HAEMODYNAMIC CONSEQUENCES OF CITRATE INFUSION IN THE ANAESTHETIZED DOG: COMPARISON BETWEEN TWO CITRATE SOLUTIONS AND THE INFLUENCE OF BETA BLOCKADE

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1 Br.J. Anaesth. (1979), 51, 513 HAEMODYNAMIC CONSEQUENCES OF CITRATE INFUSION IN THE ANAESTHETIZED DOG: COMPARISON BETWEEN TWO CITRATE SOLUTIONS AND THE INFLUENCE OF BETA BLOCKADE L. J. DROP AND D. SCHEIDEGGER SUMMARY We have compared the effects of a solution of acid-citrate-dextrose (ACD) with those of a solution of citrate-phosphate-dextrose (CPD), infused at equal rates, on blood calcium ion concentration and different indices of haemodynamic performance in 17 dogs. The influence of beta adrenergic blockade on these changes was examined. The effects of ACD and CPD were studied in five dogs and were similar. Peripheral vascular changes were the principal cause of arterial hypotension. In six dogs, propranolol 0.5 mg kg" 1 intensified the hypocalcaemia-induced left ventricular dysfunction. The rapid i.v. infusion of citrated whole blood can be associated with arterial hypotension (Denlinger and Nahrwold, 1976) as a result of a decrease in the concentration of calcium ion ([Ca 2+ ]) in the plasma (Cooper et al., 1973; Denlinger and Nahrwold, 1976; Olinger et al., 1976). This change in arterial pressure may be secondary to alterations in ventricular function or peripheral vascular function, or both. The blood preservatives which are used commonly contain either citric acid, trisodium citrate and dextrose (ACD) or trisodium citrate, citric acid, sodium phosphate and dextrose (CPD). In the blood transfusion service of the Massachusetts General Hospital, where between and units of whole blood are collected each year, ACD solution is used almost exclusively for blood preservation, primarily because of the technique employed to prepare platelet-rich plasma from donor blood for blood component therapy. Although Hedley-Whyte and associates (1976) have suggested that the CPD solution may be a better alternative for blood preservation, experimental data have not been available to demonstrate its superiority in the maintenance of haemodynamic stability in the recipient of the blood. Preliminary observations (Bunker, Bendixen and Murphy, 1962; Smith and Hurley, 1969) have suggested that the haemodynamic effects of citrate L. J. DROP, M.D.; D. SCHEIDEGGER,* M.D.; The Anaesthesia Laboratories of the Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts 02114, U.S.A. * Present address: Service de Cardiologie, Hopital Cantonal, 1200-Geneve, Switzerland. Correspondence to L. D O912/79/ O9 $01.00 loading may be more pronounced in the presence of beta blockade. However, the magnitude of this interaction has not been established. The present study was undertaken to compare the effects of an infusion of ACD solution with those of an infusion of CPD solution, administered at the same rate, upon [Ca 2+ ] and haemodynamic function in the anaesthetized dog. In addition we sought to define the extent to which the haemodynamic consequences of transient hypocalcaemia may be modified by beta blockade. METHODS Seventeen mongrel dogs of either sex (weight range kg) were anaesthetized with thiopentone 25 mg kg" 1 i.v. followed by the spontaneous inhalation of halothane % in oxygen via a cuffed endotracheal tube. Catheters were placed in the femoral artery, right atrium and pulmonary artery (Edwards Laboratories). In all animals, a period of approximately 1 h elapsed between the administration of the thiopentone and the onset of the experiment. Core temperature was monitored using an oesophageal temperature probe (Yellow Springs Instruments) and did not vary by more than 0.5 C from 37 C in any animal. Haemodynamic measurements Femoral arterial, right atrial and pulmonary arterial pressures were recorded continuously (Hewlett Packard 7788 recorder and Sanborn 267 BC transducers). Mean pulmonary artery balloon-occluded pressure (PPAQ), which was recorded at each measurement interval, was used to estimate left ventricular Macmillan Journals Ltd

2 514 BRITISH JOURNAL OF ANAESTHESIA filling pressure; mean right atrial pressure (PRA 0 ) was used to estimate right ventricular filling pressure. Mean pressures were obtained by electronic integration. Cardiac output (CO) was determined by thermodilution (Ganz and Swan, 1972). Lead II of the electrocardiogram was recorded to determine heart rate (HR). Systemic vascular resistance (SVR) was calculated according to a standard formula (Yang et al., 1972). The blood volume status of all animals was considered normal since oral intake had been unrestricted up to 1 h before the induction of anaesthesia and lactated Ringer's solution 1.5 ml kg" 1 h" 1 was administered i.v. throughout the experiment. Whole blood measurements Arterial blood samples were withdrawn for the determination of biochemical variables. The ionized calcium concentration ([Ca 2+ ]) was determined in heparinized specimens of whole blood (5 i.u. heparin per ml of whole blood) by a thermostatically controlled (37 C C) automated flow-through calciumselective electrode system (Orion SS 20). The system was calibrated as described previously (Madsen and Olgaard, 1977; Drop, Fuchs and Stulz, 1978). Blood-gas tensions and ph were measured at 37 C by the use of appropriate electrodes (Radiometer). Plasma measurements The total calcium concentration in plasma ([Ca]) was determined by EDTA titration using calcein as the indicator (Bett and Fraser, 1959), total protein by refractometry (Sunderman, 1944), and inorganic phosphorus (P ; ) was determined as the phosphomolybdate by spectrophotometry (Chen, Toribara and Warner, 1956). The concentrations of sodium (Na+) and potassium (K+) and the osmolality were determined by standard methods. Solutions The ACD solution was prepared by adding trisodium citrate g, citric acid g and dextrose 24.4 g to distilled water to a final volume of 1 litre. The calculated citrate concentration was 127 mmol litre" 1. The CPD solution was prepared by adding trisodium citrate g, citric acid g, monobasic sodium phosphate 2.22 g and dextrose g to distilled water to a final volume of 1 litre. The total citrate concentration in this solution was 111 mmol litre" 1. In both solutions, total citrate concentrations are those present in ACD and CPD solution formula A USP, but the proportions of trisodium citrate and citric acid were selected such that the concentration of Na+ would range between 149 and 152 mmol litre" 1, and this was confirmed by flame photometry. To study the effects citrate itself might have without a disturbance of calcium ion homeostasis, a solution of ACD was prepared as described, but the calcium ion concentration was titrated to approximately 1.10 mmol litre" 1 by the addition of CaCl 2. In all solutions, KC1 was added to ensure a final K + concentration of 4 mmol litre" 1 and ph was adjusted to 7.40 unit by the addition of TRIS buffer. These adjustments were necessary to avoid changes in any biochemical variable other than the one under study ([Ca 2 +]). Experimental programme Group I (w = 5). Following control measurements, one randomly selected citrate solution (ACD or CPD) was infused i.v. at a rate of 1.5 ml kg" 1 over a 30-s period. Haemodynamic measurements were made and arterial blood samples were withdrawn at 15 s and at 5-min intervals for up to 30 min following the termination of the infusion. Following a 30-min period, during which all the measured haemodynamic variables and [Ca 2+ ] had returned to their respective control values, the other citrate solution was infused at the same rate. Haemodynamic measurements were made and arterial blood specimens withdrawn as described. Group II (n = 6). ACD solution 1.5 ml kg" 1 was infused i.v. over a 30-s period and measurements made as described for group I. Following a 30-min period during which all the haemodynamic variables and [Ca 2+ ] had returned to their respective control values, beta blockade was instituted by the infusion of propranolol 0.5 mg kg" 1 i.v. and confirmed by a lack of tachycardia following an isoprenaline challenge (0.9 y.g kg" 1 over 1 min). Following a 20-min period, ACD solution 1.5 ml kg" 1 was infused again and measurements made as described in group I. Group III (n = 6). To determine whether citrate per se or the volume infused might alter haemodynamic function, the ACD solution in which [Ca 2+ ] had been titrated to 1.10 mmol litre" 1 was infused (1.5 ml kg" 1 ) and measurements made at the same time intervals as in group I. Statistical evaluation of data To determine the significance of the difference between the experimental data obtained in one group of animals Student's t test for paired data was applied. To determine the significance of the difference between data obtained in two groups of animals

3 HAEMODYNAMIC EFFECTS OF TRANSIENT HYPOCALCAEMIA 515 Student's t test for unpaired data was applied. Values are expressed as mean ± SEM. Differences were considered significant if P< RESULTS Effects of citrate Following the infusion of ACD solution i.v. in which [Ca 2+ ] had been adjusted to the normal range, the measured and calculated haemodynamic variables and all biochemical variables remained unchanged. Thus the possibility of an effect of citrate per se or the volume of fluid infused could be excluded. Effects of beta blockade The haemodynamic effects of beta blockade were examined by comparing the data obtained at normal [Ca 2+ ] before institution of beta blockade with those after beta blockade was established. Following the onset of beta blockade, HR decreased (133 ±3.2 v. 117±3.2 beat min" 1 ; /><0.001) as did CO (4.3±0.39 litre min- 1 v litre min- 1 ; P<0.05). PPA 0 increased from 5.5 ±0.6 to 7.2 ±1.0 mm Hg; P< The change in SVR was not significant. ACD v. CPD The haemodynamic variables measured before the infusion of ACD were not significantly different from those recorded before the infusion of CPD (figs 1, 2). The infusion of ACD was associated with a significant decrease in [Ca 2+ ] which was no longer significantly different from control at 30 min. The decrease in m.a.p. was significant up to 15 min. After a transient increase in CO recorded at 5 min, this variable was not different from control for the remainder of the SYSTEMIC 3000 VASCULAR RES/STANCE nnnn (dynes cm*) MEAN RIGHT A TRIAL immhg) MEAN PULMONARY ARTERY OCCLUDED ImmHg) MEAN ARTERIAL (mmhg) [Co 2 *] (immol litre' 1 ) 0.5- Control Control TIME (MIN) FIG. 1. Haemodynamic consequences of transient hypocalcaemia during halothane anaesthesia. Cardiac output either increased or remained unchanged while mean arterial pressure decreased. Thus decreased resistance in the systemic vasculature was the principal determinant of the decrease in m.a.p. The magnitude of these changes was independent of the type of citrate solution infused.

4 516 BRITISH JOURNAL OF ANAESTHESIA CARDIAC 6 OUTPUT (litre min' 1 ) 5 - ACD (1.5ml kg' 1 ) CPDU.5ml kg'j). 1 1= SEM ***P<0.05 ** P'0.02 * P<0.0\ t />< HEART RATE 140 (beat min' 1 ) 12OL 50 STROKE 40 VOLUME (ml/beat),., [C 2 Z (mmol litre' 1 ) Normok I Control 10 J_ j Control TIME (MIN) FIG. 2. Haemodynamic consequences of transient hypocalcaemia during halothane anaesthesia. M.a.p. decreased, while PPAQ increased (fig 1), with changes in CO and SV as noted here. observation period. A significant increase in PPA O was recorded 15 s following the infusion of citrate; changes in this variable were not significantly different from control thereafter. A decrease in SVR was noted up to the 5-min observation period. Increases in HR and PRA were present at 15 s only. Following i.v. infusion of CPD solution, changes in [Ca 2+ ] and in measured and calculated haemodynamic variables were not different from those recorded following ACD infusion. Influence of beta blockade on haemodynamic consequences of transient hypocalcaemia Before beta blockade, CO and SV were greater than control 5 min following ACD infusion. However, these variables were not significantly different from control despite an increase in PPK O and a decrease in m.a.p. at the corresponding time intervals when beta blockade was present (figs 3, 4). Biochemical variables and arterial blood-gas tensions The decrease in [Ca 2+ ] observed following the infusion of ACD was similar to that observed following the infusion of CPD. Values of Pa c02, ph, [Ca], Na+, K+, total protein and Pj remained unchanged throughout the observation periods and were not influenced by the type of citrate solution infused. Thus a transient decrease in [Ca 2+ ] was not apparent from a change in [Ca] (table I). DISCUSSION The results obtained in this study demonstrate that two commonly employed blood preservatives have similar effects on [Ca 2+ ] and haemodynamic function despite a 12.5% difference in total citrate concentration. Although a decrease in [Ca 2+ ] was associated with changes in both ventricular and peripheral vascular function, the alteration in peripheral vascular function (a decrease in SVR) was the principal determinant of the decreased arterial pressure. In addition, the myocardial depressant effects of transient hypocalcaemia were accentuated in the presence of beta blockade. Our data indicate that, despite a difference in total citrate concentration, the infusions of ACD and CPD

5 HAEMODYNAMIC EFFECTS OF TRANSIENT HYPOCALAEMIA 517 SYSTEMIC VASCULAR RESISTANCE (dyne. MEAN RIGHT ATRIAL (mm Hg) MEAN PULMONARY ARTERY OCCLUDED (mm Hg) _ r BEFORE 0 ADRENERG/C BLOCKADE - ACD(l.5ml kg" 1 ) I 1= SEM Halolhone Anaesthesia T"* FSl T T T 1 I 1 t AFTER 0 ADRENERG/C BLOCKADE AC0(l.5ml kg" 1 ). *** p* 0.05 * P< * P-=0.01 t P< "I _I I L \" hi'** T ;i -f _ - I L 1 MEAN ARTERIAL (mm Hg) U---J ; T T T I fcf'j (mmol litre'v 60 - t 1.5.Normal Control Control TIME (MIN) FIG. 3. Influence of beta blockade on haemodynamic consequences of citrate infusion during halothane anaesthesia. The variables shown were not significantly altered by beta blockade. TABLE I. Biochemical variables (mean ± SEM) during transient hypocalcaemia. Note that the disturbance in [Ca 2+ ] was not apparent from <[Ca] measurements. (* / 3 <0.001 v. control) ACD infusion After infusion (min) CPD infusion After infusion (min) Control Control [Ca 2+ ] (mmol litre- 1 ) 1.18± *± *± ±0.03 [Ca] (mmol litre" 1 ) ± ± ±0.1 Pi (mmol litre" 1 ) 1.3± ± ph (unit) Na+ (mmol litre- 1 ) K+ (mmol litre" 1 ) ± *± *± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±0.3

6 518 BRITISH JOURNAL OF ANAESTHESIA BEFORE /3 ADRENERGIC BLOCKADE ACD (1.5ml kg' 1 ) AFTER /? ADRENERGIC BLOCKADE AC0(l.5ml kg' 1 ) I = SEM 6 CARDIAC 5 OUTPUT (litre min' 1 ; 4 ***P<0.05 * P< * p<o.oi T t P< _ HEART RATE (beat min'v if-a I i? f i j 1 STROKE VOLUME (ml/ beat) [Ca *] (mmol'litre' 1 ) 05 /Normal 1, f^.,, II I I - - i' i i i Control Control TIME (MIN) 30 FIG. 4. Influence of beta blockade on haemodynamic consequences of citrate infusion during halothane anaesthesia. Before blockade, cardiac output and stroke volume increased significantly in response to decreased m.a.p. and increased PPAQ whereas, following blockade, alterations in CO and SV were insignificant despite decreased m.a.p. and increased in the intact animal were associated with similar alterations in [Ca 2+ ] homeostasis and haemodynamic function. We infused citrate solutions in which the citrate concentration was exactly that present in the solutions used for blood preservation as formulated in the Technical Manual of the American Association of Blood Banks (Miller, 1977). However, adjustments of [Na+], [K + ] and ph were made and the temperature was maintained at 37 C to eliminate changes in these variables and identify the effects of a change in [Ca 2+ ] only. We selected a citrate infusion of 1.5 ml kg- 1 to obtain [Ca 2+ ] values encompassing the range of hypocalcaemia encountered clinically. The volume of either preservative added to blood during collection (ACD 15 ml v. CPD 14 ml solution per 100 ml whole blood) is approximate and the maximum difference in final citrate concentration in blood, after collection, is of the order of 5%. Therefore, we compared effects of ACD with those of CPD at equal rates of infusion. Hedley-Whyte and associates (1976) noted the possible haemodynamic advantages of the i.v. infusion of CPD to the recipient of the blood. In our experiments, ACD and CPD infusion were followed by similar changes in [Ca 2+ ], and any haemodynamic advantages of one form of citrate over another were not observed. These findings are in good agreement with data of Olinger and colleagues (1976) who found that the haemodynamic consequences of ACD and CPD-stored blood were similar in patients following cardiac surgery and during haemodialysis. Our data demonstrate that, in the intact normovolaemic dog, a transient decrease in [Ca 2+ ] is associated with a similar change in m.a.p. Up to 15 min following the infusion of ACD, a decrease in m.a.p. was recorded while CO was either increased

7 HAEMODYNAMIC EFFECTS OF TRANSIENT HYPOCALCAEMIA 519 (at the 5-min observation period) or not different from control. Thus the change in m.a.p. which occurred was secondary to a decrease in the resistance to flow in the peripheral vasculature. A change in ventricular function occurred also. If myocardial contractility remained unchanged, a decrease in m.a.p. (ventricular afterload) would be expected to be associated with increased CO without a change in or with a decrease of FPA 0. In our experiments, when m.a.p. decreased, CO was either increased (at the 5-min period) or not different from control and PPA 0 increased, thus suggesting left ventricular dysfunction in addition to the change in peripheral vascular function. The magnitude of alterations in the performance of the ventricular pump secondary to the decrease in [Ca 2+ ] have been further denned recently in experiments in which data on the left ventricular function curve (LVFC) were collected during steady state deviations of [Ca 2+ ] below normal while the major haemodynamic determinants of ventricular performance (m.a.p., HR) were controlled. LVFC were displaced markedly to the right and downward (Drop et al., 1978). An effect of hypocalcaemia on the peripheral vasculature has received little attention in the past. It is possible that this peripheral site of action of hypocalcaemia has been overlooked or obscured in previous studies because of the nature of the experimental design, particularly with respect to the conditions present before the period of hypocalcaemia. For example. Bunker, Bendixen and Murphy (1962) may have overlooked the peripheral vascular manifestations of hypocalcaemia. These authors found that a decrease in the calculated [Ca 2+ ] (range mmol litre"" 1 ) was associated with a decrease in m.a.p. and a variable change in CO. According to our evaluation of their results, total peripheral resistance decreased in four of five dogs. Cooper and associates (1973) evaluated ventricular responses to the transfusion of citrated blood in the dog following a 15-min period of arterial hypotension. This condition may have influenced baseline haemodynamic variables. Denlinger and Nahrwold (1976) described arterial hypotension in a patient following the rapid transfusion of citrated blood during blood loss associated with surgery. A decrease in arterial pressure was associated with an increase in central venous pressure. However, data on PPA 0 and CO were not presented and the status of the circulating blood volume was uncertain. In clinical studies of the haemodynamic consequences of citrate-induced hypocalcaemia, the indices of haemodynamic function were recorded during and following the infusion of citrated whole blood administered to counteract a deficit in the circulating blood volume. Under these circumstances, the haemodynamic effects observed were not only those of hypocalcaemia but, in part also, those of volume loading. Hence, evaluation of the overall haemodynamic effects of hypocalcaemia may be less than satisfactory when performed in patients during blood transfusion. However, although it must be emphasized that the effects of citrate are of interest mainly in association with blood transfusion in the patient in whom the blood volume is likely to be reduced, it is important to determine the effects of a change in [Ca 2+ ] alone. Therefore, in our experiments the haemodynamic consequences of the infusion of citrate were examined in the normovolaemic dog. Our data are in agreement with those presented by Hinkle and Cooperman (1971) showing that the effects of the rapid infusion of citrated blood on [Ca 2+ ] are transient in nature. Our data are in contrast with those of Corbascio and Smith (1967) who investigated the effects of the infusion of citrate in dogs anaesthetized with nitrous oxide in oxygen with suxamethonium as the neuromuscular blocking agent. These authors showed that, following infusion of citrate, m.a.p. decreased in all animals and total peripheral resistance decreased in three of 11 dogs. A surprising finding in this study is that CO decreased without a change in peak left ventricular dpjdt. Unfortunately, [Ca 2+ ] was not measured. Although the reason for this discrepancy in results is not clear, the large variation in the changes observed in the haemodynamic variables recorded by these authors may have been related to variations in depth of anaesthesia. Controversy exists with respect to the need for calcium replacement therapy when decreased [Ca 2+ ] occurs during the transfusion of citrated blood or haemodialysis. Although Miller (1973) and Howland and others (1977) have proposed that routine calcium replacement therapy in patients during and following blood transfusion is not required, the adjustment of [Ca 2+ ] in patients may be appropriate when the disturbances in [Ca 2+ ] are severe or exist for a prolonged period of time. The amount of calcium to be infused should be guided by measurements of [Ca 2+ ]. Clinically, calcium chloride 5 mg kg- 1 may be administered and repeated if indicated by [Ca 2+ ] measurement. It appears that left ventricular dysfunction, noted in the presence of hypocalcaemia, was intensified by

8 520 BRITISH JOURNAL OF ANAESTHESIA beta blockade. Before beta blockade, CO and SV were greater than control at the 5-min observation period. In contrast, small changes in these variables were insignificant at the same time interval following beta blockade, despite a similar increase in PPA O and decrease in m.a.p. This finding may be important in patients presenting for major vascular or cardiac surgery. Propranolol therapy is common and transfusion of large amounts of banked blood is likely in these patients. It should be pointed out that conditions underlying the need for beta blocking drugs in patients may influence haemodynamic adjustment to citrate loading. The intensification by beta blockade of hypocalcaemia-induced alterations in ventricular function may be explained on the basis of a severely impaired delivery of calcium to the contractile proteins. Two factors may be responsible. With the institution of low [Ca 2+ ] in the circulating blood, available calcium within the myocardial cell may be reduced. In addition, Naylor (1967) has proposed that propranolol may impede transport of calcium from the sarcoplasmic reticulum to the contractile elements. However, it is possible also that, during hypocalcaemia, myocardial function is supported by increased catecholamines. Beta blockade would antagonize the effects of these catecholamines. ACKNOWLEDGEMENTS This study was supported in part by NIGMS grant and a grant from the Lichstenstein Stiftung, Basel, Switzerland (Dr Scheidegger). The authors wish to express their gratitude to Mrs A. M. Scheidegger and Ms C. Balkas for technical assistance and to Ayerst Laboratories for providing propranolol. Drop, L. J., Fuchs, C, and Stulz, P. M. (1978). Determination of blood ionized calcium in a large segment of the normal adult population. Clin. Chim. Acta., 89, 503. Drop, L. J. Geffin, G. A... O'Keefe, D. D., Chaffin, J. S., and Daggett, W. M. (1978). Left ventricular performance during sustained hypo- and hypercalcemia. Surg. Forum, 29, 259. Ganz, W., and Swan, H. J. C. (1972). Measurement of blood flow by thermodilution. Am. J. Cardiol., 29, 241. Hedley-Whyte, J., Burgess, G. E., Feeley, T. W., and Miller, M. G. (1976). Applied Physiology of Respiratory Care, pp Boston: Little Brown and Company. Hinkle, J. E., and Cooperman, L. H. (1971). Serum ionized calcium changes during citrated blood transfusion in anaesthetized man. Br. J. Anaesth., 43, Howland, W. S., Schweitzer, O., Carlon, G. C, and Goldiner, P. L. (1977). The cardiovascular effects of low levels of ionized calcium during massive transfusion. Surg. Gynecol. Obstet., 145, 581. Madsen, S., and Olgaard, K. (1977). Evaluation of a new automatic calcium ion analyzer. Clin. Chem., 23, 690. Miller, R. D. (1973). Complications of massive blood transfusions. Anesthesiology, 39, 82. Miller, W. V. (ed.) (1977). Technical Manual of the American Association of Blood Banks, 7th edn, p. 54. Washington D.C.: American Association of Blood Banks. Naylor, W. G. (1967). The effects of pronethalol and propranolol on lipid-facilitated transport of calcium ions. J. Pharmacol. Exp. Ther., 153, 479. Olinger, G. N., Hottenrott, C, Mulder, G. D., Maloney, J. V., Miller, J. V., Patterson, J., Sullivan, R. W., and Buckberg, G. D. (1976). Acute clinical hypocalcemic myocardial depression during rapid blood transfusion and postoperative hemodialysis. J. Thorac. Cardiovasc. Surg., 72, 503. Smith, N. T., and Hurley, E. J. (1969). Citrate infusion in dogs following autotransplantation. Arch. Surg., 98, 44. Sunderman, F. W. (1944). A rapid method for estimating serum proteins. J. Biol. Chem., 153, 139. Yang, S. S., Bentivoglio, L. G., Maranho, V., and Goldberg, H. (1972). From Cardiac Catherization Data to Hemodynamic Parameters, p. 37. Philadelphia: F. A. Davis Co. REFERENCES Bett, I. M., and Fraser, G. P. (1959). A rapid micromethod for determining serum calcium. Clin. Chim. Acta, 4, 346. Bunker, J. P., Bendixen, H. H. ; and Murphy, A. J. (1962). Hemodynamic effects of sodium citrate. N. Engl. J. Med., 266, 372. Chen, P. S., Toribara, T. Y., and Warner, H. (1956). Microdetermination of phosphorus. Anal. Chem., 28, Cooper, N., Brazier, J. R., Hottenrott, C, Mulder, D.G., Maloney, J. V., and Buckberg, G. D. (1973). Myocardial depression following citrated blood transfusion. Arch. Surg., 107, 756. Corbascio, A. N., and Smith, N. T. (1967). Hemodynamic effects of experimental hypercitremia. Anesthesiology, 28, 510. Denlinger, J. K., and Nahrwold, M. L. (1976). Cardiac failure associated with hypocalcemia. Anesth. Analg. {Cleve.), 55, 34. CONSEQUENCES HEMODYNAMIQUES DE L'INFUSION DE CITRATE SUR UN CHIEN ANESTHESIE: COMPARAISON ENTRE DEUX SOLUTIONS DE CITRATE ET INFLUENCE DU BLOCAGE BETA RESUME Nous avons compare les effets d'une solution d'acidecitrate-dextrose (ACD) avec ceux d'une solution de citratephosphate-dextrose (CPD), infusees a un taux egal, sur la concentration d'ions du calcium du sang et sur les differents indices de performances hemodynamiques, sur 17 chiens. On a etudie l'influence du blocage adrenergique beta sur ces variations. Les effets de l'acd et du CPD ont ete etudies sur cinq chiens et les resultats ont ete similaires. Les variations vasculaires peripheriques ont consume la principale cause de l'hypotension arterielle. Sur six chiens, le propranolol (a raison de 0,5 mg kg" 1 ) a intensifie la dereglement du ventricule gauche, induit par rhypocalcemie.

9 HAEMODYNAMIC EFFECTS OF TRANSIENT HYPOCALCAEMIA 521 HAMODYNAMISCHE FOLGEN EINER CITRATINFUSION IM NARKOTISIERTEN HUNDj VERGLEICH ZWEIER CITRATLOSUNGEN UND DIE EINWIRKUNG VON BETA-BLOCKADE ZUSAMMENFASSUNG Wir haben die Wirkungen einer Citratdextrosesaurelosung (ACD) mit denen einer, im gleichen Verhaltnis eingeflossten Citratphosphatdextroselosung (CPD) auf die Blutkalziumkonzentration und verschiedene hamodynamische Leistungsindexe in 17 Hunden verglichen. Es wurde der Einfluss einer beta-adrenergischen Blockade auf diese Veranderungen untersucht. Die Wirkungen von ACD und CPD wurden in fiinf Hunden studiert und erwiesen sich als gleichartig. Die Hauptursache fiir arterielle Hypotonie waren periphere Gefassveranderungen. Bei sechs Hunden verstarkte 0,5 mg kg" 1 Propanolol die durch Hypokalzamie herbeigefiihrte linksventrikulare Funktionsstorung. CONSECUENCIAS HEMODINAMICAS DE LA INFUSION DE CITRATO EN EL PERRO ANESTESIADO: COMPARACION ENTRE LAS DOS SOLUCIONES DE CITRATO Y LA INFLUENCIA DEL BLOQUEO BETA SUMARIO Comparamos los efectos de una solucion de dextrosacitrato-acido (DCA) con los de una solucion de dextrosafosfato-citrato (DFC), infusadas al mismo ritmo, sobre la concentration del ion calcio en la sangre y sobre los distintos indices de performancia hemodinamica en 17 perros. Se examino la influencia del bloqueo beta sobre dichas alteraciones. Se estudiaron los efectos de la DCA y de la DFC en cinco perros y estos eran similares. Los cambios vasculares perifericos fueron la causa principal de la hipotension arterial. En seis perros, el propanolol (0,5 mg kg~ l ) intensified la disfuncion ventricular izquierda inducida por hipocalcemia.