A comparison of the hemodynamic effects of tachycardia produced by atrial pacing and atropine

A comparison effects atrial

of the hemodynamic

of tachycardia pacing

and

produced

by

atropine

Hcrntrrd D. Kosowsky, .1l.D.” Emanuel Stein, M.D. Strn H. Lcru, il4.D. Joha W. Lister, M.D. Jucoh I. Hnjt, M.D. Anthony N. Damuto, M.D. Staten Island. N. 1’.

A

tropine has been used to produce increases in heart rate both clinicallv and in investigations relating the effects of heart rate to cardiac function. The chronotropic effect of atropine is IveIl established. However, it has not been clearly- determined whether atropine affects other cardiovascular parameters. Comparisons between the control and atropine states are difficult to evaluate because it is not clear whether the changes in hemodynamics that may’ occur are secondary, to tachvcardia or are manifestations of the vagolyrtic or direct effects of the drug. With the use of atria1 pacing it is possilJe to increase the heart rate writhout significantly altering the hemodynamic state.‘,” It is possible, therefore, to study the effects of atropine independently. of its chronotropic property- by comparing values 01~ tained with atropine to those in the resting state at similar heart rates. The present

investigation wxs designed to compare the hemodynamic effects of tachycardia produced by atria1 pacing and by atropine in normal subjects. Methods

Investigations were performed in 9 normal male volunteers, 23 to 50 years of age, during cardiac catheterization. All studies were carried out with the subjects in the supine position in a resting, nonsedated, postabsorptive state. Through an antecubital vein, a No. 7 or Y Cournand catheter w-as positioned in the main pulmonary~ artery. and a No. 5 tripolar electrode catheter \vas positioned along the lateral u-all of the right atriunt. A4 No. 18 Cournand needle was inserted into a brachial artery.. Pressures w:ere obtained by means of Statham 231) strain gauges. Cardiac outputs were determined in duplicate by the d>-e-dilution technique,

with 7.5 mg. of indocyanine green dye being injected into the pulmonary artery and with blood sampled from the brachial through a cuvette densitometer. artery All recordings were made on an eightrechannel photographic oscilloscopic corder. Cardiac outputs were calculated from the inscribed curves using the Sten-artHamilton formula. Atria1 pacing was accomplished by means of a battery-powered pacer connected to the electrode catheter. The atria were paced at various rates up to 160 heats per minute or until A-1’ block occurred, at a twice milliamperage of approximately threshold. The pacer was not turned off during the intervals between determinations. Slew arterial pressures and mean systolic pressures were planimetrically determined over two respiratory cycles. The systolic ejection time (SET) was derived from the brachial arterial pressure pulse. The tension time index (TTI) was calculated according to the method of Sarnoff and associates.3 Stroke index (SI), total peripheral resistance (TPR), mean systolic ejection rate (JISER), and left ventricular work index (L\?VI) \vere calculated from the standard formulae. In each subject, cardiac outputs, electrocardiograms, and arterial pressure tracings were recorded at sinus rhythm and after 3 to 5 minutes of atria1 pacing at various heart rates. These studies were repeated 3 minutes after the intravenous injection of 2 mg. of atropine sulfate administered over a l-minute period. Results

The data from all of the subjects are presented in Table I. Statistical analyses were made on pairs of values in individual subjects obtained at similar heart rates (within 10 beats per minute) in the control and atropine states. These values are noted by an asterisk in Table I. Cclrditrc index. The administration of atropine resulted in no significant change in cardiac index (p > .90) (Fig. 1). Increasing the heart rate by means of atria1 pacing did not significantly change the cardiac index, although there appeared to I)e a slight decrease in cardiac index at the maxi~~~u~~~ heart rates oljtained with and

lvithout atropine. The stroke index varied inversely with heart rate and was not affected by atropine at similar heart rates. Brtrchictl (irterinI pressure. The !,rachial arterial pressure, mean arterial pressure, and the mean systolic pressure \vere UIIchanged 11y atropine (p > .50) or 1)) changes in heart rate. SystoZic ejection fime. At similar heart rates there was no significant difference \)et\veen the SET obtained 1)y atropine and that obtained 1,). atria1 pacing (p > .OO) (Fig. 2). Increases in heart rate by atria1 pacing resulted in a linear increase in SET with and lvithout atropine. Tension time index. There was no significant difference between the ‘IT1 before and that after the administration of atropine at similar heart rates (p > .30) (Fig, 3). The ‘IT1 increased with heart rate, paralleling the changes in SET. l’otul peripheral resistance. The TJ’R NXS not significantly altered by the administration of atropine (p > .60) or by changes in heart rate. direcfn systolic ejection rate. At similar heart rates the JISER 1)efore and that after the administration of atropine a.ere not significantly different (p > .SOj. 1Tnder both conditions the :\ISEK varied inversely with heart rate. Lqft vcnfriwl(lr work index. The L\:12’1 was not altered I))- atropine (p > .90) or I)!, changes in heart rate. Discussion

The effect of atropine on cardiac output has lIeen extensively investigated. Several studies have shown an increase in output after intravenous atropine,4-fi although other studies in human beings and dogs failed to show any changes.?-tr Lancaster and his associates? have shown that atropine and rapid atria1 pacing both h,‘1-e an immediate effect of increasing cardiac output, with a ‘return to control values after a fe\v minutes. In the present study, since the pacer was not turned off between determinations, the effects of acutely changing the heart rate n-ere not evident. Because of the previous unavailability of similar heart rates without atropine, comparisons of other parameters that might be affected i)y atropine have not

M.F., SO

C.I'., 32

66 “118 *144 *11-L% 115.4 *l-16.\

2.74 2.99 2.71 2.91 2.92 2.74

42 2.5 19 25 2h 19

114 110 103 10.5 104 107

2.440 3,200 3 ,300 3,050

62 77 *IO6 *133 *1r50

3.92 4 0.3 5.05

* 160.1

70 80 92 92 9.z 98 95 100

1,530 1,860

3.96 4.70 4.35 3.76

63 52 4x .30 2.5 40 34 24

70 88 *1tri "144 "12512 I .30:1 *I .35.A 158rl

4.70 4.50 4.40 3.78 4.05 4.60 5.25 4.88

67 51 \Z8 27 32 3.5 39 .z I

1 2.5

611 "88 *9&A 102A 13h:Z

3.86 4.32 3.95 4.12 3 85

64 40 41 40 2x

3.78 4.70 3.87 4 47 4.36 4.70

52 4.5 .z.5 25 .z7 .1.5 .?O

3 6.1 4.10 3.68 3.49 3.58 4.11 3.43 3.92

60 45 30 36 36 40 29 27

*1 l-I:\ *128A

I).D., 40

AI)., 2.3

LB., 28

73 *114 *1.1-f

*1.54 *12oA. *I 25A *159;1

N.Q., 45

hl *92 *121 *96A 1 OOA 10311

* 1 18A 147A

I)ata

5.15

5.10

1.10 13.5 13.5 I 3.5 13.5 130 1.35

96

100 100

100 99

100 98 95 96 100

100 96 120 112 1l.Z 120

114 114 116 11.5

3,100 3,400

2,7OCJ .?,I00 3,200 2,900 3,250 3,460

2,875 3.770 4,200 4, 300 4.600 4, 700 4,600 4,800

.3, 320 1 .940 .z ,040 2 I 000 2.850 3 , 1 10

1 .io 107 00 10.1 104 HO

1,430 1.560 1,460 1,430 1,880 1.660 1,760 2,120

186

si.66

17.5

4.35 6.29 6.42 5.00 6.37 5.62 5.12

2.10

2 13 10 2,450 2,840 2 ) 060 2 , 340 1 .960 2,110

184

1 66 124 16.5 140 114 204 190 1.55 12.5 120 144 164 164

I.980 2.650 2,820 2,890 3,300

I.990 1,850 2 , 020

194 174 148

1 ,930 2 _050

151 14.3

2,460 3,180 3.320 .z.400 .z.190 .Z,220 .? , 410

2,100 1,530 1,980

154 166 141 114

1,780

149

1 , 830 1 ,630

141 1 .zfi

2,690 3 . 330 .3,500 .z , 200 3.250 3 , 330 3.520 4.080

1.640 2,180 2,440 2 1740 2.520 -) ,--710

169 153 123 134

obtained after the administration oi atropine is noted by Z\ after the HR. statistical analyses (see text). In each subject the first heart rate recorded in the subsequent HRs were obtained by atria1 pacing. _ IIR: Heart rate. CI: Cardiac index. SI: Stroke index. R.4: Mean brachial arterial time index. TPR: Total peripheral resistance. MSER: Mean systolic ejection

Asterisks control

1,520

2.700 2..?20

I 38

1.53 122 119

(*) preceding HR denote and atropine states represent

4 2x 4.51 3.81 4.16

4.15 4.01

x 00 X.06 X.20 7.23 7.55 8.60 9.X 8 7X

5.04 S 90 5.38 5.00 5.21

5.15 6.80 6.06 5.10 6.08 5.92 6.14

5.98 6.28 5.70 5.70 5 59 6.43 5.45 6.18

vaIues sinus

pressure. SE1‘: Systolic ejection time. T7‘1: rate. L6’117/: Ixft ventricular work index.

used for rhythm: Tension

I l’cltient, Age (YT.)

I

I l/l<

1

CI

~

/

SI (nzZ./Af.2)

.~~. / R-1 SET (mm. Hg)i(SK./t?ZitZ.)

~

1’7‘1

~

Tl’K I

AISEK (ml./sec./ Af.2)

’

IA v WI (Kg.M./min.l Al.?)

3.58 4.10 4 10 3.51 4.39 3.88 4.37 3.89

51 41 31 2.5 40 32 31 21

108 110 108 110 107 110 103 98

23 26 30 31 28 ,30 3I 35

2 (

880 3,000 3,350 3,560 3,050 3,300 3,250 3,460

2,420 2,140 2,110 2,490 1,950 2,260 1,890 2,010

1.58 158 136 114 157 129 140 111

5.28 6.18 6.05 5.35 6.50 5.83 0.15 5.15

\v.c., 32

82 100 “12.5 *132 *150 *130fY *1331\ *14s!l

3 44 3.79 3.80 3 82 3.55 3.79 3.64 3.26

42 38 30 28 24 28 27 22

101 100 102 104 99 103 101 106

25 26 30 32 33 30 31 32

2,670 2,700 3,200 3,380 3.520 3.240 3.410 3,520

2,320 2,110 2,140 2,180 2,240 2,160 2,200 2,650

137 145 129 118 108 123 118 102

4.74 5.17 5.30 5.30 -1.80 5.20 5.01 4.75

G.I.., 44

100 110 *130 150 *134.fI 138A

5.26 5.28 4.72 5.28 5.42 5.39

53 48 36 35 41 39

107 107 107 98 95 95

27 29 32 34 31 31

3,020 3,180 3,060 3,400 3,350 3,410

1,640 1,640 1 ,830 1,500 1,110 1,420

194 180 149 157 178 174

7.72 7.78 7 no 7 05 7.00 6 95

generally been made. In a study of the effect of atropine on coronary blood flow, Gorlin7 found that myocardial oxygen consumption per systolic second was unchanged by atropine, thus implying that the effect of atropine was solely related to its chronotropic property. Atria1 pacing provides a safe and effective means of producing increased heart rates. The impulses from the atrium are conducted through the A-V node and depolarize the ventricles in a normal fashion,l’i thus simulating sinus rhythm. Ross and associates,l and Stein and coworker2 have shown that alterations in heart rate within the physiologic range produce no change in the hemodynamic state. It is possible, therefore, to compare cardiac dynamics at similar heart rates obtained by atria1 pacing and by atropine to determine whether atropine has any effects other than those related to its chronotropic property.

In the present study, we found that the changes in cardiac dynamics produced by a dose of atropine sufficient to completely eliminate parasympathetic activityI were limited to those parameters which are directly influenced by changes in heart rate, i.e., SET, TTI, SI, and XlSER. Those parameters which have been shown to be independent of heart rate, i.e., CI, LVWI, and TPR, remained unchanged. Braunwald and associates’” have described the effect of sympathomimetic amines on shortening of the SET. Since the systolic ejection times at comparable heart rates before and after atropine are almost identical, one can infer that there is no unmasking of sympathetic activity, and that, therefore, there is no parasympathetic tone acting to control this parameter under normal conditions. Atropine resulted in no change in TTI at comparable heart rates. In so far as the TTI reflects myocardial oxygen consumption, this confirms

CONTROL

AT”OCIN4

9-b

1

I

I& ‘------Y

00

80

HEART

RATE IbaotWmin.)

100

120

140

60

HEART

?z

6000

;

4000

r K a z

100

120

100

120

140

160

ATROPINC

CONTROL

60

60

100

140

120

60

140

160

RATE (b.at.lmin.1

CONTROL

3000

g * 6 : f

2ooc

1ooc

60

80

HEART

RATE (C~w~lmln.1

100

120

140

80

100

120

140

160

Hemodynnmic

Gorlin’s findings. The RISER has been used to describe left ventricular function because it is believed to reflect the velocity of muscle shortening.‘” Its validity has l)een questioned under conditions in which the ventricular volume is changed,* and, therefore, comparisons of AISER at different heart rdteS cannot be evaluated. In this study, the 1ISER was unchanged I)y atropine at similar heart rates and stroke volumes. On the assumption that no significant change in ventricular volume occurred, this implies that atropine has no effect on left ventricular function. In conclusion, the major effect of parasympathetic blockade with atropine in normal human beings is an increase in heart rate. Any alterations in the parameters that were studied can be accounted for on the basis of change in heart rate alone. ,L\lthough the effects of vagolytic intervention on atria1 function have not yet been studied, it is apparent that blockade of parasympathetic tone in normal subjects has no significant effect on cardiovascular hemodynamics. Summary

Cardiac outputs and arterial pressures were obtained in 9 normal subjects in whom various degrees of tachycardia were induced b\r atria1 pacing before and after the intravenous administration of 2 mg. of atropine. At similar heart rates, atropine produced no change in cardiac index, stroke index, brachial arterial pressure, systolic ejection time, tension time index, total peripheral resistance, mean systolic ejection rate, or left ventricular work index. It is apparent that the effects of atropine on cardiovascular hemodynamics are limited to those related to its chronotropic effect. \Ve gratefully acknowledge the i\. Pedersen, J. Gumming, L. Carcv, ‘1‘. Halloran, and F. DaCasto.

1.

assistance of M. Moretti,

REFERENCES Ross, J., Jr., Linhart, J. I\:., and Braunwald, E.: Effects of changing heart rate in man b! electrical stimulation of the right atrium: Studies at rest, during exercise and with ieoproterellol. Gin-rllatioll 32:549, 196s.

efects of tnrhyccvdir~

599

2. Stein, El., Lister, J. \1:., Kosowsky, B. D.. Lau, S. H., and Damato, A. N.: Heart rate in man, hemodynamic studies at rest and at exercise, (abstract) Clin. Res. 13:221, 1965. .3. Sarnoff, S. J., Braunwald, E., \Velch, G. H., Jr., Case, 1~. B., Stainsby, \V. N., and Macruz, Ii. : Hemod) namic determinants of oxygen consumption of the heart, with special reference to the tension-time index, Am. J. Physiol. 192:119, 1958. H. G., and Bayliss, K. I. S.: Influence 4. Kelly, of heart rate on cardiac output: Studies with digoxin and atropine, Lancet 2:1071, 1949. 5. \Veissler, A. M., Leonard, J. J., and \Varren, J. \:.: Effects of posture and atropine on the cardiac outpllt, J. Clin. Invest. 36:1656, 1957. 6. Berr!., J. N., Thompson, H. K., Jr., Miller, D. E., and McIntosh, H. I>.: Changes in cardiac output, stroke volume and central venous pressure induced by atropine in man, AX. H~., Lau. S. H., and Damato. A. N.: Atrioventricular conduction in man: Effect of rate, exercise, ’Isoproterenol and atropine on the P-R interval, Am. J. Cardiol. 16:516, 1965. 14. Craig, F. N.: Effects of atropille, work, and heat on heart rate and sweat production in mall, J. Appl. Physiol. 4:826, 1952. 15. Braunwald, E., Sarnoff, S. J., and Stainsby, \V. N.: Determinants of duration and mean rate of ventricular ejection, Circulation Rcs. 6:319, 1958. 16. Levine, H. S., .Ueill, IV. A., \Vagman, R. J., Krxsnow. N.. and Gorlin. 12.: The effect of ex_.

II