Annals of the Royal College of Surgeons of England (I975) vol 57

Myocardial

function

following

cardiopulmonary bypass James D Wisheart BSC FRCSEd Senior Registrar in Cardiothoracic Surgery, Royal Postgraduate Medical School and Hammersmith Hospital, Lonidon

Surmmary Twenty-one patients have been studied in the 48 h after valve replacement to determine the possible contribution of abnormalities of left ventricular myocardial blood flow and oxygen consumption to the impaired cardiac performance which is sometimes evident in such patients. In the I4 patients making an uneventful recovery (Group A) the mean values for blood flow and oxygen consumption were both higher than in resting man, while the arterio-coronary sinus oxygen content difference was narrowed, with a high coronary sinus oxygen tension. Five patients had a low cardiac output (Group B) and had similar levels of blood flow and oxygen consumption to Group A, while the coronary sinus oxygen content and tension were reduced. When the heart rate was increased by pacing (Group C) myocardial oxygen consumption increased but coronary blood flow failed to rise, while the arterio-coronary sinus oxygen content difference widened slightly. It is concluded that the low postoperative cardiac output is not due to low coronary blood flow or myocardial oxygen supply, but these patients have a limited ability to increase their already high coronary blood flow. Therefore any increase in oxygen demand Arris and Galc Lecture delivered on I5th May 1974

may be met by the potentially detrimental mechanism of widening the arterio-coronary sinus di§ference, with lower coronary sinus and tissue oxygen tension.

Introduction The subject of this lecture is not anatomical, as primarily intended by Edward Arris and John Gale, but is physiological in relation to surgery. I feel that this deviation may be justified by the precedents of such previous lecturers as those eminent cardiovascular physiologists Ernest Starling in I898, Francis Bainbridge in I908, and more recently one of my own teachiers in physiology, Ian Roddie, in I963. Cardiac output is low in some patients after cardiopulmonary bypass, and as it may remain low despite energetic treatment this is an important cause of morbidity and death. Is this due to a myocardial factor? If so, is the low-output state caused by a limitation of coronary blood flow or is there some imbalance of oygen demand and supply to the heart? It is not unlikely that there would be an abnormality of myocardial function in the early postoperative period, considering the failure to protect the myocardium adequately during intracardiac surgery and

Myocardial function following cardiopulmonary bypass the fact that in most cases the heart is already the seat of established pathological change. As little is known of the physiological state of the myocardium in these circumstances it was decided to investigate the possibility that abnormalities of coronary blood flow or oxygen supply occur early after operation and may contribute to the impairment of cardiac performance. It will be shown that both left ventricular coronary blood flow and myocardial oxygen consumption are high; so clearly low cardiac output postoperatively is not due to depression of these parameters. However, some patients, probably the majority, have a restricted coronary reserve, so that a further increase in blood flow is limited. Added stress, such as tachycardia, causes an increase in oxygen demand which cannot be met by a significant increase in left ventricular blood flow, but only by the potentially detrimental mechanism of increasing oxygen extraction with a consequent reduction in coronary venous and myocardial tissue oxygen levels.

Review of myocardial physiology Before proceeding to discuss the studies in detail let us briefly review some aspects of myocardial physiology in man. Coronary blood flow in man was first measured in I948 by Eckenhoff and his colleagues', using a diffusible indicator, and they showed that the normal range of left ventricular coronary blood flow is 70-85 cm' I00 g-' minr1. Myocardial oxygen consumption is the product of the aorto-coronary sinus oxygen content difference and blood flow and has a normal range of 8-io cm' I00 g-1 min-'. Arterial oxygen content is normally I7 cm"%/ and coronary sinus oxygen content is 5 cm"/,,, leaving an aorto-coronary sinus oxygen difference of 12 cm'%/0. Should the extraction of oxygen by the myocardium increase, coronary sinus oxygen content will fall, as will coronary

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sinus oxygen tension-normally around 2.66 kPa (20 mm Hg). The change in coronary sinus oxygen tension will also be determined by the position of the oxyhaemoglobin dissociation curve. Thus if the curve is displaced to the left, for a given oxygen content the tension will be lower. The effectiveness of oxygen delivery to the myocardium may be regarded as the balance between oxygen demand and oxygen supply. Myocardial oxygen consumption or demand may rise or fall, but changes in neither consumption alone nor demand alone give us any information about the effectiveness of oxygen delivery to the myocardium. Myocardial oxygen consumption may be measured, but it is not possible at present to measure oxygen demand, even though the major determinants of oxygen need are recognized as heart rate, developed left ventricular wall tension, and the inotropic state, each of which may be individually measured. How then can the balance between demand and consumption be observed? Coronary sinus oxygen tension may be used as an indicator of the adequacy of oxygen supply. If the need tends to exceed supply, then oxygen extraction by the heart will increase as a compensatory mechanism, with a resulting decrease in coronary sinus oxygen tension. As coronary sinus oxygen tension is the same as that at the venous end of the capillaries, which in turn is closely related to myocardial tissue oxygen tension, it is therefore an indicator of tissue oxygenation. The second approach uses the myocardial handling of lactate as an indication of the adequacy of oxygen supply. If there is a lack of oxygen, causing myocardial metabolic processes to revert to an anaerobic pattern, the myocardial extraction of lactate will fall. The extraction ratio for lactate is normally around 20%, and negative ratios (that is, lactate production) are due to widespread

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James D Wisheart

anaerobic metabolism; ratios under io% indicate regional anaerobism. In response to such physiological events as tachycardia or exercise, which increase oxygen need, normal individuals increase their myocardial oxygen consumption by increasing blood flow, while the arterio-coronary sinus oxygen content difference remains virtually unchanged. How is this increased flow achieved? Flow in any vascular bed is determined directly by the pressure gradient and inversely by the vascular resistance. To all except the superficial layers of the myocardium blood flow occurs principally in diastole; thus diastolic time per minute is a further factor determining coronary blood flow. In tachycardia and exercise diastolic time and arterial pressure either fall or remain constant; therefore the increase in blood flow is achieved by a fall in coronary vascular resistance, believed to be mediated by the local production of chemical agents. Patients with ischaemic heart disease cannot be distinguished from normal subjects by measurement of blood flow, oxygen consumption, or lactate extraction at rest. Pacinginduced tachycardia or exercise causes an increase in oxygen consumption which is usually achieved by increasing coronary blood flow to the limits imposed by the disease process. A further increase in oxygen consumption may be achieved by widening the arterio-coronary sinus oxygen content difference, which is usually followed by a decrease in the extraction of lactate, indicating that insufficient oxygen is now being supplied. In the presence of valvular heart disease or congestive heart failure resting levels of blood flow and oxygen consumption are within, or very close to, the normal range. Within the limits of tolerated exercise the response of blood flow and oxygen consumption is essentially normal. In patients who had undergone valve sur-

gery Mueller and her associates' found that both blood flow and oxygen consumption varied in that they were below normal on the day after operation although high levels of both were observed on the subsquent days. The arterio-coronary sinus oxygen content difference was reduced and lactate extraction ratios were within the normal range. McGoon and his colleagues'-' studied the arteriocoronary sinus gradients of a number of substances after valve replacement. They confirmed the low arterio-coronary sinus oxygen content difference and normal extraction of lactate, but in a small number of patients who died from cardiogenic shock' the myocardial arteriovenous oxygen content difference widened to normal and beyond, with a low coronary sinus oxygen tension. These reports suggest that early after cardiopulmonary bypass there are important deviations of myocardial function, both from the normal and from the preoperative state. There is a need to confirm and complete the above reports and thus provide a secure framework within which current methods of postoperative management may be re-evaluated.

Measurement of left ventricular coronary blood flow There is one final digression before I proceed to describe the clinical studies. Measurement of blood flow based on the Fick7 principle requires precise knowledge of the amount of uptake of the indicator. This is not available in in-vivo studies for deep-seated organs such as the heart. To overcome this Kety and Schmidt8 in I945 introduced the concept of a diffusible indicator in measuring cerebral blood flow. The diffusible indicator has two properties: (i) its uptake by an organ is determined solely by blood flow and is not limited by its diffusion characteristics; (2) as the capillary and venous

Myocardial function following cardiopulmonary bypass concentration of a diffusible indicator is related to the tissue concentration by a constant, the partition coefficient, its rate of uptake per unit mass of tissue may be known. Thus knowledge of the arterial and venous concentrations of the indicator, together with the partition coefficient, permits calculation of the blood flow. Left ventricular coronary blood flow was measured in these studies with iodoantipyrine labelled with the isotope 125I as the diffusiblc indicator, a modification of the technique described by Krasnow et al. in i963' being used. Catheters were placed in the left atrium, arch of the aorta, and coronary sinus. The indicator was infused continuously into the left atrium for 3 min with a Gilford pump. Simultaneously, arterial and coronary sinus samples were withdrawn by means of a twinheaded Cole-Parmer pump and collected in I5-S aliquots, which were later counted for radioactivity with a Picker scintillation counter. These data enable curves for arterial and coronary sinus concentration of antipyrine to be constructed. Left ventricular coronary blood flow may now be calculated with a standard formula. Before carrying out studies in man we validated this technique of measuring coronary blood flow in the normal dog heart by comparing it with directly measured coronary flow. For 24 comparisons at flows ranging from 50 tO 250 cm3 ioo g-1 min-1 the regression coefficient was 0.97, as shown in Fig. i. However, certain assumptions underlie the use of this method of measuring left ventricular coronary blood flow. First, the coronary blood flow must be constant during the measurement, and indirect evidence that this was so lay in the observation of stable heart rate and left atrial and arterial pressures. The most important assumption is that of homogeneous perfusion. Blood flow to the

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normal left ventricle is distributed uniformly, but in at least some circumstances following cardioptulmonary bypass areas of myocardiumn, particularly the subendocardium, may be regionally underperfused. In such patients coronary sinus samples will be weighted in favour of the well-perfused areas as the efflux from malperfused areas is smaller in cm3 per unit mass. Thus measurement of the left ventricular coronary flow in these circumstances will reflect the wellperfused areas and will be high. Patient selection excluded those with previous myocardial infarction or overt ischaemic heart disease. The third assumption is that venous sampling is representative. To achieve this the coronary sinus catheter was placed far to the left in the coronary sinus in order to sample pure left ventricular venous efflux,

0

8,_ CO

0 E

C) O

O

oE

100

0

1. 005x + 8. 92 0.97 SY = 15.7 24 n

y r-

I

100 200 CORRECTED CORONARY SINUS FLOW

300

cm3 100g-1 min-1 Coronary blood flow in the dog esti-

FIG. I mated by the Kety-Schmidt method with iodoantipyrine compared with simultaneous corrected coronary sinus flow. Regression line shown. Each symbol represents one comparison.

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James D Wisheart

free from contamination by right ventricular sion was measured with the appropriate elecefflux or right atrial reflux. Finally, studies trode at 370C and oxygen content was with radioactive microspheres suggest that estimated in duplicate with the Lexington significant arteriovenous shunting does not oxygen content analyser. Arterial and coronary sinus lactate levels were estimated by the occur under normal circumstances, but no evidence is available in patients after cardio- enzymatic method of Marbach10 and with the Beckman Du spectrophotometer. pulmonary bypass. Further parameters were derived as follows. Tension time index (mm Hg s min'f) Clinical studies by planimetry of the dynamic Twenty-one patients were studied after valve was obtained trace. Coronary vascular resistance replacement; the aortic valve was replaced arterial s cm-5 IO-3 IOO g-1) equals mean presin I 2 patients, the mitral valve in 8, and both (dyn drop across the coronary circulation aortic and mitral valves in one. Routine sur- sure divided by left ventricular coronary blood gical techniques of cardiopulmonary bypass flow. Myocardial oxygen consumption is the were used with the Temptrol bubble oxygenaproduct of the arterio-coronary sinus oxygen tor, haemodilution, moderate hypothermia, difference and the left ventricular and flow rates of 2.2 1 min' m2. Coronary content coronary blood flow divided by ioo. The experfusion or selective deep cardiac hvpo- traction ratio of lactate equals the aortothermia was used for aortic valve replace- coronary sinus difference expressed as a perment and I5-20-min periods of elective centage of the aortic concentration of ischaemic arrest in mitral valve replacement. lactate. Ball cage prostheses were used in each case. There were 3 groups of patients. Group A Before the operation a 6o-cm (24-in) polyof the I 4 patients who enjoyed consisted vinyl catheter was inserted into the brachial uneventful postoperative recovery. The 5 an artery and passed to the arch of the aorta. B had a low cardiac outin Group After the perfusion an identical catheter patients either a catecholamine were given was passed across the right atrium into the put and the inotropic state or triinfusion to enhance coronary sinus and positioned near the left heart border. Catheters were left in both right metaphan to reduce peripheral resistance. and left atria and the pulmonary artery for Group C consisted of 9 patients in whom routine monitoring. Atrial and ventricular measurements were made before and after epicardial pacing electrodes were inserted as atrial pacing; some patients in this group were also in Group A. appropriate. In the I9 patients in Groups A and B there For each series of observations both mean and phasic arterial and atrial pressures were wvere 4 study periods during the 48 h followrecorded together with the electrocardiogram. ing surgery: first 2-4 h after return from the Cardiac index was measured in duplicate by operating theatre, then on the morning and the dye dilution method with indocyanine afternoon of the first postoperative day, and finally on the morning of the second postgreen and a Waters densitometer. Left ventricular coronary blood flow was also deter- operative day. The pacing studies in Group mined in duplicate as already described. C were carried out on the morning of the Samples were withdrawn from the arterial first postoperative day; in the case of those and coronary sinus catheters for estimation patients who were in both Group A and of oxygen content and tension. Oxygen ten- Group C the study period already mentioned

3 Cardiac index 2 (I

min-Im-2)

7

Myocardial function following cardiopulmonary bypass Group Ae Group B -- -

s T

250