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Circulation. 1995;92:155-162

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(Circulation. 1995;92:155-162.)
© 1995 American Heart Association, Inc.

Articles

Early Changes in Regional and Global Left Ventricular Function After Aortic Valve Replacement

Comparison of Crystalloid, Cold Blood, and Warm Blood Cardioplegias

Xu Y. Jin, MB, MD; Derek G. Gibson, MB, FRCP; John R. Pepper, MCHIR, FRCS

From the Academic Department of Cardiothoracic Surgery (X.Y.J., J.R.P.), National Heart and Lung Institute, and the Cardiac Department (X.Y.J., D.G.G.), Royal Brompton Hospital, London, UK.


*    Abstract
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 *Abstract
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down arrowResults
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Background The clinical effects of different cardioplegic methods on left ventricular (LV) function have not been fully elucidated, particularly in the setting of myocardial hypertrophy.

Methods and Results Sixty-four patients (mean age, 62±12 years; 41 men, 23 women) who were undergoing elective aortic valve replacement (stenosis, 49; regurgitation, 15; concomitant coronary artery bypass grafting, 22), with LV mass index 230±70 g/m2, were randomized to the following groups: antegrade crystalloid cardioplegia (CCP, 21 patients), antegrade/retrograde cold blood cardioplegia (CBP, 23 patients), or continuous retrograde warm (37°C) blood cardioplegia (WBP, 20 patients). Mean aortic cross-clamp and cardiopulmonary bypass times were 100±20 and 126±24 minutes. Positive inotropic drug therapy was required postoperatively in 9 patients after CBP, 14 after CCP, and 18 after WBP. Perioperative LV function was assessed using transesophageal M-mode echocardiography, combined with high-fidelity LV pressure recording and thermodilution cardiac output, before bypass and 0.5, 1, 3, 6, 12, and 20 hours after cross-clamp removal. There was a similar fall in LV peak circumferential wall stress at constant LV end-diastolic dimension in each group after aortic valve replacement. The increase in contraction velocity was significant from 0.5 hour with CBP; however, no significant increase occurred until 12 hours with CCP and until 20 hours with WBP. The rate and extent of LV pressure fall and early diastolic filling rate both increased with CBP, and only in this group did ventricular coordination improve. LV stroke work index was maintained with CBP throughout the postoperative period with less inotropic support than with the other two methods.

Conclusions In the hypertrophied LV, CBP offers the best preservation of myocardial physiological response and ventricular function with less inotropic support.


Key Words: cardioplegia • myocardial contraction • valves • echocardiography • surgery


*    Introduction
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 *Introduction
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down arrowResults
down arrowDiscussion
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Our ability to preserve myocardial function has continued to improve as cardiac surgery has developed. Over the past two decades, methods based on hypothermia have been generally used,1 2 3 but more recently WBP has attracted great interest.4 5 6 7 8 Differences among various animal models and protocols and the use of a wide range of outcome measures have made it difficult to extrapolate these experimental results to the clinical setting.9 10 11 12 13 14 15 16 17 18 19 The most satisfactory criterion would seem to be maintenance of normal or near-normal ventricular function,20 although assessing ventricular function early after surgery presents many practical problems. The simple measures of cardiac output and filling pressure that are usually used are insensitive. Changes in intrinsic ventricular function are frequently difficult to dissociate from those due to altered loading21 22 23 24 or due to the effects of catecholamine, both exogenous and endogenous. Loss of the normal homogeneity of ventricular function found in significant coronary artery disease or hypertrophy is a further confounding factor.25 In the present study, therefore, we used a more direct method to study LV function, both regional and global. We used transesophageal echocardiography and high-fidelity pressure measurements over the first 20 hours after surgery to study a clinically representative group of patients undergoing AVR.


*    Methods
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 up arrowAbstract
 up arrowIntroduction
 *Methods
down arrowResults
down arrowDiscussion
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Subjects
From June 1992 to the end of July 1994, we studied 64 patients undergoing elective AVR (age, 62±12 years; range, 33 to 81 years; (41 men, 23 women). Forty-nine had aortic stenosis, and 15 had predominant regurgitation. LV mass index was 230±70 g/m2 as measured by M-mode echocardiography. Twenty-two patients with concomitant coronary artery disease (20 with aortic stenosis, 2 with aortic regurgitation) received full revascularization (2±1 grafts). Early after surgery, following our normal clinical practice, positive inotropic drugs were given when cardiac index fell below 2.0 L/m2 in spite of a pulmonary artery wedge pressure >=15 mm Hg. On this basis, 23 patients required no inotropic support perioperatively (dose level=0), 27 patients received dopamine in a dose of 3 to 4.9 µg · kg-1 · min-1 (dose level=1), and 14 who failed to respond to dopamine received adrenaline in a dose of 0.02 to 0.10 µg · kg-1 · min-1 (mean, 0.06 µg · kg-1 · min-1; dose level=2). These dose levels were determined by those in clinical charge of the patients, without input from the investigators. No patients required intra-aortic balloon pump assist after surgery. This protocol was approved by the Ethics Committee of the Royal Brompton Hospital, and written informed consent was obtained from each participant. There were no side effects of this study.

Surgical Techniques
The patients were ventilated with 60% oxygen. General anesthesia was maintained with fentanyl (20 to 50 mg/kg), pancuronium oxide (0.1 mg/kg), and enflurane. A radial artery catheter and a Swan-Ganz thermodilution catheter were positioned after induction and used for hemodynamic measurements; the thermodilution catheter had its tip in the pulmonary artery. Cardiopulmonary bypass was established (ascending aortic and a single right atrial cannulation) with hemodilution (hematocrit, 20% to 25%) and systemic hypothermia (25°C nasopharyngeal temperature) when using CBP or normotheria (37°C) when using WBP. The extracorporeal circuit contained a membrane oxygenator primed with 1800 mL of crystalloid solution and 500 mL of albumin. The systemic perfusion flow rate was 2.2 L · min-1 · m-2 at 37°C, decreasing to 1.6 L · min-1 · m-2 at 25°C. A DLP triple lumen catheter was positioned in the coronary sinus and manually inflated, and its proximal pressure was monitored and maintained at 30 to 40 mm Hg during retrograde perfusion. Patients were randomized to CCP, CBP, or WBP. For CCP (20 mL/kg) St Thomas Hospital No. 1 solution, potassium 20 mEq/L at 4°C, was administered during antegrade arrest via each coronary ostium and maintained with 10 mL/kg (potassium, 6 to 8 mEq/L) every 20 minutes by antegrade perfusion. CBP was accomplished using a 4:1 dilution of systemic perfusion fluid and St Thomas Hospital No. 1 solution, potassium 20 mEq/L at 6°C given by antegrade combined retrograde arrest (20 mL/kg, first two thirds of the dose via aortic root or coronary artery and the remaining one third via coronary sinus), maintained by potassium-enriched autologous blood 10 mL/kg (potassium, 6 to 8 mEq/L) via coronary sinus every 20 minutes. A 10 mL/kg retrograde "hot shot" (37°C), which consisted of potassium-enriched (6 to 8 mEq/L) autologous blood and no other additives, was given before removal of the aortic cross clamp. For WBP, a 4:1 dilution of systemic perfusion fluid and St Thomas Hospital No. 1 solution was used. The arrest dose (20 mL/kg) was given antegradely in two thirds, and the remaining one third, retrogradely, with potassium 20 mEq/L at 37°C and a hematocrit of 20%. The maintenance dose of approximately 200 to 250 mL/min (potassium, 6 to 8 mEq/L; hemocratic, 20%; at 37°C) was administered continuously via the coronary sinus at a pressure of 30 to 40 mm Hg. There was a 2- to 3-minute interruption of retrograde WBP during suturing of the valve around each coronary ostium. In one patient, complete cardiac arrest could not be achieved after a full arrest dose of WBP, so another half arrest dose of CBP was added antegradely, and the CBP protocol was therefore substituted. All valve replacements were performed by the same surgeon (J.R.P.). The aortic valve was replaced with an aortic homograft in 29 patients, with a Toronto stentless porcine valve in 23, and with a stented valve in 12. The mean size of implanted valve was 25±2.5 mm. No patient had significant postoperative aortic regurgitation as assessed using transesophageal echocardiography. Cardiopulmonary bypass time was 126±24 minutes, and aortic cross-clamp time was 100±20 minutes. After surgery, patients were transferred to intensive care under continuous sedation (morphine, 1 mg/h; propofol, 50 to 100 mg/h IV) and receiving controlled ventilation (FIO2, 0.35 to 0.50; I-R ratio, 1:2; positive end-expiratory pressure, 1 to 2 mm Hg).

Facilities and Protocol
A 5 MHz biplanar transesophageal echocardiographic transducer (model HP 21362C, Hewlett-Packard) was positioned in the esophagus after induction and connected to a Hewlett Packard 77025A Sonos 500 ultrasound system. Once the pericardium was opened, a 4F pressure transducer–tipped catheter (Gaeltec CTC/4F/USCI, Gaeltec Ltd) was introduced into the LV with its tip located in the midportion of the cavity, via the roof of the left atrium and across the mitral valve. The transducer had a sensitivity of 5 µV · V-1 · mm Hg-1, bridge resistance 2.0 K{Omega}. Its signal output was filtered, preamplified (Gaeltec S7b, Gaeltec Ltd), and transferred into the auxiliary line of the echocardiographic system (with response frequency 0 to 1000 Hz). The calibration (to 100 mm Hg) of the pressure transducer–tipped catheter was performed electrically before the initial measurement and was checked with an air-operated dead-weight balance (Budenberg Gauge Company Ltd) after the study, when the catheter was removed. The mean left atrial pressure or pulmonary artery wedge pressure (identical within 2 mm Hg to mean left atrial pressure when the chest was open) was used to identify the LV end-diastolic pressure. Zero pressure was taken as atmospheric. After the final measurement, the transesophageal echocardiographic transducer and pressure transducer–tippedcatheter were removed, sedation was discontinued, and the patient was weaned off ventilation within 2 to 3 hours. No early mortality occurred in this group of patients.

Using the transgastric LV short-axis view, a two-dimensional image-directed M-mode echocardiogram of the LV minor axis was recorded at the level of the tips of papillary muscles and printed on paper at a speed of 100 mm/s, with a simultaneous LV pressure trace and electrocardiogram. Once positioned, the transducer remained in situ throughout the study. The location of the M-mode cursor was checked with respect to the cross-sectional display before each measurement was made. Hemodynamic measurements including heart rate (HR), thermodilution cardiac output (CO), systolic and mean systemic pressures, mean and wedged pulmonary artery pressures (or mean left atrial pressure) were recorded simultaneously with each echocardiographic measurement. Baseline measurements were made before the institution of cardiopulmonary bypass when the patients were in a stable hemodynamic state and subsequently 0.5, 1, 3, 6, 12, and 20 hours after the final removal of the aortic cross clamp (taken as zero time for postoperative measurements).

Measurements and Calculations
From the LV M-mode echocardiogram and pressure trace, the minor dimension, cavity pressure, and anterior wall thickness were digitized off-line (sampling frequency, 100 Hz), along with depth and time calibration, by computer.26 27 The onset of QRS complex of the electrocardiogram was used to identify end diastole. The time from peak rate of pressure rise (peak +dP/dt) to peak rate of pressure fall (peak -dP/dt) was taken as LV ejection time.28 29 The time point of peak -dP/dt was checked with the closure of the aortic valve on M-mode echocardiogram. Three successive heart beats were digitized at each time interval, and mean values were recorded. From the digitized output and hemodynamic data, the following variables were derived: (1) LV dimension and wall thickness; (2) LV pressure and wall stress; (3) myocardial power, work, and LV coordination; and (4) hemodynamics of systemic circulation.

LV Dimension and Wall Thickness
To determine LV dimension and wall thickness, the end-diastolic dimension, the peak rate of dimension shortening and the lengthening during early diastole, and the peak rate of anterior wall thickening were derived to assess LV regional function.

LV Pressure and Wall Stress
From LV pressure pulse, we determined mean ejection pressure (MEP), peak +dP/dt normalized to maximal developed pressure (DP) (peak +dP/dt/DP), peak -dP/dt normalized to end-systolic pressure (peak -dP/dt/ESP), minimum diastolic pressure at early diastole, and end-diastolic pressure (EDP). We used the method of Falsetti et al30 to calculate circumferential midwall stress, and the peak value during systole was derived.

Myocardial Power, Work, and LV Coordination
In systole, the rate at which the myocardium does external work (ie, the power that it develops) is given as the product of wall stress and circumferential shortening rate. Stress was referred to a position in the midwall. Its circumference at this point is given by {pi}(D+T/2), where T and D are instantaneous values of dimension and wall thickness and the shortening rate is its first differential with respect to time. Values of local power were referred to in cubic centimeters of myocardium at end diastole. The time integral of power during an entire cardiac circle was derived to give the value of myocardial stroke work.26 27 A significant change of dimension during either isovolumic period represents ventricular incoordination. We used cycle efficiency, defined as the ratio of the ventricular pressure dimension loop area to that of the rectangle that just encloses it (ie, the ratio of useful external work to the maximum possible for myocardium working over the same range of pressure and dimension), to quantify these effects of ventricular incoordination in terms of their influence on energy transfer from myocardium to the circulation.26 27

Hemodynamics of Systemic Circulation
From thermodilution cardiac output measurements and simultaneous heart rate, LV ejection pressure, and mean systemic artery pressure (BPm), we calculated LV stroke volume index (LVSVI); LV stroke work index, SWILV=LVSVIx(MEP-EDP)x0.0136x9.8 (in mJ/m-2); and the stroke work index in the systemic circulation, SWISYS=LVSVIxBPmx0.0136x9.8 (in mJ/m2).31

Statistical Methods
Continuous data were presented as mean±1 SD. MINITAB statistical software (PC version, release 8, 1991, Minitab Inc)32 was used for statistical analysis. Clinical and surgical profiles among three groups were compared by one-way ANOVA or a {chi}2 test as applicable. Possible significant sources of variance of the perioperative functional measurements with respect to time, cardioplegic method, inotropic dose level, and their interactions were first identified by multivariant ANOVA. For each parameter thus demonstrated to be significantly affected by cardioplegia or a related interaction, postoperative changes with respect to prebypass level were further assessed by one-way ANOVA combined with the multiple-pair comparisons of 95% CI (Dunnett's method, family error rate 0.10 and individual error rate 0.020) within each group, respectively. A value of P<.05 was taken as statistically significant.


*    Results
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*Results
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Comparison of Clinical Data and Prebypass Left Ventricular Performance Before Cardiopulmonary Bypass
With a randomized approach, there was a matched distribution among the groups with respect to age, sex, valve disease, LV hypertrophy, incidence of associated coronary artery disease, and extent of revascularization. The same was true for the valve substitutes implanted and for aortic cross-clamp and cardiopulmonary bypass times. However, the requirement for positive inotropic drugs after surgery was significantly different between groups, being highest after WBP (90%) and least after CBP (30%) (Table 1Down). Before cardiopulmonary bypass, there was no significant difference between the groups with respect to LV loading conditions, systolic or diastolic function, ventricular coordination, or overall hemodynamics.


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  		Table 1. Comparison of Clinical and Perioperative Data

Significant Factors Affecting Perioperative LV Loading and Function
The results of multivariant ANOVA are summarized in Table 2Down. Time, cardioplegia, inotropic dose level, and their interaction were all significant sources of variance for one or more variable.


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  		Table 2. Results of Multivariate ANOVA of Perioperative LV Loading and Function

Time
Time was not a significant source of preload variance as assessed by end-diastolic cavity dimension. It was, however, a major source of variance in afterload, the peak systolic wall stress, reflecting the valve replacement. Time also affected all other hemodynamic measurements and LV function, except myocardial power. Interactions with time were inconspicuous, the only significant one being with cardioplegia for peak -dP/dt/ESP.

Cardioplegia and Inotropic Drugs
The different requirement for positive inotropic drugs also significantly influenced ventricular systolic function, ventricular diastolic function, and hemodynamics. Interactions between cardioplegia and inotropic drugs were frequent. Neither time nor the isolated effects of cardioplegia or inotropic drugs were significant sources of variance of cycle efficiency, but the interaction between cardioplegia and inotropic dose level was very significant (P<.001).

Comparison of Perioperative Changes in LV Loading, Hemodynamics, and LV Function
LV Loading and Hemodynamics
The postoperative fall of LV afterload, as reflected by peak systolic wall stress, was similar in each group. LV preload, assessed by end-diastolic dimension, remained unchanged in each group throughout the perioperative period. From 3 hours onward, LV stroke volume index and stroke work index in systemic circulation, reflecting overall systemic hemodynamics, both increased with CBP but not with either CCP or WBP (Table 3Down).


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  		Table 3. Changes in LV Loading Condition and Hemodynamics After AVR Within Each Group

LV systolic function. As afterload fell, there was a prompt and significant increase in contraction velocity with CBP, reflected by the peak rates of circumferential dimension shortening (FigureDown) and wall thickening regionally as well as by peak +dP/dt/DP globally. In contrast, these changes were of a small amplitude, showed larger scatter, and did not reach significance until 12 to 20 hours after CCP or WBP. Peak myocardial power had fallen significantly at 6 hours with WBP. Both regional and global stroke work were well maintained with CBP apart from a transient fall in regional stroke work at 30 minutes. However, both fell consistently with CCP and WBP, the largest changes occurring at 30 minutes (0.5 hour) after CCP, and at 6 hours after WBP (Table 4Down).



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  		Figure 1. Line graph shows perioperative changes in the peak rate of circumferential shortening (Vcf) with respect to time as plotted for each group. Data are expressed as mean±1 SEM. {blacktriangleup} indicates cold blood cardioplegia; {blacktriangledown}, warm blood cardioplegia; {bullet}, crystalloid cardioplegia; and CPB, cardiopulmonary bypass. *Significance compared with prebypass level by Dunnett's method.


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  		Table 4. Changes in LV Regional and Global Systolic Function After AVR Within Each Group

LV diastolic function and coordination. In contrast to systolic function, there was no immediate change in values of diastolic function with any cardioplegia technique. Although, peak -dP/dt/ESP had increased significantly by 6 hours in each group, peak rate of dimension lengthening during early diastole had increased significantly by 12 hours with CBP and CCP but not with WBP. Furthermore, LV minimum pressure during early diastole fell significantly only with CBP at 12 and 20 hours. LV coordination, as assessed by cycle efficiency, had increased significantly, above the prebypass level by 12 hours after CBP, but showed no consistent change with CCP and actually fell with WBP at 6 hours (Table 5Down).


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  		Table 5. Changes in LV Diastolic Function and Coordination After AVR Within Each Group


*    Discussion
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*Discussion
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Aortic valve replacement provides a unique opportunity to compare possible differences in the efficacy of myocardial preservation methods. Not only is the hypertrophied ventricle very susceptible to ischemia and reperfusion injury, particularly with a prolonged aortic cross-clamp time for a complex surgery, but also the benefits of normalization of ventricular afterload can be anticipated within the first 20 hours and readily assessed in the clinical setting.33 The randomization approach offered well-matched clinical and intraoperative data, and all three groups of patients had a similar incidence of concomitant revascularization. In contrast to animal models, current ethical surgical practice requires that myocardial dysfunction should be treated when present postoperatively. This involves the use of positive inotropic drugs, given according to standardized clinical indications, at Royal Brompton Hospital indications are a cardiac index of <2 L · min-1 · m-2 in spite of a pulmonary artery wedge pressure >=15 mm Hg. In the present study, this policy resulted in significantly different dose levels among the three cardioplegic methods, the highest being necessary with WBP and the lowest with CBP. It thus becomes necessary not only to quantify the variance of LV function due to cardioplegic method, along with time and inotropic agents, but also to look for interactions between them. Our study clearly shows that cardioplegia, inotropic dose level, and presence of an interaction between them are all significant sources of variations of aspects of perioperative LV function. It is thus justifiable to look closely at the postoperative changes in these variables seen over time that are significantly affected by cardioplegic method, whether alone or in combination with inotropic drugs.

Correction of aortic stenosis causes peak LV wall stress to fall, so that according to the myocardial force-velocity relation34 35 myocardial shortening velocity should increase. However, this response was found immediately after surgery only with CBP (FigureUp). With the other two methods, the increase was delayed until 12 and 20 hours. Myocardial relaxation is often impaired in the hypertrophied ventricle,36 but this tends to improve within 12 hours of relieving the aortic stenosis.33 In our study, CBP was associated with the most consistent improvement in both the rate and the extent of ventricular pressure fall during early relaxation, as well as in early diastolic filling rate. Furthermore, it was only after CBP that ventricular coordination, assessed by cycle efficiency, improved over the same time period. If one uses all these aspects as functional end points, it can be seen that CBP with its lower catecholamine requirement clearly offers better myocardial preservation than either CCP or WBP in the hypertrophied human ventricle. Although many experimental studies have shown that positive inotropic drugs may restore the systolic function of "stunned myocardium,"37 38 our clinical finding was that even with an increased dose of inotropic drugs and using the techniques of CCP or WBP the expected response of an increased shortening velocity predicted by the force-velocity relations was not restored. However, the peak myocardial power was nearly maintained. Thus, the mechanical dysfunction commonly seen after cardiac surgery cannot be ascribed purely to impaired myocardial contractility as defined by force-velocity relations. Our observations in fact support the view that diastolic function and ventricular incoordination also play important roles.33

It is possible that the differences in the rate and extent of recovery of LV function we described were not only related to the cardioplegic regimens themselves but also to the methods of delivery. As has been pointed out by Menasche et al,19 the oxygen consumption of the hypertrophied myocardium during warm cardioplegic arrest is still quite significant. This implies that the hemoglobin concentration, perfusion flow rate, and transmural flow distribution are all likely to be critical in ensuring adequate delivery of oxygen to the myocardium and interstitial tissue. Although a flow rate of 80 mL/min with hemoglobin (Hb) 80 g/L at a perfusion pressure of 40 mm Hg has been recommended for continuous retrograde perfusion,39 and a 10-minute interruption or even multiple interruptions of perfusion have been demonstrated to be acceptable,40 41 we deliberately used at least 200 to 250 mL/min with Hb 70 to 80 g/L because we believe it to be more appropriate for the hypertrophied ventricle, and we limited interruption of perfusion to <5 minutes. The unfavorable effect of increased intercapillary distances on oxygen diffusion and the inhomogeneous distribution of myocardial perfusion in vivo have been well documented in the working hypertrophied ventricle.42 43 44 45 Similar problems may also occur during ventricular arrest, particularly the loss of intramyocardial pump function46 combined with a retrograde route may well result in regional perfusion deficits47 and microvascular maldistribution.48 The manipulation of retrograde perfusion pressure has failed to improve these shortcomings,49 but hypothermia seems to have favorable effects over normothermia on postischemic functional recovery.50 In the hypertrophied ventricle, therefore, unintentional ischemia is likely to be particularly significant during normothermia retrograde perfusion by the considerably high oxygen consumption associated with suboptimal nutrient distribution and, in particular, the subendocardium, which is the most susceptible area.51 Subendocardial ischemia results in LV dysfunction being more significant in longitudinal than in circumferential function.52 53 54 Compromised longitudinal function not only reduces the rate and extent of LV free wall thickening and thus of circumferential dimension shortening but is also a major cause of ventricular incoordination.55 A significant increase in wall thickening rate and cycle efficiency with CBP supports this hypothesis, although direct measurements are needed in a further study to confirm it.

There are several limitations to this study. We included patients with both aortic stenosis and regurgitation, and 30% had concomitant coronary artery disease. Although these factors were similarly distributed among the three groups by randomization, their presence will have caused increased baseline variances. Similarly, cardioplegia composition and its delivery time and temperature are not precisely controlled in routine clinical practice. Again, these factors are unlikely to have altered the overall results of the study, although they may have reduced its sensitivity in detecting more subtle differences between cardioplegia methods. We did not measure the oxygen saturation of the efflux during WBP, although flow rates were continuously monitored and kept well above the levels at which it has been demonstrated that significant acidosis does not occur and that residual oxygen saturation is well maintained.19 Preoperative LV stroke volume was calculated by pulmonary thermodilution catheter, so we will have underestimated its true value in 15 patients with aortic regurgitation. However, the prevalence of patients with aortic regurgitation was similar in the three groups. The validity of the techniques we used to study LV function may have been influenced by the echocardiographic transducer position. This was routinely checked and referenced to mitral valve anatomy before each determination. Mild or random variation in position among observations would increase error variance but would not lead to consistent differences between the groups. Furthermore, the change in ventricular properties with position around the ventricular circumference is small at mid-cavity level, so it is doubtful that transducer displacement by as much as 1 cm would significantly alter measured variables. The selection of measurements we made of LV systolic and diastolic function was based on the capability of the techniques we used and was thus to some extent arbitrary. We have documented their reproducibility elsewhere.33 The constancy of LV end-diastolic dimension after AVR made it unnecessary to allow for changes in preload, for example by determining preload recruitable stroke work, a technique that does not lend itself to repeated measurements in the postoperative situation. Instead, we used peak myocardial power to assess the change in contractility,35 which is quite insensitive even to the change in afterload caused by relief of aortic stenosis,33 and has clear physical dimensions, with measurements made direct rather than extrapolating. We did not construct a basic lagrangian stress-strain relation, since previous experience with identical methods has shown that in intact humans, it departs very significantly from the theoretical exponential on which it is based.56 Generally, the use of a higher dose of positive inotropes during reperfusion would not reflect favorably on the efficacy of myocardial preservation; however, we do not regard the differing doses of catecholamine used with the three cardioplegic methods as a confounding factor. Provided that their administration is based on clinically defined criteria, differing inotropic drug requirement must be regarded as an inseparable part of any cardioplegic method used in clinical practice. Attempts to dissociate the two are not, therefore, critical to the interpretation of our results.

In summary, perioperative transesophageal echocardiography together with high-fidelity ventricular pressure recording and thermodilution cardiac output offers a comprehensive and practical approach to the study of LV function in the cardiac surgical setting. The data in this study have shown that better, although still not optimal, preservation of physiological function in the hypertrophied LV can be obtained by using CBP. The theoretical advantages of WBP under currently used techniques have yet to be realized, and a full understanding of retrograde myocardial perfusion of the hypertrophic LV during arrest is needed. In the clinical setting, therefore, the hypothermia technique may still be the method of choice for preserving the hypertrophied myocardium during retrograde perfusion until a truly homogeneous and aerobic arrest can be easily and predictably achieved. To reach this ideal situation, further investigations such as modifying the composition and delivery techniques in retrograde WBP are required.


*    Selected Abbreviations and Acronyms
 
AVR = aortic valve replacement
CCP = crystalloid cardioplegia
CBP = cold blood cardioplegia
LV = left ventricle, left ventricular
WBP = warm blood cardioplegia


*    Acknowledgments
 
Supported by grants from the Wellcome Trust (ASW2, 1992), British Heart Foundation (New Clinical Initiative 3014178), Garfield Weston Trust, and Royal Brompton Hospital Special Cardiac Fund, London, UK.


*    Footnotes
 
Reprint requests to John R. Pepper, FRCS, the Academic Department of Cardiothoracic Surgery, National Heart and Lung Institute, Sydney Street, London SW3 6NP, UK.


*    References
up arrowTop
 up arrowAbstract
 up arrowIntroduction
 up arrowMethods
up arrowResults
up arrowDiscussion
*References
 

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