condition (Tables 1 & 2 ) . T h e frequency of maximal spectral power of RRI variation was E 0.2920.03 Hz, which corresponded to the freg a quency of the breathing efforts. Thus the i \-ariation consisted mainly of HF variations. SAP, DrlP and the variability in DAP did not change from the control whereas the variability in SAP was greater than in the control condition (Tables 1, 2 ) . Most of the variation occurred at the HF band and the HF component of SAP and D-4P was significantly greater than in the control.

10

10000 10 epii

TP LF MFHF

Fig. 2. R-R interval and corresponding spectral powers of R-R interval variation in an animal during control (a), after respirator!. muscles parall-sis (b), after thorax was opened (c), after thorax was opened and respiratory muscles u-ere paralysed (d), after vagotomy (e), after vagotomy and total spinal anaesthesia (0 and after pharmacological and surgical denervation (g). TP = total power, LF = low frequency band, %IF= medium frequencj- band and HF = high frequency band.

.ininials wzth intact thorax and puralysed rrspirutory muscles

Animals were paralysed to prevent breathing movements and disconnected from the respirator for 1-4 min (Fig. 2b). During this period, the mean length of the RRI and the RRI variability did not change significantly (Tables 1, 2). T h e frequent!. of maximal spectral power was 0.16 F0.03 Hz. Thus, the variability was shifted from the lower frequencies to the HF band (Fig. 3). SA4P,Drip and the total variability in S I P and DAP did not change significantly (Tables 1

Aninials with open thorax iind parulysed respiriitory rniiscIe.7

In animals with an open thorax, movements of the thorax were eliminated (Figs 1 b, 2d). There was a marked variation in the RRI, which occurred a t a frequency of 0.21 k0.03 Hz. T h e mean length of the RRI did not differ significantly from that in the control condition, neither did the RRI variability although it tended to increase (Tables 1 & 2). Again, corresponding to the frequency of maximal spectral power of the RRI variability, most of the variation was at the HF band. T h e HF component was greater than in the control condition (Fig. 3). There was also a marked variation in BP (Fig. 1 b). SAP was higher than in the control condition (Table l ) , as was the variability in SAP, which was 201.0k61.9 mmHg2. Most of the variation consisted of HF variation (Table 2 ) . T h e \-ariabilit!- in DAP did not differ from the control, but the HF component was increased (Table 2 ) . .4nininls with open thorax and zugotomy

After cutting the vagal nerves from the neck HRV diminished markedly (Fig. 2e). T h e mean length of the RRI was a t the control level. Instead, the RRI variability was only

Heart rate and blood pressure variabilitjt

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5 10000 E

I

8000 W

$ J

Q

LL

6000 LOO0

c

2000 v)

a

b

c

d

e

f

g

Fig. 3. Pooled results of power spectral analysis of R-R interval variation during different conditions in six dogs. For explanation see Figure 2. Powers are expressed as means (the whole bar) & SEM (top of the bar).

Table 1. R-R interval, systolic and diastolic pressure (mean fSEM) during control, after respiratory muscles were paralysed (Resp. paral.), after thorax was opened (Open thx), after thorax was opened and respiratory muscles were paralysed (Open thx resp. paral.), after vagotomy (Vagot.), after vagotomy and total spinal anaesthesia (Vagot. +spinal an.) and after pharmacological and surgical denervation (Total denerv.)

+

Control Resp. paral. Open thx Open thx + resp. paral. Vagot. Vagot. +spinal an. Total denerv.

R-R interval (ms)

Systolic pressure (mmHg)

Diastolic pressure (mmHg)

594 k 82 630 f40n.s. 646 37n.s. 778k47n.s. 548f 18n.s. 664f 54n.s. 662 2 55n.s.

148k6 168k 7n.s. 171 *9n.s. 176k 10" 173f 10" 88 _+ 3"" 76 f 5""

10059 109_f6n.s. 117 f5n.s. 116f5n.s. 126f8n.s. 50+ 1"" 38 f2**

Significance of difference 3s. control condirion, P > 0.05 = n.s., " P < 0.05; Lr-test, n = 6.

398 182 ms, which was less than in the control condition (Table 2). T h e frequency of maximal spectral power was 0.1 1 & 0.02 Hz. T h e LF, MF and HF components were also lower than in the control condition (Table 2, Fig. 3 ) . Vagotomy resulted in increase in SAP, but D A P did not change (Table 1). T h e variability in S A P and DAP did not differ from the control condition (Table 2 ) . Animals with open thorax, vagotomy and total spinal anaesthesia After sympathetic blockade by total spinal anaesthesia, the mean length of the RRI did not differ from that in the control condition (Table 1, Fig. 2f). T h e frequency of maximal spectral power shifted to the LF band and was at

"* P < 0.01, Mann-Whitney

0.04f0.01 Hz. T h e R R I variability was 140f 51 ms2, which was less than in the control condition, but did not differ from the condition after vagotomy (P> 0.05). When compared to control condition, the variability reduced at all frequency bands (Table 2). B P clearly decreased after total spinal anaesthesia, S A P to 8 8 + 3 m m H g and D A P to SO+ 1 mmHg. In this case, the total variability in SAP and D A P decreased significantly compared to the control condition but not compared to the condition after vagotomy (P> 0.05).

Animals with open thorax and total pharmacological and surgical denervation Finally, the a- and /3- and muscarine receptors were blocked (Fig. 2g). T h e mean length of the

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T a b l e 2 . Spectral po\\crs of R-R interral, s!-stoiic and diastolic pressure (mean iSEM) during control, after respiratory muscles nere paralysed (Resp. paral.), after thorax was opened (Open thx), after thorax was opened and respirator!- muscles were paralysed (Open thx resp. paral.), after vagotomy (Vagot.), after vagotomy and total spinal anaesthesia (1-agot. spinal an.) and after pharmacological and surgical denervation (Total deneri-).

+

+

Total power

Lou freq. power

Medium freq. power

High freq. p o er~

64.52 f 2780 8508+4h4n 7 . 309.3 + j82 n s. 12678 F 4.56in.s .Jog* 182" I 4 O i 51"" 15 6""

19365 1051 5781379n.s 94 5 30n.s. 173 1 4 3 n.6 66 t 30" 68 & 18" 9 -t 4""

3587 i 1767 944 t- 678 n.s. 137467" 3920f 3310n.s. 132 f 6 i L 10+6*" 1 1""

929 251 6986 f1631"" 2862 k 508"" 8602 _+4143" 199 k94" 61 -t 28"" 6 2""

3.3.9 i 10.7 142.1 k 72.0n.s. 1 1 0 . 0 27.4" ~ 201 .O & 61.9" 80.8 24.6n.s. 0 . 5 & 1.4"" 1.O 0. .i ""

14.1 k -i.&5 37.9 29.0n.s. 2 2 . 4 4 19.4n.s. 24.3 1 6 . 7 n . s . 33.5 13.0n.s. (0.8 1 0 . 1 ) (0.2 k 0.1)

13.5 ij.6 39.0+32.1 n.s. 6.5i.4.6n.s. 66.8 56.0n.s. 33.9+ 12.2n.s. (0.ik0.1) (0.4 5 0.1)

8.4f2.2 56.3+24.0"* 81.1+ 16.5"" 109.8 k 52.3" 13.5f3.0n.s. (4.8kl.l) (1.4 i0.4)

18.81f7.7 21.4 18.1n s . 2 . 3 - t lO.4n.s. 4.0 11.6n.s. 15.9 18.011,s. (0.8 0.2) ( 0 . 2 f0.1)

21.2i5.9 33.0+24.1n.s. 4.6+ 3.9" 30.4f28.6n.s. 22.6f7.3n.s. (0.7 i:0.2) ( 0 . 2 t0.1)

~

Spectral po\\ers of K-R inter\al (m5') Control Resp pdral Open th\ Open thx resp paral

+

Lagot

1 agot

+

spinal a n T o t d denen Spectral poiters of zistolic pressure (mmHg') ( ontrol Kcsp para1 Open thx Open thx resp pdral

+

1 agot 1 agot spinal an 1o t d clenerj +

Spectral par\ ei s of diastolic pressure (mmHg') Control Kesp pard Open thx Open thx resp paral

+

1 agot 1 agot f i p i n a l an Total denen

*

K . 8 + 10.8 11 1.4i46.2 n.s. 36.Xf 11.4n.s. lOi.4 i49.9 n s . 44.6 i I.i.0n.s. 6.4+ 2.0"" 1..3 0.2**

*

+

+

*

+

*

7.9f 1.3 57.1 F 1 3 . h . s . 19.8 i3.1"" i 3 . 0 + 50.8" 6.1 rfr 1.6n.s. (5.0f 1.6) (1.0 +o. 1)

The low, medium, and high frequent!. powers of systolic and diastolic pressure are in parenthesis because they were not included into statistical analysis, since iariabilities were at very low level and distinct peaks were not detected

RRI did not differ from the control condition. DISCUSSIOK T h e RRI variabilit!- was 15 6 ms'. It was Ion-er than in the control and in the conditions after \-agotom>-( P < 0.05) and total spinal anaesthesia ( P < O.O.i), as did the LF, %IF and HF components (Table 2 , Fig. 3). T h e frequencJ- of maximal spectral power of RRI variation was 0.05 0.02 Hz and thus, most of the variation occurred at the LF band. Alfterreceptor blockade, BP decreased further (Table 1). T h e variabilities in S.4P ( Z . O t _ O . j mmE-lg') and DAP (1.3k0.2 mmHg') \+ere lower than in the control condition, after \-agotomy (P < 0.05) and after total spinal anaesthesia (P< 0 . 0 5 ) (Table 2).

T h e purpose of the present study was, by means of spectral analysis, to evaluate the effect of intrathoracic pressure changes caused by breathing and effects of' central vagal and sympathetic modulation on I-IRV and BPV. Previously it has been proposed that during breathing, changes in intrathoracic pressure induce variation in BP, which then reflexly causes variation in HR (Bainbridge 1920, Sayers 1973, Kitney et a/. 1982, deBoer et nl. 1987). I n this study we demonstrated, that the central efferent neural activity causes HRV and BPV and that changes in intrathoracic pressure, induced by the breath-

Heart rate and blood pressure variability ing movements, are not essential in the genesis of these oscillations. In the present study, HRV and BPV remained even though the effects of the breathing movements were eliminated by thoracotomy or paralysis of respiratory muscles. After thoracotomy, the variability in SAP increased. Instead, the HRV decreased significantly after vagotomy and the BPV after total spinal anaesthesia. This implies that oscillations in the central efferent neural activity cause these variations and that alternations in intrathoracic pressure are not essential in the genesis of these variations. Our results agree with the findings of Kuwahara et al. (1990), who observed in vagotomized, paralysed, unanaesthetized and decerebrated cats with pneumothorax, oscillations in HR, which corresponded to the frequency of the intrinsic respiratory drive evaluated from efferent phrenic neural discharge. Correspondingly, Shykoff et al. (1991) showed that in anaesthetized closed chest dogs, HR modulation was synchronous with phrenic neural activity in the absence of changes in intrathoracic pressure during constant-flow ventilation. Possibly a common central cardio-respiratory rhythmicity is the origin of this variations (Langhorst et al. 1980, Koepchen et al. 1981, 1986). In the control condition of the present study, most of the HRV and BPV occurred at the M F band and corresponded to the frequency of breathing. After thoracotomy the frequency of breathing efforts increased and corresponded to the HF band. Thus, most of the variation shifted to the HF band, as also occurred in the paralysed animals. This phenomenon could be explained by the increased respiratory drive caused by stimulation of the respiratory center due to the retention of carbon dioxide (Kuwahara et al. 1990) and decrease in oxygen saturation (Naqvi et al. 1991). I n our study, the oxygen saturation was 92-9 6 yoin spontaneously breathing animals, and decreased to 57-75% in animals with open thorax or paralysed respiratory muscles. There were no significant differences (P > 0.05) between the components corresponding to the respiratory drive in the first four conditions (MF in control, HF in other conditions). It is widely accepted that respiratory sinus arrythmia in HR (usually HF component) is mediated vagally in adults (Akselrod et al. 1982, Selman 1982, Pomeranz et al. 1985, Rimoldi et al. 1990, Randall et al. 1991). Our results agree

161

with that finding, since vagotomy resulted in a 95 yo reduction of HRV compared to that in the control condition. There was also a marked reduction in the power spectral density of the band corresponding to the respiratory drive. A marked decrease in the M F and LF components were also observed, indicating that vagal activity also modulates these slower rhythms. This is in accordance with the statements of Berger et a/. (1989), Rimoldi et al. (1990), Kleiger et al. (1991) and Randall et al. (1991), but is in contrast to Pagani et al. (1986) and Inoue et al. (1990), who have proposed that M F variations only occur under sympathetic modulation. There remained some HRV after vagotomy, as reported in children with decerebration syndrome (Kero et al. 1978), in atropinized dogs (Madwed & Cohen 1991) and in decerebrated, vagotomized cats (Kuwahara 1990). It was probably due to sympathetic modulation, since the HRV tended to decrease further after the sympathetic blockade by total spinal anaesthesia. T h e decrease was, however, minimal, which may be due to low /3-sympathetic tone in dogs (Akselrod et al. 1985). After vagotomy, there was a substantial amount of MF variability in HR, as also occurred after the thorax was opened and respiratory muscle paralysed. This could be due to baroreceptor response to spontaneous vasomotor activity at that frequency (Kitney et al. 1982) through sympathetic feedback loop (deBoer et al. 1987) or due to spontaneous central cardiorespiratory oscillations (Koepchen et al. 1986). Whereas, in control conditions the M F component was dominating, probably because of the respiratory activity. After vagotomy, the total power spectral densities of SAP and DAP did not differ from the control. Instead, BPV occurred at the LF and M F bands, although it could be expected that respiratory drive would be same as in previous conditions. This conforms with Akselrod et al. (1985), who showed, by pacing the dogs heart, that HF fluctuations in BP were secondary to the variations in HR. Only after the sympathetic blockade with total spinal anaesthesia, BPV decreased and there was a concomitant decrease in BP. Our results agree with the suggestions that the sympathetic nervous system controls M F and LF variations in BP (Madwed et al. 1989, Madwed & Cohen 1991, Rimoldi et al. 1990, Inoue et al. 1991).

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A . E . Hedmnn et al.

After blocking efferent autonomic pathways, there still remained some H R V and BPI-, which further decreased b!- pharmacological receptor blockade, T h e decrease in the BP\- was concomitant with the decrease in vascular tone. T h i s agrees with the study of Jacob et a / . (1991), who demonstrated that humoral agents influencins the vascular resistance effect the lability in arterial pressure in rats with ganglionic blockade. The decrease in HRI- could be explained b>-the finding that intrinsic mechanisms of heart muscle can transfer fluctuations from B P to H R in heart transplantant patients (Bernardi et al. 1990). We used anaesthetized animals, which must be taken into account when our results are compared with those obtained with conscious animals. We chose 2-chloralose for anaesthesia, because it does not depress autonomic reflexes (Aihonen 198-5). \Ye also carried out an esperiment, in which we used pentobarbital as an anaesthetic, and found a significant decrease in HRI’. I t Has concluded that pentobarbital was not a possible anaesthetic in this kind of experiment. However, S.C.injection of buprenorphine, an analgesic combined with the chloralose anaesthesia, did not significantly influence HRI . W e used an autoregressive modelling for spectral density estimation. I t has some advantages when compared to fast Fourier transformation ( F F T ) algorithms : more consistent and smoother spectral estimation, spectral resolution is independent of the number of samples and there is n o need for windowing procedures (KaJ- & Marple 1981). T h u s it is suitable for analysis of shorter time series than FFT algorithms. 1t-e are, however, cautious to drair conclusions about changes in LF components because the power densit!- estimation ma!- not be reliable in the lowest part of the band (around 0.01 H z ) when we analysed the relatively short time series, although the frequency of maximal spectral density was constant at about 0.05 Hz. . 4 ~a method, total spinal anaesthesia and pharmacological receptor blockade were effective enough to diminish the BPV to a very low level and distinct L F , 1,lFand HF components were not detected. ‘Thus, only the total power spectral densities of S.4P and D-4P were included in the interpretation of the results in the present stud!. I n conclusion, we found that short-term variations in H R and B P are of central origin and that in the genesis of those variations the effects of changes in intrathoracic pressure during

respiratory movements are minimal. HF, MF, and obviously LF variations in FIR, are mostly mediated vagally. %IFand obviously LF oscillations in BP are modulated by the sympathetic nervous system, but HF oscillations in B P are secondary to the HR variations of the same frequency. T h e spectral analysis of H R V and BPV reflects mainly the function of the autonomic nervous system. Further studies are needed to evaluate the inter-relationship between sympathetic and parasympathetic nervous activities. This study was supported by the North-Savo Cultural Foundation and the Orion Corporation Research Foundation. Skillful technical assistance was provided b!- Mrs Raija Holopainen.

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