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Cardiovascular response to fluid loading
3 Cardiovascular response to fluid loading M. I. M. N O B L E
T h e p u r p o s e o f this c h a p t e r is t o p r e s e n t a c o n c e p t u a l f r a m e w o r k o f m e c h a n i c a l m y o c a r d i a l e v e n t s t a k i n g p l a c e d u r i n g fluid l o a d i n g . T h e s e e v e n t s a r e b e s t i l l u s t r a t e d b y s t u d y i n g fluid l o a d i n g in t h e d e n e r v a t e d h e a r t ( F i g u r e 1). 2o
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TIME (mini SALINE INFUSION STARTED Figure 1. Effect of intravenous infusion of isotonic saline in a cardiac denervated dog. LVEDP: changes in left ventricular end-diastolic pressure from arbitrary zero. CVP: central venous pressure measured from an implanted venous catheter. CO: cardiac output, SV: stroke volume, M A : maximum acceleration of blood from the left ventricle, all measured from an implanted electromagnetic flowmeter with transducer around the ascending aorta. LVdP/dtmax: maximum rate of rise of left ventricular pressure which, together with LVEDP, was measured from a micromanometer implanted in the left ventricle. HR: heart rate. The gradual heart rate increase also occurs in isolated hearts and is due to stretch-induced activation of sinus node cells, giving a faster rise of diastolic depolarization and increased frequency of firing. In innervated hearts, reflex tachycardia is added. Note the greater rise in LVEDP (which is followed by left atrial pressure, pulmonary venous pressure and wedge pressure) than occurs in CVP. Stroke volume and cardiac output are markedly increased. From Noble et al (1972) with permission.
Bailli~re's ClinicalAnaesthesiology--Vol. 2, No. 3, September 1988
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Fluid loading causes a marked rise in cardiac output accompanied by increases in central vascular pressures. In innervated hearts this response may be complicated by an overlay of reflex tachycardia. The basis of this ventricular mechanical response is best understood within the framework of the pressure-volume diagram (Weber et al, 1976; Sagawa, 1978). THE P R E S S U R E - V O L U M E RELATIONSHIP
I put this concept forward as the basic concept for consideration of cardiac mechanical function (Figure 2). It dates back to the classical work of Frank in the last century (Frank, 1895). The relationship depends on the fact that the force developed by the cardiac muscle in the ventricular wall increases with fibre length (in reality the sarcomere length: Kentish et al, 1986) while the pressure developed in the cavity depends on both this force and the cavity dimensions according to the La Place relationship (Figure 3). For this reason isovolumic pressure increases less than force with increasing volume, giving a curvilinear relationship; the same considerations apply to the relationship between the maximum rate of rise of pressure in the left ventricle (dP/dt) and left ventricular volume (Figure 2). The isovolumic pressure-volume relationship has now been defined in dogs. It was found that the left ventricle ejected down to the volume from which it would have developed the same pressure isovolumically: see the pressure-volume loop in Figure 4 at the end of ejection (Weber et al, 1976; Sagawa, 1978). If the pressure at which ejection occurs is changed, the left
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Figure 2. Relationship of left ventricular isovolumic pressure development (11) and maximum rate of rise of left ventricular pressure, dP/dt (0), to left ventricular volume.
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Figure 3. Schematic representation of a cut half of the left ventricle. The pressure developed in the cavity is the force developed in the wall divided by the cavity cross-sectional area (a, cross-hatched). The maximum rate of rise of isovolumic pressure is the maximum rate of rise of wall force divided by a. Adapted from Hefner et al (1962).
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Figure 4. The isovolumic pressure-volume curve (Figure 2) is also inscribed at the end of ejection. Continuous-line loop No. 1 shows the four phases of the cardiac cycle: filling along the diastolic pressure-volume curve at the bottom, isovolumic contraction (vertically pointing upwards at the right), ejection (horizontal arrow to the left) and isovolumic relaxation (vertical arrow pointing downwards at the left). Other points on the curve are determined by finding the end-ejection points at other ejection pressures, e.g. dashed loop No. 2.
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ventricle ejects down to a new point on the isovolumic curve (see second loop in Figure 4). Thus, the isovolumic and end-ejection pressure-volume relationships proved to be the same and to characterize the contractility of the muscle (Figure 4). This experiment cannot be done in man without cardiopulmonary bypass and has not been done as far as I am aware. However, we can still say that the end-ejection pressure-volume relationship characterizes contractility in man (Noble, 1979). Whereas the pressurevolume curve is normally inscribed at end-ejection (end-systolic volume), where the relationship has a positive slope, the dP/dt-volume curve is inscribed at end-diastolic volume (isovolumic contraction period); this relationship has a positive slope only under hypovolaemic conditions, being flat under normal conditions (Drake-Holland et al, 1988). Stimulation of the heart's contractility shifts the curves upward and to the left, while negative inotropic effects and depressed myocardial contraction shift the relationship to the right. Failure of the left ventricle to eject right down to the pressure-volume line occurs under the following circumstances, all of which arise because the dimension of time is removed from a pressure-volume loop. Thus they all occur when the ventricle does not have enough time to get to its targeted end-point at end-ejection. 1.
2.
3. 4.
With the very highest ejection pressures (see data in Weber et al, 1976). This is because the force-velocity curve of heart muscle is inverse (Abbott and Mommaerts, 1959; Daniels et al, 1984) so that at high shortening loads the velocity of shortening is very low and therefore there is insufficient time for the ventricle to reach the pressure-volume line even though it can do so at all lower pressures (Weber et al, 1976). Sometimes with extreme filling in diastole. This may entail a large stroke volume to be ejected, which takes a longer time. However, if this occurs in the normal range of stroke volume, it implies myocardial insufficiency because the normal heart ejects 1 ml extra stroke volume for every 1 ml increase in end-diastolic volume (Noble et al, 1969b), as would be predicted from Figure 5. Therefore, in this circumstance, a shift to the right still implies depression of contraction. When velocity of shortening is depressed because, for a lower velocity, more time is needed to achieve the same shortening. Again, this implies depression of contraction. Extreme abbreviation of ejection time. In practice this occurs only with abnormally early onset of relaxation under extreme adrenergic stimulation (when the control curve is left-shifted anyway) or when the isovolumic contraction time is unduly prolonged, as in incoordinated activation (left bundle branch block etc.), which again implies depression of myocardial contraction.
Thus, in spite of such problems, the end-ejection pressure-volume curve still comes up as a reliable index of myocardial contractile performance. The increase in stroke volume that accompanies fluid infusion (Figure 1) occurs as a result of the changes in the pressure-volume loop depicted in Figure 5.
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Figure 5. The effect of increased filling (dashed loop No. 2) compared with continuous loop No. 1) on the pressure-volume diagram. Stroke volume increases by the same increment as end-diastolic volume.
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Figure 6. The pressure-volume diagram in hypovolaemia (dashed loop H), i.e., hypotension and small left ventricular volumes. Fluid infusion restores loop to normal (continuous loop N).
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THE EFFECT OF FLUID L O A D I N G ON THE P R E S S U R E V O L U M E D I A G R A M IN THE N O R M A L H E A R T
Fluid loading is often required for the treatment of low cardiac output due to hypovolaemia or decreased central blood volume due to peripheral blood pooling. In such circumstances one may be dealing with a normal heart, i.e., one in which the end-ejection pressure-volume line is normal but the loop is as illustrated in Figure 6. In this case, stroke output is low simply because end-diastolic volume is low, in spite of enhancement of stroke volume by low arterial pressure. The low filling is correctly indicated by the low enddiastolic pressure, and correction of the situation by fluid loading back to a normal end-diastolic pressure is theoretically straightforward. HOW SHOULD FLUID LOADING BE MONITORED? If such fluid loading is continued to excess, left-sided vascular pressures (left ventricular end-diastolic, left atrial, pulmonary venous) rise very much more than the corresponding right-sided pressures because the left vascular compartment has much less capacity; it is as if it were much stiffer. It is therefore possible to overload with fluid to the point where high pulmonary venous pressure causes dyspnoea and eventually pulmonary oedema. Such very high left ventricular diastolic pressures can impair the diastolic filling of microvessels in the subendocardium, leading to subendocardial ischaemia (Buckberg et al, 1972) and an actual depression of ventricular mechanical function (pressure-volume curve shifted to the right). All of these effects are obviously undesirable and can be prevented by measuring a suitable leftsided pressure and stopping the fluid loading when this has reached a certain level. Such information cannot be reliably obtained from a right-sided pressure such as central venous pressure, because the greater compliance of the right compartment takes up excess fluid at much lower pressures which will not be interpreted as dangerous. WEDGE PRESSURE A N D S T R O K E V O L U M E BY S W A N - G A N Z
THERMODILUTION CATHETER The left pressure used clinically is the pulmonary capillary wedge pressure (PCWP). Intravenous catheters with a balloon inflated at the tip will be carried, by the bloodstream acting on the balloon, into the pulmonary artery and wedge in a branch. A lumen distal to the balloon transmits a pressure similar in magnitude to left atrial pressure. This can be done alone, but additional information is obtained with thermal sensors on the catheter to permit cardiac output measurements by thermodilution (Swan et al, 1970). I emphasize stroke volume rather than cardiac output (the primary measurement with this method) to keep the physician oriented as far as possible within the pressure-volume thinking framework. If an ejection fraction measurement is available (usually from a nuclear method: Muir et al,
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1977) one can calculate end-diastolic volume (LVEDV = stroke volume divided by ejection fraction). If wedge pressure is taken as an indication of left ventricular end-diastolic pressure, and systolic arterial pressure as an indication of ejection pressure, one now has an idea of three points on the pressure-volume loop (bottom right, top right, top left). If ejection fraction measurements are lacking, similar information can be obtained from an echocardiographic estimate of end-diastolic ventricular diameter (LVEDD) (Gibson, 1973). It is then possible to assess whether wedge pressure is appropriate for the L V E D V or L V E D D . If, for instance, the wedge pressure is relatively normal in spite of high L V E D V or L V E D D , it can be concluded that the patient has pre-existing chronic depression of left ventricular mechanical function leading to chronic distension of the ventricle and a rightward shift of the diastolic pressure-volume curve, i.e., increased diastolic distensibility (Figure 7). Further changes in the acute situation and response to therapy can then be assessed in relation to this base-line.
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Figure 7. Chronic cardiac failure. The pressure-volume curve is shifted downwards and to the right (O) compared with normal (B). Stroke volume is maintained but is a smaller fraction of much increased end-diastolic volume (low ejection fraction). If the ventricle becomes more compliant in diastole as the result of chronic distension, as shown here, the response to fluid loading may be relatively normal.
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Other indices based upon the S w a n - G a n z method
There was a vogue at one time for plotting stroke work against wedge pressure (so-called 'function curves': Sarnoff and Mitchell, 1962). This procedure isof limited value compared to the approach I am putting forward above. Stroke work (stroke volume times arterial pressure) is highly dependent on arterial pressure with a bell-shaped function that will cause considerable confusion when stroke work is used alone. An increase in stroke work achieved by increasing arterial pressure with consequent lowering of stroke volume is quite likely to be a retrograde therapeutic manoeuvre. PCWP or LVEDP are misleading indices to plot on the abscissa of a 'function curve' because (1) the resulting curves are very distorted by the curvature of the diastolic pressure-volume relationship (Noble, 1978), and (2) the PCWP may be decreased by the chronic increase in diastolic distensibility described above. The frequently used term 'preload' originates from isolated muscle experiments done two decades ago (Abbott and Mommaerts, 1959; Sonnenblick, 1962). At that time the apparatus was too crude to allow setting the diastolic sarcomere length (ter Keurs et al, 1980), or even the initial muscle length (Noble et al, 1969b). Therefore, the muscle was hung vertically with a weight on the bottom to produce the necessary diastolic stretch indirectly. This load was in series with, and therefore proportional to, the end-diastolic force or stress (force/cross-sectional area) measured in appropriate units (N, or N/mm2). The inappropriateness of applying this to the intact heart can be understood from the following considerations. 1. 2.
3. 4. 5.
End-diastolic wall stress is not the primary determinant of systolic performance; the primary determinant is sarcomere length. The nearest equivalent to end-diastolic sarcomere length in the intact heart is the end-diastolic fibre length, and the nearest practical measurement is the end-diastolic volume (see presentation of the pressurevolume relationship above). Even end-diastolic pressure is not a good index of end-diastolic volume because of the non-linear diastolic pressure-volume curve (above) and variable diastolic distensibility (above). The relationship of end-diastolic pressure to wall stress is complex. Measurement of wall stress can be attempted only in the exposed heart, but even then the validity has been challenged (Huisman, 1977).
It is clear then that preload, i.e. end-diastolic wall stress, is never measured or calculated clinically, and the use of the term is ambiguous. There seems to be little reason for not using a term which refers to various measurements-e.g. end-diastolic volume, end-diastolic pressure, wedge pressure---each of which has a precise definition. Preload is a jargon term which should be eliminated from the clinician's vocabulary. The term afterload originated from the same crude early isolated muscle experiment that used preloads. In this case, an extra weight was attached to the bottom of the muscle that was resting on a stop. As soon as the muscle
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was activated it could not shorten until it developed a systolic force or stress greater than the weight. The muscle then shortened and lengthened against this 'afterload' during systole. The inappropriateness of applying this term to the intact heart can be understood from the following considerations. 1. 2. 3.
The heart does not expand against a high force because the aortic valve closes at the end of muscle shortening. Systolic wall stress cannot be measured or calculated in the intact heart of a patient for the same reasons that applied to preload (see above). Systolic wall stress is not constant throughout ejection (Hefner et al, 1962; Lewartowski et al, 1972), but falls off from an early peak in ejection to ever-declining values as ejection proceeds. What then is the afferload? Peak afferload? Mid systolic afferload? Afterload averaged over the ejection period? Wall stress averaged over the whole of systole including isovolumic contraction and relaxation?
There seems to be some confusion between 'load' (which is always measured as a force or stress) and pressure, and between 'load' and resistance or impedance (Milnor, 1975). However, the latter is measured in completely different dimensions and has only an indirect interaction with the heart. These objections are based on the observation that these terms are often applied to treatment ('preload reduction', 'afterload reduction') with wholly inappropriate clinical consequences. D E T E R M I N A N T S OF W E D G E PRESSURE
The foregoing diversion serves to emphasize the fact that wedge pressure is not a determinant of left ventricular performance but, as discussed in the case of overloading a normal heart with fluid (above), it is an indication of the limit to which one can go with fluid infusion. It is therefore necessary to consider the determinants of wedge pressure in addition to filling itself. These factors are, in effect, also the dangers and contraindications of fluid-loading therapy. Left ventricular diastolicpressure-volume relationship seems to be a more appropriate term than 'compliance' because the latter is the slope of the diastolic pressure-volume curve and is almost irrelevant in practical terms. The real issue is: is left ventricular end-diastolic pressure high, normal or low at normal end-diastolic volume? For practical purposes this tells the clinician whether the left ventricle will behave as if stiff, normal or compliant, respectively. Stiff behaviour (Figure 8) is very important in the context of fluid loading because high wedge pressures are reached early, perhaps before one can attain the desired cardiac output and arterial pressure. Under these circumstances it is imperative to take alternative action to maintain fluid loading with no further wedge pressure increase. One possibility is to shift the end-ejection pressure-volume curve to the left by a positively inotropic drug; however, this is much less effective if the contractility is normal than if
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Figure 8. Effect of increased diastolic stiffness, e.g. as the result of left ventricular hypertrophy (loop 2 compared to loop 1). A higher end-diastolic pressure, arrowed (and left atrial pressure, pulmonary venous pressure, and wedge pressure), occurs at normal filling volume. Fluid infusion is limited because of the greater incidence of pulmonary oedema following an excessive rise of pulmonary venous pressure.
it is depressed. A second possibility is to administer a vasodilator, but this will lower arterial pressure and may be contraindicated if arterial pressure is already unacceptably low. The third alternative is to accelerate heart rate, which will decrease filling and stroke volume without dropping cardiac output, and enable more fluid loading to be performed until the critical wedge pressure is reached again. This introduces the factor of heart rate, which ! have avoided in my analysis so far. It must be considered in some detail (see below) because the underlying situation which facilitates fluid loading is normally accompanied by reflex tachycardia. 'Stiff' behaviour of the left ventricle usually occurs in hypertrophied hearts. However, an equally important problem is that of apparent stiffness due to interventricular reaction and to pericardial constraint.
Right ventricular and pericardial determinants of wedge pressure Since both ventricles are wrapped together in the same muscle, it is not surprising that there is mechanical interaction between the ventricles (Elzinga, personal communication) which is much increased by the presence of the pericardium. Thus, under conditions in which the pericardial sac is 'tight', the steep part of the left ventricular diastolic pressure-volume curve, which determines wedge pressure at high filling, is a function of the pericardial constriction (Kingma et al, 1986; Smiseth et al, 1987; Smith et al,
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1988). The clinical condition under which this is most likely to be a problem has been defined in experimental animals (Belenkie and Tyberg, personal communication). This condition is acute pulmonary embolization in which an acute rise in pulmonary artery pressure causes considerable distension of the right ventricle and therefore of the pericardium. Because of the tight pericardium, the left ventricle is unable to expand in diastole, and has a low end-diastolic volume and therefore a low stroke volume. Nevertheless, the left ventricular end-diastolic pressure and wedge pressure are high because the high pericardial pressure is transmitted through the left ventricular wall in diastole. When animals in this circumstance are fluid-loaded, the wedge pressure goes even higher, and pulmonary oedema develops. Similar experiences have been encountered when attempts have been made to counteract the low cardiac output of acute pulmonary embolism by fluid loading. These episodes would have been avoided if the wedge pressure had been measured and, if high, fluid loading avoided. This is a circumstance where the diastolic mechanical properties of the left ventricular muscle are normal but the behaviour of the whole ventricle in the patient is as if it were stiff. Can one infuse fluid in heart failure?
The definition of the various types of heart failure needs to be clarified:
The congestive syndrome This comprises raised systemic venous pressure, oedema, raised blood volume, extracellular fluid volume and exchangeable sodium. It is caused by sodium and water retention by the kidneys due to renal, liver, lung or heart disease, and is reversed by diuretics. It is subacute or chronic because sodium and water retention by the kidneys takes time to produce a raised venous pressure (Guz et al, 1966).
Congestive cardiac failure This is the congestive syndrome caused by heart disease.
Depression of myocardial contraction This can occur subclinically as 'myocardial insufficiency' or in congestive cardiac failure successfully controlled with diuretics. It is manifest by a shift of the pressure-volume curve to the right, and is detected clinically by a reduction in ejection fraction at normal arterial pressure. It can be acute or chronic or acute on chronic.
Left ventricular failure This can be said to be present when, in the absence of the congestive syndrome or in congestive cardiac failure successfully treated with diuretics,
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there is interference with left ventricular mechanics leading to a raised left ventricular end-diastolic pressure, raised pulmonary venous pressure and pulmonary oedema. It can be acute, chronic, or acute on chronic. In addition to myocardial depression or regional damage (as in myocardial infarction), left ventricular failure can occur without myocardial contractile depression in the following circumstances. 1.
2. 3.
Acute hypertension. At higher pressure, stroke volume is reduced; the heart therefore fills more so that end-diastolic volume is increased. Because of the stiffness of the ventricle in diastole, this leads to increased end-diastolic pressure. As ventricular distension increases, diastolic stiffness increases (upward-curving diastolic pressure-volume curve) so that filling is impaired. If reduced stroke volume is not compensated by increased filling, a vicious circle of increasing ventricular distension, raised pulmonary venous pressure and pulmonary oedema can ensue which can, at least in theory, accompany a still normal pressure-volume curve. In practice, subendocardial ischaemia will occur in the compressed inner layers of the ventricle which is normally perfused only in diastole (Buckberg et al, 1972). Functional mitral incompetence may also accompany extreme distension. Extreme tachyarrhythmia. Essentially, filling is not adequate to maintain output because of inadequate filling time. Extreme bradyarrhythmia, e.g. complete heart block. Since cardiac output = stroke volume x heart rate, cardiac output cannot be maintained with extremely low heart rate, even if stroke volume is high as a result of increased filling (Noble et al, 1966). In the extreme case, subendocardial ischaemia and functional mitral incompetence may supervene as in the case of acute hypertension; these complications can lead to a vicious circle of ever-declining pump function. Bradyarrhythmic left ventricular failure responds well to pacing.
Right ventricular failure This can be said to occur when, in the absence of the congestive syndrome or in congestive cardiac failure successfully treated with diuretics, there is interference with right ventricular mechanics leading to a raised right ventricular systolic and end-diastolic pressure with normal left atrial pressure. It can be acute, chronic, or acute on chronic.
Circulatory failure This is failure of the circulation to supply the tissues with blood flow matched to the metabolic demands. Since the arterial minus mixed venous blood oxygen content difference (A - VO2diff) equals body oxygen consumption divided by cardiac output (Fick equation), such failure is manifest by an increase in A - V O 2 d i f f . If it is not present at rest, it may be found by increasing oxygen consumption by exercise. It should now be clear that fluid loading is contraindicated in the congestive
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syndrome whatever the cause, including congestive cardiac failure and left ventricular failure, but may be helpful in the other forms. (There are a few exceptions in left ventricular failure: e.g. possibly with extreme tachyarrhythmia if a reduction in rate is not achieved, the rare case of myocardial infarction with a low wedge pressure.) In the case of right ventricular failure it is important to exclude a high wedge pressure due to pericardial constraint (see above). The case of depressed myocardial contraction is illustrated in Figure 7. The rightward shift of the end-ejection pressure curve can cause compensatory changes to maintain stroke volume, but ejection fraction is low. Such patients often have a shift in the diastolic pressure-volume curve so that the ventricle behaves as if it is more compliant than normal. Under these circumstances, fluid loading can be used when indicated (e.g. hypovolaemia) in a manner similar to the normal case. In all these circumstances the criterion as to whether fluid loading is safe or not is the wedge pressure.
THE EFFECT OF CHANGES IN H E A R T RATE ON CIRCULATORY MECHANICS
The circumstances described in this article under which heart rate varies can be understood more easily in the light of the fact that stroke volume (SV) declines almost linearly with increasing heart rate (HR) according to the formula: SV = - a ( H R ) + b Thus cardiac output ( C O ) = - a ( H R ) 2 + b ( H R ) , where a and b are parameters, a function which is low at low and high heart rates with a broad plateau of fairly constant cardiac output over the normal range of heart rate (Noble et al, 1966). The cause of the fall in stroke volume is that the shortening of filling time causes a reduction in end-diastolic volume (Noble et al, 1969a) so that: EDV = -a(HR) + c The slope of the two relationships (a) is the same because a change in end-diastolic volume causes the same absolute change in stroke volume if the ventricle adheres to the end-ejection pressure-volume relationship (Figure 5). Thus one can appreciate that tachycardia over a certain range decreases the end-diastolic volume for a fairly constant cardiac output. Fluid loading can thus be combined with tachycardia to produce an increase in cardiac output without increase in end-diastolic volume. This is the combination utilized in physiological exercise, but obviously tachycardia induced therapeutically may be contraindicated in the presence of coronary stenoses which cannot provide the increased coronary blood flow demanded by tachycardia.
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CONCLUSIONS T h e e n d - e j e c t i o n p r e s s u r e - v o l u m e curve is r e c o m m e n d e d as the t h e o r e t i c a l f r a m e w o r k for t h i n k i n g a b o u t fluid loading. M a n y of the t r a d i t i o n a l l y useful m e a s u r e m e n t s used in m o n i t o r i n g the c i r c u l a t i o n , a n d m a n y of the wellestablished t r e a t m e n t s , m a k e m o r e logical sense w h e n their m e c h a n i s m s are s t u d i e d w i t h i n the p r e s s u r e - v o l u m e f r a m e w o r k . I n most c i r c u m s t a n c e s , fluid l o a d i n g is a satisfactory m e t h o d of i n c r e a s i n g cardiac o u t p u t u n t i l the wedge p r e s s u r e reaches its safety limit. T h e clinical c i r c u m s t a n c e s m a y b e sufficiently clear-cut to e n a b l e o n e to give i n t r a v e n o u s fluids w i t h o u t m o n i t o r i n g , e.g. e m e r g e n c y t r e a t m e n t of h a e m o r r h a g e . H o w e v e r , w h e n e v e r the s i t u a t i o n is n o t clear-cut, w e d g e p r e s s u r e s h o u l d b e m e a s u r e d . W i t h s o m e a b n o r m a l hearts, m o n i t o r i n g of c e n t r a l v e n o u s p r e s s u r e i n s t e a d m a y b e a d a n g e r o u s l y i n a c c u r a t e guide.
REFERENCES
Abbott BC & Mommaerts WFHM (1959) A study of inotropic mechanisms in the papillary muscle preparation. Journal of General Physiology 42: 533-551. Buckberg GD, Fixler DE, Archie JP & Hoffman JIE (1972) Experimental subendocardial ischaemia in dogs with normal coronary arteries. Circulation Research 30: 67-81. Daniels M, Noble MIM, ter Keurs HEDJ & Wohlfart B (1984) Velocity of sarcomere shortening in rat cardiac muscle: relationship to force, sarcomere length, calcium and time. Journal of Physiology 355: 367-381. Drake-Holland AJ, Mills CJ, Noble MIM, Parker S, Pugh S & Seed WA (1988) Beat-by-beat measurement of human left ventricular mechanics during postural changes and postextrasystolic potentiation. Journal of Physiology (in press). Frank O (1895) Zur Dynamik des Herzmuskels. Zeitschriftfiir Biologie 32: 370-477. Translated by Chapman CB & Wasserman E (1959) American Heart Journal 58: 282-317,467-478. Gibson DG (1973) Estimation of left ventricular size by echocardiography. British Heart Journal 35: 128-134. Guz A, Noble MIM, Trenchard D et al (1966) The significance of a raised central venous pressure during sodium and water retention. Clinical Science 30: 295-303. Hefner LL, Sheffield LT, Cobbs GC & Klip W (1962) Relation between mural force and pressure in the left ventricle of the dog. Circulation Research 11: 654-663. Huisman RM (1977) Forces in the wall of the left ventricle. PhD thesis, Free University of Amsterdam. Kentish J, ter Keurs HEDJ, Ricciardi L, Bucx JJ & Noble MIM (1986) Comparison between the sarcomere length-force relations of intact and skinned trabeculae from rat right ventricle. Circulation Research 58: 755-768. ter Keurs HEDJ, RijnsburgerWH, van HeuningenR & Nagelsmit MJ (1980) Tensiondevelopment and sarcomere length in rat cardiac trabeculae. Circulation Research 46: 703-714. Kingma I, Smiseth OA, Belenkie I et al (1986) A mechanism for the nitroglycerin-induced downward shift of the left ventricular diastolic pressure-diameter relation. American Journal of Cardiology 57: 673-677. Lewartowski B, Sedek G & Okalska A (1972) Direct measurement of tension within left ventrieular wall of dog heart. Cardiovascular Research 6: 28--35. Milnor WR (1975) Arterial impedance as ventricular afterload. Circulation Research 36: 565-570. Muir AL, Hannah WJ, Brash HM, Baldwa V, Miller HC & Ogilvie B (1977) The assessment of left ventricular ejection fraction in patients with ischaemic heart disease by contrast ventriculography and nuclear angiography. Clinical Science 53: 55-61.
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Noble MIM (1978) The Frank-Starling curve. Clinical Science 54: 1-7. Noble MIM (1979) The Cardiac Cycle. Oxford: Blackwell Scientific Publications. Noble MIM, Trenchard D & Guz A (1966) Effect of changing heart rate on cardiovascular function in the conscious dog. Circulation Research 19: 206-214. Noble MIM, Wyler J, Milne ENC, Trenchard D & Guz A (1969a) Effect of changes in heart rate on left ventricular performance in conscious dogs. Circulation Research 24: 285-295. Noble MIM, Bowen TE & Hefner LL (1969b) Force-velocity relationship of cat cardiac muscle, studied by isotonic and quick-release techniques. Circulation Research 24: 821833. Noble MIM, Stubbs A, Trenchard D, Else W, Eisele JH & Guz A (1972) Left ventricular performance in the conscious dog with chronically denervated heart. Cardiovascular Research 6: 457-477. Sagawa K (1978) The ventricular pressure-volume diagram revisited. Circulation Research 43: 677-687. Sarnoff SJ & Mitchell JH (1962) The control of the function of the heart. In Handbook of Physiology, section 2, Circulation, Volume 1, pp 489-532. Washington DC: American Physiological Society. Smiseth OA, Scott-Douglas NW, Traboulsi M, Stone JA, Smith ER & Tyberg JV (1987) The role of the pericardium: experimental aspects. Heart Failure 3: 6-12. Smith ER, Smiseth OA, Kingma I & Tyberg JV (1988) The hemodynamic effects of the pericardium: clinical observations. Heart (in press). Sonnenblick EH (1962) Force-velocity relation in mammalian heart muscle. American Journal of Physiology 202: 931-939. Swan HJC, Ganz W, Forrester JS, Marcus H, Diamond G & Chonette D (1970) Catheterization of the heart in man with use of a flow-directed balloon-tipped catheter. New England Journal of Medicine 283:447-451. Weber KT, Janicki JS & Hefner LL (1976) Left ventricular force-length relations of isovolumic and ejecting contractions. American Journal of Physiology 231: 337-343.
T h e p u r p o s e o f this c h a p t e r is t o p r e s e n t a c o n c e p t u a l f r a m e w o r k o f m e c h a n i c a l m y o c a r d i a l e v e n t s t a k i n g p l a c e d u r i n g fluid l o a d i n g . T h e s e e v e n t s a r e b e s t i l l u s t r a t e d b y s t u d y i n g fluid l o a d i n g in t h e d e n e r v a t e d h e a r t ( F i g u r e 1). 2o
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TIME (mini SALINE INFUSION STARTED Figure 1. Effect of intravenous infusion of isotonic saline in a cardiac denervated dog. LVEDP: changes in left ventricular end-diastolic pressure from arbitrary zero. CVP: central venous pressure measured from an implanted venous catheter. CO: cardiac output, SV: stroke volume, M A : maximum acceleration of blood from the left ventricle, all measured from an implanted electromagnetic flowmeter with transducer around the ascending aorta. LVdP/dtmax: maximum rate of rise of left ventricular pressure which, together with LVEDP, was measured from a micromanometer implanted in the left ventricle. HR: heart rate. The gradual heart rate increase also occurs in isolated hearts and is due to stretch-induced activation of sinus node cells, giving a faster rise of diastolic depolarization and increased frequency of firing. In innervated hearts, reflex tachycardia is added. Note the greater rise in LVEDP (which is followed by left atrial pressure, pulmonary venous pressure and wedge pressure) than occurs in CVP. Stroke volume and cardiac output are markedly increased. From Noble et al (1972) with permission.
Bailli~re's ClinicalAnaesthesiology--Vol. 2, No. 3, September 1988
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M . I . M . NOBLE
Fluid loading causes a marked rise in cardiac output accompanied by increases in central vascular pressures. In innervated hearts this response may be complicated by an overlay of reflex tachycardia. The basis of this ventricular mechanical response is best understood within the framework of the pressure-volume diagram (Weber et al, 1976; Sagawa, 1978). THE P R E S S U R E - V O L U M E RELATIONSHIP
I put this concept forward as the basic concept for consideration of cardiac mechanical function (Figure 2). It dates back to the classical work of Frank in the last century (Frank, 1895). The relationship depends on the fact that the force developed by the cardiac muscle in the ventricular wall increases with fibre length (in reality the sarcomere length: Kentish et al, 1986) while the pressure developed in the cavity depends on both this force and the cavity dimensions according to the La Place relationship (Figure 3). For this reason isovolumic pressure increases less than force with increasing volume, giving a curvilinear relationship; the same considerations apply to the relationship between the maximum rate of rise of pressure in the left ventricle (dP/dt) and left ventricular volume (Figure 2). The isovolumic pressure-volume relationship has now been defined in dogs. It was found that the left ventricle ejected down to the volume from which it would have developed the same pressure isovolumically: see the pressure-volume loop in Figure 4 at the end of ejection (Weber et al, 1976; Sagawa, 1978). If the pressure at which ejection occurs is changed, the left
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Figure 2. Relationship of left ventricular isovolumic pressure development (11) and maximum rate of rise of left ventricular pressure, dP/dt (0), to left ventricular volume.
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CARDIOVASCULAR RESPONSE TO FLUID LOADING
Figure 3. Schematic representation of a cut half of the left ventricle. The pressure developed in the cavity is the force developed in the wall divided by the cavity cross-sectional area (a, cross-hatched). The maximum rate of rise of isovolumic pressure is the maximum rate of rise of wall force divided by a. Adapted from Hefner et al (1962).
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Figure 4. The isovolumic pressure-volume curve (Figure 2) is also inscribed at the end of ejection. Continuous-line loop No. 1 shows the four phases of the cardiac cycle: filling along the diastolic pressure-volume curve at the bottom, isovolumic contraction (vertically pointing upwards at the right), ejection (horizontal arrow to the left) and isovolumic relaxation (vertical arrow pointing downwards at the left). Other points on the curve are determined by finding the end-ejection points at other ejection pressures, e.g. dashed loop No. 2.
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M . I . M . NOBLE
ventricle ejects down to a new point on the isovolumic curve (see second loop in Figure 4). Thus, the isovolumic and end-ejection pressure-volume relationships proved to be the same and to characterize the contractility of the muscle (Figure 4). This experiment cannot be done in man without cardiopulmonary bypass and has not been done as far as I am aware. However, we can still say that the end-ejection pressure-volume relationship characterizes contractility in man (Noble, 1979). Whereas the pressurevolume curve is normally inscribed at end-ejection (end-systolic volume), where the relationship has a positive slope, the dP/dt-volume curve is inscribed at end-diastolic volume (isovolumic contraction period); this relationship has a positive slope only under hypovolaemic conditions, being flat under normal conditions (Drake-Holland et al, 1988). Stimulation of the heart's contractility shifts the curves upward and to the left, while negative inotropic effects and depressed myocardial contraction shift the relationship to the right. Failure of the left ventricle to eject right down to the pressure-volume line occurs under the following circumstances, all of which arise because the dimension of time is removed from a pressure-volume loop. Thus they all occur when the ventricle does not have enough time to get to its targeted end-point at end-ejection. 1.
2.
3. 4.
With the very highest ejection pressures (see data in Weber et al, 1976). This is because the force-velocity curve of heart muscle is inverse (Abbott and Mommaerts, 1959; Daniels et al, 1984) so that at high shortening loads the velocity of shortening is very low and therefore there is insufficient time for the ventricle to reach the pressure-volume line even though it can do so at all lower pressures (Weber et al, 1976). Sometimes with extreme filling in diastole. This may entail a large stroke volume to be ejected, which takes a longer time. However, if this occurs in the normal range of stroke volume, it implies myocardial insufficiency because the normal heart ejects 1 ml extra stroke volume for every 1 ml increase in end-diastolic volume (Noble et al, 1969b), as would be predicted from Figure 5. Therefore, in this circumstance, a shift to the right still implies depression of contraction. When velocity of shortening is depressed because, for a lower velocity, more time is needed to achieve the same shortening. Again, this implies depression of contraction. Extreme abbreviation of ejection time. In practice this occurs only with abnormally early onset of relaxation under extreme adrenergic stimulation (when the control curve is left-shifted anyway) or when the isovolumic contraction time is unduly prolonged, as in incoordinated activation (left bundle branch block etc.), which again implies depression of myocardial contraction.
Thus, in spite of such problems, the end-ejection pressure-volume curve still comes up as a reliable index of myocardial contractile performance. The increase in stroke volume that accompanies fluid infusion (Figure 1) occurs as a result of the changes in the pressure-volume loop depicted in Figure 5.
487
CARDIOVASCULAR RESPONSE TO FLUID LOADING 200
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Figure 6. The pressure-volume diagram in hypovolaemia (dashed loop H), i.e., hypotension and small left ventricular volumes. Fluid infusion restores loop to normal (continuous loop N).
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THE EFFECT OF FLUID L O A D I N G ON THE P R E S S U R E V O L U M E D I A G R A M IN THE N O R M A L H E A R T
Fluid loading is often required for the treatment of low cardiac output due to hypovolaemia or decreased central blood volume due to peripheral blood pooling. In such circumstances one may be dealing with a normal heart, i.e., one in which the end-ejection pressure-volume line is normal but the loop is as illustrated in Figure 6. In this case, stroke output is low simply because end-diastolic volume is low, in spite of enhancement of stroke volume by low arterial pressure. The low filling is correctly indicated by the low enddiastolic pressure, and correction of the situation by fluid loading back to a normal end-diastolic pressure is theoretically straightforward. HOW SHOULD FLUID LOADING BE MONITORED? If such fluid loading is continued to excess, left-sided vascular pressures (left ventricular end-diastolic, left atrial, pulmonary venous) rise very much more than the corresponding right-sided pressures because the left vascular compartment has much less capacity; it is as if it were much stiffer. It is therefore possible to overload with fluid to the point where high pulmonary venous pressure causes dyspnoea and eventually pulmonary oedema. Such very high left ventricular diastolic pressures can impair the diastolic filling of microvessels in the subendocardium, leading to subendocardial ischaemia (Buckberg et al, 1972) and an actual depression of ventricular mechanical function (pressure-volume curve shifted to the right). All of these effects are obviously undesirable and can be prevented by measuring a suitable leftsided pressure and stopping the fluid loading when this has reached a certain level. Such information cannot be reliably obtained from a right-sided pressure such as central venous pressure, because the greater compliance of the right compartment takes up excess fluid at much lower pressures which will not be interpreted as dangerous. WEDGE PRESSURE A N D S T R O K E V O L U M E BY S W A N - G A N Z
THERMODILUTION CATHETER The left pressure used clinically is the pulmonary capillary wedge pressure (PCWP). Intravenous catheters with a balloon inflated at the tip will be carried, by the bloodstream acting on the balloon, into the pulmonary artery and wedge in a branch. A lumen distal to the balloon transmits a pressure similar in magnitude to left atrial pressure. This can be done alone, but additional information is obtained with thermal sensors on the catheter to permit cardiac output measurements by thermodilution (Swan et al, 1970). I emphasize stroke volume rather than cardiac output (the primary measurement with this method) to keep the physician oriented as far as possible within the pressure-volume thinking framework. If an ejection fraction measurement is available (usually from a nuclear method: Muir et al,
489
CARDIOVASCULAR RESPONSE TO FLUID LOADING
1977) one can calculate end-diastolic volume (LVEDV = stroke volume divided by ejection fraction). If wedge pressure is taken as an indication of left ventricular end-diastolic pressure, and systolic arterial pressure as an indication of ejection pressure, one now has an idea of three points on the pressure-volume loop (bottom right, top right, top left). If ejection fraction measurements are lacking, similar information can be obtained from an echocardiographic estimate of end-diastolic ventricular diameter (LVEDD) (Gibson, 1973). It is then possible to assess whether wedge pressure is appropriate for the L V E D V or L V E D D . If, for instance, the wedge pressure is relatively normal in spite of high L V E D V or L V E D D , it can be concluded that the patient has pre-existing chronic depression of left ventricular mechanical function leading to chronic distension of the ventricle and a rightward shift of the diastolic pressure-volume curve, i.e., increased diastolic distensibility (Figure 7). Further changes in the acute situation and response to therapy can then be assessed in relation to this base-line.
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Left ventricular volume (ml} SV1 EDV1 SV2 EDV2
Figure 7. Chronic cardiac failure. The pressure-volume curve is shifted downwards and to the right (O) compared with normal (B). Stroke volume is maintained but is a smaller fraction of much increased end-diastolic volume (low ejection fraction). If the ventricle becomes more compliant in diastole as the result of chronic distension, as shown here, the response to fluid loading may be relatively normal.
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Other indices based upon the S w a n - G a n z method
There was a vogue at one time for plotting stroke work against wedge pressure (so-called 'function curves': Sarnoff and Mitchell, 1962). This procedure isof limited value compared to the approach I am putting forward above. Stroke work (stroke volume times arterial pressure) is highly dependent on arterial pressure with a bell-shaped function that will cause considerable confusion when stroke work is used alone. An increase in stroke work achieved by increasing arterial pressure with consequent lowering of stroke volume is quite likely to be a retrograde therapeutic manoeuvre. PCWP or LVEDP are misleading indices to plot on the abscissa of a 'function curve' because (1) the resulting curves are very distorted by the curvature of the diastolic pressure-volume relationship (Noble, 1978), and (2) the PCWP may be decreased by the chronic increase in diastolic distensibility described above. The frequently used term 'preload' originates from isolated muscle experiments done two decades ago (Abbott and Mommaerts, 1959; Sonnenblick, 1962). At that time the apparatus was too crude to allow setting the diastolic sarcomere length (ter Keurs et al, 1980), or even the initial muscle length (Noble et al, 1969b). Therefore, the muscle was hung vertically with a weight on the bottom to produce the necessary diastolic stretch indirectly. This load was in series with, and therefore proportional to, the end-diastolic force or stress (force/cross-sectional area) measured in appropriate units (N, or N/mm2). The inappropriateness of applying this to the intact heart can be understood from the following considerations. 1. 2.
3. 4. 5.
End-diastolic wall stress is not the primary determinant of systolic performance; the primary determinant is sarcomere length. The nearest equivalent to end-diastolic sarcomere length in the intact heart is the end-diastolic fibre length, and the nearest practical measurement is the end-diastolic volume (see presentation of the pressurevolume relationship above). Even end-diastolic pressure is not a good index of end-diastolic volume because of the non-linear diastolic pressure-volume curve (above) and variable diastolic distensibility (above). The relationship of end-diastolic pressure to wall stress is complex. Measurement of wall stress can be attempted only in the exposed heart, but even then the validity has been challenged (Huisman, 1977).
It is clear then that preload, i.e. end-diastolic wall stress, is never measured or calculated clinically, and the use of the term is ambiguous. There seems to be little reason for not using a term which refers to various measurements-e.g. end-diastolic volume, end-diastolic pressure, wedge pressure---each of which has a precise definition. Preload is a jargon term which should be eliminated from the clinician's vocabulary. The term afterload originated from the same crude early isolated muscle experiment that used preloads. In this case, an extra weight was attached to the bottom of the muscle that was resting on a stop. As soon as the muscle
CARDIOVASCULAR RESPONSE TO FLUID LOADING
491
was activated it could not shorten until it developed a systolic force or stress greater than the weight. The muscle then shortened and lengthened against this 'afterload' during systole. The inappropriateness of applying this term to the intact heart can be understood from the following considerations. 1. 2. 3.
The heart does not expand against a high force because the aortic valve closes at the end of muscle shortening. Systolic wall stress cannot be measured or calculated in the intact heart of a patient for the same reasons that applied to preload (see above). Systolic wall stress is not constant throughout ejection (Hefner et al, 1962; Lewartowski et al, 1972), but falls off from an early peak in ejection to ever-declining values as ejection proceeds. What then is the afferload? Peak afferload? Mid systolic afferload? Afterload averaged over the ejection period? Wall stress averaged over the whole of systole including isovolumic contraction and relaxation?
There seems to be some confusion between 'load' (which is always measured as a force or stress) and pressure, and between 'load' and resistance or impedance (Milnor, 1975). However, the latter is measured in completely different dimensions and has only an indirect interaction with the heart. These objections are based on the observation that these terms are often applied to treatment ('preload reduction', 'afterload reduction') with wholly inappropriate clinical consequences. D E T E R M I N A N T S OF W E D G E PRESSURE
The foregoing diversion serves to emphasize the fact that wedge pressure is not a determinant of left ventricular performance but, as discussed in the case of overloading a normal heart with fluid (above), it is an indication of the limit to which one can go with fluid infusion. It is therefore necessary to consider the determinants of wedge pressure in addition to filling itself. These factors are, in effect, also the dangers and contraindications of fluid-loading therapy. Left ventricular diastolicpressure-volume relationship seems to be a more appropriate term than 'compliance' because the latter is the slope of the diastolic pressure-volume curve and is almost irrelevant in practical terms. The real issue is: is left ventricular end-diastolic pressure high, normal or low at normal end-diastolic volume? For practical purposes this tells the clinician whether the left ventricle will behave as if stiff, normal or compliant, respectively. Stiff behaviour (Figure 8) is very important in the context of fluid loading because high wedge pressures are reached early, perhaps before one can attain the desired cardiac output and arterial pressure. Under these circumstances it is imperative to take alternative action to maintain fluid loading with no further wedge pressure increase. One possibility is to shift the end-ejection pressure-volume curve to the left by a positively inotropic drug; however, this is much less effective if the contractility is normal than if
492
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Left ventricular volume (ml)
Figure 8. Effect of increased diastolic stiffness, e.g. as the result of left ventricular hypertrophy (loop 2 compared to loop 1). A higher end-diastolic pressure, arrowed (and left atrial pressure, pulmonary venous pressure, and wedge pressure), occurs at normal filling volume. Fluid infusion is limited because of the greater incidence of pulmonary oedema following an excessive rise of pulmonary venous pressure.
it is depressed. A second possibility is to administer a vasodilator, but this will lower arterial pressure and may be contraindicated if arterial pressure is already unacceptably low. The third alternative is to accelerate heart rate, which will decrease filling and stroke volume without dropping cardiac output, and enable more fluid loading to be performed until the critical wedge pressure is reached again. This introduces the factor of heart rate, which ! have avoided in my analysis so far. It must be considered in some detail (see below) because the underlying situation which facilitates fluid loading is normally accompanied by reflex tachycardia. 'Stiff' behaviour of the left ventricle usually occurs in hypertrophied hearts. However, an equally important problem is that of apparent stiffness due to interventricular reaction and to pericardial constraint.
Right ventricular and pericardial determinants of wedge pressure Since both ventricles are wrapped together in the same muscle, it is not surprising that there is mechanical interaction between the ventricles (Elzinga, personal communication) which is much increased by the presence of the pericardium. Thus, under conditions in which the pericardial sac is 'tight', the steep part of the left ventricular diastolic pressure-volume curve, which determines wedge pressure at high filling, is a function of the pericardial constriction (Kingma et al, 1986; Smiseth et al, 1987; Smith et al,
CARDIOVASCULAR RESPONSE TO FLUID LOADING
493
1988). The clinical condition under which this is most likely to be a problem has been defined in experimental animals (Belenkie and Tyberg, personal communication). This condition is acute pulmonary embolization in which an acute rise in pulmonary artery pressure causes considerable distension of the right ventricle and therefore of the pericardium. Because of the tight pericardium, the left ventricle is unable to expand in diastole, and has a low end-diastolic volume and therefore a low stroke volume. Nevertheless, the left ventricular end-diastolic pressure and wedge pressure are high because the high pericardial pressure is transmitted through the left ventricular wall in diastole. When animals in this circumstance are fluid-loaded, the wedge pressure goes even higher, and pulmonary oedema develops. Similar experiences have been encountered when attempts have been made to counteract the low cardiac output of acute pulmonary embolism by fluid loading. These episodes would have been avoided if the wedge pressure had been measured and, if high, fluid loading avoided. This is a circumstance where the diastolic mechanical properties of the left ventricular muscle are normal but the behaviour of the whole ventricle in the patient is as if it were stiff. Can one infuse fluid in heart failure?
The definition of the various types of heart failure needs to be clarified:
The congestive syndrome This comprises raised systemic venous pressure, oedema, raised blood volume, extracellular fluid volume and exchangeable sodium. It is caused by sodium and water retention by the kidneys due to renal, liver, lung or heart disease, and is reversed by diuretics. It is subacute or chronic because sodium and water retention by the kidneys takes time to produce a raised venous pressure (Guz et al, 1966).
Congestive cardiac failure This is the congestive syndrome caused by heart disease.
Depression of myocardial contraction This can occur subclinically as 'myocardial insufficiency' or in congestive cardiac failure successfully controlled with diuretics. It is manifest by a shift of the pressure-volume curve to the right, and is detected clinically by a reduction in ejection fraction at normal arterial pressure. It can be acute or chronic or acute on chronic.
Left ventricular failure This can be said to be present when, in the absence of the congestive syndrome or in congestive cardiac failure successfully treated with diuretics,
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there is interference with left ventricular mechanics leading to a raised left ventricular end-diastolic pressure, raised pulmonary venous pressure and pulmonary oedema. It can be acute, chronic, or acute on chronic. In addition to myocardial depression or regional damage (as in myocardial infarction), left ventricular failure can occur without myocardial contractile depression in the following circumstances. 1.
2. 3.
Acute hypertension. At higher pressure, stroke volume is reduced; the heart therefore fills more so that end-diastolic volume is increased. Because of the stiffness of the ventricle in diastole, this leads to increased end-diastolic pressure. As ventricular distension increases, diastolic stiffness increases (upward-curving diastolic pressure-volume curve) so that filling is impaired. If reduced stroke volume is not compensated by increased filling, a vicious circle of increasing ventricular distension, raised pulmonary venous pressure and pulmonary oedema can ensue which can, at least in theory, accompany a still normal pressure-volume curve. In practice, subendocardial ischaemia will occur in the compressed inner layers of the ventricle which is normally perfused only in diastole (Buckberg et al, 1972). Functional mitral incompetence may also accompany extreme distension. Extreme tachyarrhythmia. Essentially, filling is not adequate to maintain output because of inadequate filling time. Extreme bradyarrhythmia, e.g. complete heart block. Since cardiac output = stroke volume x heart rate, cardiac output cannot be maintained with extremely low heart rate, even if stroke volume is high as a result of increased filling (Noble et al, 1966). In the extreme case, subendocardial ischaemia and functional mitral incompetence may supervene as in the case of acute hypertension; these complications can lead to a vicious circle of ever-declining pump function. Bradyarrhythmic left ventricular failure responds well to pacing.
Right ventricular failure This can be said to occur when, in the absence of the congestive syndrome or in congestive cardiac failure successfully treated with diuretics, there is interference with right ventricular mechanics leading to a raised right ventricular systolic and end-diastolic pressure with normal left atrial pressure. It can be acute, chronic, or acute on chronic.
Circulatory failure This is failure of the circulation to supply the tissues with blood flow matched to the metabolic demands. Since the arterial minus mixed venous blood oxygen content difference (A - VO2diff) equals body oxygen consumption divided by cardiac output (Fick equation), such failure is manifest by an increase in A - V O 2 d i f f . If it is not present at rest, it may be found by increasing oxygen consumption by exercise. It should now be clear that fluid loading is contraindicated in the congestive
CARDIOVASCULAR RESPONSE TO FLUID LOADING
495
syndrome whatever the cause, including congestive cardiac failure and left ventricular failure, but may be helpful in the other forms. (There are a few exceptions in left ventricular failure: e.g. possibly with extreme tachyarrhythmia if a reduction in rate is not achieved, the rare case of myocardial infarction with a low wedge pressure.) In the case of right ventricular failure it is important to exclude a high wedge pressure due to pericardial constraint (see above). The case of depressed myocardial contraction is illustrated in Figure 7. The rightward shift of the end-ejection pressure curve can cause compensatory changes to maintain stroke volume, but ejection fraction is low. Such patients often have a shift in the diastolic pressure-volume curve so that the ventricle behaves as if it is more compliant than normal. Under these circumstances, fluid loading can be used when indicated (e.g. hypovolaemia) in a manner similar to the normal case. In all these circumstances the criterion as to whether fluid loading is safe or not is the wedge pressure.
THE EFFECT OF CHANGES IN H E A R T RATE ON CIRCULATORY MECHANICS
The circumstances described in this article under which heart rate varies can be understood more easily in the light of the fact that stroke volume (SV) declines almost linearly with increasing heart rate (HR) according to the formula: SV = - a ( H R ) + b Thus cardiac output ( C O ) = - a ( H R ) 2 + b ( H R ) , where a and b are parameters, a function which is low at low and high heart rates with a broad plateau of fairly constant cardiac output over the normal range of heart rate (Noble et al, 1966). The cause of the fall in stroke volume is that the shortening of filling time causes a reduction in end-diastolic volume (Noble et al, 1969a) so that: EDV = -a(HR) + c The slope of the two relationships (a) is the same because a change in end-diastolic volume causes the same absolute change in stroke volume if the ventricle adheres to the end-ejection pressure-volume relationship (Figure 5). Thus one can appreciate that tachycardia over a certain range decreases the end-diastolic volume for a fairly constant cardiac output. Fluid loading can thus be combined with tachycardia to produce an increase in cardiac output without increase in end-diastolic volume. This is the combination utilized in physiological exercise, but obviously tachycardia induced therapeutically may be contraindicated in the presence of coronary stenoses which cannot provide the increased coronary blood flow demanded by tachycardia.
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CONCLUSIONS T h e e n d - e j e c t i o n p r e s s u r e - v o l u m e curve is r e c o m m e n d e d as the t h e o r e t i c a l f r a m e w o r k for t h i n k i n g a b o u t fluid loading. M a n y of the t r a d i t i o n a l l y useful m e a s u r e m e n t s used in m o n i t o r i n g the c i r c u l a t i o n , a n d m a n y of the wellestablished t r e a t m e n t s , m a k e m o r e logical sense w h e n their m e c h a n i s m s are s t u d i e d w i t h i n the p r e s s u r e - v o l u m e f r a m e w o r k . I n most c i r c u m s t a n c e s , fluid l o a d i n g is a satisfactory m e t h o d of i n c r e a s i n g cardiac o u t p u t u n t i l the wedge p r e s s u r e reaches its safety limit. T h e clinical c i r c u m s t a n c e s m a y b e sufficiently clear-cut to e n a b l e o n e to give i n t r a v e n o u s fluids w i t h o u t m o n i t o r i n g , e.g. e m e r g e n c y t r e a t m e n t of h a e m o r r h a g e . H o w e v e r , w h e n e v e r the s i t u a t i o n is n o t clear-cut, w e d g e p r e s s u r e s h o u l d b e m e a s u r e d . W i t h s o m e a b n o r m a l hearts, m o n i t o r i n g of c e n t r a l v e n o u s p r e s s u r e i n s t e a d m a y b e a d a n g e r o u s l y i n a c c u r a t e guide.
REFERENCES
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