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Ann Thorac Surg 2001;72:58-64
© 2001 The Society of Thoracic Surgeons
a Department of Cardiothoracic Surgery and Anesthesiology, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden
b Department of Cardiology, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden
Accepted for publication April 3, 2001.
Address reprint requests to Dr Alb
ge, Department of Cardiothoracic Surgery and Anesthesiology, Huddinge University Hospital, SE-141 86 Stockholm, Sweden
e-mail: anders.albage{at}thsurg.hs.sll.se
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Abstract |
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Methods. Changes in ANP, brain natriuretic peptide (BNP), antidiuretic hormone (ADH), aldosterone, and angiotensin II were measured in 16 patients (mean age 53 ± 9 years) without concomitant heart disease undergoing the Maze (III) procedure. Ten matched patients (mean age 56 ± 9 years) undergoing multivessel coronary artery bypass grafting served as controls. Measurements with hemodynamic correlates were obtained at baseline and after ventricular pacing (100 stimulations/minute), directly preoperatively, postoperatively and the first postoperative day. Weight gain and diuretic requirements were recorded.
Results. The major differences in hormonal response were significantly higher plasma levels of ADH (Maze preoperative 1.1 ± 0.4, postoperative 24.9 ± 16.7 pmol/L; controls preoperative 1.1 ± 0.1, postoperative 3.7 ± 3.5 pmol/L) and aldosterone (Maze preoperative 106 ± 94, postoperative 678 ± 343 pmol/L; controls preoperative 124 ± 79, postoperative 171 ± 93 pmol/L) in the Maze group on the first postoperative day (p < 0.001). Preoperative baseline plasma levels of ANP and pulmonary capillary wedge pressures (PCWP) were higher in the Maze group but this difference was abolished by pacing, and postoperatively, ANP levels changed in parallel to the PCWP in both groups. Diuretic requirements were significantly higher in the Maze group.
Conclusions. Substantial increases in ADH and aldosterone were observed after the Maze procedure, indicating these hormones as important determinants in postoperative fluid retention. The role for ANP in this setting may be a less prominent than previously reported.
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Introduction |
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TopAbstractIntroductionMaterial and methodsResultsCommentReferences |
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Thus, ANP is to date the most widely studied hormone in association with post-Maze fluid retention, and has been found to be significantly reduced both early [8–10] and late [8] postoperatively, in patients undergoing combined valvular and Maze procedures. However, involving solely patients with valvular heart disease and atrial fibrillation, these studies have been criticized for patient heterogeneity, obscuring the assessment of the effects of the Maze procedure per se. Furthermore, most of these studies have not addressed perioperative changes in other coexisting vasoactive hormones [8, 9]. Substantial increases in plasma levels of antidiuretic hormone (ADH) have been demonstrated after open heart operations [11, 12], possibly contributing to postoperative fluid balance changes. In addition, aldosterone, which promotes the retention of sodium and water in the kidneys, is considered to be a major actor in the pathophysiology of congestive heart failure [13].
The aim of this study was therefore to examine plasma levels of ANP, brain natriuretic peptide (BNP), ADH, aldosterone, and angiotensin II, in a perioperative case-control setting and in relation to hemodynamic variables with and without ventricular pacing, in patients undergoing isolated Maze procedures for atrial fibrillation.
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Material and methods |
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TopAbstractIntroductionMaterial and methodsResultsCommentReferences |
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Ten patients (8 men and 2 women), with a mean age of 56 ± 9 years (range 50 to 64 years) undergoing routine elective coronary artery bypass grafting (CABG) served as controls. These patients were selected and matched for age and gender. Inclusion criteria were significant three-vessel disease requiring multiple bypass grafting, a normal left ventricular ejection fraction and absence of significant concomitant heart or systemic disease. All of these patients were preoperatively in sinus rhythm.
The study was approved by the local hospital ethics commitee and all patients expressed informed consent before inclusion.
Protocol
Anesthetic methods were identical in both patient groups. After induction of anesthesia, a Swan-Ganz catheter with paceport (Baxter Edwards Swan-Ganz Paceport catheter, model 93A 1H-7.5F, Irvine, CA) was placed transcutaneously through the internal jugular vein to the pulmonary artery for measurements of right atrial pressure (RAP), PCWP, and cardiac output through thermodilution. A radial arterial line was used for on-line blood pressure monitoring and for collecting arterial blood samples. Heart rate was registered via conventional surface electrocardiogram. Ventricular pacing was achieved through the paceport lead (Baxter Edwards transluminal V-pacing probe, model 98-100H).
Hemodynamic variables were measured and arterial blood samples withdrawn for subsequent analysis at five different occasions before and after the operation. The first measurements were done with the anesthesized patient in the supine position and in a hemodynamically stable condition, directly preoperatively before skin incision, at baseline (I) and after 6 minutes of ventricular pacing at 100 stimulations/minute (II). Subsequent measurements were then done directly postoperatively after skin closure with the patient in a clinically stable hemodynamic and respiratory condition, but still intubated (III), and on the first postoperative day with the patient extubated, at baseline (IV) and after ventricular pacing for 6 minutes (V). During measurements, the patient was disconnected briefly from the ventilator when intubated, to prevent influence from positive airway pressure breathing. Rapid ventricular pacing directly after the operation was not considered clinically safe and was therefore excluded from the protocol.
On-table TEE data for atrial size were collected before surgery (I), with the analyses performed by the same physician. Two different projections (two chamber long axis and right atrium/vena cavae long axis) were used for measurements of each atrium. Postoperative patient data were recorded regarding the change in weight postoperatively as compared to preoperative dry weight, and amounts of diuretics administered intraoperatively and during the first 3 days postoperatively. Departmental clinical routines for diuretic treatment were not altered by the study. The objective in both groups was to maintain an adequate urine output postoperatively (more than 1 mL/kg per hour) and have the patients return to preoperative weight within 3 to 5 days.
Arterial blood samples were drawn and collected into ethylenediaminetetraacetic acid-treated 10-mL tubes, stored in ice, immediately refrigirator centrifugated to separate the plasma (P) and preserved at -70°C. Radioimmunoassay (RIA) analysis of ANP, BNP, ADH (vasopressin), aldosterone, and angiotensin II were then subsequently performed on all arterial blood samples collected. P-ANP was measured with RIA using a polyclonal antiserum (Peninsula Laboratories, Inc., Belmont, CA) and iodinated ANP (Euro-Diagnostica, Malmö, Sweden) as tracer. ANP was extracted from a 1.0 mL sample using solid phase extraction (Sep-Pak, Waters, Milford, MA). BNP was measured using SHIONORA BNP solid-phase immunoradiometric assay (IRMA) (CIS Bio International, Gif-Sur-Yvette Cedex, France) based on two monoclonal antisera recognizing the C-terminal region and the intramolecular ring structure of BNP, respectively. The IRMA does not cross-react (much less than 0.01%) with hANP or other related peptides. The detection limit was 0.6 pmol/L, and the intra- and interassay coefficients of variation 3.7% and 3.9%, respectively, at 43 pmol/L. P-Vasopressin was measured with RIA (Euro-Diagnostica, Sweden). Vasopressin was extracted from a 0.8-mL sample with ethanol before RIA, all according to the manufacturer’s description. S-Aldosterone was measured with RIA (Coat-a-Count Aldosterone, DPC, Los Angeles, CA). P-Angiotensin II was measured with RIA (Angiotensin II RIA, Bulmann Laboratories AG, Switzerland). Angiotensin II was extracted from a 1.2-mL sample using solid phase extraction (Sep-Pak). Total coefficient of variation was typically less than 12% for vasopressin, aldosterone and angiotensin II, and less than 30% for ANP.
Statistics
Data are presented as mean ± SD. Baseline characteristics between groups were tested with unpaired t test. Peri- and postoperative changes were tested with repeated measures analysis of variance (ANOVA) with group as between factor and data collected at the different time points as within factor. In case of a significant overall difference between groups, or interaction between group and the measured variable, contrasts were calculated for the specific time points in SuperANOVA (Abacus Concepts, Inc; Berkeley, CA). A p value of less than 0.05 was considered significant.
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Results |
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TopAbstractIntroductionMaterial and methodsResultsCommentReferences |
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Preoperative atrial size was significantly different between groups only in one of two measured diameters for each atrium (right atrial end-systolic cava-cava diameter: Maze 52 ± 9, controls 43 ± 6 mm, p < 0.05; left atrial end-systolic diameter dorsal left atrium-mitral annulus: Maze 37 ± 11, controls 27 ± 5 mm, p < 0.05). Mean cardiopulmonary bypass time and aortic occlusion time were significantly longer in the Maze group as compared to the CABG-group (170 ± 20 versus 88 ± 20 minutes and 77 ± 10 versus 43 ± 10 minutes, respectively).
Plasma levels of vasoactive hormones measured are presented in Table 1 and corresponding hemodynamic data in Table 2. The major hormonal responses postoperatively were significantly higher plasma levels of antidiuretic hormone (F = 17.1; p < 0.001) and aldosterone (F = 16.8; p < 0.001) in the Maze group as compared with the control group (Fig 1). Preoperative levels of these hormones were low and similar between groups.
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Comment |
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TopAbstractIntroductionMaterial and methodsResultsCommentReferences |
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Antidiuretic hormone (or arginine vasopressin) is involved in the homeostasis of blood volume and osmolality and conserves water by concentrating the urine, acting mainly on the collecting ducts of the kidneys [14]. In addition, high doses of ADH cause vasoconstriction, a response used in the treatment of severe vasodilatory hypotension after cardiac operations [15]. An increased ADH response during cardiac operation using cardiopulmonary bypass (CPB) has been found by several authors in adults [11] and children [12], with the postulated mechanisms being stress and relative hypotension. In one study comparing patients undergoing valvular operation or CABG, and with CPB times of approximately 150 minutes, the ADH increase was five fold during CPB and not different between groups [16]. Others authors studied 19 pediatric Fontan patients and found a 10-fold increase in ADH with a residual significant elevation up to 10 days postoperatively [12]. Interestingly, the children with the most severe fluid retention had the highest levels of ADH after operation. In the present study, the ADH response was twice as high in the Maze group directly postoperatively and continued to increase to 20-fold higher levels on the first postoperative day, whereas the ADH levels of the CABG group declined to within normal range. Thus, it is conceivable that physiologic actions of increased plasma levels of ADH play a significant role in observed fluid retention after the Maze procedure as well, although this probably represents a generalized stress response to any prolonged open heart procedure.
Aldosterone is an adrenal mineralocorticoid hormone involved in the renin-angiotensin axis for volume and blood pressure homeostasis. Its principal action is sodium and water retention as well as potassium and magnesium excretion in the distal convoluted tubules of the kidneys [14]. Recently, the hormone has gained renewed interest as a major actor in the compensatory mechanisms of heart failure [13]. In heart surgery, aldosterone has been found to increase significantly in adults [17] and in children [18]. Similarily, this is most likely another stress response to circulatory changes during cardiopulmonary bypass. In the present study, the aldosterone levels of the controls were elevated three fold early after operation but returned to normal levels after 1 day. In the Maze group, however, the aldosterone levels increased seven fold early postoperatively and were maintained at similar levels on the first postoperative day.
Spironolactone, an aldosterone receptor blocker, has recently been shown to have major positive effects in a heart failure population [13]. Cox and associates [1] used spironolactone empirically and successfully to treat fluid retention after the Maze procedure. Our data suggest that the reported effectiveness of this drug may be achieved through inhibition of elevated aldosterone levels. We have used spironolactone similarily in all Maze procedures, but the treatment was initiated after completion of the study protocol.
Regarding natriuretic peptide response, it is important to include hemodynamic correlates when release mechanisms are discussed. Throughout this study, variables such as mean blood pressure and cardiac output were similar between groups. Although ANP levels were higher in the Maze group preoperatively, which is consistent with a larger atrial size and with the effects of atrial fibrillation [7], this difference was abolished by ventricular pacing. Equalizing PCWP and heart rate between groups resulted in similar and parallel changes in ANP plasma levels (Fig 2). Significant elevations of ANP levels have been reported previously after cardiac valve and CABG operations [19], but a similar postoperative increase in relation to the measured PCWP was not evident in the present study. In contrast, significant reductions in ANP levels have been documented after combined Maze and valvular operations with an early lack of correlation between ANP levels and PCWP [8–10]. These data were not confirmed by the present study. It is possible that a more vigorous stimulation of ANP release or measurements during an extended time frame would have elicited a different response between groups. However, our data suggest that decreased levels of ANP may not be a factor of such importance as has previously been proposed in the setting of post-Maze fluid retention. It is conceivable that in the previous studies, the reduced levels of ANP could to some extent be associated with the correction of the valvular problem and improvement of congestive heart failure, rather than from the actual Maze incisions per se. In the present study, both groups of patients had the right atrial appendage either removed or ligated as part of their procedure so this variable should not be involved in the interpretation of the results.
The plasma levels of BNP did not differ significantly between the groups at any one time throughout the study, and its role in this operative situation is unclear. Angiotensin II is a very potent vasoconstrictor and extensively described in various papers on heart failure. In this study, however, there were no significant differences between groups and a major influence on the tendency of fluid retention in the Maze group is unlikely.
The major limitation in this study is associated with the comparison between the Maze group and the CABG group. Although differing in preoperative variables such as rhythm, left ventricular function and left atrial size, as well as procedure times, the two groups were similar in hemodynamic measurements throughout the study. The Maze group consisted basically of patients with lone atrial fibrillation, that is, without any other structural heart disease affecting atrial pressures or ventricular function. Similarily, for the control group, we wanted to avoid confounding factors from long-standing valvular heart disease. Hence, we believe that the similarities in hemodynamic variables justify the conclusions drawn from our observations. However, it is important to note that the elevated levels of ADH and aldosterone most likely are not specific for the Maze procedure but merely a reflection of a long and complex procedure.
Furthermore, fluid retention is a concept difficult to define or standardize. For simplicity, we elected to focus in this study on the clinically based requirements of diuretics in the early postoperative phase. The Maze group needed significantly more of diuretic therapy, probably reflecting a clinical alertness to maintain a continuous and adequate urine output and avoid fluid retention problems for several days postoperatively. As indicated by the weight changes for each group over time, the treating physicians were not overzealous.
Finally, other hormones than the ones studied might be involved as well. Urodilatin, another member of the natriuretic peptide family, was recently reported to have impact on renal excretion of sodium and water after cardiopulmonary bypass [20].
In conclusion, substantial perioperative increases in antidiuretic hormone and aldosterone indicate that these hormones are important determinants of the observed fluid retention after the isolated Maze procedure. In this study, atrial natriuretic peptide levels changed in parallel to the PCWP in both the Maze group and the control group suggesting a less prominent role for this hormone than has previously been reported.
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References |
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TopAbstractIntroductionMaterial and methodsResultsCommentReferences |
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rd S. Plasma levels of atrial natriuretic peptide at rest and during exercise in heart failure-influence of cardiac rhythm and haemodynamics. Clin Physiol 1991;11:183-196.[Medline]
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