Scand. J. clin. Lab. Invest. 39, 79-85, 1979.
Cardiac performance: optimal heart rate for maximal cardiac output
Scand J Clin Lab Invest Downloaded from informahealthcare.com by Mcgill University on 11/04/14 For personal use only.
A R N F I N N ILEBEKK, MALFRID MOLAUG MILLER, J 0 R G E N THORVALDSON & F R E D R I K K I I L University of Oslo, Institute for Experimental Medical Research, Ullevaal Hospital, Oslo, Norway
Ilebekk, A., Miller, M. M., Thorvaldson, J. & Kiil, F. Cardiac performance: optimal heart rate for maximal cardiac output. Scand. J. din. Lab. Invest. 39, 79-85, 1979.
To determine optimal heart rate for the maximal cardiac output at various levels of inotropy and blood volume, the relationship between heart rate (HR) and stroke volume (SV) was examined in anaesthetized dogs during right atrial pacing. Myocardial inotropy was raised by intravenous infusion of isoproterenol, a stimulator of adrenergic 8-receptors, and reduced by propranolol, an inhibitor of adrenergic &receptors. Circulating blood volume was increased by saline infusion. Within the range of optimal heart rate, SV and HR were inversely related: SV = k (HRo-HR), where k indicates the relationship between changes in SV and HR. The intercept with the H R axis is HR,. At constant HR a rise in inotropy increased SV and a fall in inotropy reduced SV. These changes in S V were equal at every HR, and k was therefore constant. In contrast, blood volume expansion increased SV more at low than at high HR (k increased), but HR, was not significantly changed. Calculated maximal cardiac output: k .HRoZ/4,and optimal heart rate: HRo/2, agreed with observations when maximal cardiac output was raised from 1900 to 4500 ml/min by increasing blood volume and inotropy. Optimal HR was not influenced by changes in blood volume, but was increased from 160 to 200 beatslmin by increasing inotropy. We conclude that the optimal heart rate and the maximal cardiac output can be predicted from the linear relationship between SV and HR during right atrial pacing. Key-words: blood volume; myocardial inotropy ; isoproterenol; propranolol; right atrial pacing; stroke volume A. Ilebekk, M .D., University of Oslo, Institute for Experimental Medical Research,
Ullevaal Hospital, Oslo 1, Norway
Cardiac output can be increased in response to the body’s need for increased blood supply by a rise in heart rate and stroke volume. However, 0036-55 I3/79/0200-0079 $ 02.00 431979 Medisinsk Fysiologist Forenings Forlag
stroke volume decreases when heart rate is increased in man and dog above 60-100 beats/ min by right atrial- or ventricular pacing [4,6-8, 11,13,14], but cardiac output, the product of stroke volume and heart rate, may continue to 79
80
Arnfinn Ilebekk et al.
increase. At a certain heart rate, called the optimal heart rate, cardiac output becomes maximal. A further increase in heart rate does not compensate for the fall in stroke volume and cardiac output is reduced. Provided there is a linear decrease in stroke volume when heart rate is increased [6,7,13,14], the relationship between stroke volume (SV) and heart rate (HR) can be expressed as:
Scand J Clin Lab Invest Downloaded from informahealthcare.com by Mcgill University on 11/04/14 For personal use only.
SV
=
k(HRo-HR)
(1)
where k is a constant, indicating the ratio between changes in stroke volume and heart rate, and HRo is the extrapolated heart rate at which stroke volume becomes zero. Cardiac output can be written accordingly: CO = k (HR’HRo -HR*).
(2)
Optimal heart rate is obtained by derivation: kHRo -2kHR = 0. Consequently, optimal heart rate is HRo/2 and maximal cardiac output is k *HRo2/4. The first object of the present study in anaesthetized dogs was to examine during right atrial pacing at increasing frequencies, whether the predicted and observed optimal heart rates coincide. Available information suggests that optimal heart rate increases whether venous return is raised by increasing inotropy or by expanding blood volume [3,15]. If optimal heart rate equals HR0/2 this is possible only if a rise both in preload and in inotropy increases HRo. To examine this possibility stroke volume was measured during right atrial pacing over a wide range of heart rates at control inotropy, during high inotropy induced by intravenous infusion of isoproterenol, and at low inotropy induced by propranolol administration. Blood volume was increased with saline infusions and the relationship between cardiac output and heart rate was examined in right atrial pacing experiments before and after blood volume expansion both at control and high inotropy.
METHODS Animal preparation. Fourteen mongrel dogs of either sex, weighing 12-27 kg, were anaesthetized with sodium pentobarbital, 25 mg/kg body wt, and ventilated with a positive pressure respirator (Cyclator Mark 11, British Oxygen Co,
London, England). The heart was exposed by thoracotomy in the fifth left intercostal space and suspended in a pericardial cradle. Throughout the experiments, arterial blood was examined for pH, P C O , and p o , by means of an automatic pH-blood gas analyser (Model 313, Instrumentation Laboratory Inc., Lexington, Mass.); appropriate measures were taken to keep the blood gases normal. The right atrium was paced with square-wave pulses of 1 ms duration at an effective voltage of 1.5-3 V using a Grass stimulator (Model S4G, Grass Instrument Co, Quincy, Mass.). Haemodynamic measurements. Left ventricular pressure was measured by a Statham P23Gb transducer connected to a short polyethylene catheter introduced through the left ventricular apex. Phasic blood flow in the ascending aorta was measured by an electromagnetic squarewave flowmeter (Model 367, Nycotron, Drammen, Norway). Left ventricular stroke volume (SV), coronary flow excluded, was determined by beat-to-beat integration of the flow signals. Pressure and flow with derivatives, were continuously recorded on a Sanborn multichannel oscillograph. Experimental procedure. Two series of experiments were performed. In the first series, the effects of changes in inotropy on the stroke volume and cardiac output-heart rate relationships were examined. Heart rate was increased in steps of 25 beats/min by right atrial pacing until pulsus alfernans appeared. This procedure was undertaken in eight dogs at control inotropy and during continuous isoproterenol infusion (0.2-0.3 fig/kg.min) and in four of these dogs after blockade of adrenergic 8-receptors induced by intravenous administration of propranolol (0.5 mglkg). Tn the second series of experiments in six dogs, circulating blood volume was increased by infusion of saline (0.9% NaCI). Heart rate was increased in steps of 10 beatslmin both before and after expansion of the blood volume. During the pacing experiments, maintenance infusions kept blood volume constant, as signified by the return of stroke volume to control values after stopping right atrial pacing. Surplus body fluid was then removed by an intravenous injection of 20-40 mg furosemide and after 1 h, pacing experiments were repeated during continuous
Heart rate and maximal cardiac output
lcfin
1
D lsoproterenol 0 Control DPropranolol
81
isoproterenol infusion before and after blood volume expansion.
.
Statistics. Each dog served as its own control. Wilcoxon's test for paired data was used to calculate probability values (P)[5]. A value of P>0.05 was regarded as not statistically significant.
Scand J Clin Lab Invest Downloaded from informahealthcare.com by Mcgill University on 11/04/14 For personal use only.
RESULTS
%\ "4
10 5
4 b
I
2do
ILO
250
360
Heart rate ( beatslmin)
FIG. 1. Relationship between cardiac output and heart rate (upper panel) and between stroke volume and heart rate (lower panel) during atrial pacing. The calculated maximal cardiac output and the corresponding optimal heart rate are indicated by black triangles. Mean+ SE of experiments in eight dogs (stippled line: seven dogs) at control inotropy and during isoproterenol infusion, and four dogs (stippled line: three dogs) after propran0101 administration.
Figure 1 (lower panel) shows almost linear relationships between stroke volume and heart rate at high, control and low inotropy. In individual experiments the correlation coefficient of the relationship SV = k(HRo-HR) averaged -0.98+0.01, the slope of the regression line given by k was not significantly different at the three levels of inotropy, indicating that the regression lines are parallel. HRo which is the calculated heart rate when stroke volume is zero, averaged 300, 344 and 396 beatslmin, respectively at low, control and high inotropy. Optimal heart rate (HR,/2) should therefore be 150, 172 and 198 beatsimin, whereas the observed optimal heart rates averaged 160, 180 and 200 beatsimin at low, control and high inotropy, respectively. Observed and calculated optimal heart rates were not significantly different. Figure 1 (upper panel) shows that observed and calculated maximal cardiac output were not significantly different and averaged 1900 and
TABLE I. Coefficients in equation SV = k(HRo- HR). Calculated and observed optimal heart rate and maximal cardiac output at control inotropy and during isoproterenol infusion (0.2-0.3 / r g / k g . min) before and after blood volume expansion Optimal heart rates = HR,/2
k Control inotropy Control Expansion Change
P i Isoproterenol Control Expansion Change
P
Cardiac performance: optimal heart rate for maximal cardiac output
Scand J Clin Lab Invest Downloaded from informahealthcare.com by Mcgill University on 11/04/14 For personal use only.
A R N F I N N ILEBEKK, MALFRID MOLAUG MILLER, J 0 R G E N THORVALDSON & F R E D R I K K I I L University of Oslo, Institute for Experimental Medical Research, Ullevaal Hospital, Oslo, Norway
Ilebekk, A., Miller, M. M., Thorvaldson, J. & Kiil, F. Cardiac performance: optimal heart rate for maximal cardiac output. Scand. J. din. Lab. Invest. 39, 79-85, 1979.
To determine optimal heart rate for the maximal cardiac output at various levels of inotropy and blood volume, the relationship between heart rate (HR) and stroke volume (SV) was examined in anaesthetized dogs during right atrial pacing. Myocardial inotropy was raised by intravenous infusion of isoproterenol, a stimulator of adrenergic 8-receptors, and reduced by propranolol, an inhibitor of adrenergic &receptors. Circulating blood volume was increased by saline infusion. Within the range of optimal heart rate, SV and HR were inversely related: SV = k (HRo-HR), where k indicates the relationship between changes in SV and HR. The intercept with the H R axis is HR,. At constant HR a rise in inotropy increased SV and a fall in inotropy reduced SV. These changes in S V were equal at every HR, and k was therefore constant. In contrast, blood volume expansion increased SV more at low than at high HR (k increased), but HR, was not significantly changed. Calculated maximal cardiac output: k .HRoZ/4,and optimal heart rate: HRo/2, agreed with observations when maximal cardiac output was raised from 1900 to 4500 ml/min by increasing blood volume and inotropy. Optimal HR was not influenced by changes in blood volume, but was increased from 160 to 200 beatslmin by increasing inotropy. We conclude that the optimal heart rate and the maximal cardiac output can be predicted from the linear relationship between SV and HR during right atrial pacing. Key-words: blood volume; myocardial inotropy ; isoproterenol; propranolol; right atrial pacing; stroke volume A. Ilebekk, M .D., University of Oslo, Institute for Experimental Medical Research,
Ullevaal Hospital, Oslo 1, Norway
Cardiac output can be increased in response to the body’s need for increased blood supply by a rise in heart rate and stroke volume. However, 0036-55 I3/79/0200-0079 $ 02.00 431979 Medisinsk Fysiologist Forenings Forlag
stroke volume decreases when heart rate is increased in man and dog above 60-100 beats/ min by right atrial- or ventricular pacing [4,6-8, 11,13,14], but cardiac output, the product of stroke volume and heart rate, may continue to 79
80
Arnfinn Ilebekk et al.
increase. At a certain heart rate, called the optimal heart rate, cardiac output becomes maximal. A further increase in heart rate does not compensate for the fall in stroke volume and cardiac output is reduced. Provided there is a linear decrease in stroke volume when heart rate is increased [6,7,13,14], the relationship between stroke volume (SV) and heart rate (HR) can be expressed as:
Scand J Clin Lab Invest Downloaded from informahealthcare.com by Mcgill University on 11/04/14 For personal use only.
SV
=
k(HRo-HR)
(1)
where k is a constant, indicating the ratio between changes in stroke volume and heart rate, and HRo is the extrapolated heart rate at which stroke volume becomes zero. Cardiac output can be written accordingly: CO = k (HR’HRo -HR*).
(2)
Optimal heart rate is obtained by derivation: kHRo -2kHR = 0. Consequently, optimal heart rate is HRo/2 and maximal cardiac output is k *HRo2/4. The first object of the present study in anaesthetized dogs was to examine during right atrial pacing at increasing frequencies, whether the predicted and observed optimal heart rates coincide. Available information suggests that optimal heart rate increases whether venous return is raised by increasing inotropy or by expanding blood volume [3,15]. If optimal heart rate equals HR0/2 this is possible only if a rise both in preload and in inotropy increases HRo. To examine this possibility stroke volume was measured during right atrial pacing over a wide range of heart rates at control inotropy, during high inotropy induced by intravenous infusion of isoproterenol, and at low inotropy induced by propranolol administration. Blood volume was increased with saline infusions and the relationship between cardiac output and heart rate was examined in right atrial pacing experiments before and after blood volume expansion both at control and high inotropy.
METHODS Animal preparation. Fourteen mongrel dogs of either sex, weighing 12-27 kg, were anaesthetized with sodium pentobarbital, 25 mg/kg body wt, and ventilated with a positive pressure respirator (Cyclator Mark 11, British Oxygen Co,
London, England). The heart was exposed by thoracotomy in the fifth left intercostal space and suspended in a pericardial cradle. Throughout the experiments, arterial blood was examined for pH, P C O , and p o , by means of an automatic pH-blood gas analyser (Model 313, Instrumentation Laboratory Inc., Lexington, Mass.); appropriate measures were taken to keep the blood gases normal. The right atrium was paced with square-wave pulses of 1 ms duration at an effective voltage of 1.5-3 V using a Grass stimulator (Model S4G, Grass Instrument Co, Quincy, Mass.). Haemodynamic measurements. Left ventricular pressure was measured by a Statham P23Gb transducer connected to a short polyethylene catheter introduced through the left ventricular apex. Phasic blood flow in the ascending aorta was measured by an electromagnetic squarewave flowmeter (Model 367, Nycotron, Drammen, Norway). Left ventricular stroke volume (SV), coronary flow excluded, was determined by beat-to-beat integration of the flow signals. Pressure and flow with derivatives, were continuously recorded on a Sanborn multichannel oscillograph. Experimental procedure. Two series of experiments were performed. In the first series, the effects of changes in inotropy on the stroke volume and cardiac output-heart rate relationships were examined. Heart rate was increased in steps of 25 beats/min by right atrial pacing until pulsus alfernans appeared. This procedure was undertaken in eight dogs at control inotropy and during continuous isoproterenol infusion (0.2-0.3 fig/kg.min) and in four of these dogs after blockade of adrenergic 8-receptors induced by intravenous administration of propranolol (0.5 mglkg). Tn the second series of experiments in six dogs, circulating blood volume was increased by infusion of saline (0.9% NaCI). Heart rate was increased in steps of 10 beatslmin both before and after expansion of the blood volume. During the pacing experiments, maintenance infusions kept blood volume constant, as signified by the return of stroke volume to control values after stopping right atrial pacing. Surplus body fluid was then removed by an intravenous injection of 20-40 mg furosemide and after 1 h, pacing experiments were repeated during continuous
Heart rate and maximal cardiac output
lcfin
1
D lsoproterenol 0 Control DPropranolol
81
isoproterenol infusion before and after blood volume expansion.
.
Statistics. Each dog served as its own control. Wilcoxon's test for paired data was used to calculate probability values (P)[5]. A value of P>0.05 was regarded as not statistically significant.
Scand J Clin Lab Invest Downloaded from informahealthcare.com by Mcgill University on 11/04/14 For personal use only.
RESULTS
%\ "4
10 5
4 b
I
2do
ILO
250
360
Heart rate ( beatslmin)
FIG. 1. Relationship between cardiac output and heart rate (upper panel) and between stroke volume and heart rate (lower panel) during atrial pacing. The calculated maximal cardiac output and the corresponding optimal heart rate are indicated by black triangles. Mean+ SE of experiments in eight dogs (stippled line: seven dogs) at control inotropy and during isoproterenol infusion, and four dogs (stippled line: three dogs) after propran0101 administration.
Figure 1 (lower panel) shows almost linear relationships between stroke volume and heart rate at high, control and low inotropy. In individual experiments the correlation coefficient of the relationship SV = k(HRo-HR) averaged -0.98+0.01, the slope of the regression line given by k was not significantly different at the three levels of inotropy, indicating that the regression lines are parallel. HRo which is the calculated heart rate when stroke volume is zero, averaged 300, 344 and 396 beatslmin, respectively at low, control and high inotropy. Optimal heart rate (HR,/2) should therefore be 150, 172 and 198 beatsimin, whereas the observed optimal heart rates averaged 160, 180 and 200 beatsimin at low, control and high inotropy, respectively. Observed and calculated optimal heart rates were not significantly different. Figure 1 (upper panel) shows that observed and calculated maximal cardiac output were not significantly different and averaged 1900 and
TABLE I. Coefficients in equation SV = k(HRo- HR). Calculated and observed optimal heart rate and maximal cardiac output at control inotropy and during isoproterenol infusion (0.2-0.3 / r g / k g . min) before and after blood volume expansion Optimal heart rates = HR,/2
k Control inotropy Control Expansion Change
P i Isoproterenol Control Expansion Change
P
