Mechanism of Polyuria and Natriuresis Associated with Paroxysmal Supraventricular Tachycardia

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1 Mechanism of Polyuria and Natriuresis Associated with Paroxysmal Supraventricular Tachycardia Rong-Chi TSAI, M.D., Tohru YAMAJI, M.D., Miyuki ISHIBASHI, M.D., Fumimaro TAKAKU, M.D., San-Jou YEH, M.D.,* Ying-Shiung LEE, M.D.,* Jui-Sung HUNG, M.D.,* and Delon WU, M.D.* SUMMARY Changes in plasma levels of atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) were studied in 8 patients during a 30 min period of induced supraventricular tachycardia (SVT). The mean plasma ANP concentration increased immediately after the onset of SVT, peaked at 30 min and gradually returned to the control level. The mean plasma AVP concentration, on the other hand, was suppressed during SVT and rebounded above the control level in the post-svt period. In 4 patients, SVT was associated with polyuric and natriuresis. The mean urine volume in these patients increased to 580% of the control and the mean urinary sodium excretion to 278% of the control, respectively. It was concluded that both a stimulation of ANP secretion and an inhibition of AVP release, elicited by an increase in atrial pressure, may be responsible for polyuria and natriuresis associated with SVT. Additional Indexing Words: Paroxysmal supraventricular tachycardia Atrial natriuretic peptide Arginine vasopressin Polyuria Natriuresis INCE the first description by Wenckebach,1) it is well known that polyuria is often associated with paroxysmal atrial arrhythmias or paroxysmal supraventricular tachycardia (PSVT). On the basis of changes in urine composition, this phenomenon has been attributed to transient suppression of arginine vasopressin (AVP) secretion from the neurohypophysis that is me- From the Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Tokyo, Japan and *Section of Cardiology, Department of Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan, Republic of China. Address for reprint: Rong-Chi Tsai, M.D., Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113, Japan. Received for publication July 1, Manuscript revised October 8,

2 204 TSAI, ET AL. Jan. Heart J. March 1987 diated by atrial distension.2),3) The observation by Canepa-Anson et al3) that plasma levels and urinary excretion of AVP were decreased during induced tachycardia in one patient with atrioventricular nodal tachycardia may support this hypothesis. However, the occurrence of natriuresis during paroxysms cannot be explained simply by the inhibition of AVP release. Recently, a new peptide with potent natriuretic activity (atrial natriuretic peptide: ANP) was isolated from human atrial tissue, sequenced and synthesized.4) A bolus injection (i.v.) of ANP into healthy volunteers was shown to cause diuresis, natriuresis and a fall in blood pressure.5) To determine whether ANP may be involved in the polyuria and natriuresis associated with PSVT, we examined the changes in plasma ANP and AVP levels during induced SVT. METHODS Eight patients (4 men and 4 women), aged between 28 and 58 years, were studied. Informed, written consent was obtained from the patients prior to the study. All of the patients had electrocardiographic documentation of PSVT. Intervals of PSVT attacks ranged from 2 days to 3 months. The patients had normal liver and renal function, and there was no evidence of organic heart disease or systemic hypertension. Electrophysiological studies were performed in the supine, non-sedated state. The patients were asked to void 30 min before the study and fluid intake was forbidden thereafter. A # 7 quadripolar electrocatheter was positioned across the tricuspid valve for His bundle recording and right ventricular pacing. A # 7 hexapolar electrocatheter was then introduced into the coronary sinus to record left and right atrial electrogram and to stimulate the right atrium. The distal two electrodes of both catheters were used to map the atrial activation sequence during induced SVT. After the initial electrophysiological study was done using standard multiple simultaneous intracardiac and extracardiac recordings, SVT was induced and allowed to continue for 30 min. SVT was terminated by carotid sinus massage and/or rapid atrial pacing and/or by the introduction of a single atrial premature depolarization. Blood samples were collected at 0, 1, 5, 15, 30, 32, 35, 45 and 60 min after the induction of SVT. In some patients, additional blood samples were taken every 15 min up to 90 min. Blood was transferred to a chilled tube containing EDTA and centrifuged. Plasma was stored at -80 Ž until assayed. Urine was collected before the catheterization, and 45 min after the induction of SVT.

3 Vol.28 POLYURIA AND NATRIURESIS ASSOCIATED WITH PSVT 205 No.2 Plasma concentrations of ANP were measured by a sensitive and specific radioimmunoassay after separation of ANP from plasma by means of affinity chromatography on anti-anp-coupled agarose. The details of the radioimmunoassay are described elsewhere.6) The recovery of ANP from plasma was 80.7 }1.0% (mean }SEM, n=37) and the sensitivity of the assay was 12.5 pg/ml. The coefficients of variation averaged 7.2% for intra-assay error and 11.1% for inter-assay error. Plasma levels of AVP were assayed utilizing a radioimmunoassay kit kindly provided by Mitsubishi Petrochemical Co. (Tokyo, Japan). Prior to radioimmunoassay, AVP in plasma was separated by a Sep-Pak C18 cartridge (Waters Associates, Milford, Mass., USA) and eluted with 1ml methanol. The extract was dried under a stream of nitrogen gas, reconstituted with the assay buffer and an aliquot corresponding to 0.4ml plasma was assayed according to the general procedure described previously in detail.7) The recovery of AVP from plasma was 84.7 }2.1% (mean }SEM, n=27) and the sensitivity of the assay was 0.2pg/ml. The coefficients of variation averaged 6.7% for intra-assay error and 11.0% for inter-assay error. Urinary sodium and potassium concentrations were measured by a Nova 1 ion selective electrode analyzer (Nova Biochemical, Newton, Mass., USA). Urine osmolarities were determined by freezing point depression using an Advanced Osmometer, Model 3 C2 (Needham Heights, Mass., USA). Results in the text and figures are expressed as the mean }SEM. Statistical significance was evaluated by Student's t-test. RESULTS Electrophysiological studies revealed that 6 patients had SVT utilizing a Kent bundle, one displayed atrioventricular (AV) node reentry and the remaining patient had both AV and sino-atrial node reentry. Ventricular rates increased from /min during sinus rhythm to /min after the induction of SVT. The mean systolic brachial arterial pressure dropped from 133 to 111mmHg, while no significant change was observed in the mean diastolic brachial arterial pressure. Fig.1 illustrates the changes in plasma levels of ANP and AVP during induced SVT. Plasma ANP concentrations, which ranged from 12.5 to 133 pg/ml in the control, immediately rose, peaked 15 to 35 min after the initiation of SVT and gradually decreased. The mean plasma ANP levels at 1, 5, 15, 30, 32, 35 and 45 min were significantly (p<0.05 at 1 min and 45 min; p<0.01 at 5 min, 30 min and 35 min; p<0.001 at 15 min and 32 min) higher than the control. The peak plasma ANP concentrations in individual cases

4 206 TSAI, ET AL. Jpn. Heart JM arch 1987 Fig.1. Changes in the mean plasma concentrations of atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) during induced supraventricular tachycardia (SVT). Vertical bars represent SEM and number in parentheses the number of observations. *** p< * p<0.05 vs control, ** p<0.01, Fig.2. Changes in the mean plasma concentrations of atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) during induced supraventricular tachycardia (SVT) in 4 patients with polyuria (A) and in 4 patients without polyuria (B). Vertical bars represent SEM and number in parentheses the number of observations. * p<0.05 vs control, ** p<0.01.

5 Vol.28 No.2 POLYURIA AND NATRIURESIS ASSOCIATED WITH PSVT 207 were highly variable. They ranged from 84.1 to 431pg/ml, corresponding to 240 to 1,560% of the control. No significant correlation was observed between peak plasma ANP concentrations and hemodynamic changes. Plasma AVP levels, on the other hand, began to decrease 1 min after the onset of SVT, reached a nadir between 5 and 30 min, and rebounded above the control level. The mean plasma AVP concentrations at 5 and 15 min were statistically (p<0.05) lower than the control. Four of the 8 patients voided hypo-osmolar urine 15 min after the termination of SVT. Urine volumes ranged from 4.0 to 8.9ml/min and the mean urine volume (6.1ml/min) corresponded to 580% of the control. Moreover, a concomitant increase in both sodium and potassium excretion was observed in these patients. The mean sodium and potassium excretions were 0.42 and 0.05mEq/min, which corresponded to 278% and 214% of the control, respectively. The remaining 4 patients did not pass urine 15 min after the termination of SVT. Changes in the mean plasma concentrations of ANP and AVP during induced SVT in these 2 groups are shown separately in Fig.2. The temporal patterns of plasma ANP and AVP were similar. The mean peak plasma ANP concentration was higher in the group of the patients with polyuria, although the difference was not statistically significant. DISCUSSION The present study demonstrated that plasma levels of ANP are elevated consistently during induced SVT. The result agrees with the previous reports8)-10) that attacks of paroxysmal atrial arrhythmias or PSVT are associated with a striking increase in plasma ANP concentrations. It is well known that one of the most characteristic changes during SVT is a low stroke volume with an increase in atrial pressure.11)-14) This may be due to atrial contraction against closed AV valves; i.e., the mistiming of atrial systole.11) This led to the inference that increased ANP secretion during SVT was elicited by the stretching of cardiocytes secondary to an increase in atrial pressure. The response of ANP secretion was rapid; plasma levels were already elevated 1 min after the onset of SVT in all of the patients. The peak plasma ANP concentrations, on the other hand, were markedly variable in each patient. No significant correlation was obtained between the peak plasma ANP concentrations and hemodynamic changes in individual patients. The reason for this wide variation in the maximal ANP responses remains unknown at present. Plasma ANP concentrations decreased gradually after reaching the peak

6 208 TSAI ET AL. Jpn. Heart JM arch 1987 level. The mean plasma ANP concentration declined to 50% of the peak 15 min after the termination of SVT. The biological half life of ANP in men, measured by infusion of synthetic ANP into healthy subjects, is shorter than 10 min.5) Thus, atrial cardiocytes may continue to secrete ANP after stimulation by increased atrial pressure. Plasma levels of AVP, on the other hand, began to decline after the onset of SVT. They remained low during the attack, then returned to control levels. In addition, a post-inhibition rebound rise of plasma AVP was observed. Since stretch receptors for AVP secretion are located in the left atrium,15) the observed inhibitory effect of SVT on plasma AVP concentrations may reflect suppression of AVP release due to stimulation of the receptors.16)-19) In 4 of the 8 patients, polyuria was associated with induced SVT. Polyuria during SVT may be a result of inhibition of AVP release, since a marked decrease in urine osmolarity is consistent with an increase in free water clearance due to inhibition of AVP secretion. However, it should be noted that increased sodium excretion was observed concomitantly; a decrease in AVP release per se could not account for this phenomenon. However, injections of ANP in humans result in a several-fold increase in sodium excretion.5),10),20)-22) Thus, both the stimulation of ANP secretion and the inhibition of AVP release may be responsible for polyuria and natriuresis associated with SVT. It is noteworthy that the peak plasma ANP concentrations in patients with polyuria and natriuresis ranged from 227 to 431 pg/ml, suggesting that plasma ANP levels exceeding 200pg/ml may trigger an increase in urine volume and sodium excretion. In order to answer the important question of the role of ANP in water and electrolyte homeostasis in man, however, the minimum plasma ANP level required for the induction of biological action should be carefully determined in future studies. Polyuria did not occur during SVT in the remaining 4 patients. Plasma levels of both ANP and AVP during induced SVT in these patients did not differ significantly from the patients with polyuria, suggesting that ANP and AVP levels per se are not sufficient to explain the occurrence of polyuria. However, the possibility that an increase in urine flow and sodium excretion was overlooked in patients without polyuria because of a lack of urinary urgency could not be ruled out, since urine was not collected via an indwelling catheter. REFERENCES 1. Wenckebach KF, Winterberg H: Die unregelmassige Herztatigkeit und ihre klinische Bedeutung. W Engelmann, Leipzig and Berlin, p252, 1927

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